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Glutamate-Bound NMDARs Arising from In Vivo-like Network Activity Extend Spatio-temporal Integration in a L5 Cortical Pyramidal Cell Model.

Farinella, M; Ruedt, DT; Gleeson, P; Lanore, F; Silver, RA; (2014) Glutamate-Bound NMDARs Arising from In Vivo-like Network Activity Extend Spatio-temporal Integration in a L5 Cortical Pyramidal Cell Model. PLoS Comput Biol , 10 (4) , Article e1003590. 10.1371/journal.pcbi.1003590. Green open access

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Abstract

In vivo, cortical pyramidal cells are bombarded by asynchronous synaptic input arising from ongoing network activity. However, little is known about how such 'background' synaptic input interacts with nonlinear dendritic mechanisms. We have modified an existing model of a layer 5 (L5) pyramidal cell to explore how dendritic integration in the apical dendritic tuft could be altered by the levels of network activity observed in vivo. Here we show that asynchronous background excitatory input increases neuronal gain and extends both temporal and spatial integration of stimulus-evoked synaptic input onto the dendritic tuft. Addition of fast and slow inhibitory synaptic conductances, with properties similar to those from dendritic targeting interneurons, that provided a 'balanced' background configuration, partially counteracted these effects, suggesting that inhibition can tune spatio-temporal integration in the tuft. Excitatory background input lowered the threshold for NMDA receptor-mediated dendritic spikes, extended their duration and increased the probability of additional regenerative events occurring in neighbouring branches. These effects were also observed in a passive model where all the non-synaptic voltage-gated conductances were removed. Our results show that glutamate-bound NMDA receptors arising from ongoing network activity can provide a powerful spatially distributed nonlinear dendritic conductance. This may enable L5 pyramidal cells to change their integrative properties as a function of local network activity, potentially allowing both clustered and spatially distributed synaptic inputs to be integrated over extended timescales.

Type: Article
Title: Glutamate-Bound NMDARs Arising from In Vivo-like Network Activity Extend Spatio-temporal Integration in a L5 Cortical Pyramidal Cell Model.
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pcbi.1003590
Publisher version: http://dx.doi.org/10.1371/journal.pcbi.1003590
Language: English
Additional information: �© 2014 Farinella et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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 Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: https://discovery.ucl.ac.uk/id/eprint/1430401
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