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- Title
Kv4.1, a Key Ion Channel For Low Frequency Firing of Dentate Granule Cells, Is Crucial for Pattern Separation.
- Authors
Kyung-Ran Kim; Seung Yeon Lee; Sang Ho Yoon; Yoonsub Kim; Hyeon-Ju Jeong; Sanghyeon Lee; Young Ho Suh; Jong-Sun Kang; Hana Cho; Suk-Ho Lee; Myoung-Hwan Kim; Won-Kyung Ho
- Abstract
The dentate gyrus (DG) in the hippocampus may pfay key roles in remembering distinct episodes through pattern separation, which may be subserved by the sparse firing properties of granule cells (GCs) in the DG. Low intrinsic excitability is characteristic of mature GCs, but ion channel mechanisms are not fully understood. Here, we investigated ionic channel mechanisms for firing frequency regulation in hippocampal GCs using male and female mice, and identified Kv4.1 as a key player. Immunofluorescence analysis showed that Kv4.1 was preferentially expressed in the DG, and its expression level determined by Western blot analysis was higher at 8-week than 3-week-old mice, suggesting a developmental regulation of Kv4.1 expression. With respect to firing frequency, GCs are categorized into two distinctive groups: low-frequency (LF) and high-frequency (HF) firing GCs. Input resistance (Rin) of most LF-GCs is lower than 200 Mfi, suggesting that LF-GCs are fully mature GCs. Kv4.1 channel inhibition by intracellular perfusion of Kv4.1 antibody increased firing rates and gain of the input-output relationship selectively in LF-GCs with no significant effect on resting membrane potential and Rin, but had no effect in HF-GCs. Importantly, mature GCs from mice depleted of Kv4.1 transcripts in the DG showed increased firing frequency, and these mice showed an impairment in contextual discrimination task. Our findings suggest that Kv4.1 expression occurring at late stage of GC maturation is essential for low excitability of DG networks and thereby contributes to pattern separation.
- Subjects
GRANULE cells; ION channels; DENTATE gyrus; WESTERN immunoblotting; MEMBRANE potential
- Publication
Journal of Neuroscience, 2020, Vol 40, Issue 11, p2200
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.1541-19.2020