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

*ARGAÑARAZ, CV; *ADJIMANN, TS; PERISSINOTTI, PP; SOIZA REILLY, M

Cancun

Congreso; ISSR Meeting; 2023

ISSR

Serotonin(5-hydroxytryptamine, 5-HT) neurons are implicated in the etiology andtherapeutics of anxiety and depression. Critical periods of vulnerabilityduring brain development enable maladaptive mechanisms to produce detrimentalconsequences on adult mood and emotional responses. 5-HT plays a crucial rolein these mechanisms; however, little is known about how synaptic inputs andmodulatory systems that shape the activity of early 5-HT networks mature duringpostnatal development. We investigated in mice the postnatal trajectory ofglutamate and GABA synaptic inputs to dorsal raphe nucleus (DRN) 5-HT neurons,the main source of forebrain 5-HT. High-resolution quantitative analyses witharray tomography and ex vivo electrophysiology indicate that cortical glutamateand subcortical GABA synapses undergo a profound refinement process after thethird postnatal week, whereas subcortical glutamate inputs do not. Thisrefinement of DRN inputs is not accompanied by changes in 5-HT1Areceptor-mediated inhibition over 5-HT neurons. Our study reveals a precisedevelopmental pattern of synaptic refinement of DRN excitatory and inhibitoryafferents, when 5-HT-related inhibitory mechanisms are in place. These findingscontribute to the understanding of neurodevelopmental vulnerability topsychiatric disorders.@font-face{font-family:"Cambria Math";panose-1:2 4 5 3 5 4 6 3 2 4;mso-font-charset:0;mso-generic-font-family:roman;mso-font-pitch:variable;mso-font-signature:-536870145 1107305727 0 0 415 0;}@font-face{font-family:Calibri;panose-1:2 15 5 2 2 2 4 3 2 4;mso-font-charset:0;mso-generic-font-family:swiss;mso-font-pitch:variable;mso-font-signature:-536859905 -1073697537 9 0 511 0;}p.MsoNormal, li.MsoNormal, div.MsoNormal{mso-style-unhide:no;mso-style-qformat:yes;mso-style-parent:"";margin:0cm;margin-bottom:.0001pt;mso-pagination:widow-orphan;font-size:12.0pt;font-family:"Calibri",sans-serif;mso-ascii-font-family:Calibri;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:Calibri;mso-fareast-theme-font:minor-latin;mso-hansi-font-family:Calibri;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;mso-ansi-language:ES;}.MsoChpDefault{mso-style-type:export-only;mso-default-props:yes;font-family:"Calibri",sans-serif;mso-ascii-font-family:Calibri;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:Calibri;mso-fareast-theme-font:minor-latin;mso-hansi-font-family:Calibri;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;}div.WordSection1{page:WordSection1;}