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.
Liste complète des métadonnées

Cited literature [5 references]  Display  Hide  Download
Contributor : Francesco Giovannini <>
Submitted on : Thursday, November 12, 2015 - 11:37:09 AM
Last modification on : Tuesday, December 18, 2018 - 4:40:21 PM
Document(s) archivé(s) le : Friday, February 12, 2016 - 4:56:32 PM




  • HAL Id : hal-01191426, version 1


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, ⟨⟩. ⟨hal-01191426⟩



Record views


Files downloads