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

Calcium (Ca(2+)) 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(2+) stores, membrane channels and pumps, and intracellular Ca(2+)-binding proteins. Not surprisingly, disturbances in Ca(2+) homeostasis have been linked to neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases. However, aberrations in Ca(2+) 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(2+) channels and synaptic Ca(2+)-binding proteins have been extensively studied, increasing evidence suggests a prominent role for intracellular Ca(2+) 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(2+)-handling regulators such as the sarco-ER Ca(2+) ATPase 2 (SERCA2), ryanodine receptors (RyRs), inositol triphosphate receptors (IP(3)Rs), and parvalbumin (PVALB), in the emergence of ASD, SCZ, and ADHD.