Jacques Micheau | PubMed Health

PubMed2003

Glutamate receptor function in learning and memory.

The contribution of glutamate to synaptic transmission, plasticity and development is well established; current evidence is based on diverse approaches to decipher function and malfunction of this principal transmitter. With respect to learning and memory, we are now able to identify more specifically the role played by the three main glutamate receptor classes in learning and memory: centre stage is clearly the NMDA receptor, with overwhelming evidence proving its involvement in the actual learning process (encoding), throughout the animal kingdom. This is discussed with respect to many different types of learning. Evidence for the contribution of the AMPA receptors (AMPARs) is less clear-cut due to the general problem of specificity: block of AMPARs will shutdown neuronal communication, and this will affect various components essential for learning. Therefore, the role of AMPARs cannot be established in isolation. Problems of interpretation are outlined and a specific involvement of AMPARs in the regulation of neuronal excitation related to learning is proposed. Metabotropic glutamate receptors (mGluRs) may contribute very little to the actual acquisition of new information. However, memory formation appears to require mGluRs, through the modulation of consolidation and/or recall. Overall, mGluR functions seem variable and dependent on brain structure and learning task.

Animals↗

PubMed2002

Effect of chronic inhibition of calpains in the hippocampus on spatial discrimination learning and protein kinase C.

Several behavioral and electrophysiological studies have suggested that a sustained activation of protein kinase C would be required to underlie persistent changes associated with memory formation. Limited proteolysis of PKCs by calpains, calcium-activated proteases, cleaves the catalytic and the regulatory domains, generating a free catalytic fragment termed PKM, constitutively active. In order to investigate the potential physiological importance of this limited proteolysis as a mechanism of PKC activation, we have studied the effect of the calpastatin peptide, a specific calpain inhibitor, on the learning of a spatial discrimination task in a radial maze. Thus, using osmotic micro-pumps, the calpastatin peptide was infused bilaterally into the dorsal hippocampus during the six sessions of training and the probe test. The treatment was shown to facilitate the performance of the mice on the two last training sessions and on the probe test. This behavioral effect was shown to correspond to the reduced calpain activity observed in the hippocampus at the very end of the 7-day infusion of the calpastatin peptide, suggesting a relation between both events. In addition, PKC activity measured immediately after the probe test was notably decreased in the membrane fraction of the hippocampus. Although protein levels of PKCs and calpains quantified by western blot were not affected by calpastatin infusion, we found a noticeable correlation between mu-calpain and PKCgamma levels confirming the particular relationship between both proteins. These results suggest that calpains influence on PKCs activity may affect cellular mechanisms during memory processes.

Animals↗