PROJECT 1-Neural encoding based on lateral and medial entorhinal information processing streams in behaviorally-characterized aged rats

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The hippocampus and medial temporal lobe are crucial components of the brain’s declarative memory system. Extensive damage to these structures results in devastating and permanent loss of the ability to form new, conscious memories of facts and personal experience. Aging is strongly associated with loss or change of memory functions, in both normal aging and in neuropathological conditions. The lateral entorhinal cortex (LEC) and medial entorhinal cortex (MEC) provide the large majority of medial temporal lobe input to the hippocampus. The MEC appears to provide the hippocampus with a signal about the spatial location of an organism. This signal is thought to act as a framework that allows the hippocampus to bind together the individual components of an experience that occur at a moment in space and time. This framework allows the hippocampus to form a coherent representation that is stored and later retrieved as an episodic memory. The role of the LEC in this system has been less explored. The LEC may represent the individual components that make up the content of an episodic memory. However, this role has not received as much experimental investigation and validation compared to the role of MEC. Because the LEC is particularly vulnerable in the early stages of age-related memory impairment, including Alzheimer’s Disease, it is imperative to understand in detail the types of information represented in LEC and the neural coding mechanisms that underlie these representations. Recent studies have provided two fundamental insights into LEC neural representations: (1) LEC encodes a temporal context signal that allows the brain to represent and distinguish memories of events that occur at different points in time; and (2) LEC represents the bearing of external items relative to the observer in an egocentric frame of reference. The latter insight is consistent with the notion that LEC provides the hippocampus with first-person information about the content of an episode, experienced and remembered from an egocentric perspective. We hypothesize that the mnemonic deficits that mark early stages of age- related cognitive decline and Alzheimer’s Dementia may result from the loss of normal temporal coding and egocentric coding of the LEC inputs to the hippocampus. To test this hypothesis, we will determine whether there are differences among young rats, aged rats without memory impairment, and aged rats with memory impairment in these properties of LEC neurons. These experiments promise to provide crucial new data and insights into how medial temporal lobe dysfunction produces the mild to severe memory impairments that can range from minor inconvenience to devastating incapacity in aged individuals.