Disrupting the melanin-concentrating hormone receptor 1 in mice leads to cognitive deficits and alterations of NMDA receptor function.

in European Journal of Neuroscience (2005), 21(10), 2837-44

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 (MCHR1(Neo/Neo) mice ... [more ▼]

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 (MCHR1(Neo/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 MCHR1(Neo/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. [less ▲]

Molecular Basis of Neuronal Biorhythms and Paroxysms

in Archives of Physiology & Biochemistry (1996), 104(6), 770-4

The molecular basis of the biorhythms are evoked in relation to cerebral EEG rhythms and paroxysms. Basic oscillatory phenomena have been well shown and modeled in systems such as the glycolytic pathway ... [more ▼]

The molecular basis of the biorhythms are evoked in relation to cerebral EEG rhythms and paroxysms. Basic oscillatory phenomena have been well shown and modeled in systems such as the glycolytic pathway, the oscillations of cAMP in amoebas and rhythms of the intracellular cycline during mitosis. In excitable cells the intracellular calcium and cAMP oscillations exhibit a signalling system with many advantages. Thus the question arises: to what extent can the EEG paroxysms observed in epileptic syndrome be due to disturbances in such basic molecular pathways that underlie intracellular molecular oscillations? The usefulness of the absence-rat-model and the implication the T type Ca(2+)-channel of the thalamic nuclei in the pathophysiology of this epileptic syndrome are discussed. [less ▲]