title: Unifying Views of Autism Spectrum Disorders: A Consideration of Autoregulatory Feedback Loops.
abstract: Understanding the mechanisms underlying autism spectrum disorders (ASDs) is a challenging goal. Here we review recent progress on several fronts, including genetics, proteomics, biochemistry, and electrophysiology, that raise motivation for forming a viable pathophysiological hypothesis. In place of a traditionally unidirectional progression, we put forward a framework that extends homeostatic hypotheses by explicitly emphasizing autoregulatory feedback loops and known synaptic biology. The regulated biological feature can be neuronal electrical activity, the collective strength of synapses onto a dendritic branch, the local concentration of a signaling molecule, or the relative strengths of synaptic excitation and inhibition. The sensor of the biological variable (which we have termed the homeostat) engages mechanisms that operate as negative feedback elements to keep the biological variable tightly confined. We categorize known ASD-associated gene products according to their roles in such feedback loops and provide detailed commentary for exemplar genes within each module.
authors.affiliation: Department of Neuroscience and Physiology, Neuroscience Institute, New York University Langone Medical Center, New York, NY 10016, USA.
authors.forename: Caitlin
authors.initials: C
authors.lastname: Mullins
authors.affiliation: Department of Neuroscience and Physiology, Neuroscience Institute, New York University Langone Medical Center, New York, NY 10016, USA.
authors.forename: Gord
authors.initials: G
authors.lastname: Fishell
authors.affiliation: Department of Neuroscience and Physiology, Neuroscience Institute, New York University Langone Medical Center, New York, NY 10016, USA. Electronic address: richard.tsien@nyumc.org.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Tsien
mesh_terms: D000067877:Autism Spectrum Disorder / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000473:pathology* / Q000503:physiopathology; D025461:Feedback, Physiological / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D009415:Nerve Net / Q000503:physiopathology*; D009474:Neurons / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology