Stress resilience is an active and multifactorial process manifested by structural, functional, and molecular changes in synapses

Abstract

Stress resilience is the ability of neuronal networks to maintain function despite exposure to stress. In this study, we investigated whether stress resilience is an actively developed dynamic process in adult mice. To assess the resilient and anhedonic behavioral phenotypes developed after induction the chronic unpredictable stress, we quantitatively characterized the structural and functional plasticity of excitatory synapses in the hippocampus using a combination of proteomic, electrophysiological, and imaging methods. Our results indicate that stress resilience is a dynamic and multifactorial process manifested by structural, functional, and molecular changes in synapses. We reveal that chronic stress influences palmitoylation, the profiles of which differ between resilient and anhedonic animals. We also observed that stress resilience is associated with structural compensatory plasticity of the postsynaptic parts of synapses.One Sentence SummaryCompensatory remodeling of dendritic spines at the structural and molecular levels underlies stress resilience.

A chronic unpredictable stress protocol to model anhedonic and resilient behaviors in C57BL/6J mice

“…If no additional tests are planned, we suggest that such mice should be excluded from further analyses ( Figure 2 E). In line with our previous experiments ( Baczynska et al., 2022 ; Bijata et al., 2022 ), a rule of thumb is to exclude animals classified as resilient that exhibit FST immobility time above the values observed in control mice. Maintaining the ‘purity’ of the population of resilient animals is particularly important in obtaining reliable and repeatable results of subsequent analyses, e.g., biochemical analyses.…”

“…This may be because of unnoticeable disturbances during behavioral testing. However, anhedonic and resilient animals exhibit unique molecular differences in the brain that may be used to confirm anhedonia or resilience ( Baczynska et al., 2022 ; Bijata et al., 2022 ; Gorinski et al., 2019 ). Due to the high repeatability of the method and the ease of performing the test, in our opinion, the best assay confirming anhedonia is gel zymography allowing to determine the activity of MMP-9 in the hippocampus.…”

“…This may be due to technical limitations of the behavioral tests used. In the case of large discrepancies in the results of both behavioral tests (SPT and FST), we recommend the use of a biochemical test to confirm anhedonia or resilience, e.g., measurement of MMP-9 activity in the hippocampus ( Baczynska et al., 2022 ; Bijata et al., 2022 ; Gorinski et al., 2019 ). If no additional tests are planned, we suggest that such mice should be excluded from further analyses ( Figure 2 E).…”

“…The protocol can generate anhedonic and resilient mice at roughly equal frequencies, providing a reliable model for translational research. For complete details on the use and execution of this protocol, please refer to Baczynska et al. (2022) , Bijata et al.…”

“…For complete details on the use and execution of this protocol, please refer to Baczynska et al. (2022) , Bijata et al.…”