This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Neurogenesis is the production of new cells in the brain. Molecular cues regulating this process include a wide range of growth and survival factors, but a regulatory link between neurogenesis and neurotransmitter activity has been less explored. Norepinephrine (NE), an endogenous neurotransmitter, may be involved in promoting neurogenesis through the activation of alpha1A adrenergic receptors (ARs). The goal of this project is to obtain additional evidence for a possible role of alpha1AARs in neurogenesis. Recently, our research group found that mice genetically engineered to overexpress alpha1AARs were significantly less prone to hyperexcitability (epileptic seizures) and had enhanced learning and memory processes. These animals also appear to possess more interneurons, particularly in their hippocampi, an area of the brain critical for learning and memory, highly susceptible to seizures, and often involved in temporal lobe epilepsies. Based on this preliminary evidence, we have hypothesized that NE, through activation of alpha 1AARs is stimulating both the production and function of interneurons, and that this leads to improved cognitive abilities even in aged animals. To test this hypothesis, we proposed the following specific aims using mice greater than 12 months in age.
Aim 1 : Identify the alpha 1AR subtypes mediating the effects of NE on hippocampal interneurons.
Aim 2 : Test the effects of alpha 1AR overexpression in hippocampal interneuron populations.
Aim 3 : Determine the effects of alpha1 AR activation on cognitive function.
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