Kinetic Organization of Ca²⁺ Signals That Regulate Synaptic Release Efficacy in Sympathetic Neurons

Abstract

ABSTRACTsignals operating near Ca 21 sources in the AZ are organized into discrete fast and slow temporal phases that remodel exocytosis and short-term plasticity to ensure long-term stability in acetylcholine release efficacy.

Synaptic vesicle glycoprotein 2A modulates vesicular release and calcium channel function at peripheral sympathetic synapses

“…Our approach differs from previous studies using transgenic mouse models to reduce SV2A levels, which may potentially be confounded by accompanying compensatory and/or developmental changes (Crèvecœur et al ., ). Throughout, the siRNA experiments were controlled by an appropriate nsRNA; in this regard, the nsRNA construct produced control parameters, including EPSP amplitude, RRP size, overall vesicle count and synaptic depression characteristics, which were in good agreement with control data from our previous studies in SCG neurons (Krapivinsky et al ., ; Ma et al ., ; Tanifuji et al ., ; Mori et al ., ), suggesting that the injection of RNA had no detrimental effects per se on basal cell physiology in this experimental system (Ma & Mochida, ).…”

“…It was also reported that SV2B deletion in rod bipolar cells caused a slowing in recovery of membrane capacitance in response to a train of stimuli, potentially reflecting a slowing in the rate of endocytosis (Wan et al ., ). These effects were proposed to occur secondarily to changes in Ca 2+ signaling (see also Mori et al ., ). Overall, our data support a scenario whereby, in control conditions, empty release slots are filled rapidly after the cessation of high‐frequency stimulation through vesicles from the recycling pool, whereas, under conditions of SV2A knockdown, this process takes longer and appears to be more reliant on slower endocytic pathways.…”

“…For example, the observed RRP attenuation is characteristic of reduced Ca 2+ influx through presynaptic VDCCs (Xu & Wu, ) and increased synaptic depression can be caused by decreased RRP size and altered replenishment and/or impaired VDCC function (Zucker & Regehr, ). In addition, the slowed recovery from RRP depletion seen is consistent with a reduction in presynaptic Ca 2+ (Mori et al ., ). Here, we demonstrate, for the first time, that SV2A knockdown reduces whole‐cell I Ca .…”

“…SV2A deficits in the fast phase are also proposed to delay RRP replenishment from the RP and cause impaired, i.e. temporally delayed, Ca 2+ -dependent long-term vesicle replenishment from the RP to the RRP following depletion (Mori et al, 2014). It was also reported that SV2B deletion in rod bipolar cells caused a slowing in recovery of membrane capacitance in response to a train of stimuli, potentially reflecting a slowing in the rate of endocytosis (Wan et al, 2010).…”

Millisecond Ca²⁺ dynamics activate multiple protein cascades for synaptic vesicle control

“…1 ). 9 , 12 ) The SCG neuron has a large cell body and nucleus that allows for the manipulation of gene expression and protein function in mature neurons via acute microinjection of cDNA, small interfering RNA (siRNA), dominant-negative transgenes, peptides, antibodies, and/or metabolites, 9 , 13 – 16 ) an approach not technically feasible for cultured neurons from the central nervous system. In addition, synaptic activity and short-term plasticity, because they relate to the size and replenishment of functional SVs pools, can be accurately monitored by recording excitatory postsynaptic potentials (EPSPs) evoked by APs in presynaptic neurons.…”