Expression of neuropeptides

Abstract

Methods of expressing a neuropeptide in a neuron of a subject are described. Methods of altering a behavior in a subject in need thereof are described. Kits are described. Vectors are described.

What is claimed is: 
     
         1 . A kit comprising:
 a first nucleic acid encoding a neuropeptide and operably linked to a first promoter configured to drive expression in a neuron;   a second nucleic acid encoding a conditional receptor configured to increase activity of a neuron that expresses the conditional receptor upon binding of an agonist or application of a stimulus to the conditional receptor, wherein the second nucleic acid is operably linked to the first promoter or a second promoter configured to drive expression in the neuron,   wherein either
 (a) a single vector comprises the first nucleic acid, the second nucleic acid, and either
 (i) the first promoter, or 
 (ii) the first promoter and the second promoter, or 
 
 (b) a first vector comprises the first nucleic acid and the first promoter, and a second vector comprises the second nucleic acid and the second promoter. 
   
     
     
         2 . The kit of  claim 1 , wherein (a) the kit comprises the single vector, further comprising a single promoter that is operably linked to the first nucleic acid and second nucleic acid, the single promoter configured to drive expression specifically in neuropeptidergic neurons. 
     
     
         3 . The kit of  claim 1 , wherein (b) the kit comprises the first vector and the second vector,
 the first vector comprising the first promoter that is operably linked to the first nucleic acid, the first promoter configured to drive expression specifically in a neuropeptidergic neuron, and   the second vector comprising the second promoter that is operably linked to the second nucleic acid, the second promoter configured to drive expression specifically in the neuropeptidergic neuron.   
     
     
         4 . The kit of  claim 1 , wherein (a) the single vector comprises an AAV, and/or (b) the first vector and second vector each comprises an AAV. 
     
     
         5 . The kit of  claim 1 , wherein the neuropeptide comprises a neurokinin. 
     
     
         6 . The kit of  claim 5 , wherein the neurokinin is selected from the group consisting of neurokinin A, neurokinin B, and substance P. 
     
     
         7 . The kit of  claim 3 , wherein the first promoter and second promoter are each a neuropeptide promoter. 
     
     
         8 . The kit of  claim 1 , further comprising the agonist or the stimulus. 
     
     
         9 . The kit of  claim 1 , wherein the neuron is a neuropeptidergic neuron. 
     
     
         10 . The kit of  claim 9 , wherein the neuropeptidergic neuron is a neuron of one or more of the antero-dorsal bed nucleus of the stria terminalis (dBNSTa), central nucleus of the amygdala (CeA), dorsomedial hypothalamus (DMH), and the anterior cingulate cortex (ACC). 
     
     
         11 . The kit of  claim 1 , wherein the conditional receptor comprises a hM3DREADD and the agonist comprises clozapine-N-oxide, or wherein the conditional receptor comprises an optogenetic channel and the agonist comprises electromagnetic radiation. 
     
     
         12 . A vector comprising:
 a first nucleic acid encoding a neuropeptide and operably linked to a first promoter configured to drive expression in a neuron; and   a second nucleic acid encoding an conditional receptor configured to increase activity of a neuron that expresses the conditional receptor upon binding of an agonist or application of a stimulus to the conditional receptor, wherein the second nucleic acid is operably linked to the first promoter or a second promoter configured to drive expression in the neuron.   
     
     
         13 . The vector of  claim 12 , wherein the vector comprises an adeno-associated virus (AAV). 
     
     
         14 . The vector of  claim 12 , comprising a single promoter that is operably linked to the first nucleic acid and second nucleic acid, the single promoter configured to drive expression specifically in neuropeptidergic neurons. 
     
     
         15 . The vector of  claim 12 , wherein the first promoter is configured to drive expression specifically in a neuropeptidergic neuron, and the second promoter is configured to drive expression specifically in the neuropeptidergic neuron. 
     
     
         16 . The vector of  claim 12 , wherein the neuropeptide comprises a neurokinin. 
     
     
         17 . The vector of  claim 15 , wherein the neurokinin is selected from the group consisting of neurokinin A, neurokinin B, and substance P. 
     
     
         18 . The vector of  claim 12 , wherein the neuron is a neuropeptidergic neuron. 
     
     
         19 . the vector of  claim 19 , wherein the neuropeptidergic neuron is a neuron of one or more of the antero-dorsal bed nucleus of the stria terminalis (dBNSTa), central nucleus of the amygdala (CeA), dorsomedial hypothalamus (DMH), and the anterior cingulate cortex (ACC). 
     
     
         20 . The vector of  claim 12 , wherein the conditional receptor comprises a hM3DREADD and the agonist comprises clozapine-N-oxide, or wherein the conditional receptor comprises an optogenetic channel and the agonist comprises electromagnetic radiation.