Group II metabotropic glutamate receptors in the aging brain

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ABSTRACT The deterioration of neural circuits in the brain is a contributing factor to the perceptual deficits associated with aging. The long-term goals of our research are to understand the molecular and neural alterations that underlie age-related perceptual impairments. The primary objective of this R03 pilot proposal is to characterize the molecular neuropharmacological alterations to Group II metabotropic glutamate receptors (mGluRs), which enable glutamatergic inhibition at forebrain synapses. The central hypothesis is that the expression of these Group II mGluRs is altered with age in the neocortex. This is rationalized to result in changes to the balance of excitation and inhibition in the neocortex and contribute to the emergence of age-related sensory perceptual deficits. Several neuroanatomical and neurophysiological features of these receptors have been identified, which forms the basis for the proposed investigation. The specific aims of this project are to characterize the alterations to Group II mGluRs in the neocortex with age by examining: 1) changes in the neuroanatomical expression patterns of these receptors and 2) alterations to forebrain neurophysiological responses mediated by pharmacological activation of these receptors. The proposed experiments are expected to identify the age- related changes to Group II mGluRs in the neocortex and guide our future investigations aimed at directly linking these receptor alterations with the perceptual deficits experienced during aging and ultimately restoring normal behavior in this model system. These experiments will have a positive impact by illuminating the potentially important role of Group II mGluRs in age-related perceptual deficits and as a prospective therapeutic target for these conditions.