FINKELSTEIN PDF

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!