Selective refinement of glutamate and GABA synapses on dorsal raphe 5-HT neurons during postnatal life

Author:

Argañaraz Carla V.1ORCID,Adjimann Tamara S.1ORCID,Perissinotti Paula P.1ORCID,Soiza-Reilly Mariano1ORCID

Affiliation:

1. Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires , Buenos Aires C1428EGA, Argentina

Abstract

ABSTRACT Serotonin (5-hydroxytryptamine, 5-HT) neurons are implicated in the etiology and therapeutics of anxiety and depression. Critical periods of vulnerability during brain development enable maladaptive mechanisms to produce detrimental consequences on adult mood and emotional responses. 5-HT plays a crucial role in these mechanisms; however, little is known about how synaptic inputs and modulatory systems that shape the activity of early 5-HT networks mature during postnatal development. We investigated in mice the postnatal trajectory of glutamate and GABA synaptic inputs to dorsal raphe nucleus (DRN) 5-HT neurons, the main source of forebrain 5-HT. High-resolution quantitative analyses with array tomography and ex vivo electrophysiology indicate that cortical glutamate and subcortical GABA synapses undergo a profound refinement process after the third postnatal week, whereas subcortical glutamate inputs do not. This refinement of DRN inputs is not accompanied by changes in 5-HT1A receptor-mediated inhibition over 5-HT neurons. Our study reveals a precise developmental pattern of synaptic refinement of DRN excitatory and inhibitory afferents, when 5-HT-related inhibitory mechanisms are in place. These findings contribute to the understanding of neurodevelopmental vulnerability to psychiatric disorders. This article has an associated ‘The people behind the papers’ interview.

Funder

Consejo Nacional de Investigaciones Científicas y Técnicas

Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación

International Brain Research Organization

International Society for Neurochemistry

Publisher

The Company of Biologists

Subject

Developmental Biology,Molecular Biology

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