Project 2: Cellular Studies of Drug Action
PI, Robert Malenka (Stanford)

This Project combines mouse mutagenesis, viral-mediated gene transfer, and cellular electrophysiological recording techniques to examine changes in synaptic and membrane properties of ventral tegmental area (VTA) dopamine neurons and their targets—medium spiny neurons (MSNs) in the nucleus accumbens (NAc)—elicited by drugs of abuse. We are striving to identify subtypes of neurons in both brain regions that show differential responses to drug and natural rewards as well as to aversive stimuli. In addition, we are interested in the role played by expression of transcription factors that have been shown, by the other Projects of this Program Project Grant, to exert significant effects on the rewarding properties of drugs of abuse. One example is CREB, which we have shown reduces an animal's sensitivity to drugs of abuse via activation of NAc medium spiny neurons.

Identification of subtypes of VTA dopamine neurons and the modulation of their excitatory synapses by rewarding and aversive stimuli. Dopamine neurons projecting to the lateral shell of the nucleus accumbens (NAc) can be found in the anterior and posterior VTA (yellow dots) while those projecting to PFC and NAc medial shell are mainly located in the posterior VTA (red and green dots).
From Lammel et al., Neuron, 2011.

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