Organization of the Intrinsic Connectionsof the Monkey Amygdaloid Complex:Projections Originating in the Lateral

Nucleus

ASLA PITKANEN1 AND DAVID G. AMARAL2*1A.I. Virtanen Institute, University of Kuopio, FIN-70 211 Kuopio, Finland

2Department of Psychiatry and Center for Neuroscience, University of California-Davis,Davis, California 95616

ABSTRACTWe have used the anterograde tracer, Phaseolus vulgaris-leucoagglutinin (PHA-L) to

study the intrinsic projections of the lateral nucleus of the Macaca fascicularis monkeyamygdaloid complex. A reanalysis of the monkey lateral nucleus indicated that there are atleast four distinct cytoarchitectonic divisions: dorsal, dorsal intermediate, ventral intermedi-ate, and ventral. The major projections within the lateral nucleus originate in the dorsal,dorsal intermediate, and ventral intermediate divisions and terminate in the ventral division.The ventral division also projects to itself but does not project significantly to the other divisions ofthe lateral nucleus. Thus, the ventral division appears to be a site of convergence for informationentering all other portions of the lateral nucleus. There are substantial regional and topographicdifferences in the projections from each of the lateral nucleus divisions to other amygdaloid nuclei.The dorsal division projects to all divisions of the basal and accessory basal nuclei, to theperiamygdaloid cortex, the nucleus of the lateral olfactory tract, the dorsal division of theamygdalohippocampal area, and the lateral capsular nuclei. The dorsal intermediate divisionprojects to the intermediate and parvicellular divisions of the basal nucleus, to the parvicellulardivision of the accessory basal nucleus, and to the periamygdaloid cortex. The ventral intermediatedivision projects to the magnocellular division of the accessory basal nucleus and to the parvicellulardivision of the basal nucleus. The major projections from the ventral division are directed to theparvicellular division of the basal nucleus, the parvicellular division of the accessory basal nucleus,the medial nucleus, and the periamygdaloid cortex. Projections from all portions of the lateralnucleus to the central nucleus are generally very light. It appears, therefore, that each division of thelateral nucleus originates topographically organized projections to the other amygdaloid areas thatterminate in distinct portions of the target regions. The topographic organization of intrinsicamygdaloid projections raises the possibility that serial and parallel sensory processing may takeplace within the amygdaloid complex. J. Comp. Neurol. 398:431–458, 1998. r 1998 Wiley-Liss, Inc.

Indexing terms: amygdala; anterograde tracer; immunohistochemistry; primate; temporal lobe

The amygdala is a cytoarchitectonically complex struc-ture (Price et al., 1987; Amaral et al., 1992) that has beenimplicated in diverse behavioral functions ranging fromthe recognition of emotionally significant visual and audi-tory stimuli to the regulation of autonomic and endocrineresponses to these signals (Ledoux, 1992; Bechara et al.1995; LaBar et al., 1995; Scott et al., 1997). The amygdalahas also been associated with the mediation of stimulus-reward associative memories (Gaffan, 1992; Aggleton,1993), regulation of attentional processes (Gallagher andHolland, 1994), perception of facial affect (Adolphs et al.,1994; Young et al., 1995), and the interpretation of expres-

sive body movements (Bonda et al., 1996). Relatively littleis known, however, concerning the mechanisms by whichthe amygdala carries out these functions. In particular, itis not clear how the amygdala integrates information from

Grant sponsor: National Institutes of Health; Grant numbers: RR00169and R37 MH41479; Grant sponsor: Academy of Finland; Grant sponsor:Saastamoinen Foundation.

*Correspondence to: Dr. David G. Amaral, Center for Neuroscience, UCDavis, 1544 Newton Court, Davis, CA95616. E-mail: dgamaral@ucdavis.edu

Received 23 May 1995; Revised 2 April 1998; Accepted 2 April 1998

THE JOURNAL OF COMPARATIVE NEUROLOGY 398:431–458 (1998)

r 1998 WILEY-LISS, INC.

different afferent sources, how it processes the sensoryinformation that it receives, or how this information ischanneled ultimately to the major output nuclei. The lackof information concerning intrinsic amygdaloid circuitryhas become increasingly troublesome because the amyg-dala has now been linked clearly to a variety of humandiseases, including temporal lobe epilepsy (Hudson et al.,1993), Alzheimer’s disease (Hooper and Vogel, 1976), andschizophrenia (Reynolds, 1992).

The lateral nucleus is the major recipient of sensoryinformation from sensory association cortices (Price et al.,1987; Amaral et al., 1992). Visual information arisesmainly from inferotemporal cortex, gustatory and somato-sensory information arises from insular cortex, and audi-tory information arises from the superior temporal gyrus.Although it has been suggested that sensory information issegregated by modality within the lateral nucleus (Turner,1981), this conclusion has been controversial (Van Hoesen,1981). Recent studies from our own laboratory indicatethat there is a relatively high level of sensory separation inat least some portions of the monkey lateral nucleus(Stefanacci et al., 1996). However, there is virtually noinformation available on the organization of connectionswithin the lateral nucleus. High levels of interconnectivitymight integrate initially separated sensory inputs, whereasfew intranuclear connections would tend to maintainsensory segregation. It is equally unclear to what extent,and through which routes, information arriving in thelateral nucleus might be integrated with sensory or poly-sensory information arriving in the other amygdaloidnuclei. Inputs from the orbitofrontal cortex, for example,terminate primarily in the basal and accessory basalnuclei (Porrino et al., 1981). It would be interesting todetermine the extent to which these inputs are associatedwith visual information arriving, for example, from theinferotemporal cortex and terminating initially in thelateral nucleus. Finally, although it is commonly believedthat the sensory information arriving at the lateral nucleusis evaluated in the process of generating an appropriatespecies-specific response (LeDoux, 1992), the links be-tween sensory input and behavioral output are entirelyunknown.

Earlier studies demonstrated that the monkey lateralnucleus projects to the accessory basal nucleus, the centralnucleus, the medial nucleus, and the periamygdaloidcortex (PAC; Aggleton, 1985). More recently, we found an

undescribed yet robust projection from the lateral nucleusto the basal nucleus (Pitkanen and Amaral, 1991). Thisfinding raised the possibility that the monkey lateralnucleus might have a substantially richer complement ofintranuclear and internuclear intrinsic connections thanwas appreciated before and motivated this more compre-hensive reanalysis of its connectivity. In other species,recent detailed connectional studies (rat: Pitkanen et al.,1995; cat: Smith and Pare, 1994) do indeed indicate thatthe projections originating in the lateral nucleus are bothmore extensive and topographically organized. The pre-sent study is part of an ongoing program that is aimed atelucidating the intrinsic and extrinsic connections of themonkey amygdaloid complex. Here, we describe the intra-amygdaloid connections originating in the lateral nucleus,which were identified by using the anterograde tracer,Phaseolus vulgaris-leucoagglutinin (PHA-L).

MATERIALS AND METHODS

Animals and surgery

Sixteen male Macaca fascicularis monkeys (mean weight3.3 kg, range 2.5–4.5 kg) were used in this study. AnimalsM11–88 through M2–90 were preanesthetized with ket-amine HCl (10 mg/kg, i.m.), brought to a surgical level ofanesthesia with sodium pentobarbital (15 mg/kg, i.p.), andsupplemented as needed with additional intravenous dosesof sodium pentobarbital. Animals M3–90 through M15–91,were preanesthetized with an initial intramuscular dose ofketamine HCl, fitted with a tracheal cannula, and broughtto a surgical level of anesthesia with isoflurane. Allsurgeries were performed under sterile conditions, and theanimal’s heart rate, respiration, temperature, and bloodoxygenation were monitored throughout the procedure.The animal subject was placed in a Kopf stereotaxicapparatus, a midline incision was made, and a small burrhole was drilled in the skull at a position appropriate forthe injection of tracer. The coordinates for the PHA-Linjections were based on the atlas of Szabo and Cowan(1984): The dorsoventral coordinate for the injection wasdetermined by recording extracellular unit activity alongthe injection trajectory, as described previously (Amaraland Price, 1984). A glass micropipette (tip diameter 15–30µm) was lowered into the lateral nucleus, and a 2.5%solution of PHA-L in 0.1 M sodium phosphate buffer,

Abbreviations

AAA anterior amygdaloid areaAB accessory basal nucleusABmc accessory basal nucleus, magnocellular divisionABpc accessory basal nucleus, parvicellular divisionABvm accessory basal nucleus, ventromedial divisionAHA amygdalohippocampal areaAHAd amygdalohippocampal area, dorsal divisionAHAv amygdalohippocampal area, ventral divisionB basal nucleusBi basal nucleus, intermediate divisionBmc basal nucleus, magnocellular divisionBpc basal nucleus, parvicellular divisionCE central nucleusCEl central nucleus, lateral divisionCEm central nucleus, medial divisionCOa anterior cortical nucleusCOp posterior cortical nucleusEC entorhinal cortexH hippocampus

I intercalated nucleusL lateral nucleusLd lateral nucleus, dorsal divisionLdi lateral nucleus, dorsal intermediate divisionLv lateral nucleus, ventral divisionLvi lateral nucleus, ventral intermediate divisionM medial nucleusmc magnocellular division of the accessory basal nucleusNLOT nucleus of the lateral olfactory tractPAC periamygdaloid cortexPAC1 periamygdaloid cortex 1PAC2 periamygdaloid cortex 2PAC3 periamygdaloid cortex 3PACo periamygdaloid cortex, oral divisionPACs periamygdaloid cortex, sulcal divisionPIR, Pir piriform cortexPL paralaminar nucleusvm ventromedial division of the accessory basal nucleus

432 A. PITKANEN AND D.G. AMARAL

pH 7.4, was iontophoretically injected (5-µA pulsed DCcurrent, 7 seconds on and 7 seconds off, for 40–45 minutes).Postoperatively, the monkeys received analgesics as neededand prophylactic doses of antibiotics. All procedures werecarried out under an approved University of California-Davis Institutional Animal Care and Use Protocol andstrictly adhered to National Institutes of Health policieson primate animal subjects.

