A Candidate Circuit Approach to Investigating Autism

Abstract

A major problem in understanding mechanisms of pathogenesis in autism spectrum disorder (ASD) is deciphering how risk factors act via the brain to influence the behavioral symptoms of this disorder. We may start to bridge this gap in our understanding by systematically examining the structure and function of cell types that make up circuits underlying behavioral endophenotypes in animal models for ASD. A confluence of advances in basic behavioral neurobiology, in ASD mechanisms and animal models, and in genetic tools for imaging and manipulating brain circuits will make this possible. Through a process of elimination of candidates and comparison across models, we may hope to understand how ASD risk factors influence the development and function of neural circuitry at the level of genetically defined cell types. As an example of how this candidate circuit approach may be applied to investigating ASD, here I focus on social behavior as an endophenotype, and I discuss recent findings regarding the development and function of the oxytocin system, which is implicated in both normal social behavior and ASD pathogenesis. I stress the importance of a collaborative, multidisciplinary approach to probing candidate cell types and circuits across mouse models of ASD.

Detection of Genomic Imbalances by Array-Based Comparative Genomic Hybridization in Bulgarian Patients with Autism Spectrum Disorders

“…HIRIP3 is a widely expressed gene that interacts directly with HIRA, a major candidate for the DiGeorge syndrome and related developmental disorders (2). MAPK3 is expressed in human fetal and adult brains and MAPK3 acts as an intermediary across several pathways that have been implicated in ASDs pathogenesis, including: serotonin , oxytocin and il-6/immune signaling (31). qPRt encodes a key enzyme in the catabolism of quinolinate that acts as a most potent endogenous excitotoxin to neurons.…”

Hormonal imprinting in the central nervous system: causes and consequences

“…Mint gyógyszer felhasználható a depresszió, a szorongás, a szkizofrénia és az autizmus kezelésében. Állatkísérle-tek és emberen végzett megfi gyelések mutatják, hogy az oxitocinkezelés hatással van a szociális magatartás zavaraira (például a szkizofrénia és autizmus [54] fellépésére), miközben az agyi oxitocinrendszer befolyá-solása hatással van az említett jelenségekre [55,56]. Éppen ezért e hormon alkalmazása előtérbe került az autizmus és szkizofrénia terápiájában [56,57,58].…”

Endophenotypes and biomarkers: an approach to molecular genetic studies of mental disorders - Endofenotipos y biomarcadores: un enfoque hacia el estudio genético molecular de los trastornos mentales

“…In mice, it was described that the anxiolytic effects of oxytocin may be mediated via oxytocin receptors expressed on serotonergic neurons. 34 Other phenotypes such as insulin resistance, obesity, and hyperglycemia are very common among BD patients, suggesting some degree of phatophysiological overlap affected by a common genetic background.…”