STRESS SUSCEPTIBILITY–DEPENDENT SYNAPTIC ORGANIZATION OF ACC INHIBITORY AND EXCITATORY NEURONS

Aim: We investigated differences in excitatory synaptic inputs from ventral tegmental area (VTA), ventral hippocampus (VH) and basolateral amygdala (BLA) onto anterior cingulate cortex (ACC) excitatory neurons (E-to-E) and interneurons (E-to-I) across cortical layers between stress susceptible (SS) and stress resilient (SR) mice.
Methods: We labeled E-to-E and E-to-I synaptic inputs from VTA, VH and BLA using multicolor eGRASP. Three weeks later, 24 mice were exposed to chronic social defeat stress. Then we divided mice into SS and SR according to their social interaction with a novel mouse. We acquired high resolution, multispectral, 3D tiles from ACC columns using confocal microscopy. We detected synapses using automatic methods.
Results: We detected more than 165,000 synapses and 500,000 dendritic segments. Among E-to-E synapses, decrease in VH-ACC ratio and increase in BLA-ACC ratio to all detected synapses in layer 5b (L5b) and 6 (L6) were seen in SS mice. In L6, the ratio of dendritic segments receiving excitatory inputs from different brain regions was increased in SS mice. Among E-to-I synapses, VTA-ACC synapse ratio to all detected synapses in L5b and L6 was increased with chronic stress. In L5b, the ratio of IN dendritic segments receiving inputs from all three brain regions was increased in SS mice.
Conclusions: With stress susceptibility, E-to-E BLA inputs outweigh VH inputs in the major output layers of ACC. E-to-I inputs from VTA may play a modulatory role. I-to-E mapping and computational modeling can reveal the role of VTA inputs. This work was supported by Hacettepe University (TSA-2020-18753).