Forebrain elimination of cacna1c mediates anxiety-like behavior in mice

The CACNA1C gene encoding the Cav1.2 subunit of the L-type calcium channel has emerged as a new candidate gene for neuropsychiatric disease, including bipolar disorder, major depression, schizophrenia and autism.1, 2, 3 We report that global haploinsufficiency, forebrain-specific elimination and prefrontal cortex (PFC)-specific knockdown of cacna1c all increase anxiety-related behavior in mice, a prominent component of the forms of neuropsychiatric disease in which aberrations in CACNA1C have been implicated, without affecting compulsive behavior. Constitutive cacna1c heterozygous mice (HET) were evaluated in three behavioral assays related to anxiety: open field test, light–dark conflict test and elevated plus maze (EPM). HETs displayed anxiety-like behavior in the EPM (Figure 1a), spending significantly less time exploring the open arms compared with wild-type littermate controls (WT; F1,19=6.437; P