title: Disruption of Transient Serotonin Accumulation by Non-Serotonin-Producing Neurons Impairs Cortical Map Development.
abstract: Polymorphisms that alter serotonin transporter SERT expression and functionality increase the risks for autism and psychiatric traits. Here, we investigate how SERT controls serotonin signaling in developing CNS in mice. SERT is transiently expressed in specific sets of glutamatergic neurons and uptakes extrasynaptic serotonin during perinatal CNS development. We show that SERT expression in glutamatergic thalamocortical axons (TCAs) dictates sensory map architecture. Knockout of SERT in TCAs causes lasting alterations in TCA patterning, spatial organizations of cortical neurons, and dendritic arborization in sensory cortex. Pharmacological reduction of serotonin synthesis during the first postnatal week rescues sensory maps in SERTGluΔmice. Furthermore, knockdown of SERT expression in serotonin-producing neurons does not impair barrel maps. We propose that spatiotemporal SERT expression in non-serotonin-producing neurons represents a determinant in early life genetic programming of cortical circuits. Perturbing this SERT function could be involved in the origin of sensory and cognitive deficits associated with neurodevelopmental disorders.
authors.affiliation: Department of Molecular Pharmacology and Rose F. Kennedy Intellectual and Developmental Disabilities Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Chen
authors.affiliation: Departments of Pharmacology & Psychiatry, Silvio O. Conte Center for Neuroscience Research, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Ran
authors.initials: R
authors.lastname: Ye
authors.affiliation: Center for Autism Research and Translation and Department of Physiology & Biophysics and Section of Human Genetics in Pediatrics, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: J Jay
authors.initials: JJ
authors.lastname: Gargus
authors.affiliation: Departments of Pharmacology & Psychiatry, Silvio O. Conte Center for Neuroscience Research, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Randy D
authors.initials: RD
authors.lastname: Blakely
authors.affiliation: Dominick P. Purpura Department of Neuroscience and Rose F. Kennedy Intellectual and Developmental Disabilities Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Kostantin
authors.initials: K
authors.lastname: Dobrenis
authors.affiliation: Department of Molecular Pharmacology and Rose F. Kennedy Intellectual and Developmental Disabilities Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA. Electronic address: jiying.sze@einstein.yu.edu.
authors.forename: Ji Ying
authors.initials: JY
authors.lastname: Sze