The CaMKII family consists of four closely related genes that encode for α, β, γ, and δ isoforms, which associate as homomers or heteromers to form holoenzymes comprised of 12 functional units.228 CaMKIIα is expressed heavily in the cortex and amygdala, moderately in the NAc, and very moderately in the VTA and midbrain.6 CaMKII is involved in many aspects of neuronal function including synaptic plasticity, gene expression, and neurotransmitter synthesis and release.229 Each functional holoenzyme subunit contains a catalytic and a regulatory domain; the regulatory domain includes an auto-inhibition sequence, a calmodulin binding site, and sites for autophosphorylation.228 CaMKIIs are activated by the binding of calcium to calmodulin (which acts as a calcium sensor), resulting in release of auto-inhibition allowing for autophosphorylation within the regulatory domain.
