FINKELSTEIN PDF

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Optogene(c tool development and applica(on to dissec(ng dopaminergic circuitry in social behavior

Joel Finkelstein CCARE Deisseroth Lab Bioengineering Dept. Stanford University 6.28.2012


What are the neural circuits involved in same-­‐sex social behavior?

Social behavior is impaired in many psychiatric disorders like au(sm, depression, schizophrenia and social anxiety disorder


Brain regions implicated in social behavior

The neurotransmiRer dopamine, produced in the ventral tegmental area (VTA), is thought to promote a variety of social behaviors Young and Wang Nat. Rev. Neurosci. 2001


Optogene(cs can be used to control a gene(cally-­‐specified cell type within a complex heterogeneous network

Dopamine neuron

Inhibitory neuron

Channelrhodopsin-­‐2 (ChR2): light-­‐gated ca(on channel derived from algae

ChR2 channels

Dopamine neuron ac(vated Neighboring neurons unaffected


Expression of ChR2 in neurons allows light-­‐induced ac(on poten(al genera(on with millisecond precision

Transgenic mouse expressing Cre in a specific cell type

Virus containing Cre-­‐dependent ChR2 injected into brain

Only Cre-­‐expressing neurons sensi(zed to blue light

Optogene(cs allows you to determine the causal role of a specific cell type in behavior


Targe(ng VTA dopaminergic neurons


Are VTA dopaminergic neurons causally involved in social approach behavior? Behavioral paradigm: home cage social interac(on with a novel stranger mouse


Op(cal s(mula(on of VTA dopaminergic neurons during social interac(on

Light OFF

Light ON


Op(cal s(mula(on of VTA dopaminergic neurons significantly increases social interac(on


The social effect cannot be aRributed to non-­‐specific changes in locomo(on or novel object inves(ga(on Open field test

Novel object inves(ga(on


Acknowledgements Team Dopamine:

Kay Tye

Lisa Gunaydin

Hsing-­‐Chen Tsai

Joel Finkelstein

Joanna Maas

Lief Fenno

Kelly Zalocusky

Raag Airan

Ilka Diester

Avishek Adhikari

Logan Grosenick

Julie Mirzabekov

Isaac Kauvar

James Doty

Karl Deisseroth


Special Thanks to Jim Doty, Lisa Gunaydin, Karl Deisseroth and CCARE


Thank you!


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