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.

Description

CROSS REFERENCE TO RELATED APPLICATION[0001]This application is a divisional of U.S. Ser. No. 13 / 882,670 filed, Aug. 12, 2013, which is a national stage filing under 35 U.S.C. 371 of PCT / US2011 / 059295, filed Nov. 4, 2011, which claims priority to U.S. Provisional Application No. 61 / 410,692 filed on Nov. 5, 2010, each of which applications is incorporated herein by reference in its entirety.FIELD OF THE INVENTION[0002]This application pertains to compositions comprising animal cells expressing light-responsive opsin proteins on their plasma membranes and methods of using the same to selectively hyperpolarize cholinergic interneurons residing in microcircuits of the nucleus accumbens or dorsal striatum to affect one or more behaviors associated with reward-related conditioning in the animal.BACKGROUND[0003]Substance abuse and dependency are important problems facing societies all over the world. According to the World Drug Report 2008, about 5% of the world population uses illicit dru...

AI Technical Summary

Benefits of technology

[0015]Particular embodiments of the present disclosure are directed toward inhibition of targeted cells within structures involved in natural reward-related behaviors and / or for reward learning including, but not necessarily limited to, the nucleus accumbens (NAc) or the dorsal striatum. In a particular example, the targeting of specific cholinergic neurons within the NAc is particularly well suited for disrupting the release of acetylcholine by these cholinergic neurons. It has been discovered that such neural inhibition can be effective to targeted neural inhibition can reduce or eliminate undesired effects on the reinforcement of other behaviors, e.g., appetitive or aversive responses. Aspects of the present disclosure relate to stimulation that is specific to temporal, spatial and / or cell-types. In certain embodiments, this inhibition is performed using an optogenetic system that involves the expression of light-responsive opsins in the cells of the neural circuit. In other embodiments, the inhibition can be performed using direct electrical stimulus. Still other embodiments allow for the use of temporally-precise pharmaceuticals.

Problems solved by technology

Substance abuse and dependency are important problems facing societies all over the world.

Substance abuse and dependency result in enormous loss of productive manpower all over the world and imposes costs on governments and societies in terms of treatment support, insurance payouts, and spending on prevention and de-addiction programs.

In spite of these advances, the neurophysiological substrates underlying complex human behaviors, such as substance abuse and dependency (addiction) remain poorly understood, despite emerging information on the role that specific areas of the brain play in these behaviors.

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