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Distinct mechanisms of Up state maintenance in the medial entorhinal cortex and neocortex

Digby, RJ; Bravo, DS; Paulsen, O; Magloire, V; (2017) Distinct mechanisms of Up state maintenance in the medial entorhinal cortex and neocortex. Neuropharmacology , 113 (Part A) pp. 543-555. 10.1016/j.neuropharm.2016.11.009. Green open access

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Abstract

The medial entorhinal cortex (mEC) is a key structure which controls the communication between the hippocampus and the neocortex. During slow-wave sleep, it stands out from other cortical regions by exhibiting persistent activity that outlasts neocortical Up states, decoupling the entorhinal cortex-hippocampal interaction from the neocortex. Here, we compared the mechanisms involved in the maintenance of the Up state in the barrel cortex (BC) and mEC using whole cell recordings in acute mouse brain slices. Bath application of an NMDA receptor antagonist abolished Up states in the BC, and reduced the incidence but not the duration of Up states in the mEC. Conversely, blockade of kainate receptors decreased Up state duration in the mEC, but not in the BC. Voltage clamp recordings demonstrated the presence of a non-NMDA glutamate receptor-mediated slow excitatory postsynaptic current, sensitive to the selective kainate receptor antagonist UBP-302, in layer III neurons of the mEC, which was not observed in the BC. Moreover, we found that kainate receptor-mediated currents assist in recovery back to the Up state membrane potential following a current-induced hyperpolarisation of individual cells in the mEC. Finally, we were able to generate Up state activity in a network model of exponential integrate-and-fire neurons only supported by AMPA and kainate receptor-mediated currents. We propose that synaptic kainate receptors are responsible for the unique properties of mEC Up states.

Type: Article
Title: Distinct mechanisms of Up state maintenance in the medial entorhinal cortex and neocortex
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.neuropharm.2016.11.009
Publisher version: http://doi.org/10.1016/j.neuropharm.2016.11.009
Language: English
Additional information: Copyright © 2016 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
Keywords: Up state, Slow oscillation, Medial entorhinal cortex, Barrel cortex, Kainate receptor, NMDA receptor
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Experimental Epilepsy
URI: https://discovery.ucl.ac.uk/id/eprint/1554241
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