Seeburg, Peter H.; Sprengel, Rolf; Köhr, Georg; Osten, Pavel
A dogma in the Neurosciences states that learning causes long-lasting changes in chemical synapses of the brain. The goal of the Department of Molecular Neurobiology at the MPI for Medical Research is to describe the function of key molecules for such changes. Most synapses in the brain are excitatory in nature and operate with the chemical transmitter L-glutamate, which when released upon an impulse from the sending part of the synapse (presynaptic specialization), diffuses across the synaptic cleft and binds to postsynaptically localized specific receptors. Binding of glutamate opens an inherent pore in the receptors, such that for a brief moment (several msec) positively charged ions (cations) flow into the nerve cell, shifting the cell from its resting state to an excited state by depolarizing its membrane potential. Genetic manipulation of glutamate receptors (GluRs) in the mouse alters synaptic function and may impair or – more rarely – enhance learning abilities. The following investigations highlight important functional aspects of glutamate receptors in spatial learning for which the hippocampus, a prominent brain structure, is essential, and also in olfactory learning in olfactory synapses. Moreover, the expression of functionally altered GluRs can evoke neurodegenerative diseases such as epilepsy and amyotrophic lateral sclerosis.