Behavior is the result of concerted action of neurons from various brain regions. Each brain region may contain many types of neurons, each expressing different genes and projecting to different brain regions. Thus, not all neurons in a brain region may be relevant to a specific behavior. In fact, neighboring neurons may be involved in completely different, sometimes opposing, behaviors depending on their connectivity with neurons in other regions. Therefore, in order to truly understand the neural substrates of a specific behavior it is essential to identify and target specific neurons with known connectivity patterns.

The nucleus accumbens (NAc) and the ventral pallidum (VP) are two regions in the basal ganglia that are deeply involved in the execution of motivated behavior, and uncontrolled motivated behavior is tightly linked with permanent synaptic changes in these two regions. The NAc and the VP receive various inputs and project to many brain regions and thus neurons of the NAc and VP participate in many different neural circuits. Moreover, the NAc and the VP are themselves interconnected in a complex manner. Recent studies show that synaptic plasticity in the NAc after exposure to drugs is not homogenous and occurs at specific synapses. Thus, loss of control on motivated behavior is likely to be mediated by subpopulations in the NAc and the VP that form dedicated microcircuits. Identifying and targeting these specific microcircuits and the synaptic changes therein leading to addictive behavior is therefore crucial.

Our lab is interested in the plasticity occurring at specific synapses that may underlie the transition from normal motivation to pathological reward seeking, such as that seen in drug addiction and compulsive overeating. We do this by identifying the relevant microcircuits, detecting synaptic changes in animal models of pathological motivation and targeting the aberrant synapses in vivo in attempt to reverse the addictive behavior.

Toolbox

1)     Patch-clamp electrophysiology

2)     Optogenetics

3)     Chemogenetics

4)     Mouse behavioral models

5)     Neural tracing

6)     Immunohistochemistry

7)     Fluorescence imaging

8)     Recombinant viral vectors for targeted gene delivery