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
Young and Wang Nat. Rev. Neurosci. 2001
The neurotransmiRer dopamine, produced in the ventral tegmental area (VTA), is thought to promote a variety of social behaviors
Optogene(cs can be used to control a gene(cally-‐specified cell type within a complex heterogeneous network
Dopamine neuron
Inhibitory neuron
ChR2 channels
Dopamine neuron ac(vated Neighboring neurons unaffected
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
Virus containing Cre-‐dependent ChR2 injected into brain
Transgenic mouse expressing Cre in a specific cell type
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
Behavioral paradigm: home cage social interac(on with a novel stranger mouse
Are VTA dopaminergic neurons causally involved in social approach behavior?
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: Lisa Gunaydin Joel Finkelstein
Lief Fenno Raag Airan
Avishek Adhikari
Julie Mirzabekov
Kay Tye Hsing-‐Chen Tsai
Joanna Maas Kelly Zalocusky
Ilka Diester
Logan Grosenick Isaac Kauvar
James Doty Karl Deisseroth
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