Dipanwita Ghose, PhD

The nucleus accumbens (NAc) is a part of the mesolimbic dopamine system and integrates excitatory, inhibitory and modulatory inputs to optimize motivated behaviors. Dynamic alterations in synaptic transmission within this circuit are strongly implicated in development and expression of addictive disorders. My research helps to identify the role of NAc circuitry and neural mechanisms underlying drug addiction. More specifically, my current project is designed to study synaptic physiology in the nucleus accumbens and adaptations that occur in response to in vivo drug exposure. Understanding the effects of cocaine experience on synaptic physiology involves understanding the contribution of both excitatory and inhibitory transmission and the final balance between these mechanisms that regulate NAc output and the way it is altered with drug abuse. This project focuses on the role of inhibitory interneurons in NAc and alterations in their activity with drug abuse. Briefly, some of the experimental approaches are

1) Breed mice in which the Parvalbumin containing interneurons (PV-INs) are marked with a red fluorescent protein for identification or a conditional channel rhodopsin for stimulation.
2) Study synaptic inputs onto these interneurons utilizing optogenetics (input specificity) and performing whole-cell patch-clamp recordings from the INs.
3) Elicit inhibitory transmission from these interneurons onto NAc medium spiny neurons by stimulating these INs optogenetically and studying its effects in a pathway specific manner using whole cell patch clamp technique.
4) Determine effects of drug experience on PV INs.


Max Joffe

Within the last decade, the advent of optogenetics and transgenic mice has permitted the interrogation and deconstruction of specific neurocircuits. In vivo cocaine experience is known to alter glutamate signaling at within the nucleus accumbems (NAc), but how a drug history affects transmission from the midline nuclei of the thalamus (mThal) to the NAc has not been reported. Therefore a major component of my dissertation work is the evaluation of inputs from the mThal to the NAc core in the context of cocaine exposure. I found that cocaine exposure and abstinence induced striking input- and cell type-specific changes in NMDAR function in the NAc core. Of note, we discovered that cocaine exposure enriches GluN2C/D-containing NMDARs at mThal-D1(+) NAc core synapses. Since these receptors are expressed at very low levels in the striatum and CNS, they represent an exciting avenue for the development of potential therapies.