Rhythms of Hippocampal Function and Memory Deficits After Moderate Prenatal Alcohol Exposure

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PROJECT SUMMARY/ABSTRACT Fetal Alcohol Spectrum Disorders involve morphologic and neurobiological abnormalities in offspring subjected to prenatal alcohol exposure. Although not as well studied as high exposure, moderate prenatal alcohol exposure represents the most common and undetected form in humans. While learning and memory deficits have been well characterized at the behavioral level in humans with Fetal Alcohol Spectrum Disorders and in animal models of moderate prenatal alcohol exposure, few studies have determined the circuit or systems level mechanisms. A complete understanding of the neural bases of memory deficits after moderate prenatal alcohol exposure is needed to ultimately identify treatments that may mitigate impacts later in life. In our previous work, we determined that rats with moderate prenatal alcohol exposure are significantly impaired in learning a task that requires the acquisition of an association between an object and its spatial location, called the object-place paired-associate task. Previous studies have demonstrated that disruption to the hippocampus impairs object-place associations. The hippocampal involvement in object-place learning and memory is critically dependent on synchronized rhythmic activity of hippocampal cell populations occurring at slow and fast frequencies. During active behavior, hippocampal cell activity can be organized by coupling between a slow rhythm called theta and a fast rhythm called gamma. During immobility, hippocampal neural activity is organized within a fast rhythm called a sharp wave-ripple. Theta-gamma coupling, and the expression of sharp wave-ripples, are thought to have a critical role in the encoding and consolidation of hippocampal dependent memories, respectively. Whether moderate prenatal alcohol exposure disrupts hippocampal theta-gamma coupling or characteristics of hippocampal sharp wave-ripples during performance of a learning and memory task has not been experimentally investigated. In two specific aims, we will test the hypotheses that impaired learning and memory after moderate prenatal alcohol exposure is associated with uncoupling of hippocampal theta-gamma rhythms and a disruption in the sharp wave-ripples characteristics and that these alterations to hippocampal rhythmic activity are associated with impairments in object-place learning and memory. The aims of this proposal will significantly advance our understanding of the neurobiological mechanisms of learning and memory deficits after moderate prenatal alcohol exposure.