Perfusion and fixation of the brain

After a 12–14 day survival period, animals were deeplyanesthetized and perfused intracardially with one of thefollowing fixatives: 1) pH-shift fixation (cases M8–89,M9–89, M10–89, M3–90, M6–90, M9–90, M10–90, M1–91,M5–91, and M11–91): 0.9% NaCl 4°C, 250 ml/minute for 2minutes; 4% paraformaldehyde in 0.1 M sodium acetatebuffer, pH 6.5, 4°C, 250 ml/minute for 5 minutes and 100ml/minute for 15 minutes; 4% paraformaldehyde in 0.1 Msodium-borate buffer, pH 9.5, 4°C, 100 ml/minute for 30minutes. 2) Immunofixation (cases M11–88, M6–91, M7–91, M13–91, and M15–91): 1% paraformaldehyde in 0.1 Msodium-phosphate buffer, pH 7.2, 4°C, 250 ml/minute for 2minutes; 4% paraformaldehyde in 0.1 M sodium-phos-phate buffer, pH 7.2, 4°C, 250 ml/minute for 10 minutesand 100 ml/minute for 50 minutes. 3) One animal wasperfused by using paraformaldehyde-lysine-periodate(PLP) fixation (case M2–90: 4% paraformaldehyde, 0.075 ML-lysine, 0.01 M periodate, 0.0375 M sodium phosphate) asfollows: 0.9 M NaCl, 4°C, 250 ml/minute for 2 minutesfollowed by PLP-fixative, 4°C, 250 ml/minute for 10 min-utes and 100 ml/minute for 50 minutes. The brain wasthen blocked stereotaxically, postfixed in the final fixativesolution for 6 hours, and placed into a solution containing10% glycerol and 2% dimethylsulfoxide (DMSO) for 1 dayfollowed by 20% glycerol and 2% DMSO for 3 days. Thebrain was frozen by using the isopentane method de-scribed by Rosene et al. (1986) and stored at 270°C untilcut. Frozen sections were cut in the coronal plane at athickness of 30 µm with a sliding microtome and wereplaced into a cryoprotectant tissue collecting solution (30%ethylene glycol, 25% glycerin in 0.05 M sodium-phosphatebuffer; TCS). The sections were stored at 220°C until theywere processed immunohistochemically for the visualiza-tion of PHA-L.

Immunohistochemical staining of PHA-L

A 1-in-8 series of free-floating sections throughout theamygdala was processed essentially by using the methoddescribed by Gerfen and Sawchenko (1984), with slightmodifications. Sections were removed from TCS andwashed three times in 0.02 M potassium phosphate-buffered saline (KPBS), pH 7.4. To reduce nonspecificbinding, sections were incubated in a blocking solutioncontaining 0.5% Triton X-100 and 5% normal goat serum(NGS) in KPBS at room temperature for 6–8 hours. Thesections were then transferred to the primary antiserumsolution containing rabbit anti-PHA-L (diluted 1:8,000–1:12,000; B275; Dako, Carpinteria, CA), 0.3% Triton X-100,and 2% NGS in KPBS and incubated at 4°C for 2 days.After the primary antiserum incubation, the sections wereincubated in a solution containing biotinylated goat anti-rabbit immunoglobulin G (dilution 1:227; BA-1000; VectorLaboratories, Burlingame, CA), 0.3% Triton X-100, and 2%NGS in KPBS at room temperature for 1 hour. Thereafter,the sections were incubated in avidin-biotin solution (Elite

kit PK-6100, Vector Laboratories or BioStain basic kit11–001, Biomeda) for 45 minutes. The sections were thenrecycled into biotinylated secondary antiserum solutionand avidin-biotin solution for 45 minutes and 30 minutes,respectively. To visualize the PHA-L, sections were incu-bated in a solution containing 0.05% diaminobenzidineand 0.04% H2O2 in KPBS at room temperature for 8–45minutes. The sections were mounted on gelatin-coatedslides, defatted, and intensified with OsO4 and thiocarbo-hydrazide by using the method of Lewis et al. (1986).

Other histological procedures

An adjacent series of sections was stained with thioninto help determine the cytoarchitectonic boundaries of thedifferent amygdaloid nuclei. In addition, some of thePHA-L-stained sections were counterstained with Giemsa,which also intensifies the diaminobenzidine reaction prod-uct. We also stained a 1-in-16 series of sections from eachcase for acetylcholinesterase (AChE) to better define theboundary between the lateral and the very intenselyAChE1 basal nucleus (Hedreen et al., 1985). We also had alibrary of cases available for analysis in which series ofsections through the amygdala were processed immunohis-tochemically with antibodies raised against parvalbuminand calbindin-D28k (Pitkanen and Amaral, 1993a,b). All ofthese preparations were reanalyzed to define and establishthe boundaries of the different divisions of the lateralnucleus.

Analysis of sections

The sections were analyzed by using brightfield anddarkfield microscopy. The PHA-L labeling was consideredto constitute a terminal plexus if the labeled fibers inseveral successive sections were thin, branched, and vari-cose. If the labeled fibers were thick and straight and hadfew varicosities, then they were considered to be fibers enpassage. The camera lucida drawings of the boundaries ofthe various amygdaloid nuclei were drawn from adjacentthionin-stained sections with Canvas software on a Macin-tosh computer (Apple Computers, Cupertino, CA). Theoutlines were superimposed on the darkfield photomicro-graphs to indicate the location of the PHA-L1 terminalplexus. The locations of PHA-L-labeled cell bodies at thelateral nucleus injection site were plotted by using acomputer-aided digitizing system (Minnesota Datamet-rics, St. Paul, MN). These plots, on which the outlines ofnuclear boundaries were superimposed, were used tolocalize the injection sites within the lateral nucleus.

Low-power darkfield and brightfield photomicrographswere taken with a Nikon Multiphot 4 3 5 inch system(Tokyo, Japan). Higher magnification photomicrographswere taken with a Leitz Dialux 20 microscope equippedwith a Wild MPS 55 camera system.

RESULTS

Nomenclature of the amygdaloid nuclei

We have previously provided detailed descriptions of thenomenclature used for the nuclei of the monkey amygda-loid complex (Price et al, 1987; Amaral et al. 1992). Briefly,the deep nuclei include the lateral nucleus (previouslydivided into ventrolateral and dorsomedial divisions but,here, divided into dorsal, dorsal intermediate, ventralintermediate, and ventral divisions), the basal nucleus

INTRINSIC CONNECTIONS OF THE MONKEY AMYGDALA 433

(divided into magnocellular, intermediate, and parvicellu-lar divisions), the accessory basal nucleus (partitioned intomagnocellular, parvicellular, and ventromedial divisions),and the paralaminar nucleus. The superficial areas in-clude the anterior cortical nucleus, the medial nucleus, thenucleus of the lateral olfactory tract, the periamygdaliodcortex (PAC-divided into five subregions: oral division[PACo], corticies 1–3 [PAC1, PAC2, PAC3], and sucaldivision [PACs]), and the posterior cortical nucleus. Theremaining areas consist of the anterior amygdaloid area,the central nucleus (divided into lateral and medial subdi-visions), the amygdalohippocampal area (which has dorsaland ventral divisions), and the intercalated nuclei.

We previously divided the lateral nucleus into ventrolat-eral and dorsomedial subdivisions. This was based onobservations of Nissl-stained sections and AChE prepara-tions. Even in these preliminary analyses, however, it wasclear that there was substantially greater heterogeneity inthe lateral nucleus than in the two subdivisions identified.This view was confirmed from analysis of the projections

originating in the lateral nucleus and from observationsmade in a series of immunohistochemical studies (Pit-kanen and Amaral, 1993a,b). We have concluded that thelateral nucleus is actually divisible into at least foursubdivisions. The four subdivisions have been named:dorsal, dorsal intermediate, ventral intermediate, andventral. The positions of the different divisions and thecorrespondence of these divisions with patterns of stainingfor calbindin-D28k, AChE, and parvalbumin are shown oncoronal sections in Figures 1 and 2.

Dorsal division. The dorsal division is located in thedorsal portion of approximately the rostral half of thelateral nucleus (Fig. 1). The dorsal division appears to befairly homogeneous in appearance and encompasses whathas sometimes been called the claustral portion of thelateral nucleus. In Nissl preparations, the neurons of thedorsal division are medium to large in size and have apyramidal or modified pyramidal shape with a clearlyvisible nucleus and nucleolus (Figs. 1, 3A). The dorsaldivision demonstrates numerous parvalbumin-positive and

Fig. 1. Cytoarchitectonic characteristics of the dorsal, dorsal inter-mediate, ventral intermediate, and ventral divisions of the lateralnucleus. A: Brightfield photomicrograph from a Nissl-stained sectionshowing the location of dorsal, dorsal intermediate, and ventraldivisions of the lateral nucleus in the rostral portion of the amygdala.B: Brightfield photomicrograph from a Nissl-stained section demon-

strating the location of dorsal intermediate, ventral intermediate, andventral divisions of the lateral nucleus at the midlevel of the nucleus.Dashed lines indicate the boundaries between the divisions. Asteriskindicates the beginning of the amygdalohippocampal area. For abbre-viations, see list. Scale bar 5 500 µm.

434 A. PITKANEN AND D.G. AMARAL

calbindin-28k-positive (Fig. 2A) neurons and fibers but hasonly light AChE staining.

