EFFECTS OF EARLY LIFE ADVERSITY ON BEHAVIOR AND BRAIN CIRCUITRY: FOCUS ON THE THALAMIC RETICULAR NUCLEUS

Early-life stress deeply impacts brain development and is an acknowledged predisposing factor for psychiatric disorders. The thalamic reticular nucleus (TRN), the main inhibitory hub of the thalamus, is associated with multiple psychopathologies, rendering this structure relevant when researching effects of early adversity. We developed a murine model (MS-SI) consisting in exposure to maternal separation (postnatal day [P]7-P21) and post-weaning social isolation (P21 until sacrifice [P90]). To study behavioral alterations and histological outcomes in the TRN, we conducted an open field test (P79) and performed immunohistochemistry to examine parvalbumin-expressing (PV+) neurons – the main cellular component of the TRN –, perineuronal nets (PNNs, labeled with Wisteria floribunda agglutinin [WFA]) and polysialylated-neural cell adhesion molecule (PSA-NCAM), both of them plasticity modulators. Because psychiatric disorders show sex-related differences, we analyzed female and male data grouped and separately. In the open field test, we observed an increase in the total distance traveled and in the rotation count in the female and pooled groups, related to psychotic-like phenotypes. We found enhanced immunofluorescence of PV+ neurons and PNNs in MS-SI female mice along the TRN’s dorsoventral axis, possibly revealing augmented activity and reduced plasticity. We also observed an increase in the area covered by PV and WFA staining in this group. Conversely, MS-SI males displayed diminished PNN immunofluorescence in the ventral TRN. These results highlight the importance of studying the TRN when investigating neurodevelopmental impacts of early-life adversity, proven its vulnerability. Future analyses will reveal possible changes in glial markers or alterations in other relevant nuclei.