Aging is associated with declining function across a broad spectrum of behavioral and biological measures. This component of the program project will pursue a combination of behavioral and neurophysiological studies aimed at characterizing the nature and range of alterations in neuronal representations associated with aging:
Specific Aim 1 : Exploiting a recent finding of hippocampal neuronal activity patterns closely associated with memory performance in young animals, we will characterize the nature of performance-related abnormalities in hippocampal representation associating with aging. These studies will determine whether memory errors are associated with compromised stability of hippocampal spatial representations, or retrieval of inappropriate memory representations.
Specific Aim 2 : Extending on findings on the previous funding period, we will examine the development of new hippocampal spatial representations when animals are presented with a novel environment. These studies will examine interference from previous perceptual stimuli and behavioral strategies, and the stability and selectivity of new representations, and the rate and extent to which new representations anchor to salient cues. Parallel studies will determine if the development of new hippocampal representations is impaired in aging, and to what extent the impairment is due to intrusions of existing representations.
Specific Aim 3 : We will use our well developed paradigm for delayed non-match to sample (DNMS) to examine the nature of memory representations in the prefrontal cortex and perirhinal-entorhinal cortex of aged animals. These studies will determine whether the impairment in DNMS performance in aged rats results from a deficiency in processing of task rules by the prefrontal cortex, or a deficiency in sustaining memory representations in the perirhinal-entorhinal cortex, or both. In addition, these studies will determine whether there are age related abnormalities in interactions among cortical areas and the hippocampus associated with stimulus evaluation and memory. Each of these experiments is designed to test specific hypotheses about the nature of age related cognitive decline: that aging is associated with abnormalities in hippocampal and cortical representations, and age- related memory involves loss of basal forebrain regulation of hippocampal or cortical information processing, and loss of the plasticity of synaptic mechanisms.
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