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Sabahaddin Taha Solakoglu, Evren Erdener, Olga Gliko, Alp Can, Uygar Sumbul, Emine Eren-Kocak
Abstract
Aims: Investigation of differences in synaptic inputs from ventral tegmental area (VTA), ventral hippocampus (VH) and basolateral amygdala (BLA) on anterior cingulate cortex(ACC) neurons across all cortical layers between stress susceptible (SS) and stress resilient (SR) mice. Methods: Projections from VTA, VH and BLA excitatory neurons were labeled with cyan, green and yellow pre-eGRASP and ACC pyramidal neurons were labeled with post-eGRASP and TagRFP-T. Three weeks later, 10 mice were exposed to chronic social defeat stress for 10 days and on 11th day mice were divided into SS and SR groups according to their social interaction scores with a novel mouse. High resolution, multispectral, 3D tiles were acquired with confocal microscopy from ACC columns. Images were stitched, signals unmixed and deconvolved. Dendrites were reconstructed and synapses were detected automatically. Results: More than 75,000 synapses on almost 275,000 dendritic segments detected across the ACC columns. There was a significant reduction in VH-ACC ratio and increase in BLA-ACC ratio to all detected synapses in deep layer 5 and 6 in SS mice. In layer 6, there was a significant increase in the ratio of dendritic segments receiving inputs from different brain regions in SS mice. Conclusion: In SS mice BLA-to-ACC inputs outweighed VH-to-ACC inputs in the major output layers of ACC. These in turn altered stress response by causing a disorganization in intralaminar microcircuits of Layer 5&6 and interlaminar integration of information across superficial and deep layers. This work was supported by Hacettepe University Scientific Research Projects Coordination Unit (TSA-2020-18753).