FREQUENCY DETECTION AND TEMPORALLY DISPERSED SYNAPTIC SIGNAL ASSOCIATION THROUGH A METABOTROPIC GLUTAMATE-RECEPTOR PATHWAY

IN the classical view, a central neuron integrates incoming synaptic i nformation by simple algebraic summation of the resultant bioelectrica l signals that coincide in time, The voltage dependence of the NMDA (N -methyl-D-aspartate) type of ionotropic glutamate receptor endows neur ons with an additional tool that allows one synaptic input to influenc e another, providing again, that the two are active simultaneously(1). Here we identify a new mechanism by which non-coincident signals gene rated by different synaptic inputs are integrated, The device serves t o regulate neuronal excitation through G-protein-coupled, metabotropic glutamate receptors (mGluRs)(2) in a powerful and specific manner. We show that, in cerebellar Purkinje cells, a single activation of the c limbing-fibre input markedly potentiates mGluR-mediated excitation at parallel-fibre synapses(3). The potentiation results; from a transient rise in cytosolic Ca2+ which is 'memorized' in such a way that it pro motes excitation through mGluRs for about two minutes. A Ca2+-transien t is also effective if imposed up to two seconds after parallel-fibre stimulation. By allowing temporally and spatially dispersed synaptic s ignals to be assimilated, this mechanism adds a new element to the com putational power of central neurons.