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

ARGANÃRAZ, CARLA; ADJIMANN, TAMARA S.; PERISSINOTTI, PAULA P; SOIZA-REILLY, MARIANO

Cancun

Congreso; 20th International Meeting in 2023. ISSR 2023: ?Serotonin on the Mexican Caribbean?; 2023

Selective refinement of glutamate and GABA synapses on dorsal raphe 5-HT neurons duringpostnatal lifeCarla V., Arganãraz*, Tamara S., Adjimann*, Paula P., Perissinotti, Mariano, Soiza-ReillyInstituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE), Consejo Nacional de InvestigacionesCientíficas y Técnicas (CONICET), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires,Buenos Aires (C1428EGA), Argentina.Serotonin (5-hydroxytryptamine, 5-HT) neurons are implicated in the etiology and therapeutics of anxiety anddepression. Critical periods of vulnerability during brain development enable maladaptive mechanisms toproduce detrimental consequences on adult mood and emotional responses. 5-HT plays a crucial role inthese mechanisms; however, little is known about how synaptic inputs and modulatory systems that shapethe activity of early 5-HT networks mature during postnatal development. We investigated in mice thepostnatal 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 vivoelectrophysiology indicate that cortical glutamate and subcortical GABA synapses undergo a profoundrefinement process after the third postnatal week, whereas subcortical glutamate inputs do not. Thisrefinement of DRN inputs is not accompanied by changes in 5-HT1A receptor-mediated inhibition over 5-HTneurons. Our study reveals a precise developmental pattern of synaptic refinement of DRN excitatory andinhibitory afferents, when 5-HT-related inhibitory mechanisms are in place. These findings contribute to theunderstanding of neurodevelopmental vulnerability to psychiatric disorders.*equal contributionSupport:- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET, PIP 2021-2023).- Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación (PICT 2019-00807 to M.S.-R. and PICT 2019-02040 to P.P.P.).- International Brain Research Organization (Return home).- International Society for Neurochemistry – CAEN (Return home).