Insights into the role of intracellular calcium signaling in the neurobiology of neurodevelopmental disorders.

Calcium (Ca) comprises a critical ionic second messenger in the central nervous system that is under the control of a wide array of regulatory mechanisms, including organellar Ca stores, membrane channels and pumps, and intracellular Ca-binding proteins. Not surprisingly, disturbances in Ca homeostasis have been linked to neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases. However, aberrations in Ca homeostasis have also been implicated in neuropsychiatric disorders with a strong neurodevelopmental component including autism spectrum disorder (ASD) attention-deficit hyperactivity disorder (ADHD) and schizophrenia (SCZ). While plasma membrane Ca channels and synaptic Ca-binding proteins have been extensively studied, increasing evidence suggests a prominent role for intracellular Ca stores, such as the endoplasmic reticulum (ER), in aberrant neurodevelopment. In the context of the current mini-review, we discuss recent findings implicating critical intracellular Ca-handling regulators such as the sarco-ER Ca ATPase 2 (SERCA2), ryanodine receptors (RyRs), inositol triphosphate receptors (IPRs), and parvalbumin (PVALB), in the emergence of ASD, SCZ, and ADHD.