Increased GluK1 Subunit Receptors in Corticostriatal Projection from the Anterior Cingulate Cortex Contributed to Seizure‐Like Activities

Author:

Li Xu‐Hui12ORCID,Shi Wantong1,Zhao Zhi‐Xia1,Matsuura Takanori23,Lu Jing‐Shan1,Che Jingmin4,Chen Qi‐Yu5,Zhou Zhaoxiang26,Xue Man1,Hao Shun7,Xu Fang5,Bi Guo‐Qiang5,Kaang Bong‐Kiun8,Collingridge Graham L.2,Zhuo Min1267ORCID

Affiliation:

1. Center for Neuron and Disease Frontier Institute of Science and Technology Xi'an Jiaotong University Xi'an Shaanxi 710049 China

2. Department of Physiology Faculty of Medicine University of Toronto Medical Science Building, 1 King's College Circle Toronto Ontario M5S 1A8 Canada

3. Department of Orthopaedics School of Medicine University of Occupational and Environmental Health Yahatanishi‐ku Kitakyushu 807–8555 Japan

4. Shaanxi Provincial Key Laboratory of Infection and Immune Diseases Shaanxi Provincial People's Hospital Xi'an Shaanxi 710068 China

5. CAS Key Laboratory of Brain Connectome and Manipulation Interdisciplinary Center for Brain Information The Brain Cognition and Brain Disease Institute Shenzhen Institute of Advanced Technology Shenzhen Guangdong 518055 China

6. Department of Neurology First Affiliated Hospital of Guangzhou Medical University Guangzhou Guangdong 510130 China

7. Department of Pharmacology Qingdao University School of Pharmacy Qingdao Shandong 266071 China

8. Department of Biological Sciences College of Natural Sciences Seoul National University Seoul 151–746 South Korea

Abstract

AbstractThe 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.

Funder

National Natural Science Foundation of China

Fundamental Research Funds for the Central Universities

Publisher

Wiley

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