Dorsal intermediate division. The dorsal intermedi-ate division is the most heterogeneous division of thelateral nucleus. It begins nearly at the rostral pole of theamygdala and extends to the caudal pole of the lateralnucleus (Figs. 1, 2). In the caudal one-third of the amyg-dala, where the dorsal division has ended, the dorsalintermediate division forms the dorsal surface of thelateral nucleus. In Nissl preparations, neurons in thedorsal intermediate division have a variety of shapes andsizes, with subregions of different cell types and celldensities. Neurons range from small and round to angularor multipolar (Fig. 3B). Many of the neurons are verydarkly stained in Nissl preparations and are often groupedinto small clusters. It is likely that further work will leadto distinction of two or more independent divisions withinthe dorsal intermediate division.

The dorsal intermediate division has a very low densityof calbindin-D28k staining that stands in contrast to the

higher density of staining in both the dorsal and theventral divisions (Fig. 2A). The dorsal intermediate divi-sion also stains lightly in AChE preparations (Fig. 2B). Asin the dorsal division, there is dense staining for parvalbu-min immunoreactivity in the dorsal intermediate division(Fig. 2C).

Ventral intermediate division. The ventral interme-diate division is located in the middle one-third of thelateral nucleus rostrocaudally and forms a relatively nar-row area that has a ventrolateral-to-dorsomedial, obliqueorientation (Figs. 1, 2). In Nissl preparations, it is com-posed of a relatively homogeneous population of large,round neurons (Fig. 3C). This relative homogeneity ofneuronal constituents distinguishes it from the dorsallyadjacent dorsal intermediate division. The neuronal pack-ing density in the ventral intermediate division is lowerthan in the dorsal and dorsal intermediate divisions but ishigher than in the ventral division. The ventral intermedi-ate division stains heavily for AChE (Fig. 2B) and appearsto be equivalent to what has been referred to previously as

Fig. 2. Chemoarchitectonic characteristics of the dorsal, dorsalintermediate, ventral intermediate, and ventral divisions of thelateral nucleus. A: Brightfield photomicrograph from a section thatwas processed immunohistochemically for the detection of calbindin-D28k (CB). Note the intense staining in the dorsal and ventraldivisions. In the dorsal intermediate division, the density of immuno-reactivity is light. B: Brightfield photomicrograph from a sectionadjacent to the Nissl-stained section shown in Figure 1B stainedhistochemically for the enzyme acetylcholinesterase (AChE). Noteintense labeling of the ventral intermediate division. C: Brightfield

photomicrograph from a section that was processed immunohistochemi-cally for the detection of parvalbumin (PARV). The section was takenfrom the same rostrocaudal level as the section shown in B and inFigure 1B. Note the intense staining in the dorsal intermediatedivision. The ventral intermediate division contains numerous large,multipolar neurons; the density of terminal labeling, however, islighter than in the dorsal intermediate division. The ventral division islightly labeled in the PARV preparation. For abbreviations, see list.Scale bar 5 500 µm.

INTRINSIC CONNECTIONS OF THE MONKEY AMYGDALA 435

the ventrolateral division of the lateral nucleus (Price etal. 1987). This division also contains a substantial amountof calbindin-D28k-immunopositive elements. The ventralintermediate division contains a large number of parvalbu-min-positive neurons, even though the density of terminallabeling is lighter than in the dorsal intermediate division(Fig. 2C).

Ventral division. The ventral division begins at therostral pole of the lateral nucleus and continues through-out its rostrocaudal extent, making up most of the ventraland medial borders of the lateral nucleus (Figs. 1, 2). InNissl preparations, its major distinguishing characteristicis its relatively low density of neurons (Fig. 3D). Theneurons are variable in size and shape, with many large,round cells. The ventral division, like the dorsal division,demonstrates a high density of cell and fiber staining forcalbindin-D28k (Fig. 2A). At the rostral pole of the lateralnucleus, where the dorsal and ventral divisions make upmost of its dorsoventral extent, calbindin-D28 forms a

nearly continuous band of immunostaining throughout thenucleus. In contrast, there are relatively few parvalbumin-positive cells and terminals in the ventral division (Fig.2C). Similarly, the ventral division stains lightly for AChErelative to the ventral intermediate division (Fig. 2B).

Methodological aspects

Effects of the type of fixation on the appearance of

PHA-L labeling. The clearest PHA-L labeling offibers and terminals was achieved when the brain wasfixed by using the pH-shift procedure. The 4% para-formaldehyde fixation at pH 7.4 (immunofixa-tion) also produced good staining. The PLP-fixationprotocol resulted in clearly immunostained axons,but high background staining tended to obscure the label-ing.

The PHA-L injection site could be determined easily dueto strong staining of neuronal cell bodies and dendrites.

Fig. 3. High-magnification brightfield photomicrographs that illus-trate the unique cytoarchitectonic characteristics from the differentdivisions of the lateral nucleus. A: The dorsal division (Ld) containsneurons with cell bodies that are medium to large in size and have apyramidal or modified pyramidal shape.Arrows indicate large, pyrami-dal-shaped neurons with clearly visible nuclei and nucleoli. B: Manycell bodies in the dorsal intermediate division (Ldi) are darkly stained

and angular. Arrows indicate one of the neuronal clusters that istypical for this division. C: The ventral intermediate division (Lvi) iscomposed of a homogeneous population of large, round neurons.D: The most characteristic features of the ventral division (Lv) are thelow packing density of neurons and the high degree of variability intheir sizes and shapes. Scale bar 5 50 µm.

436 A. PITKANEN AND D.G. AMARAL

The mean number of PHA-L labeled neurons was esti-mated to be approximately 1,224 and varied from 400 cellsto 3,992 cells (data not shown). The distribution of labeledfibers and terminals in each case appeared to be moredependent on the location of the injection site than on thenumber of labeled neurons.

Location of PHA-L injections in the lateral nucleus.

The locations of injection sites in the different divisions ofthe lateral nucleus are summarized in Table 1 and areillustrated in Figure 4. In two cases, the injection involvedmainly the dorsal division (cases M7–91 and M10–90; afew cells were also labeled in the intermediate division ofthe basal nucleus, the anterior amygdaloid area, and therostral paralaminar nucleus). Six injections were locatedin the dorsal intermediate division (cases M9–90; M8–89;M9–89; M2–90; in which a few labeled cells were alsolocated in the ventromedial putamen; and M10–89). Incase M11–91, labeled neurons were located within thelateral nucleus but were uncharacteristically distributedfor nearly 4–5 mm dorsoventrally along the pipette tract.Most of the labeled cells, however, were located in thedorsal and dorsal intermediate divisions. Three injectionswere located in the ventral intermediate division (casesM13–91, M15–91, and M1–91), and five were in theventral division (case M3–90, in which a few cells werelocated in the paralaminar nucleus ventrally adjacent tothe lateral nucleus; and cases M6–90, M11–88, M5–91,and M6–91). Taken together, the injections involved alldivisions of the lateral nucleus and essentially all rostro-caudal levels of the nucleus.

Distribution of PHA-L-labeled fibersand terminals

Connections within the lateral nucleus. We beginour description of the intrinsic projections of the lateralnucleus by summarizing the organization of its intra-nuclear connections.

Injections located in the dorsal division. Injectionslocated in the dorsal division produced a relatively heavyprojection to the dorsal division itself (Table 1, Fig. 5).Fiber and terminal labeling was heaviest at the level of theinjection site or rostral to it. The dorsal division alsoprojected heavily to the ventral division, particularly to itsrostral half. Very little labeling was found in the dorsalintermediate and ventral intermediate divisions. In casesin which the injections involved the rostrolateral portion ofthe dorsal division, the lateral capsular nuclei (Amaraland Bassett, 1989) also received a projection.

Injections located in the dorsal intermediate division.Injections located in the dorsal intermediate division led toonly light labeling within the division (Figs. 6, 7). Thedorsal intermediate division gave rise to light projectionsto the rostral portion of the dorsal division and to theventral intermediate division. A substantially heavierprojection was directed to the rostrocaudal two-thirds ofthe ventral division.

Injections located in the ventral intermediate division.Injections located in the ventral intermediate divisiongave rise to a moderately heavy projection to itself thatwas distributed rostrally and caudally from the injectionsite (Fig. 8). Few if any labeled fibers were directed to thedorsal or dorsal intermediate divisions. Again, the ventralintermediate division was observed to originate a heavyprojection to the ventral division, particularly its caudalhalf (Table 1, Fig. 8D,E).

Injections located in the ventral division. Injectionsplaced in the ventral division resulted in a moderateintradivisional connection that was densest at the level ofthe injection site and caudal to it (Figs. 9, 10). Very littlelabeling was seen in the ventral intermediate division, andhardly any labeled fibers were observed in the dorsalintermediate or dorsal divisions (Table 1).

To summarize, the dorsal, dorsal intermediate, andventral intermediate divisions are weakly connected withone another, but they all send substantial projections tothe ventral division (Fig. 11). The dorsal division projectsmost heavily to the rostral half, the dorsal intermediatedivision projects to the rostral two-thirds, and the ventralintermediate division projects to the caudal half of theventral division. The ventral division itself has heavyintradivisional connections that seem to be directed primar-ily rostrocaudally. The ventral division, however, does notproject substantially to any other division of the lateralnucleus. Thus, there is a general dorsoventral flow ofinformation in the lateral nucleus to the ventral divisionthat has the potential for further integration throughsubstantial intradivisional, associational connections.

Projections of the lateral nucleusto the deep nuclei

Basal nucleus. All divisions of the lateral nucleusprojected to some portion of the basal nucleus. The projec-tions appear to be topographically organized, i.e., therostrocaudal and mediolateral location of the terminalfield depends on which division of the lateral nucleus isinjected (Table 1). A preliminary report on lateral nucleusprojections to the basal nucleus has been published (Pit-kanen and Amaral, 1991).

