Postnatal Refinement of Synaptic Afferents to Dorsal Raphe 5-HT Neurons: Implications for Psychiatric Disorders

ADJIMANN, TAMARA S.; ARGAÑARAZ, CARLA; FERNANDEZ, SEBASTIAN P.; BARIK, JACQUES; PERISSINOTTI, PAULA P; SOIZA-REILLY, MARIANO

FLORIDA

Congreso; ACNP 62nd Annual Meeting; 2023

P292. Postnatal Refinement of Synaptic Afferents to DorsalRaphe 5-HT Neurons: Implications for Psychiatric DisordersTamara S. Adjimann*, Carla V. Argañaraz*, Sebastian P.Fernandez, Jacques Barik, Paula P. Perissinotti, Mariano SoizaReilly*IFIBYNE-CONICET-UBA, Buenos Aires, ArgentinaBackground: Serotonin (5-hydroxytryptamine, 5-HT) neurons areimplicated in the etiology and therapeutics of anxiety anddepression. Critical periods of vulnerability during brain development enable maladaptive mechanisms to produce detrimentalconsequences on adult mood. 5-HT plays a pivotal role in thesemechanisms, however, little is known about how synaptic inputsshaping the activity of 5-HT networks mature during postnataldevelopment. We investigated in mice the postnatal trajectory ofglutamate and GABA synaptic inputs to dorsal raphe nucleus(DRN) 5-HT neurons, a main source of forebrain 5-HT.Methods: In C57BL/6 and Swiss mice (both sexes) we applied amultidisciplinary approach combining high-resolution morphological analyses (array tomography) together with ex-vivo patchclamp recordings and pharmacology. Data were analyzed bymultifactorial ANOVA followed by Tukey’s comparisons.Results: Our results showed that cortical glutamate synapsesundergo a profound refinement process between the third andfourth postnatal weeks (p < 0,05), while subcortical glutamateinputs do not. Next, we asked whether this neurodevelopmentalprocess could be altered in a mouse model of early-life emotionalvulnerability. In this model, a brief exposure to fluoxetine(p.o.10mg/kg/day) during the first two postnatal weeks results inlong-lasting depressive-like and anxiety behaviors. We found thatfluoxetine-treated mice (both sexes) had a selective increase incortical synaptic inputs to 5-HT neurons as early as the followingday after the treatment cessation (p < 0,05 vs. sucrosetreated mice).Conclusions: This suggests that postnatal fluoxetine exposurecould enhance the synaptogenic potential of cortical inputsinfluencing the early activity of 5-HT neurons. Our studycontributes to the understanding of neurodevelopmental vulnerability to psychiatric disorders.Keywords: Serotonin, Synapses, Anxiety and Depression, CircuitDevelopment, Prefrontal CortexDisclosure: Nothing to disclose.