Differential expression of GABAA receptor subunits δ and α6 mediates tonic inhibition in parvalbumin and somatostatin interneurons in the mouse hippocampus

Tzu-Hsuan Huang; Yi-Sian Lin; Chiao-Wan Hsiao; Liang-Yun Wang; Musa Iyiola Ajibola; Wahab Imam Abdulmajeed; Yu-Ling Lin; Yu-Jui Li; Cho-Yi Chen; Cheng-Chang Lien; Cheng-Di Chiu; Irene Han-Juo Cheng

doi:10.3389/fncel.2023.1146278

Differential expression of GABA_A receptor subunits δ and α6 mediates tonic inhibition in parvalbumin and somatostatin interneurons in the mouse hippocampus

Front Cell Neurosci. 2023 Jul 20:17:1146278. doi: 10.3389/fncel.2023.1146278. eCollection 2023.

Authors

Tzu-Hsuan Huang^#¹, Yi-Sian Lin^#^{2

3}, Chiao-Wan Hsiao^#^{1

4}, Liang-Yun Wang², Musa Iyiola Ajibola^{5

6}, Wahab Imam Abdulmajeed^{5

6

7}, Yu-Ling Lin⁵, Yu-Jui Li⁵, Cho-Yi Chen^{2

8}, Cheng-Chang Lien^{4

5

6

8}, Cheng-Di Chiu^{9

10

11

12}, Irene Han-Juo Cheng^{1

4

8}

Affiliations

¹ Institute of Brain Science, National Yang Ming Chiao Tung University, Taipei, Taiwan.
² Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei, Taiwan.
³ Program in Genetics and Genomics, Baylor College of Medicine, Houston, TX, United States.
⁴ Program in Molecular Medicine, National Yang Ming Chiao Tung University and Academia Sinica, Taipei, Taiwan.
⁵ Institute of Neuroscience, National Yang Ming Chiao Tung University, Taipei, Taiwan.
⁶ Taiwan International Graduate Program in Interdisciplinary Neuroscience, College of Life Sciences, National Yang Ming Chiao Tung University and Academia Sinica, Taipei, Taiwan.
⁷ Department of Physiology, Faculty of Basic Medical Sciences, College of Health Sciences, University of Ilorin, Ilorin, Nigeria.
⁸ Brain Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan.
⁹ Department of Neurosurgery, China Medical University Hospital, Taichung, Taiwan.
¹⁰ Spine Center, China Medical University Hospital, Taichung, Taiwan.
¹¹ Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan.
¹² School of Medicine, China Medical University, Taichung, Taiwan.

^# Contributed equally.

Abstract

Inhibitory γ-aminobutyric acid (GABA)-ergic interneurons mediate inhibition in neuronal circuitry and support normal brain function. Consequently, dysregulation of inhibition is implicated in various brain disorders. Parvalbumin (PV) and somatostatin (SST) interneurons, the two major types of GABAergic inhibitory interneurons in the hippocampus, exhibit distinct morpho-physiological properties and coordinate information processing and memory formation. However, the molecular mechanisms underlying the specialized properties of PV and SST interneurons remain unclear. This study aimed to compare the transcriptomic differences between these two classes of interneurons in the hippocampus using the ribosome tagging approach. The results revealed distinct expressions of genes such as voltage-gated ion channels and GABA_A receptor subunits between PV and SST interneurons. Gabrd and Gabra6 were identified as contributors to the contrasting tonic GABAergic inhibition observed in PV and SST interneurons. Moreover, some of the differentially expressed genes were associated with schizophrenia and epilepsy. In conclusion, our results provide molecular insights into the distinct roles of PV and SST interneurons in health and disease.

Keywords: GABAA receptor; GABRD; RNA-seq; RiboTag; parvalbumin (PV); somatostatin (SST); tonic inhibition.

Grants and funding

This work was supported by the Ministry of Science and Technology, Taiwan (Grant Nos. MOST 111-2321-B-A49-005, MOST 111-2320-B-A49-305, MOST 109-2320-B-010-015-MY3, MOST 111-2320-B-A49-009-MY3, MOST 111-2636-E-A49-006, and MOST 111-2221-E-A49-130-MY3), NSTC 112-2321-B-A49-009, in part by the National Health Research Institutes, Taiwan (Grant No. NHRI-EX 111-11135NI), and by the China Medical University and Hospital (Grant No. DMR-111-097).