Target cell type-dependent differences in presynaptic release probability (Pr ) and short-term plasticity are intriguing features of cortical microcircuits that increase the computational power of neuronal networks. Here, we tested the hypothesis that different voltage-gated Ca2+ channel densities in presynaptic active zones (AZs) underlie different Pr values. Two-photon Ca2+ imaging, triple immunofluorescent labeling, and 3D electron microscopic (EM) reconstruction of rat CA3 pyramidal cell axon terminals revealed ∼1.7-1.9 times higher Ca2+ inflow per AZ area in high Pr boutons synapsing onto parvalbumin-positive interneurons (INs) than in low Pr boutons synapsing onto mGluR1α-positive INs. EM replica immunogold labeling, however, demonstrated only 1.15 times larger Cav2.1 and Cav2.2 subunit densities in high Pr AZs. Our results indicate target cell type-specific modulation of voltage-gated Ca2+ channel function or different subunit composition as possible mechanisms underlying the functional differences. In addition, high Pr synapses are also characterized by a higher density of docked vesicles, suggesting that a concerted action of these mechanisms underlies the functional differences.SIGNIFICANCE STATEMENT Target cell type-dependent variability in presynaptic properties is an intriguing feature of cortical synapses. When a single cortical pyramidal cell establishes a synapse onto a somatostatin-expressing interneuron (IN), the synapse releases glutamate with low probability, whereas the next bouton of the same axon has high release probability when its postsynaptic target is a parvalbumin-expressing IN. Here, we used combined molecular, imaging, and anatomical approaches to investigate the mechanisms underlying these differences. Our functional experiments implied an approximately twofold larger Ca2+ channel density in high release probability boutons, whereas freeze-fracture immunolocalization demonstrated only a 15% difference in Ca2+ channel subunit densities. Our results point toward a postsynaptic target cell type-dependent regulation of Ca2+ channel function or different subunit composition as the underlying mechanism.
Pubmed ID: 28115484 RIS Download
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This polyclonal targets mouse mGluR1a, 945-1127 aa (NM_016976)
View all literature mentionsThis polyclonal targets Parvalbumin
View all literature mentionsThis unknown targets KV3.1b (KCNC1) Channel
View all literature mentionsThis polyclonal targets Ca2+ channel (N-type, alpha-1B subunit)
View all literature mentionsThis polyclonal targets Ca2+ channel (P/Q-type, alpha-1A subunit)
View all literature mentionsThis polyclonal targets ANTI-ELFN2 antibody produced in rabbit
View all literature mentionsThis monoclonal targets parvalbumin
View all literature mentionsThis unknown targets KV3.1b (KCNC1) Channel
View all literature mentionsThis polyclonal targets Ca2+ channel (N-type, alpha-1B subunit)
View all literature mentionsThis polyclonal targets Ca2+ channel (P/Q-type, alpha-1A subunit)
View all literature mentionsThis polyclonal targets ANTI-ELFN2 antibody produced in rabbit
View all literature mentionsThis monoclonal targets parvalbumin
View all literature mentionsThis polyclonal targets mouse mGluR1a, 945-1127 aa (NM_016976)
View all literature mentionsThis polyclonal targets Ca2+ channel (P/Q-type, alpha-1A subunit)
View all literature mentionsThis unknown targets KV3.1b (KCNC1) Channel
View all literature mentionsThis polyclonal targets Ca2+ channel (N-type, alpha-1B subunit)
View all literature mentionsThis polyclonal targets ANTI-ELFN2 antibody produced in rabbit
View all literature mentionsThis polyclonal targets mouse mGluR1a, 945-1127 aa (NM_016976)
View all literature mentionsThis polyclonal targets Parvalbumin
View all literature mentionsThis monoclonal targets parvalbumin
View all literature mentionsThis polyclonal targets mouse mGluR1a, 945-1127 aa (NM_016976)
View all literature mentionsThis polyclonal targets mouse mGluR1a, 945-1127 aa (NM_016976)
View all literature mentionsThis polyclonal targets mouse mGluR1a, 945-1127 aa (NM_016976)
View all literature mentionsThis polyclonal targets mouse mGluR1a, 945-1127 aa (NM_016976)
View all literature mentions