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

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

DEVELOPMENT

COMPANY OF BIOLOGISTS LTD

Lugar: Cambridge; Año: 2022

0950-1991

Serotonin (5-hydroxytryptamine, 5-HT) neurons are implicated in theetiology and therapeutics of anxiety and depression. Critical periodsof vulnerability during brain development enable maladaptivemechanisms to produce detrimental consequences on adult moodand emotional responses. 5-HT plays a crucial role in thesemechanisms; however, little is known about how synaptic inputsand modulatory systems that shape the activity of early 5-HTnetworks mature during postnatal development. We investigated inmice the postnatal trajectory of glutamate and GABA synaptic inputsto dorsal raphe nucleus (DRN) 5-HT neurons, the main source offorebrain 5-HT. High-resolution quantitative analyses with arraytomography and ex vivo electrophysiology indicate that corticalglutamate and subcortical GABA synapses undergo a profoundrefinement process after the third postnatal week, whereassubcortical glutamate inputs do not. This refinement of DRN inputsis not accompanied by changes in 5-HT1A receptor-mediatedinhibition over 5-HT neurons. Our study reveals a precisedevelopmental pattern of synaptic refinement of DRN excitatory andinhibitory afferents, when 5-HT-related inhibitory mechanisms are inplace. These findings contribute to the understanding ofneurodevelopmental vulnerability to psychiatric disorders.