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

Research output: Contribution to journalArticle

30 Citations (Scopus)

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 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.

Original languageEnglish (US)
Pages (from-to)346-358
Number of pages13
JournalCell Reports
Volume10
Issue number3
DOIs
StatePublished - Jan 20 2015

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Neurons
Serotonin
Axons
Serotonin Plasma Membrane Transport Proteins
Neuronal Plasticity
Genetic programming
Autistic Disorder
Polymorphism
Psychiatry
Pharmacology
Networks (circuits)

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Disruption of Transient Serotonin Accumulation by Non-Serotonin-Producing Neurons Impairs Cortical Map Development. / Chen, Xiaoning; Ye, Ran; Gargus, J. Jay; Blakely, Randy D.; Dobrenis, Kostantin; Sze, Ji Ying.

In: Cell Reports, Vol. 10, No. 3, 20.01.2015, p. 346-358.

Research output: Contribution to journalArticle

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