A New Class of Synaptic Response Involving Calcium Release in Dendritic Spines

In the classical view, transmission of signals across synapses in the mammalian brain involves changes in the membrane potential of the postsynaptic cell. The use of high-resolution cellular imaging has revealed excitatory synapses at which postsynaptic, transient alterations in calcium ion concentration are tightly associated with electrical responses. Here, by investigating the synapse between parallel glutamatergic fibres and Purkinje cells in the mouse cerebellum, we identify a class of postsynaptic responses that consist of transient increases in dendritic Ca2+ concentration but not changes in somatic membrane potential. Our results indicate that these synaptic Ca2+ transients are mediated by activation of metabotropic glutamate-responsive mGluR1-type receptors and require inositol-1,4,5-trisphosphate-mediated Ca2+ release from intradendritic stores. The new type of synaptic response is restricted to postsynaptic microdomains, which range, depending on the frequency of stimulation, from individual spines to small spinodendritic compartments. Thus, the synaptic Ca2+-release signal may be one of the critical cues that determine the input specificity of long-term depression, a well-established form of activity-dependent plasticity at these synapses.