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Selective Pharmacological Modulation of Pyramidal Neurons and Interneurons in the CA1 Region of the Rat Hippocampus

Martina, Marzia and Comas, Tanya and Mealing, Geoffrey (2013) Selective Pharmacological Modulation of Pyramidal Neurons and Interneurons in the CA1 Region of the Rat Hippocampus. Journal of Neuroscience, 4. ISSN 1663-9812

Abstract

The hippocampus is a complex network that consists of tightly regulated interaction between excitation and inhibition. In Alzheimer’s disease (AD) and other neurodegenerative disorders in which cognitive functions such as learning and memory are severely impaired, the inhibition-excitation balance in the hippocampal neuronal circuitry is impaired. Increasing evidence suggest that, due to the role of N-methyl-D-aspartate receptor (NMDAR) in learning and memory, dysfunctions in NMDAR functions may play a pivotal role in the pathogenesis of numerous neurodegenerative disorders. The uncompetitive NMDAR antagonist memantine, clinically used for the treatment of AD, may restore the inhibition-excitation balance in the hippocampus. The mechanism through which memantine exerts its action is, however, not clear. To better understand the effect of memantine on the hippocampal neuronal circuit, we studied the pharmacology of memantine on the NMDAR currents of pyramidal cells (PCs) and interneurons (Ints) in the CA1 region of the hippocampus. Using whole-cell patch-clamp recordings on acute rat hippocampal slices, we found that memantine antagonism of NMDAR currents was more effective in PCs than Ints. In particular, using specific NMDAR subunit antagonists, we found that the effect of memantine varies depending on the molecular make up of the NMDAR that the neurons express. Our results open new avenues for studies on the mechanism of action of memantine.

Item Type: Article
Keywords: Pyramidal neurons, Interneurons, NMDA receptor, NVP-AAM077, Ro25-6981
Date Deposited: 26 Apr 2016 23:46
Last Modified: 26 Apr 2016 23:46
URI: https://oak.novartis.com/id/eprint/4899

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