Projections to the parvicellular division of the basalnucleus. All divisions of the lateral nucleus projectedheavily to the parvicellular division of the basal nucleus(Table 1, Figs. 5–10). The projections show both rostrocau-dal and mediolateral topographies.

Rostrocaudal topography. All injections into the lat-eral nucleus lead to labeling throughout a substantialrostrocaudal extent of the parvicellular basal nucleus.Injections located in the dorsal or dorsal intermediatedivisions of the lateral nucleus, however, project mostheavily to the rostral half of the parvicellular basalnucleus (Figs. 5–7), and injections located in the ventralintermediate (Fig. 8) and ventral divisions (Figs. 9, 10)project most heavily to the caudal half of the parvicellulardivision.

Mediolateral topography. Lateral nucleus projectionsare generally heavier to the lateral half of the parvicellulardivision of the basal nucleus. This is true for injectionsinvolving the dorsal (Fig. 5), dorsal intermediate (Figs. 7,8), and ventral intermediate divisions (Fig. 8). Injectionslocated in the ventral division of the lateral nucleus, incontrast, also project to the medial portion of the parvicel-lular basal nucleus (Figs. 9, 10). The projections from theventral division of the lateral nucleus form distinct patchesof fibers and terminals in the parvicellular division of thebasal nucleus (Fig. 9C).

Projections to the intermediate division of the basalnucleus. In general, the density of terminal labeling islighter in the intermediate division than in the parvicellu-lar division of the basal nucleus (Table 1), although theintermediate division receives strong projections from atleast the dorsal intermediate division (Figs. 6, 7). The

INTRINSIC CONNECTIONS OF THE MONKEY AMYGDALA 437

TAB

LE

1.D

istr

ibu

tion

ofP

has

eolu

svu

lgar

is-l

euco

aggl

uti

nin

-Lab

eled

Fib

ers

and

Term

inal

s

Nu

clei

Inje

ctio

nlo

cati

on(d

ivis

ion

wit

hh

igh

est

nu

mbe

rof

labe

led

neu

ron

s)

Dor

sald

ivis

ion

(Ld)

Dor

sali

nte

rmed

iate

divi

sion

(Ldi

)V

entr

alin

term

edia

tedi

visi

on(L

vi)

Ven

tral

divi

sion

(Lv)

M7-

911

M10

-90

M9-

902

M11

-91

M8-

891

M9-

89M

2-90

M10

-891

M13

-91

M15

-911

M1-

91M

3-90

1M

6-90

M11

-88

M5-

91M

6-91

1

Dee

pn

ucl

eiL

ater

alD

orsa

l●●●

●●

●●

●●

●●

●C

C●

●C

CC

Dor

sali

nte

rmed

iate

C●

C●

●●

●●

●C

CC

●C

●C

Ven

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ure

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ensi

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inal

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ng;

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projections terminate most heavily in the lateral half ofthe rostral two-thirds of the intermediate division. A weakrostrocaudal gradient is also apparent. Injections locatedrostrally give rise to projections to the more rostral por-tions of the intermediate division than injections locatedcaudally. The ventral and ventral intermediate divisions

do not appear to provide substantial inputs to the interme-diate division of the basal nucleus. Injections located in theventral intermediate (Fig. 8) and ventral (Figs. 9, 10)divisions of the lateral nucleus give rise to thick, un-branched fibers that pass through the intermediate divi-sion of the basal nucleus seemingly without contributing a

Fig. 4. Schematic line drawings of coronal sections (A–D; arrangedfrom rostral to caudal, respectively) through the monkey amygdaloidcomplex indicating the location of Phaseolus vulgaris-leucoagglutinin(PHA-L) injection sites in experiments that were analyzed in the

present study. Each injection is indicated by a different shadingpattern. The anteroposterior coordinates shown in the upper rightcorner of each drawing are taken from the atlas of Szabo and Cowan(1984). For abbreviations, see list.

INTRINSIC CONNECTIONS OF THE MONKEY AMYGDALA 439

Fig

.5.

A–F

:Dar

kfiel

dph

otom

icro

grap

hs

wit

hn

ucl

ear

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ines

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own

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ean

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Fig

s.6–

10;

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eads

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cate

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icbo

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gure

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ich

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Ph

aseo

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-leu

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in(P

HA

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ctio

ns

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eren

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ons

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Fig

ure

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ism

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ral,

and

Fis

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ich

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omen

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ived

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ght

proj

ecti

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thre

eca

ses

(cas

esM

10–9

0,M

11–8

8,an

dM

6–91

).F

orab

brev

iati

ons,

see

list

.Sca

leba

r5

1m

m.

Fig

.6.

A–F

:C

ase

M8–

89,

inw

hic

hm

ost

ofth

eP

has

eolu

svu

lgar

is-l

euco

aggl

uti

nin

(PH

A-L

)-la

bele

dn

euro

ns

wer

elo

cate

din

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rost

ral

port

ion

ofth

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rsal

inte

rmed

iate

divi

sion

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eth

atth

epr

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tion

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rvic

ellu

lar

divi

sion

ofth

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saln

ucl

eus

ish

eavi

est

rost

rall

y(B

).T

he

inje

ctio

nsi

teis

indi

cate

dby

anar

row

inD

.Ast

eris

kin

dica

tes

are

gion

that

,

inth

ion

inpr

epar

atio

ns,

appe

ars

tria

ngu

lar

insh

ape

and

isco

mpo

sed

ofla

rge,

dark

lyst

ain

edce

lls

asso

ciat

edw

ith

peri

amyg

dalo

idco

rtex

(see

Am

aral

and

Bas

sett

,19

89).

For

abbr

evia

-ti

ons,

see

list

.Sca

leba

r5

1m

m.

Fig

.7.

A–F

:C

ase

M10

–89,

inw

hic

hth

eP

has

eolu

svu

lgar

is-l

euco

aggl

uti

nin

(PH

A-L

)-la

bele

dn

euro

ns

wer

elo

cate

din

the

cau

dal

hal

fof

the

dors

alin

term

edia

tedi

visi

onof

the

late

ral

nu

cleu

s.T

he

inje

ctio

nsi

teis

indi

cate

dby

anar

row

inD

.Ast

eris

kin

dica

tes

are

gion

that

,in

thio

nin

prep

arat

ion

s,ap

pear

str

ian

gula

rin

shap

ean

dis

com

pose

dof

larg

e,da

rkly

stai

ned

cell

sas

soci

ated

wit

hpe

riam

ygda

loid

cort

ex(s

eeA

mar

alan

dB

asse

tt,

1989

).F

orab

brev

iati

ons,

see

list

.Sca

leba

r5

1m

m.

Fig

.8.

A–F

:C

ase

M15

–91,

inw

hic

hth

eP

has

eolu

svu

lgar

is-l

euco

aggl

uti

nin

(PH

A-L

)-la

bele

dn

euro

ns

wer

elo

cate

din

the

mid

dle

one-

thir

dof

the

ven

tral

inte

rmed

iate

divi

sion

ofth

ela

tera

lnu

cleu

s.N

ote

that

the

proj

ecti

onto

the

parv

icel

lula

rdi

visi

onof

the

basa

lnu

cleu

s

ish

eavi

est

mor

eca

uda

lly

(C,D

)th

anin

case

M10

–89

(com

pare

wit

hF

ig.7

).T

he

inje

ctio

nsi

teis

indi

cate

dby

anar

row

inC

.For

abbr

evia

tion

s,se

eli

st.S

cale

bar

51

mm

.

Fig

.9.

A–E

:C

ase

M3–

90,

inw

hic

hm

ost

ofth

eP

has

eolu

svu

lgar

is-l

euco

aggl

uti

nin

(PH

A-L

)-la

bele

dn

euro

ns

are

loca

ted

inth

ero

stra

lon

e-th

ird

ofth

eve

ntr

aldi

visi

onof

the

late

ral

nu

cleu

s.N

ote

that

the

proj

ecti

onte

rmin

ates

thro

ugh

out

the

med

iola

tera

lex

ten

tof

the

parv

icel

lula

rdi

visi

onof

the

basa

ln

ucl

eus

rost

rall

y.T

he

inje

ctio

nsi

teis

indi

cate

dby

anar

row

inA

.Not

eal

soth

epa

tch

yap

pear

ance

ofte

rmin

alla

beli

ng

inth

epa

rvic

ellu

lar

divi

sion

ofth

eba

sal

nu

cleu

sin

C.

For

abbr

evia

-ti

ons,

see

list

.Sca

leba

r5

1m

m.

Fig

.10

.A

–F:

Cas

eM

6–91

,in

wh

ich

mos

tof

the

Ph

aseo

lus

vulg

aris

-leu

coag

glu

tin

in(P

HA

-L)-

labe

led

neu

ron

sw

ere

loca

ted

inth

eca

uda

lon

e-th

ird

ofth

eve

ntr

aldi

visi

onof

the

late

raln

ucl

eus.

Not

eth

atth

epr

ojec

tion

term

inat

esth

rou

ghou

tth

efu

llm

edio

late

rale

xten

tof

the

parv

icel

lula

rdi

visi

onof

the

cau

dal

basa

ln

ucl

eus.

Th

ein

ject

ion

site

isin

dica

ted

by

clos

edar

row

inD

.In

A,t

he

aste

risk

indi

cate

sa

regi

onth

at,i

nth

ion

inpr

epar

atio

ns,

appe

ars

tria

ngu

lar

insh

ape

and

isco

mpo

sed

ofla

rge,

dark

lyst

ain

edce

lls

asso

ciat

edw

ith

peri

amyg

-da

loid

cort

ex(s

eeA

mar

alan

dB

asse

tt,

1989

).In

D,

the

open

arro

win

dica

tes

the

med

ial

exte

nsi

onof

the

basa

lnu

cleu

s.F

orab

brev

iati

ons,

see

list

.Sca

leba

r5

1m

m.

terminal plexus. These passing fibers appeared to be inroute to the accessory basal nucleus and the PAC.

