Laboratory of Neuromodulation and Behavior
Our lab studies brain function at the level of neuronal circuits and systems that underlie specific behaviors. Our main interests revolve around neuronal circuits that underlie motivated behavior and reward-based learning and memory. We have two major research programs that use a variety of techniques: addiction and cognitive neuroscience.
Our program of addiction research investigates the neural circuitry underlying the vulnerability to relapse and enhanced drug craving that occurs during protracted abstinence from chronic drug exposure. Most recently, we have explored the role of catecholamines and the neuropeptide orexin in these phenomena using the conditioned place preference and self-administration paradigms. Current projects include: a) determining the relevant neural inputs to and output targets of the orexin system during the expression of a conditioned place preference for cocaine or morphine, in rats that are drug naïve or have undergone dependence and protracted abstinence (tract tracing, microinjections, CPP, Fos staining), b) investigating the role of the orexin system and interrelated circuitry in cue- and drug prime-elicited reinstatement of drug- and food-seeking following chronic self-administration (self-administration, local microinjections, tract tracing, Fos staining), and c) studying the therapeutic potential of modafinil for cocaine and opiate addiction (CPP, self-administration).
In addition to direct studies of drug use, we are also interested in better characterizing the neural circuits that may interact with the orexin system in the promotion of reward-seeking behaviors. Current projects in this vein include investigating the relationship between the orexin system and the dopamine system of the ventral tegmental area using single-neuron electrophysiology combined with pharmacological manipulations.
Our cognitive neuroscience research focuses on behavioral control, broadly defined. Current research projects investigate the role of the locus coeruleus and related areas (such as frontal cortical regions) in attention, decision-making, response inhibition, and learning. These studies primarily employ simultaneous unit recordings from multiple sites in brains of rats performing behavioral tasks that address these and related cognitive processes. Future studies will also involve recordings from orexin neurons in hypothalamus, dopamine neurons in ventral tegmental area, and related regions. Techniques employed in these studies include behavioral electrophysiology, neural microstimulation, regional inactivation, and systemic pharmacological manipulations. These techniques are combined with sophisticated cognitive tasks designed to better understand the neural underpinnings of cognitive phenomena.
Our cognitive neuroscience research is also relevant to our research in addiction, as much of addiction involves changes in neural circuits that underlie attention, decision-making, response inhibition, and learning. One goal is to use our cognitive neuroscience approach to better understand the neural substrates that underlie such cognitive elements in addiction and drug abuse.
Self-administration (food and drug), cognitive testing, conditioned place preference, intracerebral microinjections in behaving animals, neural tract tracing (CTb, WGA) including trans-synaptic tracing (PRV), immunohistochemistry for a variety of transmitter and IEG molecules, single-neuron electrophysiology (both anesthetized and behavioral), local drug application onto recorded neurons from multibarrel pipettes in anesthetized animals, microstimulation (electrical and chemical), regional inactivation.
A particularly exciting new technology being used is cell-type specific neuronal gene transduction using viral vectors, where viruses that are injected in vivo into specific brain areas can insert genetic material into neurons so that only neurons of a specific type (eg, orexin neurons) express novel proteins that allow subsequent manipulation of these cells by optical or pharmacological means.
All studies are in rats, though future studies in mice are possible.