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RESEARCH The long-range goal of our research is to contribute to a better understanding of the neural mechanisms involved in the establishment and maintenance of memory. Previous studies have identified a system of structures in the medial temporal lobe that is critical for declarative memory, the ability for the conscious recollection of facts and events. This system of structures includes the hippocampus and the surrounding cortical regions. These are the structures that are affected first in Alzheimer’s disease, and previous studies have demonstrated that lesions of these structures produce profound memory deficits. It is unclear, however, how these structures work together during memory formation and retrieval. In our research, we are working to identify the neural signals that mediate cooperation between the hippocampus and the surrounding cortex by recording simultaneously from multiple neurons across these regions in awake, behaving monkeys that have been trained to perform various types of memory tasks. This research provides an opportunity to directly investigate neuronal interaction across medial temporal lobe regions as well as possible functional distinctions between these regions. The Role of Synchronous Neural Activity in Memory Formation The objective of this research is to test a new hypothesis to explain the brain’s ability to form memories. Memory formation appears to be accomplished through coordinated activity within the Medial Temporal Lobe (MTL), and interactions of this complex with neocortex. However, the physiological mechanisms underlying these interactions are unknown. We hypothesize that modulation in synchronization within and between MTL structures is an important mechanism by which the brain forms memories. We record MTL activity in monkeys performing visual behavioral tasks and we assess the extent to which memory formation is associated with changes in neuronal synchronization within and among MTL structures. We also use pharmacological techniques to modulate neuronal synchronization and behavioral performance. Phase synchronization of spikes in the gamma-band (30-80 Hz) may be particularly relevant for memory formation, because synchronization in this range would ensure that spikes arrive at downstream targets within ~10 ms of one another, i.e., within one-half of a gamma cycle. Such close temporal spike alignment may lead to enhanced synaptic efficacy, which is considered to be one of the primary information storage principles in the brain. The Circuitry of Memory Formation and Retrieval Because of its anatomical connectivity, the Entorhinal Cortex (EC) is well-positioned to play a critical role in hippocampal-cortical interaction. The EC originates the majority of the cortical input to the hippocampus and is the recipient of a large feedback projection from the hippocampus. Furthermore, these connections are segregated within the EC such that it is primarily the superficial layers that project to the hippocampus and the deep layers that receive hippocampal output. Recent evidence from rat EC slices suggests that EC neurons display layer-specific physiological properties. Additionally, recordings in rats during free exploration and sleep have identified distinct patterns of activity in superficial and deep layers of EC. These findings raise the possibility that hippocampal inputs and outputs support memory in different ways. The objective of this project is to identify the memory-related activity of superficial- and deep-layer EC neurons in awake, behaving monkeys. By examining layer-specific differences in firing rates, as well as oscillatory and synchronous activity, in relation to different aspects of memory tasks, we expect to be able to advance our understanding of hippocampal-cortical interaction and the neural circuitry of memory formation and retrieval. Recent Posters
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