Projections to the magnocellular division of the basalnucleus. Only the dorsal and dorsal intermediate divi-sions of the lateral nucleus give rise to significant projec-tions to the magnocellular division of the basal nucleus(Table 1). These projections typically terminate through-out the rostrocaudal and mediolateral extents of themagnocellular division of the basal nucleus (e.g., seeFig. 7). In case M10–90, the projection was somewhatheavier at rostral levels of the magnocellular basal nucleus.However, the PHA-L injection in that case labeled someneurons in the rostral intermediate and magnocellulardivisions of the basal nucleus, which may have contributedto the rostrally situated terminal labeling.

To summarize, the dorsal and dorsal intermediate divi-sions of the lateral nucleus innervate all divisions of thebasal nucleus (Fig. 12). The ventral intermediate andventral divisions, however, project mainly to the parvicel-lular division of the basal nucleus. The dorsal and dorsalintermediate divisions tend to project more heavily torostral levels of the basal nucleus, and the ventral andventral intermediate divisions project primarily to caudallevels of the basal nucleus. Projections from all divisionstend to be heavier to the lateral aspect of the basal nucleusexcept for those that arise in the ventral division, whichare distributed more evenly across the mediolateral extentof the parvicellular division of the basal nucleus.

Paralaminar nucleus. The pattern and density oflabeling in the paralaminar nucleus closely resemble those

of the labeling seen in the parvicellular division of thebasal nucleus (Table 1, Figs. 5–10). Thus, injections involv-ing the dorsal (Fig. 5) and dorsal intermediate (Figs. 6, 7)divisions of the lateral nucleus give rise to light projectionsthat terminate mostly in the lateral half of the paralami-nar nucleus. Neurons in the ventral division of the lateralnucleus project more medially in the paralaminar nucleus(Figs. 9, 10). Like the projections to the basal nucleus,there is a weak rostrocaudal topography of the projectionsto the paralaminar nucleus; the dorsal divisions of thelateral nucleus project rostrally, whereas the ventral divi-sions project caudally.

Accessory basal nucleus. The accessory basal nucleusis the major target of projections from the lateral nucleus.The heaviest projections originate from the dorsal, ventralintermediate, and ventral divisions of the lateral nucleus(Table 1). Although all subdivisions of the accessory basalnucleus receive prominent projections from the lateralnucleus, the location of terminal labeling depends onwhich division of the lateral nucleus gives rise to theprojection (Table 1). Moreover, although the general topo-graphic relationships outlined for the basal nucleus alsohold true for the accessory basal nucleus, there are somecomplexities in the topography that are not evident in thebasal nucleus projections (Fig. 12).

Projections to the parvicellular division of the acces-

sory basal nucleus

Rostrocaudal topography. The dorsal and dorsal inter-mediate divisions of the lateral nucleus project to rostraland midrostrocaudal levels of the parvicellular divisions ofthe accessory basal nucleus, whereas the ventral interme-diate division projects more heavily to midrostrocaudaland caudal levels (Fig. 12).

Mediolateral topography. The lateral half of the lateralnucleus projects most heavily to the medial portion of theparvicellular division of the accessory basal nucleus,whereas medial portions of the lateral nucleus project tolateral portions of the parvicellular accessory basal nucleus(Fig. 12).

Projections to the magnocellular division of the accessorybasal nucleus. The heaviest projection to the magnocellu-lar division of the accessory basal nucleus originates in theventral intermediate division of the lateral nucleus(Table 1). The projection terminates most heavily in thecaudal two-thirds of the magnocellular division. Only oneother injection (case M7–91) led to substantial labeling inthe magnocellular division of the accessory basal nucleus.In that case, the injection was located in the dorsal divisionof the lateral nucleus and resulted in labeling that waslocated mainly in the rostral one-third of the magnocellu-lar division (Fig. 5). Other injections in the dorsal, dorsalintermediate, and ventral divisions resulted in very lightprojections to the magnocellular division of the accessorybasal nucleus (Table 1, Fig. 12).

Projections to the ventromedial division of the accessorybasal nucleus. All divisions of the lateral nucleus projectto the ventromedial division of the accessory basal nucleus(Table 1). In general, the projection from the lateralnucleus to the ventromedial division is weak and typicallycovers only the ventral portion of the division. The projec-tion is most prominent from the dorsal division of thelateral nucleus (Fig. 12).

To summarize, the parvicellular division of the accessorybasal nucleus is the major intrinsic target of the lateralnucleus. Although all portions of the lateral nucleus project

Fig. 11. Summary diagram demonstrating the major intranuclearconnections of the lateral nucleus. The thickness of the lines corre-sponds to the magnitude of the indicated projections.

446 A. PITKANEN AND D.G. AMARAL

Ld

Ldi

Lvi

Lv

ABpc

ABpc

ABvm ABpcABmc

ABmc

Bi

Bpc

Bpc

Bpc

Bi

Bi

Bmc

ROSTRAL

MID

CAUDAL

ROSTRAL

MID CAUDAL

Projections to thebasal nucleus

Projections to theaccessory basal nucleus

dorsal

ventral

med

iallate

ral

Fig. 12. This diagram summarizes the topography of the majorprojections from the different divisions of the lateral nucleus to thebasal and accessory basal nucleus: Three rostrocaudal levels (rostral,mid, and caudal) of each nucleus are presented. Each division of thelateral nucleus is indicated by a different color code. The color anddensity of dots in the basal nucleus and the accessory basal nucleirepresent the origin and density of projections, respectively. Note thatthe dorsal and dorsal intermediate divisions of the lateral nucleus

project heavily to the lateral aspects of the basal nucleus and to therostral two-thirds of the accessory basal nucleus. The ventral interme-diate and ventral divisions project to the parvicellular division of thebasal nucleus and to the more medial and caudal aspects of theaccessory basal nucleus. The orientation of the schematic diagrams isindicated in the upper left corner of the figure. For abbreviations, seelist.

to the parvicellular division, the heaviest projections arisefrom the dorsal and ventral divisions. The magnocellulardivision of the accessory basal nucleus receives a morelimited input from the lateral nucleus that is strongestfrom the ventral intermediate division. Finally, the ventro-medial division of the accessory basal nucleus generallyreceives a lighter input than the other two divisions, andthis arises mainly from the dorsal division of the lateralnucleus. Thus, the magnocellular and parvicellular divi-sions of the accessory basal nucleus receive their heaviestinputs from different portions of the lateral nucleus(Table 1, Fig. 12).

Superficial nuclei

PAC. In the present study we have divided the PACinto five subdivisions: PACo, PAC1, PAC2, PAC3, andPACs. In addition, there is a narrow region of the corticalsurface located in the caudal one-third of the amygdalabetween PAC3 and PACs that received a substantial inputfrom the lateral nucleus. Typically, the labeling in thisregion (see Figs. 10D, 13C,E, arrows) is continuous withequally heavy labeling in the parvicellular division of thebasal nucleus. This continuity of labeling suggests thatthis region is a medial extension of the basal nucleus ontothe cortical surface. This conclusion is also supported bythe continuity of dense staining for AChE (Fig. 13B). Theneurons in this region, however, are smaller and moredarkly stained than those in the surrounding regions (Fig.13A,D), including the parvicellular division of the basalnucleus. Although we would tentatively include this regionwithin the basal nucleus, this conclusion will need furthersupport from additional studies.

PACo. PACo is the most rostral of the PAC areas andbegins as a bulbous extension of the rostromedial temporallobe (Carmichael et al., 1994). Because we have notincluded this region previously in our studies of themonkey amygdaloid complex, we will briefly describe itschief cytoarchitectonic features. In coronal sections, thetransversely cut layer I appears first. More caudally, layerII cells appear in the ventral portion of the bulbousextension. Thereafter, the full three layers of the PACo areevident and are located between the dorsally situatedpiriform cortex and the ventrally located entorhinal cor-tex. At a more caudal level, PACo is bordered ventrally byPAC1. Layer II is the most conspicuous characteristic ofPACo: It is composed of arch-like clusters of darkly stained,spherical neurons (Fig. 14A). The upper portion of layer IIIis columnar and is continuous with layer II neuronalclusters. The deep portion of layer III is composed of large,round, lightly stained cells.

The heaviest projections from the lateral nucleus to thePAC terminate in PACo and PAC3. In fact, fiber andterminal labeling in PACo is among the heaviest of anystructure in the amygdala. The projection to PACo origi-nates primarily from the dorsal intermediate and ventraldivisions of the lateral nucleus. Labeled fibers and termi-nals originating in the dorsal and dorsal intermediatedivisions of the lateral nucleus innervate layers III and II.In one case (M8–89), some labeled fibers were also ob-served in layer I running parallel to the pial surface (Fig.14B). The projection from the ventral division of the lateralnucleus preferentially terminates in the deep portion oflayer III. Ventral injections produce only a few labeledfibers in the more superficial portions of the PACo. The

ventral intermediate division of the lateral nucleus doesnot project to the PACo.

PAC1 and PACs. The lateral nucleus projects onlyweakly to PAC1 and PACs (Table 1). The few labeled fibersobserved in this region mainly innervate layer III of thesecortical areas.

PAC2. PAC2 receives a substantially greater inputfrom the lateral nucleus than PACs and PAC1. The heavi-est projection to PAC2 originates in the dorsal and dorsalintermediate divisions of the lateral nucleus (Table 1),with a much lighter projection arising in the ventraldivision. Typically, we found a plexus of criss-crossingfibers located in layers II and III of PAC2 that occasionallycontinued into layer I (Fig. 14C,D).

