Optogenetic control of inputs to the ventral tegmental area

Abstract

The present disclosure provides a method of inducing or modulating reward- or aversive-related behaviors in animals using light-responsive opsins. The present disclosure provides methods of identifying or screening compounds that may be used to treating mental disorders, or are relevant to disrupt or improve reward- or aversive related behaviors.

What is claimed is: 
     
         1 . A method of modulating a reward- or aversive-related behavior in a mammal, the method comprising:
 a) expressing in one or both of two inputs to the ventral tegmental area (VTA) from the laterodorsal tegmentum and the lateral habenula a light-responsive opsin polypeptide; and   b) exposing the input to light,   wherein said exposing modulates a reward- or aversive-related behavior in the mammal.   
     
     
         2 . The method of  claim 1 , wherein said light-responsive opsin polypeptide comprises an amino acid sequence having at least about 90% amino acid sequence identity to an amino acid depicted in  FIGS. 6A-H . 
     
     
         3 . A non-human animal model of a reward- or aversive-related behavioral disorder, wherein said non-human animal expresses a light-responsive opsin polypeptide in one or both of two inputs to the ventral tegmental area (VTA) from the laterodorsal tegmentum (LDT) and the lateral habenula (LHb). 
     
     
         4 . A method of identifying an agent that modulates a reward- or aversive-related behavior in an individual, the method comprising:
 a) administering a test agent to a non-human animal of  claim 3 ; and   b) determining the effect of the test agent on a reward- or aversive-related behavior exhibited by said non-human animal when the light-responsive opsin polypeptide is activated by light, wherein a test agent that reduces an adverse reward- or aversive-related behavior is considered a candidate agent for treating a reward- or aversive-related behavioral disorder.