O’Neill, Nathanael;
Lignani, Gabriele;
(2023)
From the Subiculum to the Anterior Nuclei of the Thalamus: The Key to Hippocampal Seizure Generalization?
Epilepsy Currents
, 13
(1)
, Article 5010. 10.1177/15357597221147356.
(In press).
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Abstract
Epilepsy is considered a circuit-level dysfunction associated with imbalanced excitation-inhibition, it is therapeutically necessary to identify key brain regions and related circuits in epilepsy. The subiculum is an essential participant in epileptic seizures, but the circuit mechanism underlying its role remains largely elusive. Here we deconstruct the diversity of subicular circuits in a mouse model of epilepsy. We find that excitatory subicular pyramidal neurons heterogeneously control the generalization of hippocampal seizures by projecting to different downstream regions. Notably, anterior thalamus projecting subicular neurons bidirectionally mediate seizures, while entorhinal cortex-projecting subicular neurons act oppositely in seizure modulation. These two subpopulations are structurally and functionally dissociable. An intrinsically enhanced hyperpolarization-activated current and robust bursting intensity in anterior thalamus-projecting neurons facilitate synaptic transmission, thus contributing to the generalization of hippocampal seizures. These results demonstrate that subicular circuits have diverse roles in epilepsy, suggesting the necessity to precisely target specific subicular circuits for effective treatment of epilepsy.
| Type: | Article |
|---|---|
| Title: | From the Subiculum to the Anterior Nuclei of the Thalamus: The Key to Hippocampal Seizure Generalization? |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1177/15357597221147356 |
| Publisher version: | https://doi.org/10.1177/15357597221147356 |
| Language: | English |
| Additional information: | Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
| UCL classification: | UCL 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/10164572 |
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