PAC3. Like PACo and PAC2, PAC3 receives a lateralnucleus projection that originates primarily from thedorsal, rostral portion of the dorsal intermediate andventral divisions of the lateral nucleus (Table 1). Projec-tions typically terminate in layers II and III and areorganized topographically (Fig. 14E,F). The heaviest pro-jection originates in the ventral division, which contrib-utes fibers and terminals to both the rostral level and thecaudal level of PAC3. Projections originating in the dorsaland dorsal intermediate divisions, in contrast, terminatemost heavily in the rostral half of PAC3 and are lightermore caudally. The ventral intermediate division projectslightly throughout the rostrocaudal extent of PAC3.

Nucleus of the lateral olfactory tract. The projectionfrom the lateral nucleus to the nucleus of the lateralolfactory tract is light in most cases (Table 1). The heaviestprojection originates from the dorsal division of the lateralnucleus (Fig. 5). The projection typically ends in layers IIand III of the nucleus of the lateral olfactory tract andterminates throughout its full rostrocaudal extent (Fig.14G,H).

Medial nucleus. The projections from the lateralnucleus to the medial nucleus demonstrate a distinctlaminar termination that is related to the origin of theprojection (Table 1). The heaviest projection to the medialnucleus originates in the ventral division of the lateralnucleus. The projection terminates more heavily in layersII and III than in layer I (Fig. 15E,F). Injections located inthe dorsal or dorsal intermediate divisions of the lateralnucleus, in contrast, originate a projection that terminatespreferentially in layer I of the medial nucleus (Fig. 15G,H).The ventral intermediate division does not project to themedial nucleus.

Anterior cortical nucleus. The anterior corticalnucleus receives a light projection from the dorsal, dorsalintermediate, and ventral divisions of the lateral nucleus(Table 1). The projection terminates mainly in layers IIand III nucleus (Fig. 15C,D).

Posterior cortical nucleus. The dorsal and ventralintermediate divisions of the lateral nucleus give rise tothe major projections to the posterior cortical nucleus(Table 1). The dorsal division of the lateral nucleus projectsto layer II of the rostral portion of the posterior corticalnucleus. The ventral intermediate division projects prefer-entially to layer I of the caudal portion of the posteriorcortical nucleus.

Other nuclei

Central nucleus: Medial and lateral divisions. Theprojection from the lateral nucleus to the medial andlateral divisions of the central nucleus is extremely light

448 A. PITKANEN AND D.G. AMARAL

Fig. 13. A medial extension of the parvicellular division of thebasal nucleus (case M6–91)? A: Brightfield photomicrograph from aNissl-stained section. Brackets indicate the area (between the arrow-heads) shown at higher magnification in D. Asterisk indicates thelocation of the pipette track. B: Higher acetylcholinesterase (AChE)staining intensity is seen in this region. Open arrows in panels B-Eindicate the region shown in brackets in panel A. C: Darkfieldphotomicrograph from an adjacent Phaseolus vulgaris-leucoaggluti-nin (PHA-L)-stained section. Solid arrow indicates the location of theinjection. D: Higher magnification brightfield photomicrograph from a

Nissl section that shows the cytoarchitectonic organization of thisregion (arrows). E: Higher magnification darkfield photomicrographfrom the PHA-L-stained section showing the terminal plexus in thisregion (arrows). This cortical area is not like any other region of theperiamygdaloid cortex (PAC), and the labeled fibers form a continua-tion with the fiber plexus, terminating in the parvicellular division ofthe basal nucleus. This provides suggestive evidence that this regionconstitutes a medial extension of the basal nucleus onto the corticalsurface of the amygdala. For abbreviations, see list. Scale bars 5 1 mmin C (also applies to A,B), 200 µm in E (also applies to D).

INTRINSIC CONNECTIONS OF THE MONKEY AMYGDALA 449

Fig. 14. Higher magnification photomicrographs demonstratingdetails of the terminal labeling in different portions of the periamygda-loid cortex (PAC). The photomicrographs on the left are brightfieldphotomicrographs from Nissl-stained sections adjacent to the photomi-crographs on the right, which are darkfield photomicrographs fromPhaseolus vulgaris-leucoagglutinin (PHA-L)-stained sections. A,B: Inthe PAC, oral division (PACo; case M8–89; PHA-L injection into thedorsal intermediate division), note the darkly stained cellular clusters

in layer II and columnar organization of the upper portion of layer IIIin the Nissl preparation. The PHA-L-labeled terminals in this caseextend through all layers of the PACo. C,D: PAC2 (case M8–89).E,F: PAC3 (case M7–91; PHA-L injection into the dorsal division).G,H: Nucleus of the lateral olfactory tract (NLOT; case M7–91).Different layers are indicated with Roman numerals. Scale bar 5200 µm.

Fig. 15. Higher magnification photomicrographs demonstratingterminal labeling in different amygdaloid areas. On the left arebrightfield photomicrographs from Nissl-stained sections adjacent tothose on the right, which are darkfield photomicrographs of Phaseolusvulgaris-leucoagglutinin (PHA-L)-stained sections. A,B:Anterior amyg-daloid area (case M15–91; PHA-L injection into the ventral intermedi-ate division). C,D: Anterior cortical nucleus (case M8–89; PHA-L

injection into the dorsal intermediate division). E,F: Medial nucleus(case M6–91; PHA-L injection into the ventral division of the lateralnucleus). Note that the labeling is heavier in layers II and III than inlayer I. G,H: Medial nucleus (case M8–89; PHA-L injection into thedorsal intermediate division of the lateral nucleus). Note that, in thiscase, the labeling is heaviest in layer I. Scale bar 5 200 µm.

(Table 1, Figs. 5–10) and originates only from the dorsal,rostral portion of the dorsal intermediate and ventraldivisions of the lateral nucleus. Perhaps the most interest-ing aspect of the lateral nucleus projection to the centralnucleus involves that component that terminates aroundthe lateral aspect of the central nucleus (Fig. 16). InNissl-stained sections, the cells in the region laterallyadjacent to the central nucleus, which we have labeledCE*, are medium-sized and more darkly stained than theneurons in the lateral division of the central nucleus. Atthe caudal pole of the central nucleus, the CE* continuescaudally to form a shell around the caudolateral centralnucleus. The CE* can also be differentiated from thecentral nucleus on the basis of AChE staining: The CE*stains much more darkly than either the lateral division orthe medial division of the central nucleus (Fig. 16B,E).

Interestingly, the CE* region receives a projection from alldivisions of the lateral nucleus. The heaviest projectionoriginates in the ventral intermediate and ventral divi-sions of the lateral nucleus. Although additional analyseswill be necessary for confirmation, it is possible that CE* ishomologous to the lateral capsular division of the centralnucleus (McDonald, 1982; Cassell et al., 1986), whichclearly receives an input from the lateral nucleus (Pit-kanen et al., 1995).

Anterior amygdaloid area. There is only a weakprojection to the anterior amygdaloid area from the lateralnucleus (Table 1) that arises primarily from the ventralintermediate and ventral divisions (Fig. 15A,B).

Amygdalohippocampal area. We have previously di-vided the amygdalohippocampal area into two subdivi-sions: a rostrally located dorsal amygdalohippocampal

Fig. 16. A–F: Terminal labeling in the central nucleus (caseM6–91; Phaseolus vulgaris-leucoagglutinin [PHA-L] injection locatedin the ventral division). Two rostrocaudal levels are presented (themore rostral level is shown in A–C, and the more caudal level is shownin D–F). A and D are brightfield photomicrographs from Nissl-stainedsections that demonstrate the boundaries of the different divisions ofthe lateral nucleus. CE* indicates a region located lateral and caudalto the central nucleus that may be homologous to the lateral capsulardivision of the rat central nucleus. Arrowheads indicate the lateralborder of the CE*. B and E are brightfield photomicrographs fromacetylcholinesterase (AChE)-stained sections adjacent to the Nissl

sections. Note the intensely stained region, CE* (bordered laterally bywhite-tailed arrows), located lateral to the lateral division of thecentral nucleus. C and F are darkfield photomicrographs from PHA-L-stained sections adjacent to the AChE- and Nissl-stained sections.Very few labeled fibers are found in the medial and lateral divisions ofthe central nucleus. The CE* region, however, (bordered laterally bywhite-tailed arrows) demonstrates a moderate density of labeled fibers(large open arrows) at both rostrocaudal levels. Small open arrows inA–C indicate the same blood vessel as the small open arrows in D–F.Scale bar 5 500 µm.

452 A. PITKANEN AND D.G. AMARAL

area and a caudally located ventral amygdalohippocampalarea (Pitkanen and Amaral, 1992). Projections from thelateral nucleus provide a clear indication of the boundary(Fig. 17A,B) of the amygdalohippocampal area (which islightly labeled) with the accessory basal nucleus (which isheavily labeled). The dorsal, ventral intermediate, andventral divisions of the lateral nucleus give rise to lightprojections to the amygdalohippocampal area. The dorsaldivision projects preferentially to the rostral portion of thedorsal amygdalohippocampal area, whereas the ventralintermediate and ventral divisions of the lateral nucleusproject to both divisions of the amygdalohippocampal area(Fig. 17C,D).

Intercalated nuclei. Only one PHA-L injection (caseM6–91) that was located in the caudal one-third of theventral division resulted in a heavy projection to theintercalated nuclei. In that case, the innervated interca-lated nucleus was located between the magnocellulardivision of the basal nucleus and the central nucleus (Fig.10E).

