The general anaesthetic etomidate inhibits the excitability of mouse thalamocortical relay neurons by modulating multiple modes of GABAA receptor-mediated inhibition
| Autor: | Jeremy J. Lambert, Murray B. Herd, Delia Belelli |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Male
phasic inhibition Neural Inhibition Action Potentials Inhibitory postsynaptic potential spill-over inhibition nucleus reticularis Tonic (physiology) tonic inhibition Mice Thalamus Postsynaptic potential Etomidate medicine Animals Mice Knockout Neurons Chemistry GABAA receptor General Neuroscience Long-term potentiation Molecular and Synaptic Mechanisms Receptors GABA-A Mice Inbred C57BL medicine.anatomical_structure Inhibitory Postsynaptic Potentials Synapses Female Neuron Neuroscience Anesthetics Intravenous medicine.drug |
| Zdroj: | The European Journal of Neuroscience |
| ISSN: | 1460-9568 0953-816X |
| Popis: | Modulation of thalamocortical (TC) relay neuron function has been implicated in the sedative and hypnotic effects of general anaesthetics. Inhibition of TC neurons is mediated predominantly by a combination of phasic and tonic inhibition, together with a recently described 'spillover' mode of inhibition, generated by the dynamic recruitment of extrasynaptic γ-aminobutyric acid (GABA)A receptors (GABAA Rs). Previous studies demonstrated that the intravenous anaesthetic etomidate enhances tonic and phasic inhibition in TC relay neurons, but it is not known how etomidate may influence spillover inhibition. Moreover, it is unclear how etomidate influences the excitability of TC neurons. Thus, to investigate the relative contribution of synaptic (α1β2γ2) and extrasynaptic (α4β2δ) GABAA Rs to the thalamic effects of etomidate, we performed whole-cell recordings from mouse TC neurons lacking synaptic (α1(0/0) ) or extrasynaptic (δ(0/0) ) GABAA Rs. Etomidate (3 μm) significantly inhibited action-potential discharge in a manner that was dependent on facilitation of both synaptic and extrasynaptic GABAA Rs, although enhanced tonic inhibition was dominant in this respect. Additionally, phasic inhibition evoked by stimulation of the nucleus reticularis exhibited a spillover component mediated by δ-GABAA Rs, which was significantly prolonged in the presence of etomidate. Thus, etomidate greatly enhanced the transient suppression of TC spike trains by evoked inhibitory postsynaptic potentials. Collectively, these results suggest that the deactivation of thalamus observed during etomidate-induced anaesthesia involves potentiation of tonic and phasic inhibition, and implicate amplification of spillover inhibition as a novel mechanism to regulate the gating of sensory information through the thalamus during anaesthetic states. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|