Alcohol impairs the cognitive processes that lead to the initial encoding of new memories. The narrowing of the scope of attention and the slowing of working memory produced by alcohol bring about a diminished capacity to encode the details of new episodic memories. The 5-92 Hz electrophysiological oscillation recorded in the mammalian brain called the theta rhythm has consistently been shown to coordinate the flow of memory-bound stimulus information into the hippocampus. We have observed that the hippocampal theta rhythm synchronizes with the entorhinal cortex during memory encoding and with the prefrontal cortex during memory retrieval. The theta rhythm synchronizes with stimulus encoding and retrieval by resetting the phase of its oscillatory activity, locking the rhythm to the onset of stimulus. We have reported previously some predictable dose-dependent changes in the theta rhythm following acute exposure to alcohol. The rhythm not only slows down but diminishes theta reset. These neurophysiological effects of alcohol have not been studied with respect to memory encoding and retrieval of stimulus information. The current proposal outlines three experiments that are designed to investigate the hypotheses that low to moderate doses of alcohol (0.25 - 1.0 g/kg) impair encoding of new memories but do not impair retrieval of established memories, and that ethanol does this by disrupting the synchronization of theta between critical structures responsible for these functions. In the first experiment, a traditional measure of spatial working memory, the delayed nonmatch to position task, is used to assess the effects of ethanol on theta synchronization relative to stimulus encoding and retrieval. In the second experiment, an operant task is used to determine the optimal parameters in which to assess the effects of ethanol on memory encoding, consolidation and retrieval, and these parameters will be used in the third experiment to determine the role of theta resetting on these memory processes. The results from these studies will provide important new neuroanatomical, neurophysiological and behavioral insights into memory functions known to be affected by moderate doses of alcohol.
In this study we are examining the effects of acute ethanol exposure on the neural mechanisms of memory encoding and retrieval. Previous findings have shown that ethanol affects encoding of memory to a greater extent than retrieval of memory. We present preliminary evidence that a type of rhythmic neural activity in the brain called theta activity is synchronized between different brain regions depending on whether an animal is in the process of encoding or retrieving information. With this proposal, we will examine the effects of ethanol at low to moderate doses on these neural mechanisms of memory encoding and retrieval in an animal model to ascertain whether they can account for the known behavioral differences that have been observed in humans with an eye toward better understanding the brain structures and processes that are vulnerable to impairment by ethanol.
