Investigating the effects of propofol-induced tonic inhibition on rhythmic neural activity in a hippocampal interneuron network

Abstract : Propofol is an anaesthetic agent commonly used in surgical operations for the induction and maintenance of general anaesthesia. Propofol-induced sedation is achieved by positively modulating GABAergic inhibitory activity, as the drug binds on GABA A receptors enhancing their activation [1]. GABA A receptors are ubiquitous in the brain [2], and can be present both within synap-tic clefts, as well as on extrasynaptic locations along the dendrites where they mediate tonic in-hibitory currents. Synaptic GABAergic interactions between sparsely connected interneurons are thought to play an important role in the generation and maintenance of rhythmic neural activity, in particular in the γ-band (20 − 80) Hz [3]. This oscillatory frequency range is often recorded in functionally-coupled brain regions for cooperation during memory tasks. One such example is cortico-hippocampal synchronisation during long-term memory consolidation [4]. This work studies the effect of propofol-induced tonic inhibition on the oscillations elicited in a network of hippocampal Hodgkin-Huxley GABA interneurons [3]. The action of propofol on extrasynaptic GABAergic receptors was modelled by varying the conductance g of a tonic current in the form Iton = g(V − Eton ) as described in [5]. To measure the synchronisation of the neural activity in the network we used the coherence metric K defined in [3], where a value of 1 indicates global synchrony across all neurons. In the absence of tonic inhibition g = 0nS, the network synchronises its activity with K = 0.4 at an oscillatory frequency of ∼ 43 Hz. Increasing doses of propofol reduce the overall network activity and slow down its oscillations until a critical value of g = 14nS at which the synchronisation increases abruptly reaching a plateau at K = 0.8, and the mean firing rate increases. These results point towards a possible mechanism for the emergence of paradoxical excitation under general anaesthesia.
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Submitted on : Thursday, November 12, 2015 - 11:37:09 AM
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Francesco Giovannini, Jean-Baptiste Schneider, Laure Buhry. Investigating the effects of propofol-induced tonic inhibition on rhythmic neural activity in a hippocampal interneuron network. Eleventh Bernstein Conference 2015, Sep 2015, Heidelberg, Germany. Proceedings of the Eleventh Bernstein Conference 2015, 2015, ⟨http://www.nncn.de/en/bernstein-conference/2015⟩. ⟨hal-01191426⟩

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