title: Distinct mechanisms of Up state maintenance in the medial entorhinal cortex and neocortex.
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.
authors.affiliation: Department of Physiology, Development and Neuroscience, Physiological Laboratory, University of Cambridge, Downing Street, Cambridge, CB2 3EG, UK.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Digby
authors.affiliation: Department of Physiology, Development and Neuroscience, Physiological Laboratory, University of Cambridge, Downing Street, Cambridge, CB2 3EG, UK.
authors.forename: Diego S
authors.initials: DS
authors.lastname: Bravo
authors.affiliation: Department of Physiology, Development and Neuroscience, Physiological Laboratory, University of Cambridge, Downing Street, Cambridge, CB2 3EG, UK. Electronic address: op210@cam.ac.uk.
authors.forename: Ole
authors.initials: O
authors.lastname: Paulsen
authors.affiliation: Department of Physiology, Development and Neuroscience, Physiological Laboratory, University of Cambridge, Downing Street, Cambridge, CB2 3EG, UK; Department of Clinical and Experimental Epilepsy, Institute of Neurology, University of College London, Queen Square, London, WC1N 3BG, UK. Electronic address: v.magloire@ucl.ac.uk.
authors.forename: Vincent
authors.initials: V
authors.lastname: Magloire
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D018728:Entorhinal Cortex / Q000502:physiology*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019579:Neocortex / Q000502:physiology*; D009415:Nerve Net / Q000502:physiology*; D009924:Organ Culture Techniques; D018092:Kainic Acid Receptors / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology
chemical_list: D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate
keywords: Barrel cortex; CNQX (PubChem CID: 3721046); GYKI-53655 (PubChem CID: 126758); Gabazine (PubChem CID: 107895); Kainate receptor; Medial entorhinal cortex; NMDA receptor; Slow oscillation; UBP-302 (PubChem CID: 6420161); Up state; d-AP5 (PubChem CID: 135342)