Optogenetic control of reward-related behaviors

Abstract

Provided herein are compositions and methods for disrupting at least one reward-related behavior in an individual through the use of light-responsive opsin proteins used to control the polarization state of the cholinergic intemeurons of the nucleus accumbens or the striatum.

1 .- 8 . (canceled) 
     
     
         9 . A method for disrupting reward-related behavior in an individual comprising: administering a polynucleotide encoding a light-responsive opsin protein to the individual, wherein the light-responsive opsin protein is expressed on the cell membrane of cholinergic interneurons in the nucleus accumbens or the striatum of the individual, and the protein is responsive to light and is capable of inducing membrane hyperpolarization of the interneurons when the interneurons are illuminated with the light, whereby activating the protein by the light disrupts at least one reward-related behavior in the individual. 
     
     
         10 .- 33 . (canceled) 
     
     
         34 . A system comprising:
 a) a set of cholinergic neurons of a nucleus accumbens, wherein the cholinergic neurons express a light-responsive opsin polypeptide;   b) an optical delivery system for exciting the cholinergic neurons by activating the light-responsive opsin;   c) a drug delivery device for providing a drug to the set of cholinergic neurons; and   d) a monitoring device for assessing the activity of the set of cholinergic neurons in response to the drug.   
     
     
         35 . (canceled) 
     
     
         36 . The system of  claim 34 , wherein the monitoring device is further configured to assess the activity of the set of cholinergic neurons by monitoring the release of acetylcholine. 
     
     
         37 . The system of  claim 34 , wherein the light-responsive opsin polypeptide is a hyperpolarizing opsin. 
     
     
         38 . The system of  claim 37 , wherein the light-responsive opsin polypeptide is a light-responsive chloride ion pump and comprises an amino acid sequence having at least 90% amino acid sequence identity to the amino acid sequence set forth in NpHR (SEQ ID NO:1). 
     
     
         39 . The system of  claim 38 , wherein the light-responsive opsin polypeptide comprises an endoplasmic reticulum (ER) export signal. 
     
     
         40 . The system of  claim 39 , wherein the ER export signal comprises the amino acid sequence FXYENE, wherein X is any amino acid. 
     
     
         41 . The system of  claim 38 , wherein the light-responsive opsin polypeptide comprises a trafficking signal that enhances transport of the opsin polypeptide to the plasma membrane. 
     
     
         42 . The system of  claim 37 , wherein the light-responsive opsin polypeptide comprises an amino acid sequence having at least 90% amino acid sequence identity to the amino acid sequence set forth in GtR3 (SEQ ID NO:4). 
     
     
         43 . The system of  claim 42 , wherein the light-responsive opsin polypeptide comprises an endoplasmic reticulum export signal. 
     
     
         44 . The system of  claim 34 , wherein the optical delivery system comprises a light emitting diode. 
     
     
         45 . The system of  claim 34 , wherein the optical delivery system comprises a solid state laser diode. 
     
     
         46 . A method for assessing the addictive properties of a substance, the method comprising:
 a) exposing cholinergic neurons of a nucleus accumbens present in the system of  claim 34  to the substance;   b) activating the light-responsive opsin polypeptide with light, thereby modulating the activity of the cholinergic neurons; and   c) monitoring the activity of the modulated cholinergic neurons after exposure to the substance.   
     
     
         47 . The method according to  claim 46 , wherein the activity of modulated cholinergic neurons after exposure to the substance is monitored through electrical activity. 
     
     
         48 . The method according to  claim 47 , wherein the electrical activity comprises action potentials/firing of modulated cholinergic neurons after exposure to the substance. 
     
     
         49 . The method according to  claim 46 , wherein the activity of modulated cholinergic neurons after exposure to the substance is monitored through the release of acetylcholine. 
     
     
         50 . The method according to  claim 46 , wherein activating the light-responsive opsin polypeptide further comprises applying an electrical pulse through one or more electrodes positioned near the cholinergic neurons. 
     
     
         51 . The method according to  claim 46 , wherein activating the light-responsive opsin polypeptide further comprises releasing a drug at a location proximate to the cholinergic neurons. 
     
     
         52 . The method according to  claim 46 , wherein activating the light-responsive opsin polypeptide further comprises applying a magnetic field to a location proximate to the cholinergic neurons.