| Popis: |
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(2+) 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(2+) 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(2+) entry in PV(+) interneurones but only at a supraclinical concentration (3 μM). CONCLUSIONS: Anaesthetic-agent-selective effects on presynaptic Ca(2+) 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(2+), which are similar between isoflurane and sevoflurane. |
