Optically-controlled cns dysfunction

Abstract

Provided herein are animals expressing light-responsive opsin proteins in the basal lateral amygdala of the brain and methods for producing the same wherein illumination of the light-responsive opsin proteins causes anxiety in the animal. Also provided herein are methods for alleviating and inducing anxiety in an animal as well as methods for screening for a compound that alleviates anxiety in an animal.

1 .- 31 . (canceled) 
     
     
         32 . A method for alleviating anxiety in an individual, the method comprising:
 (a) administering directly into the brain of the individual an effective amount of a recombinant expression vector comprising a nucleic acid encoding a light-responsive opsin that comprises an amino acid sequence having at least 90% amino acid sequence identity to any one of SEQ ID NOs:6-11, wherein the nucleic acid is operably linked to a promoter that controls the specific expression of the opsin in the glutamatergic pyramidal neurons of the basolateral amygdala (BLA), wherein the opsin is expressed in the glutamatergic pyramidal neurons of the BLA, wherein the opsin is an opsin that induces depolarization by light;   (b) implanting a beveled cannula over the centrolateral nucleus (CeL) to prevent light delivery to the BLA somata; and   (c) delivering light from a light delivery device ensheathed in the beveled cannula to selectively illuminate the opsin in the glutamatergic pyramidal neurons in the central nucleus of the amygdala (CeA) to alleviate anxiety.   
     
     
         33 . The method of  claim 32 , comprising selectively illuminating the centrolateral nuclei (CeL) to alleviate anxiety. 
     
     
         34 . The method of  claim 32 , wherein the opsin comprises an amino acid sequence having at least 95% amino acid sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs:6-11. 
     
     
         35 . The method of  claim 32 , wherein the opsin comprises an amino acid sequence having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO:6. 
     
     
         36 . The method of  claim 32 , wherein the opsin comprises an amino acid sequence having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO:7. 
     
     
         37 . The method of  claim 32 , wherein the opsin comprises an amino acid sequence having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO:8. 
     
     
         38 . The method of  claim 32 , wherein the opsin comprises an amino acid sequence having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO:9. 
     
     
         39 . The method of  claim 32 , wherein the opsin comprises an amino acid sequence having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO:10. 
     
     
         40 . The method of  claim 32 , wherein the opsin comprises an amino acid sequence having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO:11. 
     
     
         41 . The method of  claim 32 , wherein the recombinant vector is an adeno-associated vector, a retroviral vector, an adenoviral vector, or a lentiviral vector. 
     
     
         42 . The method of  claim 32 , wherein the promoter is a CaMKIIa promoter. 
     
     
         43 . The method of  claim 32 , wherein said light delivery device comprises an optical fiber. 
     
     
         44 . The method of  claim 32 , wherein the beveled cannula is beveled to form a 45-55-degree angle for the restriction of the illumination to the CeA. 
     
     
         45 . The method of  claim 44 , wherein the beveled cannula guide comprises a long side that shields the posterior-lateral portion of the light delivery device. 
     
     
         46 . The method of  claim 32 , further comprising delivering one or more of a pharmacological agent, an electrical stimulus, or a magnetic stimulus to the individual.