Primary cultures of granule cells (GCs) from rat cerebellar cortex were used to determine whether bioelectric activity, via a Ca²⁺/calmodulin-dependent protein kinase (CaMK) signaling cascade, modulates expression and exon selection in the type 1 inositol trisphosphate receptor (IP₃R1). IP₃R1 contains or lacks three exons (S1, S2, S3) that are regulated in a regionally and temporally-specific manner. The neuronal, or long, form of IP₃R1 is distinguished from peripheral tissues by inclusion of the S2 exon. Although previous studies indicate IP₃R1s are undetectable in the cerebellar granular layer in vivo, receptor protein and mRNA are induced in cultured GCs grown in medium supplemented with 25mM KCl or NMDA, two trophic agents that promote long-term survival, compared to GCs grown in 5mM KCl. IP₃R1 induction in response to 25mM KCl or NMDA is attenuated by co-addition of voltage sensitive calcium channel or NMDA receptor antagonists, respectively. Actinomycin D, CaMK and calcineurin antagonists likewise suppress induction. Unlike the major variants of IP₃R1 in Purkinje neurons, which lack S1 and S3, GCs grown with trophic agents express mRNAs containing these exons. Both neuronal types contain S2. Evidence using mutant mice with Purkinje cell lesions, laser-microdissected granule neurons from slices, and explant cultures indicates that GCs predominantly express the S1-containing variant of IP₃R1 in vivo.