Selective pharmacological modulation of pyramidal neurons and interneurons in the CA1 region of the rat hippocampus

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DOIResolve DOI: http://doi.org/10.3389/fphar.2013.00024
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TypeArticle
Journal titleFrontiers in Pharmacology
ISSN1663-9812
Volume4-Mar
Article numberArticle 24
SubjectAMPA receptor; dizocilpine; memantine; n methyl dextro aspartic acid receptor; n methyl dextro aspartic acid receptor 1; n methyl dextro aspartic acid receptor 2A; n methyl dextro aspartic acid receptor 2B; n methyl dextro aspartic acid receptor 2C; animal cell; animal tissue; article; cell structure; cellular distribution; concentration response; controlled study; dose response; drug antagonism; excitatory postsynaptic potential; hippocampal CA1 region; hyperpolarization; inhibitory postsynaptic potential; interneuron; membrane steady potential; nerve cell stimulation; neurotransmission; nonhuman; patch clamp; protein expression; pyramidal nerve cell; rat; stratum radiatum
AbstractThe hippocampus is a complex network tightly regulated by interactions between excitatory and inhibitory neurons. In neurodegenerative disorders where cognitive functions such as learning and memory are impaired this excitation-inhibition balance may be altered. Interestingly, the uncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist memantine, currently in clinical use for the treatment of Alzheimer's disease, may alter the excitation-inhibition balance in the hippocampus. However, the specific mechanism by which memantine exerts this action is not clear. To better elucidate the effect of memantine on hippocampal circuitry, we studied its pharmacology on NMDAR currents in both pyramidal cells (PCs) and interneurons (Ints) in the CA1 region of the hippocampus. Applying whole-cell patch-clamp methodology to acute rat hippocampal slices, we report that memantine antagonism is more robust in PCs than in Ints. Using specific NMDAR subunit antagonists, we determined that this selective antagonism of memantine is attributable to specific differences in the molecular make-up of the NMDARs in excitatory and inhibitory neurons. These findings offer new insight into the mechanism of action and therapeutic potential of NMDA receptor pharmacology in modulating hippocampal excitability. © 2013 Martina, Comas and Mealing.
Publication date
LanguageEnglish
AffiliationNational Research Council Canada (NRC-CNRC); Human Health Therapeutics (HHT-TSH)
Peer reviewedYes
NPARC number21269981
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Record identifier4f56b050-b79b-4207-98e0-ffb72b4c50a6
Record created2013-12-13
Record modified2016-05-09
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