Disruption of Transient Serotonin Accumulation by Non-Serotonin-Producing Neurons Impairs Cortical Map Development
Xiaoning Chen,
Ran Ye,
J. Jay Gargus,
Randy D. Blakely,
Kostantin Dobrenis,
Ji Ying Sze
Affiliations
Xiaoning Chen
Department of Molecular Pharmacology and Rose F. Kennedy Intellectual and Developmental Disabilities Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA
Ran Ye
Departments of Pharmacology & Psychiatry, Silvio O. Conte Center for Neuroscience Research, Vanderbilt University, Nashville, TN 37232, USA
J. Jay Gargus
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
Randy D. Blakely
Departments of Pharmacology & Psychiatry, Silvio O. Conte Center for Neuroscience Research, Vanderbilt University, Nashville, TN 37232, USA
Kostantin Dobrenis
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
Ji Ying Sze
Department of Molecular Pharmacology and Rose F. Kennedy Intellectual and Developmental Disabilities Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA
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 SERTGluΔ mice. 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.
