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!