Homeostatic Presynaptic Plasticity Is Specifically Regulated by P/Q-type Ca2+ Channels at Mammalian Hippocampal Synapses

• Published in: Cell reports (Cambridge) Vol. 21; no. 2; pp. 341 - 350
• Main Authors: Jeans, Alexander F., van Heusden, Fran C., Al-Mubarak, Bashayer, Padamsey, Zahid, Emptage, Nigel J.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 10.10.2017; Cell Press; Elsevier
• Subjects: homeostatic plasticity; neurotransmitter release; P/Q-type channelopathy; pHluorin; synapse; voltage-gated calcium channel; homeostatic plasticity; P/Q-type channelopathy; voltage-gated calcium channel; synapse; neurotransmitter release; pHluorin
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2017.09.061

Voltage-dependent Ca2+ channels (VGCC) represent the principal source of Ca2+ ions driving evoked neurotransmitter release at presynaptic boutons. In mammals, presynaptic Ca2+ influx is mediated mainly via P/Q-type and N-type VGCC, which differ in their properties. Changes in their relative contributions tune neurotransmission both during development and in Hebbian plasticity. However, whether this represents a functional motif also present in other forms of activity-dependent regulation is unknown. Here, we study the role of VGCC in homeostatic plasticity (HSP) in mammalian hippocampal neurons using optical techniques. We find that changes in evoked Ca2+ currents specifically through P/Q-type, but not N-type, VGCC mediate bidirectional homeostatic regulation of both neurotransmitter release efficacy and the size of the major synaptic vesicle pools. Selective dependence of HSP on P/Q-type VGCC in mammalian terminals has important implications for phenotypes associated with P/Q-type channelopathies, including migraine and epilepsy. [Display omitted] •P/Q-type VGCC regulate homeostatic synaptic plasticity (HSP) in mammals•Changes in synaptic vesicle pool sizes during HSP are also mediated via P/Q-type VGCC•Expression of HSP is independent of N-type VGCC regulation•P/Q-type regulation of HSP may explain phenotypes of P/Q-type channelopathies Jeans at al. show that both basal neurotransmission and synaptic vesicle pool sizes are specifically regulated by the presynaptic P/Q-type voltage-gated Ca2+ channel during HSP at mammalian hippocampal synapses. This may shed light on mechanisms underlying phenotypes associated with P/Q-type channelopathies, including migraine and epilepsy.