Loss of Cav1.2 channels impairs hippocampal theta burst stimulation-induced long-term potentiation

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.