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  

Targe(ng  VTA  dopaminergic  neurons  

Behavioral  paradigm:  home  cage  social  interac(on  with  a  novel  stranger  mouse    

Are  VTA  dopaminergic  neurons  causally  involved  in  social  approach  behavior?  

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:  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  

   

 

 

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

Thank  you!