basal ganglia ppt
TRANSCRIPT
Basal Ganglia
Direct and Indirect Pathways and Connections
Mary K. Vaughan, Ph.D.
Basal Ganglia Game Plan
Neostriatum a.k.a. Striatum
Dorsal component of neostriatum
Caudate nucleus Putamen
Ventral component of striatum
Nucleus accumbens**Olfactory tubercle -
Important in Limbic Loop in phase 3
Somatotopy of Inputs to the Caudate and Putamen
Head of the caudate Frontal eye fields and prefrontal cortex
Dorsal PutamenInput from leg area of cortex
Ventral putamenInput from face and hand area of cortex
PaleostriatumConsists of two subnuclei
globus pallidus interna (Gpi)globus pallidus externa (Gpe)
GPe
GPi
Substantia nigraFound in the mesencephalonConsists of two subnuclei
substantia nigra pars compacta (SNpc)substantia nigra pars reticulata (SNpr)
Substantia nigra
Subthalamic nucleus
Subthalamic nucleus
Four Nuclei of Basal GangliaCaudate/putamenGlobus pallidus
GPiGPe
Substantia nigrapars compacta (SNpc)pars reticulata (SNpr)
Subthalamic nucleus
Ansa lenticularis
Ansa lenticularis exits from the globus pallidus interna (Gpi), comes around the internal capsule and joins other tracts of the thalamic fasciculus
Lenticular Fasciculus
Lenticular fasciculus exits from Gpi and forms part of the border of the subthalamic nucleus
Joins other tracts in thalamic fasciculus
Thalamic FasciculusA collection of tracts that are destined for the VL and some for the VA as well.
Composed of the:Lenticular fasciculusAnsa lenticularisNigrothalamic tractDentatothalamic tract from cerebellum
Subthalamic Fasciculus
A loop connectingGPe with STN via GABAergic pallido-subthalmic projections
Subthalamic nucleus projects back to the GPi via subthalamo-pallidal excitatory glutaminergic projections
Output Thalamic Nuclei
Part of the basal ganglia output back to the cortex
Output thalamic nuclei
Part of thalamic output back to the cortex
Other output to nuclei of the brain stem
Pedunculopontine nuclei – a nucleus of the old motor system in the locomotor area of the reticular formation
Tectum, particularly superior colliculus
Parallel Circuits in Basal Ganglia
Information flow through the basal ganglia is separated into five distinct parallel circuits each with its own direct and indirect pathway.
Motor loopOculomotor loopDorsolateral prefrontal loopLateral orbitofrontal loopLimbic loop
Today
Phase 3
Loops of the Basal GangliaEach loop
Starts from specific areas of cortexPasses through distinct regions of the basal gangliaModulates different areas of the thalamusReturns to distinct cortical regions that requested the information
Motor Loop
Starts in supplementary motor cortex, primary motor and premotor corticesProjects mainly to putamenProjections to thalamus include
VLoVACM
CM
DeLong’s Direct and Indirect Pathways
He proposed that basal ganglia output can be grouped into two projection systems
Direct pathwayIndirect pathway
It has been proposed that the basal ganglia are parallel processing information
They appear to function in “balanced opposition”
Neurotransmitters
GABA – inhibitoryGlutamate – StimulatoryAcetylcholine – within neostriatumNeuropeptides – co-localized with GABA
EnkephalinSubstance P/dynorphin
DopamineD1 – stimulates adenylate cyclase activityD2 – inhibits adenylate cyclase activity
Striatal Cholinergic Interneurons
Cholinergic interneurons in the striatum are stimulatory particularly in the indirect pathway
Centrally active anticholinergic, antiparkinsonian drugs act via muscarinic receptors and reduce activity of striatal cholinergic interneurons
Striatal cholinergic interneurons
Direct Pathway
Glu (Stimulation)GABA (Inhibition)GABA (Inhibition)Glu (Stimulation)
Indirect Pathway
GluGABAGABAGluGABAGlu
Parkinson’s Disease
BradykinesiaPill-rolling tremorMasked faciesMicrographiaMicrophoniaMarche de petit pasPostural InstabilityAutonomic dysfunctionFestinating gaitSeborrheaCramps of feet or toesDecreased eyeblink
Signs and Symptoms
BradykinesiaSlow and small stepsMasked facies (little movement, staring)Small handwriting
Resting tremor (pill rolling tremor)Postural instabilityRigidity
Pathology in Parkinson’s Disease
Loss of dopamine containing neurons in the pars compacta of substantia nigra
Depletion of dopamine in striatum which correlates with severity of dopamine cell loss in the SNpc at post-mortem
Progressive Stages
MPTP
N-methyl-2,3,4,6-tetrahydropyridine is a dopamine neurotoxin that selectively destroys SNpc neurons
Produces Parkinson’s disease in man and primates
Causes loss of dopamine in striatum
Drug-Induced Parkinson’s Disease
Drugs that deplete brain dopamine e.g., reserpine
Drugs that block dopamine receptors e.g., phenothiazine and butyrophenoneantipsychotic drugs
Reversible upon drug elimination
Huntington’s Disease
DementiaHyperactivity
Huntington’s Disease
Autosomal dominant
Caused by an abnormal CAG repeat
Normal 11-34Abnormal 38-121
Caudate nucleus dies
Progressive dementia
Usually manifested in the 40’s
Genetic test now available
Hemiballism
Discrete unilateral lesion of the subthalamic nucleus
Forceful, violent and persistent hyperkinetic movements
Involves the contralateral limbs and mainly the proximal musculature
Wilson’s disease Hepatolenticular degeneration
Autosomal recessive disorder of chromosome 13Onset usually 13-25 yearsAccumulation of copper in liverKayser-Fleischer rings in eye due to CuPutamen degenerates
Sydenham’s choreaAn autoimmune disease caused by rheumatic feverChorea may last 3-6 weeksUsually seen in childrenAlso called St. Vitus dance
Take home message
Alterations in output via the indirect striatal projection systems is the key to understanding the different basal ganglia disorders.
Decrease activity of STN neuronsdirect lesion - hemiballismincreased inhibition - Huntington’s chorea
Increase activity of STN neuronsIncrease activity of STN neurons - Parkinson’s disease