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-specied cell type within a complex heterogeneous network

Dopamine neuron

ChR2 channels

Inhibitory neuron

Dopamine neuron ac(vated Neighboring neurons unaected

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

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

Transgenic mouse expressing Cre in a specic 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 specic 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 signicantly increases social interac(on

The social eect cannot be aRributed to non-specic changes in locomo(on or novel object inves(ga(on
Open eld test Novel object inves(ga(on

Acknowledgements
Team Dopamine:
Lisa Gunaydin Joel Finkelstein Lief Fenno Raag Airan Avishek Adhikari Julie Mirzabekov James Doty Karl Deisseroth Kay Tye Hsing-Chen Tsai Joanna Maas Kelly Zalocusky Ilka Diester Logan Grosenick Isaac Kauvar

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

Thank you!