Optically-Controlled CNS Dysfunction
AssigneeThe Board of Trustees of Leland Stanford Jnior Universtiy
InventorsKarl Deisseroth, Kay Tye, Lief Fenno
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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.
Claims26
A non-human animal comprising a light-responsive opsin expressed in glutamatergic pyramidal neurons of the basolateral amygdala (BLA), wherein the opsin is an opsin which induces hyperpolarization by light, and wherein the selective illumination of the opsin in the BLA-centrolateral nucleus (BLA-CeL) induces anxiety of the animal.
A non-human animal comprising a light-responsive opsin expressed in the glutamatergic pyramidal neurons of the basolateral amygdala (BLA), wherein the opsin is an opsin that induces depolarization by light, and wherein the selective illumination of the opsin in the BLA-centrolateral nucleus (BLA-CeL) reduces anxiety of the animal.
A recombinant vector for delivering a nucleic acid to glutamatergic pyramidal neurons of the basolateral amygdala (BLA) in an individual, wherein the vector comprises a nucleotide sequence encoding a light-responsive opsin and the nucleic acid is operably linked to a promoter that controls the specific expression of the opsin in the glutamatergic pyramidal neurons.
(canceled)
A method of delivering a nucleic acid to glutamatergic pyramidal neurons of the basolateral amygdala (BLA) in an individual, comprising administering to the individual an effective amount of a vector comprising a nucleotide sequence encoding a light-responsive opsin, wherein the nucleotide sequence is operably linked to a promoter that controls the specific expression of the opsin in the glutamatergic pyramidal neurons.
A coronal brain tissue slice comprising BLA, CeL, and CeM, wherein a light-responsive opsin is expressed in the glutamatergic pyramidal neurons of the BLA.
A method for screening for a compound that alleviates anxiety, comprising
- (a) administering a compound to an animal having anxiety induced by selective illumination of an opsin expressed in the glutamatergic pyramidal neurons of the basolateral amygdala (BLA), wherein the animal comprises a light-responsive opsin expressed in the glutamatergic pyramidal neurons of the BLA, wherein the opsin induces hyperpolarization when stimulated by light;
- and
- (b) determining the anxiety level of the animal, wherein a reduction of the anxiety level indicates that the compound is a candidate agent for treating anxiety.
A method for alleviating anxiety in an individual, comprising:
- (a) administering to the individual an effective amount of a vector comprising a nucleotide sequence encoding a light-responsive opsin, wherein the nucleotide sequence 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 induces depolarization when stimulated by light;
- and
- (b) selectively illuminating the opsin in the glutamatergic pyramidal neurons in the BLA-centrolateral nucleus (BLA-CeL) to alleviate anxiety.
A method for inducing anxiety in an individual, comprising:
- (a) administering to the individual an effective amount of a vector comprising a nucleotide sequence encoding an opsin, wherein the nucleotide sequence 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, wherein the opsin induces hyperpolarization when stimulated by light;
- and
- (b) selectively illuminating the opsin in the glutamatergic pyramidal neurons in the BLA-centrolateral nucleus (BLA-CeL) to induce anxiety.
-31. (canceled)
Dependencies are inferred from the claim text.