ABSTRACT

CACNA1 C, which codes for the Ca_v1.2 isoform of L-type Ca²⁺ channels (LTCCs), is a prominent risk gene in neuropsychiatric and neurodegenerative conditions. A role forLTCCs, and Ca_v1.2 in particular, in transcription-dependent late long-term potentiation (LTP) has long been known. Here, we report that elimination of Ca_v1.2 channels in glutamatergic neurons also impairs theta burst stimulation (TBS)-induced LTP in the hippocampus, known to be transcription-independent and dependent on N-methyl D-aspartate receptors (NMDARs) and local protein synthesis at synapses. Our expansion of the established role of Ca_v1.2channels in LTP broadens understanding of synaptic plasticity and identifies a new cellular phenotype for exploring treatment strategies for cognitive dysfunction.

摘要

CACNA1 C编码L型Ca ²⁺通道（LTCC）的Ca _v 1.2同工型，是神经精神病和神经退行性疾病中的重要风险基因。LTCC，尤其是Ca _v 1.2在转录依赖性晚期长期增强（LTP）中的作用早已为人所知。在这里，我们报告说，消除谷氨酸能神经元中的Ca _v 1.2通道也会损害theta爆发刺激（TBS）诱导的海马LTP，这是转录独立的并且依赖于N-甲基D-天冬氨酸受体（NMDARs）和局部突触中的蛋白质合成。我们扩大了Ca _v的既定作用LTP中的1.2通道可拓宽对突触可塑性的理解，并确定新的细胞表型，以探索认知功能障碍的治疗策略。