Intraamygdaloid fiber pathways

Labeled fiber projections within the lateral nucleus itselfor from the lateral nucleus to the basal nucleus radiatefrom the injection site and extend directly to their site oftermination (Figs. 5–10, 13C). Projections to the accessorybasal nucleus from the dorsal and dorsal intermediatedivisions travel either dorsal to or through the magnocellu-lar and intermediate divisions of the basal nucleus toreach their targets (Figs. 5–7). Projections from the ven-tral intermediate and ventral divisions to the accessorybasal nucleus, however, pass through the intermediateand parvicellular divisions of the basal nucleus (Figs.8–10, 13C). Sometimes, the terminal plexus in the parvicel-lular division of the accessory basal nucleus forms acontinuation with the terminal plexus in the parvicellulardivision of the basal nucleus (Figs. 6, 7, 10). Projections tothe anterior cortical nucleus, the medial nucleus, and thePAC also travel directly from the injection site to the targetarea. To the anterior cortical nucleus, the fibers travel in

Fig. 17. A–D: Projections from the lateral nucleus to the amygdalo-hippocampal area (case M15–91; Phaseolus vulgaris-leucoagglutinin[PHA-L] injection into the ventral intermediate division). Two rostro-caudal levels are presented (A and B are more rostral, and C and D aremore caudal). A and C are brightfield photomicrographs from Nissl-stained sections. B and D are darkfield photomicrographs from the

adjacent PHA-L-stained sections. In B, note the abrupt change in thedensity of labeling at the border between the accessory basal nucleusand the dorsal division of the amygdalohippocampal area (indicatedwith a dashed line and arrows in A and B). More caudally, only thelateral portion of the amygdalohippocampal area receives a projection(D). For abbreviations, see list. Scale bar 5 500 µm.

INTRINSIC CONNECTIONS OF THE MONKEY AMYGDALA 453

the space between the deep nuclei and the anterior amyg-daloid area (Fig. 6). To the medial nucleus, the labeledfibers pass through the dorsal portions of the basal andaccessory basal nucleus (Fig. 10). Very few fibers are seenin the so-called ‘‘associational’’ fiber bundles located be-tween the lateral and basal nuclei or between the basaland accessory basal nuclei. The projections directed to themore caudomedially located areas, such as the posteriorcortical nucleus and the amygdalohippocampal area, passthrough the parvicellular division of the basal nucleus(Figs. 8–10).

DISCUSSION

We have traced the intraamygdaloid connections origi-nating in the lateral nucleus of the macaque monkey brainby using the discrete anterograde tracer, PHA-L. Themerit of this technique is that it allows the placement ofrelatively small injections in various positions throughoutthe lateral nucleus. Because of the precise localization ofinjection sites, a relatively rich topographic organizationhas been observed for the lateral nucleus projections.Moreover, due to the lack of background staining of thetracer, even local intralateral nucleus projections areobserved easily.

In the only previous report concerning the intrinsicconnectivity of the monkey amygdaloid complex, Aggleton(1985) found that the lateral nucleus projected to theaccessory basal nucleus, PAC, medial nucleus, centralnucleus, and amygdalohippocampal area. Because thatstudy employed relatively large injections of 3H aminoacids, however, it proved extremely difficult to identifyconnections between adjacent nuclei. We previously foundthat the lateral nucleus gives rise to a fairly prominentprojection to the basal nucleus (Pitkanen and Amaral,1991). Given the possibility that other local connections ofthe monkey lateral nucleus remained undiscovered, weundertook the present reanalysis of these connections. Inthe course of carrying out the current studies, we alsoreexamined the cytoarchitectonic organization of the lat-eral nucleus. These studies were informed both by the dataemerging from the PHA-L studies as well as other chemo-anatomical data. We have concluded that the lateralnucleus has four cytoarchitectonically distinct subdivi-sions (dorsal, dorsal intermediate, ventral intermediate,and ventral) that have different intraamygdaloid connec-tions. We have been able to confirm most of the connectionsdescribed by Aggleton (1985) except for the projection tothe central nucleus.

Classical cytoarchitectonic studies of the primate amyg-daloid complex have often partitioned the lateral nucleusinto several subdivisions. Koikegami (1963), for example,reviewed data from a variety of previous studies, includinghis own, and concluded that the lateral nucleus of themonkey has seven subdivisions. Based on our own analysisof Nissl-stained material as well as histochemical andimmunohistochemical preparations, we have concludedthat there are at least four subdivisions. Perhaps themajor contribution of the current study is the finding thateach of these divisions gives rise to a unique complement ofintrinsic connections. Each division gives rise to projec-tions to itself, to one or more of the other divisions of thelateral nucleus, and to one or more of the other amygdaloidnuclei, and all of these projections demonstrated a veryorderly, even point-to-point, topographic organization. At

least two general organizational principles emerged fromanalysis of the data. First, within the lateral nucleus,there is a general flow of information from the dorsallysituated divisions to the ventral division. The ventraldivision, therefore, has the potential for building an inte-grated representation of information entering the rest ofthe lateral nucleus. Second, the internuclear projections ofthe lateral nucleus were organized such that the dorsaldivisions of the lateral nucleus tended to project moreheavily to rostral levels of the recipient nuclei, and ventraldivisions of the lateral nucleus projected to caudal levels ofthe other nuclei. This raises the interesting possibility thatsensory information entering different parts of the lateralnucleus may remain relatively segregated through severalstages of intrinsic amygdaloid circuitry. To discuss thisfurther, we will briefly review data addressing the issue ofwhere the lateral nucleus receives its sensory information?

Origin and topography of cortical inputs tothe lateral nucleus and the relationship to

intranuclear connections

The lateral nucleus is the primary entry point forcortical sensory information to the monkey amygdaloidcomplex. It receives visual information from the unimodalvisual area TE (Herzog and Van Hoesen, 1976; Aggleton etal., 1980; Turner et al., 1980; Turner, 1981; Van Hoesen,1981; Iwai and Yukie, 1987; Iwai et al., 1987; Webster etal., 1991), somatosensory information from the posteriorinsula (Mufson et al., 1981; Turner, 1981; Van Hoesen,1981; Friedman et al., 1986), auditory information fromthe auditory association cortex TA (Turner et al., 1980; VanHoesen, 1981), and gustatory information from the ante-rior insular cortex (Turner et al., 1980; Van Hoesen, 1981).Based on the studies of Turner et al. (1980) and VanHoesen (1981), the terminal fields of projections fromdifferent sensory modalities overlap only partially. Visualinformation, for example, terminates predominantly in thedorsolateral portion of the lateral nucleus. Somatosensoryinformation and gustatory information terminate preferen-tially in the dorsomedial half of the lateral nucleus.Auditory inputs are directed to ventrolateral portions ofthe lateral nucleus. Although a comparison of the locationof afferent inputs from different modalities described inearlier studies with the divisions of the lateral nucleusdescribed in the present study must be considered prelimi-nary, it appears that the dorsal, dorsal intermediate, andventral intermediate divisions of the lateral nucleus arethe regions that receive these sensory inputs. The dorsaldivision of the lateral nucleus, for example, seems to beinnervated preferentially by visually related inputs aris-ing from the inferotemporal cortex (Turner et al., 1980;Van Hoesen, 1981; Iwai and Yukie, 1987; Iwai et al., 1987;Webster et al., 1991).

The present study demonstrates that the dorsal, dorsalintermediate, and ventral intermediate divisions of thelateral nucleus have relatively meager connections withintheir division compared with the more robust projectionsthat they contribute to the ventral division. The ventraldivision, in contrast, gives rise to substantial intradivi-sional connections but almost no projections to the otherdivisions. The ventral division, therefore, may reasonablybe portrayed as the polysensory convergence region of thelateral nucleus. It is of interest that this portion not onlyprojects to the parvicellular division of the basal nucleus(which receives input from other polysensory cortical

454 A. PITKANEN AND D.G. AMARAL

regions, such as the subiculum and areas TF and TH of theparahippocampal cortex; Stefanacci et al., 1996), but it isthe only region of the lateral nucleus that projects promi-nently to the entorhinal cortex (Pitkanen and Amaral,unpublished observations), which receives cortical sensoryinputs only from other polysensory regions. Given theheterogeneity of inputs to the lateral nucleus as well as thedifferences in local connectivity, it is of interest to considerthe relationships of the various divisions of the lateralnucleus with other regions of the amygdaloid complex.

Channeling of information from the lateralnucleus to the other amygdaloid areas

The lateral nucleus gives rise to substantial intraamyg-daloid projections to the basal and accessory basal nucleiand to the PAC. The projections from different divisions ofthe lateral nucleus, however, terminate in different divi-sions of the recipient nuclei. The dorsal division, forexample, projects to all divisions of the basal and accessorybasal nuclei. The dorsal intermediate division also sends asignificant projection to all divisions of the basal nucleus,but its projections to the accessory basal nucleus aresubstantially lighter than those from the dorsal division.The ventral intermediate division, in contrast, sends onlya light projection to the basal nucleus involving mainly theparvicellular division. In contrast, it projects heavily to themagnocellular division of the accessory basal nucleus. Theventral division projects heavily to the parvicellular divi-sion of basal nucleus and to the parvicellular division ofthe accessory basal nucleus. Even when two or moredivisions of the lateral nucleus project to the same divisionof a recipient nucleus, the topographic organization of theprojections tends to keep the terminal fields segregated.Thus, the dorsal divisions tend to project to more rostrallevels of a particular subdivision of a recipient nucleus,whereas the ventral divisions of the lateral nucleus projectto more caudal levels of the subdivision. These data lead tothe suggestion that, unlike the hippocampal formation, inwhich intrinsic connections tend to be highly divergent(Amaral and Witter, 1989), there appears to be a morediscrete or point-to-point flow of information within theintrinsic circuitry of the amygdaloid complex.

