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...
Autores principales: | , , , , , , |
---|---|
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 |