Cargando…

Activity of the Lateral Hypothalamus during Genetically Determined Absence Seizures

(1) Background: Absence seizures (ASs) are sudden, transient lapses of consciousness associated with lack of voluntary movements and generalized 2.5–4 Hz spike-wave discharges (SWDs) in the EEG. In addition to the thalamocortical system, where these pathological oscillations are generated, multiple...

Descripción completa

Detalles Bibliográficos
Autores principales: Sere, Péter, Zsigri, Nikolett, Raffai, Timea, Furdan, Szabina, Győri, Fanni, Crunelli, Vincenzo, Lőrincz, Magor L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431596/
https://www.ncbi.nlm.nih.gov/pubmed/34502374
http://dx.doi.org/10.3390/ijms22179466
_version_ 1783750974778638336
author Sere, Péter
Zsigri, Nikolett
Raffai, Timea
Furdan, Szabina
Győri, Fanni
Crunelli, Vincenzo
Lőrincz, Magor L.
author_facet Sere, Péter
Zsigri, Nikolett
Raffai, Timea
Furdan, Szabina
Győri, Fanni
Crunelli, Vincenzo
Lőrincz, Magor L.
author_sort Sere, Péter
collection PubMed
description (1) Background: Absence seizures (ASs) are sudden, transient lapses of consciousness associated with lack of voluntary movements and generalized 2.5–4 Hz spike-wave discharges (SWDs) in the EEG. In addition to the thalamocortical system, where these pathological oscillations are generated, multiple neuronal circuits have been involved in their modulation and associated comorbidities including the serotonergic system. Neuronal activity in one of the major synaptic input structures to the brainstem dorsal raphé nucleus (DRN), the lateral hypothalamus (LH), has not been characterized. (2) Methods: We used viral tract tracing and optogenetics combined with in vitro and in vivo electrophysiology to assess the involvement of the LH in absence epilepsy in a genetic rodent model. (3) Results: We found that a substantial fraction of LH neurons project to the DRN of which a minority is GABAergic. The LH to DRN projection can lead to monosynaptic iGluR mediated excitation in DRN 5-HT neurons. Neuronal activity in the LH is coupled to SWDs. (4) Conclusions: Our results indicate that a brain area involved in the regulation of autonomic functions and heavily innervating the RN is involved in ASs. The decreased activity of LH neurons during SWDs could lead to both a decreased excitation and disinhibition in the DRN. These results support a long-range subcortical regulation of serotonergic neuromodulation during ASs and further our understanding of the state-dependence of these seizures and some of their associated comorbidities.
format Online
Article
Text
id pubmed-8431596
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-84315962021-09-11 Activity of the Lateral Hypothalamus during Genetically Determined Absence Seizures Sere, Péter Zsigri, Nikolett Raffai, Timea Furdan, Szabina Győri, Fanni Crunelli, Vincenzo Lőrincz, Magor L. Int J Mol Sci Article (1) Background: Absence seizures (ASs) are sudden, transient lapses of consciousness associated with lack of voluntary movements and generalized 2.5–4 Hz spike-wave discharges (SWDs) in the EEG. In addition to the thalamocortical system, where these pathological oscillations are generated, multiple neuronal circuits have been involved in their modulation and associated comorbidities including the serotonergic system. Neuronal activity in one of the major synaptic input structures to the brainstem dorsal raphé nucleus (DRN), the lateral hypothalamus (LH), has not been characterized. (2) Methods: We used viral tract tracing and optogenetics combined with in vitro and in vivo electrophysiology to assess the involvement of the LH in absence epilepsy in a genetic rodent model. (3) Results: We found that a substantial fraction of LH neurons project to the DRN of which a minority is GABAergic. The LH to DRN projection can lead to monosynaptic iGluR mediated excitation in DRN 5-HT neurons. Neuronal activity in the LH is coupled to SWDs. (4) Conclusions: Our results indicate that a brain area involved in the regulation of autonomic functions and heavily innervating the RN is involved in ASs. The decreased activity of LH neurons during SWDs could lead to both a decreased excitation and disinhibition in the DRN. These results support a long-range subcortical regulation of serotonergic neuromodulation during ASs and further our understanding of the state-dependence of these seizures and some of their associated comorbidities. MDPI 2021-08-31 /pmc/articles/PMC8431596/ /pubmed/34502374 http://dx.doi.org/10.3390/ijms22179466 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sere, Péter
Zsigri, Nikolett
Raffai, Timea
Furdan, Szabina
Győri, Fanni
Crunelli, Vincenzo
Lőrincz, Magor L.
Activity of the Lateral Hypothalamus during Genetically Determined Absence Seizures
title Activity of the Lateral Hypothalamus during Genetically Determined Absence Seizures
title_full Activity of the Lateral Hypothalamus during Genetically Determined Absence Seizures
title_fullStr Activity of the Lateral Hypothalamus during Genetically Determined Absence Seizures
title_full_unstemmed Activity of the Lateral Hypothalamus during Genetically Determined Absence Seizures
title_short Activity of the Lateral Hypothalamus during Genetically Determined Absence Seizures
title_sort activity of the lateral hypothalamus during genetically determined absence seizures
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431596/
https://www.ncbi.nlm.nih.gov/pubmed/34502374
http://dx.doi.org/10.3390/ijms22179466
work_keys_str_mv AT serepeter activityofthelateralhypothalamusduringgeneticallydeterminedabsenceseizures
AT zsigrinikolett activityofthelateralhypothalamusduringgeneticallydeterminedabsenceseizures
AT raffaitimea activityofthelateralhypothalamusduringgeneticallydeterminedabsenceseizures
AT furdanszabina activityofthelateralhypothalamusduringgeneticallydeterminedabsenceseizures
AT gyorifanni activityofthelateralhypothalamusduringgeneticallydeterminedabsenceseizures
AT crunellivincenzo activityofthelateralhypothalamusduringgeneticallydeterminedabsenceseizures
AT lorinczmagorl activityofthelateralhypothalamusduringgeneticallydeterminedabsenceseizures