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.
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.
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