title: Target Cell Type-Dependent Differences in Ca2+Channel Function Underlie Distinct Release Probabilities at Hippocampal Glutamatergic Terminals.
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 differentPrvalues. 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 highPrboutons synapsing onto parvalbumin-positive interneurons (INs) than in lowPrboutons synapsing onto mGluR1α-positive INs. EM replica immunogold labeling, however, demonstrated only 1.15 times larger Cav2.1 and Cav2.2 subunit densities in highPrAZs. 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, highPrsynapses are also characterized by a higher density of docked vesicles, suggesting that a concerted action of these mechanisms underlies the functional differences.SIGNIFICANCE STATEMENTTarget 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.
authors.affiliation: Laboratory of Cellular Neurophysiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, 1083 Budapest, Hungary, and.|János Szentágothai School of Neurosciences, Semmelweis University, 1085 Budapest, Hungary.
authors.forename: Tímea
authors.identifier: 0000-0002-2488-5734
authors.initials: T
authors.lastname: Éltes
authors.affiliation: Laboratory of Cellular Neurophysiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, 1083 Budapest, Hungary, and.|János Szentágothai School of Neurosciences, Semmelweis University, 1085 Budapest, Hungary.
authors.forename: Tekla
authors.identifier: 0000-0002-7513-2716
authors.initials: T
authors.lastname: Kirizs
authors.affiliation: Laboratory of Cellular Neurophysiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, 1083 Budapest, Hungary, and nusser@koki.hu noemi.holderith@koki.mta.hu.
authors.forename: Zoltan
authors.identifier: 0000-0001-7004-4111
authors.initials: Z
authors.lastname: Nusser
authors.affiliation: Laboratory of Cellular Neurophysiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, 1083 Budapest, Hungary, and nusser@koki.hu noemi.holderith@koki.mta.hu.
authors.forename: Noemi
authors.identifier: 0000-0002-0024-3980
authors.initials: N
authors.lastname: Holderith
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism* / Q000648:ultrastructure; D018698:Glutamic Acid / Q000145:classification / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology*; D066298:In Vitro Techniques; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000648:ultrastructure; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D010320:Parvalbumins / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000648:ultrastructure; D011336:Probability; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism / Q000648:ultrastructure; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D002118:Calcium; D015220:Calcium Channels; D018698:Glutamic Acid; D008239:Lysine; D009419:Nerve Tissue Proteins; D010320:Parvalbumins; D018094:Receptors, Metabotropic Glutamate; D005680:gamma-Aminobutyric Acid; C000602318:ELFN1 protein, human; C104077:metabotropic glutamate receptor type 1; C013411:biocytin
keywords: Ca2+; EM tomography; electron microscopy; hippocampus; immunogold labeling; two-photon imaging