Asynchronous GABA release generates long-lasting inhibition at a hippocampal interneuron–principal neuron synapse

Hippocampal GABAergic interneurons show diverse molecular and morphological properties. The functional significance of this diversity for information processing is poorly understood. Here we show that cholecystokinin (CCK)-expressing interneurons in rat dentate gyrus release GABA in a highly asynchronous manner, in contrast to parvalbumin (PV) interneurons. With a gamma-frequency burst of ten action potentials, the ratio of asynchronous to synchronous release is 3:1 in CCK interneurons but is 1:5 in parvalbumin interneurons. N-type channels trigger synchronous and asynchronous release in CCK interneuron synapses, whereas P/Q-type Ca2+ channels mediate release at PV interneuron synapses. Effects of Ca2+ chelators suggest that both a long-lasting presynaptic Ca2+ transient and a large distance between Ca2+ source and sensor of exocytosis contribute to the higher ratio of asynchronous to synchronous release in CCK interneuron synapses. Asynchronous release occurs at physiological temperature and with behaviorally relevant stimulation patterns, thus generating long-lasting inhibition in the brain.

[1]  M. Verhage,et al.  Differential release of amino acids, neuropeptides, and catecholamines from isolated nerve terminals , 1991, Neuron.

[2]  W. G. Van der Kloot.  Estimating the timing of quantal releases during end‐plate currents at the frog neuromuscular junction. , 1988, The Journal of physiology.

[3]  G. Buzsáki,et al.  Interneurons of the hippocampus , 1998, Hippocampus.

[4]  R. K. Simpson.  Nature Neuroscience , 2022 .

[5]  W. Regehr,et al.  Determinants of the Time Course of Facilitation at the Granule Cell to Purkinje Cell Synapse , 1996, The Journal of Neuroscience.

[6]  D. E. Koegel.  of the , 1941 .

[7]  R. Silver,et al.  Shunting Inhibition Modulates Neuronal Gain during Synaptic Excitation , 2003, Neuron.

[8]  P W Gage,et al.  Phasic secretion of acetylcholine at a mammalian neuromuscular junction. , 1980, The Journal of physiology.

[9]  Christof Koch,et al.  Shunting Inhibition Does Not Have a Divisive Effect on Firing Rates , 1997, Neural Computation.

[10]  T. Freund,et al.  Differences between Somatic and Dendritic Inhibition in the Hippocampus , 1996, Neuron.

[11]  L. Trussell,et al.  Inhibitory Transmission Mediated by Asynchronous Transmitter Release , 2000, Neuron.

[12]  P. Jonas,et al.  Efficacy and Stability of Quantal GABA Release at a Hippocampal Interneuron–Principal Neuron Synapse , 2000, The Journal of Neuroscience.

[13]  T. Freund,et al.  Postnatal development and migration of cholecystokinin-immunoreactive interneurons in rat hippocampus , 2003, Neuroscience.

[14]  E Neher,et al.  Usefulness and limitations of linear approximations to the understanding of Ca++ signals. , 1998, Cell calcium.

[15]  B Sakmann,et al.  Calcium Channel Types with Distinct Presynaptic Localization Couple Differentially to Transmitter Release in Single Calyx-Type Synapses , 1999, The Journal of Neuroscience.

[16]  M. Frotscher,et al.  Fast synaptic inhibition promotes synchronized gamma oscillations in hippocampal interneuron networks , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[17]  P. Jonas,et al.  Presynaptic short‐term depression is maintained during regulation of transmitter release at a GABAergic synapse in rat hippocampus , 2002, The Journal of physiology.

[18]  Frances S. Chance,et al.  Gain Modulation from Background Synaptic Input , 2002, Neuron.

[19]  B. Sakmann,et al.  Transmitter release modulation by intracellular Ca2+ buffers in facilitating and depressing nerve terminals of pyramidal cells in layer 2/3 of the rat neocortex indicates a target cell‐specific difference in presynaptic calcium dynamics , 2001, The Journal of physiology.

[20]  C. McBain,et al.  Potassium conductances underlying repolarization and after‐hyperpolarization in rat CA1 hippocampal interneurones. , 1995, The Journal of physiology.

[21]  B. Gähwiler,et al.  Either N- or P-type Calcium Channels Mediate GABA Release at Distinct Hippocampal Inhibitory Synapses , 1997, Neuron.

[22]  T. Südhof.  Synaptotagmins: Why So Many?* , 2002, The Journal of Biological Chemistry.

[23]  M A Xu-Friedman,et al.  Presynaptic strontium dynamics and synaptic transmission. , 1999, Biophysical journal.

