The functional effects of alcohol abuse on the brain are varied and wide-ranging.  Impairments in tasks of attention, impulse control, and behavioral flexibility have all been associated with alcohol abuse. The critical role of the prefrontal cortex (PFC) in planning and goal-directed behavior suggests it may play an important function in drug seeking, which itself is an aberrant type of goal-directed behavior. This suggestion is supported by experimental observations in both animals and humans. The executive function of the PFC depends upon integration of information from sensory motor cortices (e.g. sensory attributes), limbic structures (e.g. value), and hippocampal and parahippocampal cortices (e.g. early and recent history). However, how these various brain regions interact and exchange information in the alcohol addicted brain is not clear.

Numerous reports have observed rhythmic coupling between separate brain regions, and it has been proposed that this coupling indicates exchange of information. Of particular interest are recent observations that firing of deep-layer pyramidal neurons in the PFC are phase-locked to the hippocampal theta rhythm during performance of a working memory task (a measure of executive functioning). This coherent oscillatory activity, or phase coding, could represent exchange of information between neural networks. Consistent with this, it has recently been demonstrated that locally synchronized neural networks phase synchronize their rhythmic activity across long-range connections. Thus, the increase in strength of synchronization of the PFC to the hippocampal theta rhythm during performance of a specific task likely reflects their degree and efficiency of information exchange.

This ARC supported pilot project utilizes state-of-the-art multielectrode array recording procedures in the behaving rat to determine whether communication between the hippocampus and PFC is altered by chronic alcohol exposure. This will involve simultaneously recording neuronal activity of a population of neurons in the PFC and hippocampus while the rat performs a working memory task and during operant self-administration of ethanol. It is hypothesized that chronic ethanol will reduce synchronization (phase-coding) between the PFC and hippocampus during performance of a working memory task. In contrast, it is hypothesized that there is will an increase in synchronization during cue-induced reinstatement of ethanol self-administration. These are highly novel studies that will begin to provide important insight into how neuronal interactions through neuronal synchronization is altered in the alcoholic.