Increased GluK1 Subunit Receptors in Corticostriatal Projection from the Anterior Cingulate Cortex Contributed to Seizure‐Like Activities
The corticostriatal connection plays a crucial role in cognitive, emotional, and motor control. However, the specific roles and synaptic transmissions of corticostriatal connection are less studied, especially the corticostriatal transmission from the anterior cingulate cortex (ACC). Here, a direct glutamatergic excitatory synaptic transmission in the corticostriatal projection from the ACC is found. Kainate receptors (KAR)-mediated synaptic transmission is increased in this corticostriatal connection both in vitro and in vivo seizure-like activities. GluK1 containing KARs and downstream calcium-stimulated adenylyl cyclase subtype 1 (AC1) are involved in the upregulation of KARs following seizure-like activities. Inhibiting the activities of ACC or its corticostriatal connection significantly attenuated pentylenetetrazole (PTZ)-induced seizure. Additionally, injection of GluK1 receptor antagonist UBP310 or the AC1 inhibitor NB001 both show antiepileptic effects. The studies provide direct evidence that KARs are involved in seizure activity in the corticostriatal connection and the KAR-AC1 signaling pathway is a potential novel antiepileptic strategy.
Authors
- Takanori Matsuura (ORCID: https://orcid.org/0000-0001-7539-1227)
- Jingshan Lu (ORCID: https://orcid.org/0000-0002-5963-0723)
- Zhaoxiang Zhou (ORCID: https://orcid.org/0009-0009-5576-5012)
- Graham L. Collingridge (ORCID: https://orcid.org/0000-0002-9572-5359)
- Min Zhuo (ORCID: https://orcid.org/0000-0001-9062-3241)
- Guo‐Qiang Bi (ORCID: https://orcid.org/0000-0001-8735-3818)
- Jingmin Che (ORCID: https://orcid.org/0000-0002-4006-6384)
- Bong‐Kiun Kaang (ORCID: https://orcid.org/0000-0001-7593-9707)
- Shun Hao (ORCID: https://orcid.org/0009-0009-8865-8870)
- Qi‐Yu Chen (ORCID: https://orcid.org/0000-0002-5707-6220)
- Xu‐Hui Li (ORCID: https://orcid.org/0000-0003-4376-6252)
- Wantong Shi
- Man Xue
- Fang Xu (ORCID: https://orcid.org/0009-0000-7486-3640)
- Zhi‐Xia Zhao
Institutions
- Qingdao University (CN)
- Seoul National University (KR)
- University of Toronto (CA)
- University of Occupational and Environmental Health Japan (JP)
- Canada Research Chairs (CA)
- Shaanxi Provincial People's Hospital (CN)
- First Affiliated Hospital of Guangzhou Medical University (CN)
- Shenzhen Institutes of Advanced Technology (CN)
- Xi'an Jiaotong University (CN)
- Guangzhou Medical University (CN)
Publication Details
- Journal
- Advanced Science
- Published
- 2024-09-03
- DOI
- https://doi.org/10.1002/advs.202308444
- Citations
- 3
- Primary Topic
- Neuroscience and Neuropharmacology Research
- Type
- article
- Field-Weighted Citation Impact
- 0.80
Funders
- National Natural Science Foundation of China
- Canadian Institutes of Health Research
- Fundamental Research Funds for the Central Universities