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Feedforward inhibition ahead of ictal wavefronts is provided by both parvalbumin‐ and somatostatin‐expressing interneurons

Lookup NU author(s): Ryley Parrish, Neela Codadu, Connie Mackenzie-Gray Scott, Professor Andrew Trevelyan



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2019 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society Key points: There is a rapid interneuronal response to focal activity in cortex, which restrains laterally propagating activity, including spreading epileptiform activity. The interneuronal response involves intense activation of both parvalbumin- and somatostatin-expressing interneurons. Interneuronal bursting is time-locked to glutamatergic barrages in the pre-ictal period. Ca 2+ imaging using conditional expression of GCaMP6f provides an accurate readout of the evolving firing patterns in both types of interneuron. The activation profiles of the two interneuronal classes are temporally offset, with the parvalbumin population being activated first, and typically, at higher rates. Abstract: Previous work has described powerful restraints on laterally spreading activity in cortical networks, arising from a rapid feedforward interneuronal response to focal activity. This response is particularly prominent ahead of an ictal wavefront. Parvalbumin-positive interneurons are considered to be critically involved in this feedforward inhibition, but it is not known what role, if any, is provided by somatostatin-expressing interneurons, which target the distal dendrites of pyramidal cells. We used a combination of electrophysiology and cell class-specific Ca 2+ imaging in mouse brain slices bathed in 0 Mg 2+ medium to characterize the activity profiles of pyramidal cells and parvalbumin- and somatostatin-expressing interneurons during epileptiform activation. The GCaMP6f signal strongly correlates with the level of activity for both interneuronal classes. Both interneuronal classes participate in the feedfoward inhibition. This contrasts starkly with the pattern of pyramidal recruitment, which is greatly delayed. During these barrages, both sets of interneurons show intense bursting, at rates up to 300Hz, which is time-locked to the glutamatergic barrages. The activity of parvalbumin-expressing interneurons appears to peak early in the pre-ictal period, and can display depolarizing block during the ictal event. In contrast, somatostatin-expressing interneuronal activity peaks significantly later, and firing persists throughout the ictal events. Interictal events appear to be very similar to the pre-ictal period, albeit with slightly lower firing rates. Thus, the inhibitory restraint arises from a coordinated pattern of activity in the two main classes of cortical interneurons.

Publication metadata

Author(s): Parrish RR, Codadu NK, Mackenzie-Gray Scott C, Trevelyan AJ

Publication type: Article

Publication status: Published

Journal: Journal of Physiology

Year: 2019

Volume: 597

Issue: 8

Pages: 2297-2314

Print publication date: 15/04/2019

Online publication date: 19/02/2019

Acceptance date: 19/02/2019

Date deposited: 02/04/2019

ISSN (print): 0022-3751

ISSN (electronic): 1469-7793

Publisher: Wiley-Blackwell Publishing Ltd


DOI: 10.1113/JP277749


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Funder referenceFunder name
MR/J013250/1Medical Research Council (MRC)