How voltage-gated calcium channels gate forms of homeostatic synaptic plasticity

Abstract

Throughout life, animals face a variety of challenges such as developmental growth, the presence of toxins, or changes in temperature. Neuronal circuits and synapses respond to challenges by executing an array of neuroplasticity paradigms. Some paradigms allow neurons to up- or downregulate activity outputs, while countervailing ones ensure that outputs remain within appropriate physiological ranges. A growing body of evidence suggests that homeostatic synaptic plasticity (HSP) is critical in the latter case. Voltage-gated calcium channels gate forms of HSP. Presynaptically, the aggregate data show that when synapse activity is weakened, homeostatic signaling systems can act to correct impairments, in part by increasing calcium influx through presynaptic CaV2-type channels. Increased calcium influx is often accompanied by parallel increases in the size of active zones and the size of the readily releasable pool of presynaptic vesicles. These changes coincide with homeostatic enhancements of neurotransmitter release. Postsynaptically, there is a great deal of evidence that reduced network activity and loss of calcium influx through CaV1-type calcium channels also results in adaptive homeostatic signaling. Some adaptations drive presynaptic enhancements of vesicle pool size and turnover rate via retrograde signaling, as well as de novo insertion of postsynaptic neurotransmitter receptors. Enhanced calcium influx through CaV1 after network activation or single cell stimulation can elicit the opposite response—homeostatic depression via removal of excitatory receptors. There exist intriguing links between HSP and calcium channelopathies—such as forms of epilepsy, migraine, ataxia, and myasthenia. The episodic nature of some of these disorders suggests alternating periods of stable and unstable function. Uncovering information about how calcium channels are regulated in the context of HSP could be relevant toward understanding these and other disorders.

Paliperidone Protects SH-SY5Y Cells Against MK-801-Induced Neuronal Damage Through Inhibition of Ca2+ Influx and Regulation of SIRT1/miR-134 Signal Pathway

“…Previous studies demonstrate that calcium ions are transferred into cells major by voltage-gated calcium channels which participate in depolarizing signal [14,29]. In this study, the SH-SY5Y cells were treated with MK-801 for 24 h in vitro, and the membrane potential depolarized from −60 to −20 mV.…”

“…Especially, paliperidone offered neuroprotective effects in recent studies. For example, paliperidone protected SH-SY5Y cells against cell death induced by β-amyloid peptide (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35), N-methyl-4-phenylpyridinium ion [10]. In addition, paliperidone reduced the caspase-3 expression and protected SK-N-SH cells against neurotoxicity induced by dopamine [11].…”

Glutamatergic Mechanisms Associated with Seizures and Epilepsy

“…In the kindling model of epilepsy (Potschka et al 2002), Homer 1a -overexpressing mice show delays in kindling acquisition (Potschka et al 2002), and Homer 1a is up-regulated in response to SE (Cavarsan et al 2012). Homer 1a protein normally contributes to homeostatic scaling (Hu et al 2010), which is likely aberrant in chronic seizures (Frank 2014). In addition to the observed dysregulation of Homer 1a in seizure models, expression of other synaptic plasticity-associated immediate early genes (IEGs), including c-Fos and Arc, have also been shown to be dysregulated in animal models of chronic seizures (Klein et al 2004;Christensen et al 2010).…”

The guanine-exchange factor Ric8a binds the calcium sensor NCS-1 to regulate synapse number and probability of release

“…In many neuron types -motor neurons in particular -these two features appear to be regulated in an antagonistic manner; cells with more synapses exhibit lower probability of release per synapse, whereas cells with fewer synapses show a higher probability of release. Although Ca 2+ is the major signal regulating both of these neuronal features (Augustine and Charlton, 1986;Komuro and Rakic, 1996;Zheng, 2000; for reviews see Pang and Südhof, 2010;Meriney and Dittrich, 2013;Frank, 2014), and heterotrimeric G protein complexes have been implicated as mediators (Renden and Broadie, 2003;Wolfgang et al, 2004;Klose et al, 2010; reviewed by Ross, 2008;Schmitz, 2014), a mechanistic link between Ca 2+ surge and G protein signaling is still unknown. Shedding light on this issue is relevant and urgent, because many cognitive diseases, most of which are without an effective treatment, result from the abnormal regulation of synapses.…”