Abstract
Kv1.3 belongs to the voltage-gated potassium (Kv) channel family, which is widely expressed in the central nervous system and associated with a variety of neuropsychiatric disorders. Kv1.3 is highly expressed in the olfactory bulb and piriform cortex and involved in the process of odor perception and nutrient metabolism in animals. Previous studies have explored the function of Kv1.3 in olfactory bulb, while the role of Kv1.3 in piriform cortex was less known. In this study, we investigated the neuronal changes of piriform cortex and feeding behavior after smell stimulation, thus revealing a link between the olfactory sensation and body weight in Kv1.3 KO mice. Coronal slices including the anterior piriform cortex were prepared, whole-cell recording and Ca2+ imaging of pyramidal neurons were conducted. We showed that the firing frequency evoked by depolarization pulses and Ca2+ influx evoked by high K+ solution were significantly increased in pyramidal neurons of Kv1.3 knockout (KO) mice compared to WT mice. Western blotting and immunofluorescence analyses revealed that the downstream signaling molecules CaMKII and PKCĪ± were activated in piriform cortex of Kv1.3 KO mice. Pyramidal neurons in Kv1.3 KO mice exhibited significantly reduced paired-pulse ratio and increased presynaptic Cav2.1 expression, proving that the presynaptic vesicle release might be elevated by Ca2+ influx. Using Golgi staining, we found significantly increased dendritic spine density of pyramidal neurons in Kv1.3 KO mice, supporting the stronger postsynaptic responses in these neurons. In olfactory recognition and feeding behavior tests, we showed that Kv1.3 conditional knockout or cannula injection of 5-(4-phenoxybutoxy) psoralen, a Kv1.3 channel blocker, in piriform cortex both elevated the olfactory recognition index and altered the feeding behavior in mice. In summary, Kv1.3 is a key molecule in regulating neuronal activity of the piriform cortex, which may lay a foundation for the treatment of diseases related to piriform cortex and olfactory detection.
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Funding
This work is supported by National Natural Sciences Foundation of China (32000685), Knowledge Innovation Program of Wuhan-Shuguang Project (2022020801020412), Natural Sciences Foundation of Hubei Province (2020CFB348), and Fundamental Research Funds for the Central Universities, South-Central Minzu University (CZQ23026) to QZ, partly by National Natural Sciences Foundation of China (81373379, 81641186), National Key R and D Program of China (2019YFC1712402), and Fundamental Research Funds for the Central Universities, South-Central Minzu University (CZZ19005) to SY.
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QRZ and SJY designed research; YSZ, HBT, SSL, KQL, WYS, KYL, YYL, LYC and LZ performed research; YSZ, HBT, SSL, KQL, WYS, KYL, YYL analyzed data; QRZ wrote the paper.
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Zhou, Ys., Tao, Hb., Lv, Ss. et al. Effects of Kv1.3 knockout on pyramidal neuron excitability and synaptic plasticity in piriform cortex of mice. Acta Pharmacol Sin 45, 2045ā2060 (2024). https://doi.org/10.1038/s41401-024-01275-y
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DOI: https://doi.org/10.1038/s41401-024-01275-y
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