Early-life stress modulates the development of prefrontal-raphe circuits and stress-responses of serotonin neurons

ARGAÑARAZ, CV; SOIZA REILLY M

CABA

Congreso; Congreso de la Sociedad Argentina de Investigación en Neurociencias; 2022

SAN

Early adversity representsa main risk factor for the emergence of psychiatric disorders in adult life. Inmice, postnatal days 2 to 14 constitute a critical period of vulnerability whenstressors and environmental perturbations can alter the maturation ofprefrontal circuits. Maternal separation (MS) has been well-established as amodel to study the impact of early-life stress on neurodevelopment. MS duringthe critical period produces morpho-functional changes in the prefrontal cortex(PFC), accompanied by increases in depressive-like and anxiety behaviors. PFCdescending circuits exert a top-down regulatory control over the dorsal raphenucleus (DRN), the main source of forebrain serotonin (5-HT). Activation of PFCafferents in the DRN increases active stress-coping strategies and moodcontrol. We studied whether MS during the critical period could modify thesynaptic architecture of the developing PFC-to-DRN circuit. We analyzed theabundance of glutamatergic (vGLUT1/vGLUT2) and GABAergic (GAD2) synapticafferents in the DRN after the last MS exposure (at day 15). Synaptic boutonswere quantitatively analyzed using the high-resolution immunofluorescencetechnique Array Tomography. We find that MS increases the prefrontal innervationsonto DRN neurons, without affecting either subcortical glutamate or GABAafferents. Our study indicates a selective developmental effect of stress onthe PFC-to-DRN circuit, likely contributing to emotional vulnerability in theMS model.@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;}@font-face{font-family:Roboto;panose-1:2 11 6 4 2 2 2 2 2 4;mso-font-alt:Arial;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:auto;mso-font-signature:0 0 0 0 0 0;}p.MsoNormal, li.MsoNormal, div.MsoNormal{mso-style-unhide:no;mso-style-qformat:yes;mso-style-parent:"";margin-top:0cm;margin-right:0cm;margin-bottom:10.0pt;margin-left:0cm;line-height:115%;mso-pagination:widow-orphan;font-size:11.0pt;font-family:"Calibri",sans-serif;mso-fareast-font-family:Calibri;mso-ansi-language:EN-US;}.MsoChpDefault{mso-style-type:export-only;mso-default-props:yes;font-size:11.0pt;mso-ansi-font-size:11.0pt;mso-bidi-font-size:11.0pt;font-family:"Calibri",sans-serif;mso-ascii-font-family:Calibri;mso-fareast-font-family:Calibri;mso-hansi-font-family:Calibri;mso-bidi-font-family:Calibri;mso-ansi-language:EN-US;}.MsoPapDefault{mso-style-type:export-only;margin-bottom:10.0pt;line-height:115%;}div.WordSection1{page:WordSection1;}