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 PKCα 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.
摘要：
Kv1.3属于电压门控钾（Kv）通道家族，在中枢神经系统中广泛表达，并与各种神经精神疾病有关。Kv1.3在嗅球和梨状皮层中高度表达，并参与动物的气味感知和营养代谢过程。以前的研究已经探索了Kv1.3在嗅球中的功能，而Kv1.3在梨状皮层中的作用鲜为人知。在这项研究中,我们研究了嗅觉刺激后梨状皮质神经元的变化和进食行为，从而揭示了Kv1.3KO小鼠的嗅觉和体重之间的联系。准备包括前梨状皮质的冠状切片，对锥体神经元进行全细胞记录和Ca2+成像。我们表明，与WT小鼠相比，Kv1.3敲除（KO）小鼠的锥体神经元中去极化脉冲引起的放电频率和高K溶液引起的Ca2内流显着增加。Western印迹和免疫荧光分析表明，下游信号分子CaMKII和PKCα在Kv1.3KO小鼠的梨状皮层中被激活。Kv1.3KO小鼠的金字塔神经元表现出显著降低的成对脉冲比率和增加的突触前Cav2.1表达,证明Ca2流入可能会增加突触前囊泡的释放。用高尔基染色,我们发现Kv1.3KO小鼠锥体神经元的树突棘密度显著增加，支持这些神经元更强的突触后反应。在嗅觉识别和进食行为测试中，我们发现Kv1.3条件性敲除或套管注射5-(4-苯氧丁氧)补骨脂素，一个Kv1.3通道阻滞剂，梨状皮层中的嗅觉识别指数均升高，并改变了小鼠的喂养行为。总之,Kv1.3是调节梨状皮质神经元活动的关键分子，这可能为梨状皮层相关疾病的治疗和嗅觉检测奠定基础。