[24]  Stuart G. Cull-Candy,et al.  Single-Channel Properties of Synaptic and Extrasynaptic GABAA Receptors Suggest Differential Targeting of Receptor Subtypes , 1999, The Journal of Neuroscience.

[25]  V. Shahrezaei,et al.  Competition between Phasic and Asynchronous Release for Recovered Synaptic Vesicles at Developing Hippocampal Autaptic Synapses , 2022 .

[26]  Y. Goda,et al.  Two components of transmitter release at a central synapse. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[27]  E. Neher,et al.  Estimating Transmitter Release Rates from Postsynaptic Current Fluctuations , 2001, The Journal of Neuroscience.

[28]  R. Llinás,et al.  Three distinct kinetic groupings of the synaptotagmin family: candidate sensors for rapid and delayed exocytosis. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[29]  Tamás F Freund,et al.  Interneuron Diversity series: Rhythm and mood in perisomatic inhibition , 2003, Trends in Neurosciences.

[30]  J. Lambert,et al.  Tetanus-induced asynchronous GABA release in cultured hippocampal neurons , 2000, Brain Research.

[31]  B. Walmsley,et al.  Counting quanta: Direct measurements of transmitter release at a central synapse , 1995, Neuron.

[32]  G. Westbrook,et al.  Desensitized states prolong GABAA channel responses to brief agonist pulses , 1995, Neuron.

[33]  Hartmut Schmidt,et al.  Mutational analysis of dendritic Ca2+ kinetics in rodent Purkinje cells: role of parvalbumin and calbindin D28k , 2003, The Journal of physiology.

[34]  G. Buzsáki,et al.  Neuronal Oscillations in Cortical Networks , 2004, Science.

[35]  J. Behrends,et al.  Sr2+‐dependent asynchronous evoked transmission at rat striatal inhibitory synapses in vitro , 1999, The Journal of physiology.

[36]  F. Conti,et al.  Nonstationary noise analysis and application to patch clamp recordings. , 1992, Methods in enzymology.

[37]  W. Regehr,et al.  Delayed Release of Neurotransmitter from Cerebellar Granule Cells , 1998, The Journal of Neuroscience.

[38]  R. Tsien,et al.  Pharmacological dissection of multiple types of Ca2+ channel currents in rat cerebellar granule neurons , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[39]  George Kunos,et al.  Presynaptic Specificity of Endocannabinoid Signaling in the Hippocampus , 2001, Neuron.

[40]  Massimo Scanziani,et al.  Routing of spike series by dynamic circuits in the hippocampus , 2004, Nature.

[41]  A. Marty,et al.  Developmental Changes in Parvalbumin Regulate Presynaptic Ca2+ Signaling , 2005, The Journal of Neuroscience.

[42]  G. Buzsáki,et al.  Gamma (40-100 Hz) oscillation in the hippocampus of the behaving rat , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[43]  Peter Somogyi,et al.  Cell surface domain specific postsynaptic currents evoked by identified GABAergic neurones in rat hippocampus in vitro , 2000, The Journal of physiology.

[44]  Jeffrey S. Diamond,et al.  Asynchronous release of synaptic vesicles determines the time course of the AMPA receptor-mediated EPSC , 1995, Neuron.

[45]  P. Somogyi,et al.  Synchronization of neuronal activity in hippocampus by individual GABAergic interneurons , 1995, Nature.

[46]  David Attwell,et al.  Tonic and Spillover Inhibition of Granule Cells Control Information Flow through Cerebellar Cortex , 2002, Neuron.

[47]  Attila Losonczy,et al.  Persistently active cannabinoid receptors mute a subpopulation of hippocampal interneurons. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[48]  Alex M Thomson,et al.  Physiological and morphological diversity of immunocytochemically defined parvalbumin‐ and cholecystokinin‐positive interneurones in CA1 of the adult rat hippocampus , 2002, The Journal of comparative neurology.

[49]  B. Sakmann,et al.  Calcium Secretion Coupling at Calyx of Held Governed by Nonuniform Channel–Vesicle Topography , 2002, The Journal of Neuroscience.

[50]  C. Jahr,et al.  Differential Control of Synaptic and Ectopic Vesicular Release of Glutamate , 2004, The Journal of Neuroscience.

[51]  J. Lisman.  Relating Hippocampal Circuitry to Function Recall of Memory Sequences by Reciprocal Dentate–CA3 Interactions , 1999, Neuron.

[52]  Chris J. McBain,et al.  Interneurons unbound , 2001, Nature Reviews Neuroscience.