Overview of lateral nucleus connections andfunctional implications

The heaviest projections from the lateral nucleus to thebasal nucleus are directed to the parvicellular division. Infact, all divisions of the lateral nucleus send a substantialprojection to the parvicellular division of the basal nucleus.The parvicellular division of the basal nucleus, in turn,gives rise to projections to the hippocampal formation,thalamus, striatum, and frontal lobe (for review, seeAmaral et al. 1992). Interestingly, the projections from thelateral nucleus to the parvicellular division of the basalnucleus are highly topographically organized and oftenterminate in a patchy fashion. This raises the possibilitythat the lateral nucleus projections might activate subsetsof neurons in the parvicellular division of the basal nucleusthat interact with only certain of the brain regions towhich it projects. The parvicellular division of the basalnucleus receives differentially localized inputs from otherbrain regions as well. Aggleton (1986), for example, foundthat the projection from the hippocampus terminatedmore heavily in the medial portion of the parvicellularbasal nucleus whereas, the perirhinal cortex projects more

laterally. The finding that the dorsal, dorsal intermediate,and ventral intermediate divisions also project to theparvicellular basal nucleus indicates that this regionreceives incoming sensory information both in a relativelyunprocessed state and after convergence within the ven-tral division of the lateral nucleus.

The intermediate and magnocellular divisions of thebasal nucleus receive substantial projections from thedorsal and dorsal intermediate divisions of the lateralnucleus, which are connected with the visual associationcortices of the inferotemporal cortex (Turner et al., 1980;Van Hoesen, 1981; Iwai and Yukie, 1987; Iwai et al., 1987;Webster et al., 1991). What is interesting about thisconnection (and discussed more fully in Pitkanen andAmaral, 1991) is that the magnocellular and intermediatedivisions of the basal nucleus give rise to the major returnprojection to the visual cortex (Mizuno et al., 1981; Tiggeset al., 1982, 1983; Amaral and Price, 1984; Amaral, unpub-lished observations). In fact, these projections innervatethe very earliest stages of cortical visual processing in areaV1 (Amaral and Price, 1984). Thus, the connections fromthe dorsal and dorsal intermediate divisions of the lateralnucleus to the intermediate and magnocellular divisions ofthe basal nucleus provide a relatively short route by whichthe amygdala may influence early stages of visual process-ing. This pathway also provides the substrate for visualinformation derived from the temporal lobe to trisynapti-cally modify information processing in some of the otheroutputs of the magnocellular basal nucleus, such as theorbitofrontal cortex.

The lateral nucleus also projects heavily to the accessorybasal nucleus. In fact, based on the density of termination,the accessory basal nucleus is perhaps the major site oftermination of the lateral nucleus. Most of the projectionsare directed to the parvicellular division, particularly, toits rostral half. The magnocellular division receives aprominent projection from the ventral intermediate divi-sion of the lateral nucleus. Previous studies have shownthat the magnocellular division of the accessory basalnucleus, rather than the parvicellular division, is intercon-nected with the visual association cortex (Turner et al.,1980; Van Hoesen, 1981; Iwai and Yukie, 1987; Iwai et al.,1987; Webster et al., 1991). Thus, the visually relatedportion of the accessory basal nucleus is not as heavilyconnected with the dorsal division of the lateral nucleus asthe visually related areas in the basal nucleus.

In the autoradiographic study of Aggleton (1985), theventral portion of the lateral nucleus was shown to projectto the medial nucleus. We confirmed this finding andobserved that the ventral division of the lateral nucleusoriginates a heavy projection to the deep layers of themedial nucleus, whereas the dorsal division is the origin ofa heavy projection to the superficial layer of the medialnucleus. These connections may provide one route bywhich incoming sensory information may influence hypo-thalamic function to elicit autonomic and endocrine re-sponses (see Price et al., 1987).

The PAC is the major site of termination for olfactoryinformation entering the amygdaloid complex (Turner etal., 1978). It is noteworthy that the visually related dorsaldivision of the lateral nucleus as well as the ‘‘polysensory’’ventral division give rise to the most prominent inputs tothe PAC. This raises the possibility that the PAC may beone site of visual-olfactory association.

INTRINSIC CONNECTIONS OF THE MONKEY AMYGDALA 455

Aggleton (1985) described a substantial projection fromthe lateral nucleus to the central nucleus. We were unableto confirm this projection and found only a light projectionfrom the lateral nucleus to the central nucleus. Onepossible explanation for this discrepancy is that the rela-tively large 3H-amino acid injections in the Aggleton studymay have involved the basal nucleus somewhat, and it wasprojections from this nucleus rather than from the lateralnucleus that were observed. We have observed that, whenPHA-L injections are placed in the magnocellular divisionof the basal nucleus, there are prominent projections to thecentral nucleus (Amaral, unpublished observations).

In contrast to the relative lack of connections to thecentral nucleus proper, we did observe a heavy projectionfrom the lateral nucleus to the region that forms a capsulearound the lateral and caudal borders of the centralnucleus. Cytoarchitectonically, this region is different bothfrom the other divisions of the central nucleus and fromthe adjacent putamen. We provisionally consider thisregion to be homologous to the lateral capsular division ofthe central nucleus of the rat (McDonald, 1982; Cassell etal., 1986). In the rat, the lateral capsular division of thecentral nucleus receives a strong input from the lateralnucleus (Pitkanen et al., 1995). It will be interesting todetermine whether these ‘‘lateral capsular neurons’’ in themonkey have subcortical projections similar to those of thecentral nucleus proper.

Comparison of the intraamygdaloidconnections originating in the rat, cat, and

monkey lateral nucleus

Smith and Pare (1994) have described the intraamygda-loid connections of the lateral nucleus in cat by using thePHA-L method, and we have conducted a similar study inthe rat (Pitkanen et al., 1995). In rat, cat, and monkey, themajor intraamygdaloid targets of the lateral nucleus arethe basal and accessory basal nuclei. Although we havedemonstrated in rat and monkey that the PAC, the medialnucleus, and the amygdalohippocampal area receive projec-tions from at least some portions of the lateral nucleus,Smith and Pare found only a light projection to the PACand found little or no projection to the other areas in thecat. Those authors reported that, in the cat, the medialportion of the lateral division of the central nucleusreceived a prominent projection from the lateral nucleus.We have found projections from the lateral nucleus, asdescribed above, only to the lateral capsular division of therat central nucleus and perhaps the homologous area inthe monkey. Whether there are real species differencebetween the cat on the one hand and the rat and monkeyon the other hand remains to be determined.

We currently have little information concerning thetransmitter content of the intraamygdaloid connections inmonkey. Most efferent intraamygdaloid terminals originat-ing in the lateral nucleus in the rat (Stefanacci et al., 1992)and all in the cat (Smith and Pare, 1994) make asymmetricsynapses with dendritic spines or shafts of the postsynap-tic neurons, suggesting that they are excitatory. In the cat,these projections appear to be glutamatergic (Smith andPare, 1994).

Functional significance

The primate amygdaloid complex has been implicated inthe role of interpreting sensory information in relation to

species-specific needs or preferences. This function may beinvolved in interpretations that have substantial survivalvalue, such as recognizing prey vs. predator, but it mayalso have more subtle goals, such as interpreting andproducing gestures in social communication. In line withanimal studies, recent functional imaging studies of hu-mans have provided convincing evidence that the amyg-dala is involved in judging the emotional significance ofboth visual and auditory stimuli. For example, the humanamygdala has been shown to be involved intimately in theevaluation of facial affect (Adolphs et al., 1994; Young etal., 1995), perception of expressive body movements (Bondaet al., 1996), and recognition of vocal affect (Scott et al.,1997). There is little concrete information available, how-ever, concerning how the amygdala achieves these interpre-tive functions and evokes appropriate, species-specificresponses. For instance, do these sensory interpretationsand the resultant evocation of appropriate behaviors takeplace within the amygdala, or is the amygdala simply aperceptual filter for salient visual or other sensory images,which then evoke appropriate species-specific behaviorsthrough connections with other structures (Damasio, 1989)?

Given the facts that the lateral nucleus receives rela-tively segregated sensory information from several sen-sory modalities, that there is multimodal convergence ofthis information in the ventral division of the lateralnucleus, and that all divisions give rise to projections toseveral of the other amygdaloid nuclei, one could suggestthe following speculation. The lateral nucleus may beconsidered to act as a perceptual filter that has, as itsprimary role, the interpretation of the species-specificsalience of incoming sensory stimuli. The outputs of thelateral nucleus to other amygdaloid nuclei would be in-volved in orchestrating the autonomic, visceral, sensory,motor, and mnemonic components of an appropriate behav-ioral response. The topographic organization of sensoryinputs to the lateral nucleus may relate to the evocativecapacity of incoming stimuli. Thus, if an organism vieweda predator or heard the characteristic sound of its ap-proach, then either sensory input might be sufficient toelicit an escape response. The instigation of the behavioralresponse, therefore, might be the result of the output ofunimodal regions of the lateral nucleus. However, if theorganism’s view is obscured or if the sound of the predatoris muffled, then perhaps only the conjunction of the visualand auditory stimuli (now interpreted by the ventraldivision of the lateral nucleus) would be sufficient to clarifythe situation and result in an appropriate response. Clearly,a concise evaluation of the behavioral roles of the amyg-dala will necessitate sophisticated electrophysiologicaland behavioral analyses. However, a necessary componentfor understanding the function of the amygdala will be theexplication of the routes through which sensory informa-tion can flow through its various nuclei and corticalregions. The current study is a first step in providing adetailed circuit diagram of the primate amygdala. Futurepapers will provide equally detailed analyses of each of theother major nuclei of the amygdaloid complex.

ACKNOWLEDGMENTS

We thank Ms. Janet Weber and Ms. Mary Ann Lawrencefor histological assistance and Mr. Kris Trulock for photo-graphic processing. This work was conducted in part at the

456 A. PITKANEN AND D.G. AMARAL

California Regional Primate Research Center in Davis,California. A.P. was supported by the Academy of Finland,the Fogarty International Fellowship (1 F05 TW04343),and the Saastamoinen Foundation.

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