Distinct effects of volatile and intravenous anaesthetics on presynaptic calcium dynamics in mouse hippocampal GABAergic neurones.

BACKGROUND

General anaesthetics have marked effects on synaptic transmission, but their neuronal and circuit-level effects remain unclear. The volatile anaesthetic isoflurane differentially inhibits synaptic vesicle exocytosis in specific neuronal subtypes, but whether other common anaesthetics also have neurone-subtype-specific actions is unknown.

METHODS

We used the genetically encoded fluorescent Ca sensor GCaMP6f to compare the pharmacological effects of isoflurane, sevoflurane, propofol, and ketamine on presynaptic excitability in hippocampal glutamatergic neurones and in hippocampal parvalbumin-, somatostatin-, and vasoactive intestinal peptide-expressing (PV, SST, and VIP, respectively) GABAergic interneurones.

RESULTS

Isoflurane and sevoflurane depressed activity-driven presynaptic Ca transients in a neurone-type-specific manner, with greater potency for inhibition of glutamate and SST compared with PV and VIP neurone presynaptic activation. In contrast, clinical concentrations of propofol (1 μM) or ketamine (15 μM) had no significant effects on presynaptic activation. Propofol potentiated evoked Ca entry in PV interneurones but only at a supraclinical concentration (3 μM).

CONCLUSIONS

Anaesthetic-agent-selective effects on presynaptic Ca entry have functional implications for hippocampal circuit function during i.v. or volatile anaesthetic-mediated anaesthesia. Hippocampal interneurones have distinct subtype-specific sensitivities to volatile anaesthetic actions on presynaptic Ca, which are similar between isoflurane and sevoflurane.