Frequency detection and temporally dispersed synaptic signal association through a metabotropic glutamate receptor pathway.

In the classical view, a central neuron integrates incoming synaptic information by simple algebraic summation of the resultant bioelectrical signals that coincide in time. The voltage dependence of the NMDA (N-methyl-D-aspartate) type of ionotropic glutamate receptor endows neurons with an additional tool that allows one synaptic input to influence another, providing, again, that the two are active simultaneously. Here we identify a new mechanism by which non-coincident signals generated by different synaptic inputs are integrated. The device serves to regulate neuronal excitation through G-protein-coupled, metabotropic glutamate receptors (mGluRs) in a powerful and specific manner. We show that, in cerebellar Purkinje cells, a single activation of the climbing-fibre input markedly potentiates mGluR-mediated excitation at parallel-fibre synapses. The potentiation results from a transient rise in cytosolic Ca2+ which is 'memorized' in such a way that it promotes excitation through mGluRs for about two minutes. A Ca2+-transient is also effective if imposed up to two seconds after parallel-fibre stimulation. By allowing temporally and spatially dispersed synaptic signals to be assimilated, this mechanism adds a new element to the computational power of central neurons.