Standing (1973)Miller, Li, Desimone (1991)Li, Miller, Desimone (1993)

Xiang, Brown (1998)

Recognition / Familiarity Memory

Daisuke Hattori, Yoshinori Aso, Kurtis Swartz,Gerald Rubin, Larry Abbott, Richard Axel (2017)

in Flies

Daisuke’s Dog

Odor-less solvent exposure Odor exposure 1 Odor exposure 2

Oil / Odor alternating exposure trials

Fraction of flies that stop grooming

0

0.5 ** Odor Oil

KC

PN

MBON

Yoshi Aso, Daisuke Hattori

DAN

The mushroom body endows organisms with a degree of free will or intelligent control over instinctive actions

- Dujardin, 1850

ORN

PN

KC

Yoshi Aso, Daisuke Hattori

KC

PN

KC

PN

MBON

Yoshi Aso, Daisuke Hattori

from Yoshinori Aso, Daisuke Hattori

Mushroom body output neurons Dopaminergic neurons

Aso, Hattori, Yu, Johnston, Iyer, Ngo, Dionne, Abbott, Axel, Tanimoto, Rubin (2014)

from Yoshinori Aso, Daisuke Hattori

Mushroom body output neurons Dopaminergic neurons

Punishment

Reward

Approach

Avoidance

Aso et al. (2014)

active

active

active

MBON-α'3

KCsMBON-α'3

Odor: 4-methylcyclohexanol (MCH)

Time (s)

Raw GCaMP

PID

1

2

3

0

1

0 30 60 90 120

0

1

5Trial number

10

Aversive Neutral AttractiveBEN -> MCH

norm

aliz

ed

odor

resp

onse

Suppression is Observed for all Odors but is Stimulus Specific

0

1

5Trial number

10

0

1

5Trial number

10

0

1

5Trial number

10

0

1

5Trial number

10

0

1

5Trial number

10

3-octanol acetophenone 3-methyl-1-butanol isopentyl acetate hexyl acetate

2016

10 min 20 min

2016

60 min

16

norm

aliz

ed

resp

onse

0

1

0 min

5

Trial number

10 15 2016

Suppression is persistent

MBON-α'3

KCsMBON-α'3

PPL1-α'3

PPL1-α'3

MCH

1s

0

13-octanolbenzaldehyde

mineral oil (solvent)

ΔF/F0

Odor activates PPL1-α'3

normalized MBON-α'3

odor response

0

1

5Trial number

10

PPL1α'3>Kir2.1 PPL1α'3-SplitGAL4 only UAS-Kir2.1 only

PPL1-α'3 activity is required for suppression of MBON-α'3

PPL1α'3> Kir2.1

MBONα'3> GCaMP

KCsMBON-α'3

PPL1-α'3

active

active

Novel odor

silentFamiliar odor

norm

aliz

ed

resp

onse

to

MC

H

0

1

Trial number5 10 15 16 20

{Odor} x 15 (~5 min)

Novel odor enhances decay of familiarity

normalized odor response

0

1MCH

Light only

OCTControl

Recovery of MBON response upon PPL1-α'3 activation in the absence of odor

PPL1α'3> CsChrimson (activated)

0

1

Trials

PPL1α'3> CsChrimson

MBONα'3> GCaMP

Trials

KCsMBON-α'3

PPL1-α'3

Odor A

Odor B

Bidirectional effect of dopamine contributes to generation of novelty response without saturation

active

active

Frac

tion

of fl

ies

that

st

op g

room

ing

Cessation of grooming ~ alerting response to novel odorN

orm

aliz

ed

MBO

N-α

'3

odor

resp

onse

Oil / Odor alternating exposure trials

0

0.5Odor Oil

1

5Trial number

10

0

MBON-α'3 activity Behavior

Optogenetic Activation of MBON-α'3 Elicits an Alerting Response And Disrupts Grooming

0 0

Frac

tion

of fl

ies

that

st

op g

room

ing

0

1

MBONα'3>CsChrimson MBONα'3-SplitGAL4 only UAS-CsChrimson only

Light only

**

Odor + Light

*

0

1

Silencing MBON-α'3 Eliminates the Alerting Response

Odor exposure trial 1

Frac

tion

of fl

ies

that

st

op g

room

ing

0

1

MBONα'3>Kir2.1 MBONα'3-SplitGAL4 only UAS-Kir2.1 only

*

00

1

00

1trial 2 trial 3

MBON-α'3

MBON excitation: novelty MBON suppression: familiarity KCs

MBON-α'3

PPL1-α'3

PPL1-α'3

The α'3 compartment represents novelty and familiarity

MBON-α’3

normalized odor response

0

1

5Trial number

10

Suppression of MBON-α'3 is not due to sensory adaptation

α'/β' KCs

MBON-α’3

normalized odor response

0

1

5Trial number

10

Other MBONs

Suppression is specific to MBON-α'3

MBON-α'2 MBON-β1>α MBON-β'2mp MBON-β2β'2a

MBON input =NX

i=1

wiRKCi

if KCi active wi ! 0

if KCi inactive wi ! wi + ↵(1 � wi)

when odor is presented (fraction f of KCs active)

20 40 60 80 100 120 140 160 180 200

50

100

150

200

250

300

350

KCs

odors

20 40 60 80 100 120 140 160 180 200

50

100

150

200

250

300

350 0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

KC-to

-MBO

N c

onne

ctio

n

odors

strength

0 20 40 60 80 100 120 140 160 180 200

MBO

N re

spon

se a

mpl

itude

odors

signal lifetime

noise

MBON input =NX

i=1

wiRKCi

if KCi active wi ! 0

if KCi inactive wi ! wi + ↵(1 � wi)

w = 1 � f1 � (1 � f )(1 � ↵)

�2w = 1 � f

1 � (1 � f )(1 � ↵)2 �

f1 � (1 � f )(1 � ↵)

!2

⌧ =�1

ln⇣(1 � f )(1 � ↵)

⌘

SNR =w�w

when odor is presented (fraction f of KCs active)

0 0.01 0.02 0.03 0.04 0.05

alpha3

4

5

6

7

sign

al-to

-noi

se ra

tio

0 0.01 0.02 0.03 0.04 0.05

alpha10

15

20

25

lifet

ime

(odo

rs)