Major impairments of glutamatergic transmission and long-term synaptic plasticity in the hippocampus of mice lacking the melanin-concentrating hormone receptor-1.
Publisher DOI
PubMed ID
20592115
Abstract
The hypothalamic neuropeptide melanin-concentrating hormone (MCH) plays important roles in energy homeostasis, anxiety, and sleep regulation. Since the MCH receptor-1 (MCH-R1), the only functional receptor that mediates MCH functions in rodents, facilitates behavioral performance in hippocampus-dependent learning tasks, we investigated whether glutamatergic transmission in CA1 pyramidal cells could be modulated in mice lacking the MCH-R1 gene (MCH-R1(-/-)). We found that both α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-d-aspartate (NMDA) receptor-mediated transmissions were diminished in the mutant mice compared with their controls. This deficit was explained, at least in part, by a postsynaptic down-regulation of these receptors since the amplitude of miniature excitatory postsynaptic currents and the NMDA/AMPA ratio were decreased. Long-term synaptic potentiation (LTP) was also impaired in MCH-R1(-/-) mice. This was due to an altered induction, rather than an impaired, expression because repeating the induction stimulus restored LTP to a normal magnitude. In addition, long-term synaptic depression was strongly diminished in MCH-R1(-/-) mice. These results suggest that MCH exerts a facilitatory effect on CA1 glutamatergic synaptic transmission and long-term synaptic plasticity. Recently, it has been shown that MCH neurons fire exclusively during sleep and mainly during rapid eye movement sleep. Thus these findings provide a mechanism by which sleep might facilitate memory consolidation.
Date Issued
2010-09
Publication Type
Article
Subject(s)
Language(s)
en
Author(s)
Pachoud, Bastien | |
Ravassard, Pascal | |
Luppi, Pierre-Hervé | |
Grisar, Thierry | |
Lakaye, Bernard | |
Salin, Paul-Antoine |
Additional Credits
Journal
Journal of neurophysiology
Publisher
American Physiological Society
ISSN
0022-3077
Access(Rights)
restricted