Understanding the neural circuitry that underlies reward-related behavior is essential for developing precise and effective treatments for addictive behavior. While many brain regions are important for the manifestation and expression of reward-related behavior, the nucleus accumbens (NAc) is thought to be a brain nucleus critical for translating the affective state of an organism into a motor action. Because the NAc is heterogeneous;receiving diverse glutamatergic inputs from areas such as the basolateral amygdala (BLA) and medial prefrontal cortex (mPFC) as well as dopaminergic input from the ventral tegmental area, it has been difficult to study the contribution of a specific synaptic connections in controlling behavior. To circumvent this, we propose here to use optogenetic stimulation of channelrhodopsin-2 (ChR2) to specifically control neural transmission from the BLA and mPFC to the NAc. We will first selectively introduce ChR2 into glutamatergic neurons of the BLA and mPFC and characterize their firing properties with optical stimulation. Following expression of ChR2 in specific subsets of glutamate terminals in the NAc, we will characterize afferent-specific neurotransmission by examine synaptic strength and glutamate release probability. Finally, We will assay whether optical stimulation of BLA or mPFC to NAc synapses can reinforce behavioral responding, thus promoting goal-directed behavior. These experiments could provide important and novel information about the ability of particular excitatory inputs into the NAc to sustain reinforcement while also defining a minimal unit within a neural circuit that can drive reward-related behavior.

Public Health Relevance

Gaining a better understanding of the specific wiring of the brain is important for further developing effective treatments for diseases and disorders such as drug addiction. The experiments described in this proposal aim to test the role of two specific components of brain circuitry in mediating reward- related behavior. These studies may lead to a better understanding of neural circuitry and potentially lead to the discovery of new therapeutic targets for treating addiction.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Exploratory/Developmental Grants (R21)
Project #
7R21DA029325-02
Application #
8138039
Study Section
Neurobiology of Motivated Behavior Study Section (NMB)
Program Officer
Lin, Geraline
Project Start
2010-04-01
Project End
2012-03-31
Budget Start
2010-06-01
Budget End
2011-03-31
Support Year
2
Fiscal Year
2010
Total Cost
$222,000
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Psychiatry
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
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Stamatakis, Alice M; Sparta, Dennis R; Jennings, Joshua H et al. (2014) Amygdala and bed nucleus of the stria terminalis circuitry: Implications for addiction-related behaviors. Neuropharmacology 76 Pt B:320-8
Cui, Changhai; Noronha, Antonio; Morikawa, Hitoshi et al. (2013) New insights on neurobiological mechanisms underlying alcohol addiction. Neuropharmacology 67:223-32
Sparta, Dennis R; Jennings, Joshua H; Ung, Randall L et al. (2013) Optogenetic strategies to investigate neural circuitry engaged by stress. Behav Brain Res 255:19-25
Stuber, Garret D; Mason, Alex O (2013) Integrating optogenetic and pharmacological approaches to study neural circuit function: current applications and future directions. Pharmacol Rev 65:156-70
Jennings, Joshua H; Sparta, Dennis R; Stamatakis, Alice M et al. (2013) Distinct extended amygdala circuits for divergent motivational states. Nature 496:224-8
Britt, Jonathan P; Benaliouad, Faiza; McDevitt, Ross A et al. (2012) Synaptic and behavioral profile of multiple glutamatergic inputs to the nucleus accumbens. Neuron 76:790-803
Stamatakis, Alice M; Stuber, Garret D (2012) Activation of lateral habenula inputs to the ventral midbrain promotes behavioral avoidance. Nat Neurosci 15:1105-7
Stuber, Garret D; Britt, Jonathan P; Bonci, Antonello (2012) Optogenetic modulation of neural circuits that underlie reward seeking. Biol Psychiatry 71:1061-7
van Zessen, Ruud; Phillips, Jana L; Budygin, Evgeny A et al. (2012) Activation of VTA GABA neurons disrupts reward consumption. Neuron 73:1184-94

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