Neuronal Ca²⁺ signalling at rest and during spontaneous neurotransmission

Abstract

Action potential driven neuronal signalling drives several electrical and biochemical processes in the nervous system. However, neurons can maintain synaptic communication and signalling under resting conditions independently of activity. Importantly, these processes are regulated by Ca2+ signals that occur at rest. Several studies have suggested that opening of voltage‐gated Ca2+ channels near resting membrane potentials, activation of NMDA receptors in the absence of depolarization or Ca2+ release from intracellular stores can drive neurotransmitter release as well as subsequent signalling in the absence of action potentials. Interestingly, recent studies have demonstrated that manipulation of resting neuronal Ca2+ signalling yielded pronounced homeostatic synaptic plasticity, suggesting a critical role for this resting form of signalling in regulation of synaptic efficacy and neuronal homeostasis. Given their robust impact on synaptic efficacy and neuronal signalling, neuronal resting Ca2+ signals warrant further mechanistic analysis that includes the potential role of store‐operated Ca2+ entry in these processes.

STIM Protein-NMDA2 Receptor Interaction Decreases NMDA-Dependent Calcium Levels in Cortical Neurons

“…Ca 2+ influx into neuronal cells depends on NMDARs, AMPARs, VGCCs, as well as SOCE that trigger Orai/TRPs channels and STIM proteins [20,21,[34][35][36]. The role of NMDARs in nSOCE remains unclear.…”

“…However, Ca 2+ entry in neurons primarily remains under control by well-defined (VGCCs), which are localized in the cell soma, dendrites, and nerve terminals [33], and receptor-operated channels (ROCs), such as AMPARs and NMDARs, that function at both synaptic and extrasynaptic sites [34][35][36]. NMDARs belong to the family of ionotropic receptors that respond to extracellular glutamate.…”

Properties of multivesicular release from mouse rod photoreceptors support transmission of single-photon responses

“…It is generally accepted that under conditions of low release probability (e.g., when a neuron is hyperpolarized), vesicle exocytosis occurs stochastically, obeying Poisson statistics (Malagon et al, 2016;Miki, 2019;Zhang and Peskin, 2015). Spontaneous release can be Ca 2+ -independent or due to chance openings of voltage-gated Ca 2+ channels (Cork et al, 2016;Kavalali, 2015Kavalali, , 2019. The persistence of spontaneous events in rods held at −70 mV, even after blocking Ca 2+ channels with extracellular Cd 2+ or strongly buffering intracellular Ca 2+ with 10 mM BAPTA, showed evidence for Ca 2+ -independent release (Hays et al, 2020b).…”

Properties of multi-vesicular release from rod photoreceptors support transmission of single photon responses

“…It is generally accepted that under conditions of low release probability (e.g., when a neuron is hyperpolarized), vesicle exocytosis occurs stochastically, obeying Poisson statistics (Malagon et al, 2016; Miki, 2019; Zhang and Peskin, 2015). Spontaneous release can be Ca 2+ -independent or due to chance openings of voltage-gated Ca 2+ channels (Cork et al, 2016; Kavalali, 2015, 2019). The persistence of spontaneous events in rods held at -70 mV, even after blocking Ca 2+ channels with extracellular Cd 2+ or strongly buffering intracellular Ca 2+ with 10 mM BAPTA, showed evidence for Ca 2+ -independent release (Hays et al, 2020b).…”