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

Stress resilience is the ability of neuronal networks to maintain their function despite the stress exposure. Using a mouse model we investigate stress resilience phenomenon. To assess the resilient and anhedonic behavioral phenotypes developed after the induction of 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 an active and multifactorial process manifested by structural, functional, and molecular changes in synapses. We reveal that chronic stress influences palmitoylation of synaptic proteins, whose profiles differ between resilient and anhedonic animals. The changes in palmitoylation are predominantly related with the glutamate receptor signaling thus affects synaptic transmission and associated structures of dendritic spines. We show that stress resilience is associated with structural compensatory plasticity of the postsynaptic parts of synapses in CA1 subregion of the hippocampus.