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Modular propagation of epileptiform activity: Evidence for an inhibitory veto in neocortex

Lookup NU author(s): Professor Andrew Trevelyan

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Abstract

What regulates the spread of activity through cortical circuits? We present here data indicating a pivotal role for a vetoing inhibition restraining modules of pyramidal neurons. We combined fast calcium imaging of network activity with whole-cell recordings to examine epileptiform propagation in mouse neocortical slices. Epileptiform activity was induced by washing Mg 2+ ions out of the slice. Pyramidal cells receive barrages of inhibitory inputs in advance of the epileptiform wave. The inhibitory barrages are effectively nullified at low doses of picrotoxin (2.5-5 μM). When present, however, these inhibitory barrages occlude an intense excitatory synaptic drive that would normally exceed action potential threshold by approximately a factor of 10. Despite this level of excitation, the inhibitory barrages suppress firing, thereby limiting further neuronal recruitment to the ictal event. Pyramidal neurons are recruited to the epileptiform event once the inhibitory restraint fails and are recruited in spatially clustered populations (150-250 μm diameter). The recruitment of the cells within a given module is virtually simultaneous, and thus epileptiform events progress in intermittent (0.5-1 Hz) steps across the cortical network. We propose that the interneurons that supply the vetoing inhibition define these modular circuit territories. Copyright © 2006 Society for Neuroscience.


Publication metadata

Author(s): Trevelyan AJ, Sussillo D, Watson BO, Yuste R

Publication type: Article

Publication status: Published

Journal: Journal of Neuroscience

Year: 2006

Volume: 26

Issue: 48

Pages: 12447-12455

Date deposited: 04/08/2010

ISSN (print): 0270-6474

ISSN (electronic): 1529-2401

Publisher: Society for Neuroscience

URL: http://dx.doi.org/10.1523/JNEUROSCI.2787-06.2006

DOI: 10.1523/JNEUROSCI.2787-06.2006

PubMed id: 17135406


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