Finkelstein PDF | Dopamine | Earth & Life Sciences

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  

ChR2     channels  

Inhibitory     neuron  

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  

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:  
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!  

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