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

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.