Major Impairments of Glutamatergic Transmission and Long-Term Synaptic Plasticity in the Hippocampus of Mice Lacking the Melanin-Concentrating Hormone Receptor-1
Journal of Neurophysiology. 2010-09-01; 104(3): 1417-1425
DOI: 10.1152/jn.01052.2009
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1. J Neurophysiol. 2010 Sep;104(3):1417-25. doi: 10.1152/jn.01052.2009. Epub 2010
Jun 30.
Major impairments of glutamatergic transmission and long-term synaptic plasticity
in the hippocampus of mice lacking the melanin-concentrating hormone receptor-1.
Pachoud B(1), Adamantidis A, Ravassard P, Luppi PH, Grisar T, Lakaye B, Salin PA.
Author information:
(1)Unité Mixte de Recherche 5167 du Centre National de la Recherche Scientifique,
Institut Fédératif des Neurosciences de Lyon (IFR19), Université Claude, Lyon,
France.
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.
DOI: 10.1152/jn.01052.2009
PMCID: PMC4073994
PMID: 20592115 [Indexed for MEDLINE]