Disrupting the melanin‐concentrating hormone receptor 1 in mice leads to cognitive deficits and alterations of NMDA receptor function
- 27 May 2005
- journal article
- Published by Wiley in European Journal of Neuroscience
- Vol. 21 (10) , 2837-2844
- https://doi.org/10.1111/j.1460-9568.2005.04100.x
Abstract
In order to investigate the physiological properties of the melanin-concentrating hormone (MCH) we have generated and used mice from which the MCH receptor 1 gene was deleted (MCHR1Neo/Neo mice). Complementary experimental approaches were used to investigate alterations in the learning and memory processes of our transgenic model. The ability of the knockout strain to carry out the inhibitory passive avoidance test was found to be considerably impaired although no significant differences were observed in anxiety levels. This impaired cognitive property prompted us to explore modifications in N-methyl d-aspartate (NMDA) responses in the hippocampus. Intracellular recordings of CA1 pyramidal neurons in hippocampal slices from the MCHR1Neo/Neo mice revealed significantly decreased NMDA responses. Finally, using in situ hybridization we found a 15% reduction in NMDAR1 subunit in the CA1 region. These results show for the first time a possible role for MCH in the control of the function of the NMDA receptor.Keywords
This publication has 58 references indexed in Scilit:
- THE AMYGDALA MODULATES THE CONSOLIDATION OF MEMORIES OF EMOTIONALLY AROUSING EXPERIENCESAnnual Review of Neuroscience, 2004
- Melanin-concentrating hormone functions in the nervous system: food intake and stressEmerging Therapeutic Targets, 2003
- Melanin-concentrating hormone, hippocampal nitric oxide levels and memory retentionPeptides, 2002
- Melanin‐concentrating hormone depresses L‐, N‐, and P/Q‐type voltage‐dependent calcium channels in rat lateral hypothalamic neuronsThe Journal of Physiology, 2002
- Molecular Cloning and Functional Characterization of MCH2, a Novel Human MCH ReceptorJournal of Biological Chemistry, 2001
- Increased Expression of mRNA Encoding Ferritin Heavy Chain in Brain Structures of a Rat Model of Absence EpilepsyExperimental Neurology, 2000
- Isolation and Identification of Melanin-Concentrating Hormone as the Endogenous Ligand of the SLC-1 ReceptorBiochemical and Biophysical Research Communications, 1999
- Cloning of the rat brain cDNA encoding for the SLC-1 G protein-coupled receptor reveals the presence of an intron in the geneBiochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1998
- Memory Formation: The Sequence of Biochemical Events in the Hippocampus and Its Connection to Activity in Other Brain StructuresNeurobiology of Learning and Memory, 1997
- Hydrogen peroxide hyperpolarizes rat CA1 pyramidal neurons by inducing an increase in potassium conductanceBrain Research, 1995