Mapping miniature synaptic currents to single synapses using calcium imaging reveals heterogeneity in postsynaptic output

The amplitudes and kinetics of miniature excitatory synaptic currents (MESCs) in mammalian central neurons vary widely. It is unclear whether this variability occurs at each synapse or arises from differences among a heterogeneous population of synapses. Furthermore, it is not known how variability in these currents would affect their associated postsynaptic Ca2+ transients. To address these questions, we conducted simultaneous Ca2+ imaging and patch-clamp recordings from cultured cortical neurons and mapped individual MESCs to identified synapses displaying coincident dendritic miniature synaptic Ca2+ transients (MSCTs). Measurements of MSCTs at dendritic sites that displayed multiple events revealed that MSCT amplitude varied considerably at each site. Simultaneous measurement of MESCs and MSCTs at these sites indicated that variability in coincident synaptic currents contributes to the differences in Ca2+ transient amplitude. The ability of single synapses to exhibit variable output may enable them to engage intracellular signaling pathways at different levels of intracellular Ca2+.