Frontolimbic substrates of drug addiction and motivated behavior

Drug addiction and other neuropsychiatric conditions involve complex interactions between brain areas including the nucleus accumbens, hippocampus, and prefrontal cortex. Our previous work has characterized the role of interactions between hippocampus and nucleus accumbens in cocaine conditioned place preference, finding evidence that selective potentiation of specific hippocampal inputs to accumbens stores information linking certain spatial contexts to drug use. This provides a possible mechanistic substrate for the well known phenomenon by which relapse is triggered by exposure to “people, places, and things” previously associated with drug use.

Our current work studies the mechanisms by which hippocampus and accumbens influence prefrontal cortex as a basis for both physiological reward valuation and the pathological overvaluation of drugs of abuse. To this end, we are utilizing a range of techniques, including simultaneous multisite silicon probe recordings, in vivo two photon and light field imaging, and optogenetic manipulation in transgenic mice and rats in several behavioral tasks including drug self-administration.

Developing novel translational strategies for targeting frontolimbic circuits in drug addiction

Drug addiction represents a large public health burden for which few effective biologically-based treatments exist. We aim to develop novel gene-based tools and validate anatomical targets for future translational studies in human subjects. Our previous work in this area has focused on using DREADDs to modulate nucleus accumbens and suppress alcohol consumption in a model of binge drinking. Our current work expands this to include other brain areas in drug self-administration models. We have also developed several novel molecular tools enabling manipulation of synaptic plasticity with greater precision than previously possible, as well as improved versions of existing opto- and chemogenetic tools with properties favorable for use in human subjects.