Noradrenergic stimulation of α1 adrenoceptors in the medial prefrontal cortex mediates acute stress-induced facilitation of seizures in mice
Abstract Stress is one of the critical facilitators for seizure induction in patients with epilepsy. However, the neural mechanisms underlying this facilitation remain poorly understood. Here, we investigated whether noradrenaline (NA) transmission enhanced by stress exposure facilitates the inducti...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-05-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-35242-0 |
| _version_ | 1797822896688594944 |
|---|---|
| author | Kazuhei Niitani Shiho Ito Shintaro Wada Shoma Izumi Naoya Nishitani Satoshi Deyama Katsuyuki Kaneda |
| author_facet | Kazuhei Niitani Shiho Ito Shintaro Wada Shoma Izumi Naoya Nishitani Satoshi Deyama Katsuyuki Kaneda |
| author_sort | Kazuhei Niitani |
| collection | DOAJ |
| description | Abstract Stress is one of the critical facilitators for seizure induction in patients with epilepsy. However, the neural mechanisms underlying this facilitation remain poorly understood. Here, we investigated whether noradrenaline (NA) transmission enhanced by stress exposure facilitates the induction of medial prefrontal cortex (mPFC)-originated seizures. In mPFC slices, whole-cell current-clamp recordings revealed that bath application of picrotoxin induced sporadic epileptiform activities (EAs), which consisted of depolarization with bursts of action potentials in layer 5 pyramidal cells. Addition of NA dramatically shortened the latency and increased the number of EAs. Simultaneous whole-cell and field potential recordings revealed that the EAs are synchronous in the mPFC local circuit. Terazosin, but not atipamezole or timolol, inhibited EA facilitation, indicating the involvement of α1 adrenoceptors. Intra-mPFC picrotoxin infusion induced seizures in mice in vivo. Addition of NA substantially shortened the seizure latency, while co-infusion of terazosin into the mPFC inhibited the effect of NA. Finally, acute restraint stress shortened the latency of intra-mPFC picrotoxin infusion-induced seizures, whereas prior infusion of terazosin reversed this stress-induced shortening of seizure latency. Our findings suggest that stress facilitates the induction of mPFC-originated seizures via NA stimulation of α1 adrenoceptors. |
| first_indexed | 2024-03-13T10:15:59Z |
| format | Article |
| id | doaj.art-a3e1ba048e5049d5bdf99d0083ea07d0 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-13T10:15:59Z |
| publishDate | 2023-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-a3e1ba048e5049d5bdf99d0083ea07d02023-05-21T11:14:50ZengNature PortfolioScientific Reports2045-23222023-05-0113111310.1038/s41598-023-35242-0Noradrenergic stimulation of α1 adrenoceptors in the medial prefrontal cortex mediates acute stress-induced facilitation of seizures in miceKazuhei Niitani0Shiho Ito1Shintaro Wada2Shoma Izumi3Naoya Nishitani4Satoshi Deyama5Katsuyuki Kaneda6Laboratory of Molecular Pharmacology, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa UniversityLaboratory of Molecular Pharmacology, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa UniversityLaboratory of Molecular Pharmacology, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa UniversityLaboratory of Molecular Pharmacology, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa UniversityLaboratory of Molecular Pharmacology, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa UniversityLaboratory of Molecular Pharmacology, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa UniversityLaboratory of Molecular Pharmacology, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa UniversityAbstract Stress is one of the critical facilitators for seizure induction in patients with epilepsy. However, the neural mechanisms underlying this facilitation remain poorly understood. Here, we investigated whether noradrenaline (NA) transmission enhanced by stress exposure facilitates the induction of medial prefrontal cortex (mPFC)-originated seizures. In mPFC slices, whole-cell current-clamp recordings revealed that bath application of picrotoxin induced sporadic epileptiform activities (EAs), which consisted of depolarization with bursts of action potentials in layer 5 pyramidal cells. Addition of NA dramatically shortened the latency and increased the number of EAs. Simultaneous whole-cell and field potential recordings revealed that the EAs are synchronous in the mPFC local circuit. Terazosin, but not atipamezole or timolol, inhibited EA facilitation, indicating the involvement of α1 adrenoceptors. Intra-mPFC picrotoxin infusion induced seizures in mice in vivo. Addition of NA substantially shortened the seizure latency, while co-infusion of terazosin into the mPFC inhibited the effect of NA. Finally, acute restraint stress shortened the latency of intra-mPFC picrotoxin infusion-induced seizures, whereas prior infusion of terazosin reversed this stress-induced shortening of seizure latency. Our findings suggest that stress facilitates the induction of mPFC-originated seizures via NA stimulation of α1 adrenoceptors.https://doi.org/10.1038/s41598-023-35242-0 |
| spellingShingle | Kazuhei Niitani Shiho Ito Shintaro Wada Shoma Izumi Naoya Nishitani Satoshi Deyama Katsuyuki Kaneda Noradrenergic stimulation of α1 adrenoceptors in the medial prefrontal cortex mediates acute stress-induced facilitation of seizures in mice Scientific Reports |
| title | Noradrenergic stimulation of α1 adrenoceptors in the medial prefrontal cortex mediates acute stress-induced facilitation of seizures in mice |
| title_full | Noradrenergic stimulation of α1 adrenoceptors in the medial prefrontal cortex mediates acute stress-induced facilitation of seizures in mice |
| title_fullStr | Noradrenergic stimulation of α1 adrenoceptors in the medial prefrontal cortex mediates acute stress-induced facilitation of seizures in mice |
| title_full_unstemmed | Noradrenergic stimulation of α1 adrenoceptors in the medial prefrontal cortex mediates acute stress-induced facilitation of seizures in mice |
| title_short | Noradrenergic stimulation of α1 adrenoceptors in the medial prefrontal cortex mediates acute stress-induced facilitation of seizures in mice |
| title_sort | noradrenergic stimulation of α1 adrenoceptors in the medial prefrontal cortex mediates acute stress induced facilitation of seizures in mice |
| url | https://doi.org/10.1038/s41598-023-35242-0 |
| work_keys_str_mv | AT kazuheiniitani noradrenergicstimulationofa1adrenoceptorsinthemedialprefrontalcortexmediatesacutestressinducedfacilitationofseizuresinmice AT shihoito noradrenergicstimulationofa1adrenoceptorsinthemedialprefrontalcortexmediatesacutestressinducedfacilitationofseizuresinmice AT shintarowada noradrenergicstimulationofa1adrenoceptorsinthemedialprefrontalcortexmediatesacutestressinducedfacilitationofseizuresinmice AT shomaizumi noradrenergicstimulationofa1adrenoceptorsinthemedialprefrontalcortexmediatesacutestressinducedfacilitationofseizuresinmice AT naoyanishitani noradrenergicstimulationofa1adrenoceptorsinthemedialprefrontalcortexmediatesacutestressinducedfacilitationofseizuresinmice AT satoshideyama noradrenergicstimulationofa1adrenoceptorsinthemedialprefrontalcortexmediatesacutestressinducedfacilitationofseizuresinmice AT katsuyukikaneda noradrenergicstimulationofa1adrenoceptorsinthemedialprefrontalcortexmediatesacutestressinducedfacilitationofseizuresinmice |