Target Cell Type-Dependent Differences in Ca 2+ Channel Function Underlie Distinct Release Probabilities at Hippocampal Glutamatergic Terminals

  • Éltes T
  • Kirizs T
  • Nusser Z
  • et al.
N/ACitations
Citations of this article
46Readers
Mendeley users who have this article in their library.

Abstract

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.

Cite

CITATION STYLE

APA

Éltes, T., Kirizs, T., Nusser, Z., & Holderith, N. (2017). Target Cell Type-Dependent Differences in Ca 2+ Channel Function Underlie Distinct Release Probabilities at Hippocampal Glutamatergic Terminals . The Journal of Neuroscience, 37(7), 1910–1924. https://doi.org/10.1523/jneurosci.2024-16.2017

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free