Increasing evidence from human brain imaging studies indicates that depression alters structural and functional connectivity in brain regions governing cognition and emotions. Consistent with this, unpredictable chronic mild stress (UCMS), a mouse model of depression, causes dendritic atrophy and spine loss in neurons laying in cortical and limbic regions. Based on data showing that the plant anti-stress hormone methyl jasmonate (MJ) rescues the UCMS-induced depressive behavioral phenotype, here we examine whether the compound also prevents the occurrence of neuronal and synaptic connectivity defects in the hippocampus, prefrontal cortex, and amygdala. Male C57BL/6 mice (n=6) were injected with MJ (50 mg/kg) or saline (SAL) before each of the two daily exposure to UCMS administered over 14 days. On day 15, mice were sacrificed via cervical dislocation, and their brains were processed for Golgi-Cox staining, western blot, and immunohistochemistry analyses. Additional groups of UCSM-exposed mice were treated with MJ or SAL in a stress–free condition. Data were analyzed using descriptive statistics, Neurolucida, Image J, and ANOVA at α0.05. In the fear conditioning test, MJ significantly decreased freezing duration (20.53±4.00s) against stress (73.56±5.16s). Our results confirm that MJ prevents the manifestation of depressive-like behaviors and reveal that this effect persists after treatment cessation. Moreover, they show that, in the three regions of interest, UCMS-exposed mice treated with SAL exhibit a massive reduction in the dendritic arbor of the BLA (40.13±1.22) against SAL (100.30±5.11) and MJ (68.00±2.22); H-CA1 (22.13±2.42) against SAL (65.13±9.59) and MJ (48.13±4.57); and PFC (11.60±0.86) against SAL (42.75±3.48) and MJ (23.20±0.90); as well as spine density in the BLA (0.51±0.01) against SAL (0.94±0.02) and MJ (0.75±0.01), H-CA1 (0.47±0.02) against SAL (0.98±0.03) and MJ (0.85±0.03), and PFC (0.84±0.03) against SAL (1.53±0.05) and MJ (1.41±0.04). We also observed a significant decrease in CREB expression level and a lower number of parvalbumin-positive cells than UCMS-non exposed mice injected with MJ or SAL. Remarkably, these alterations were entirely rescued by MJ treatment. Thus, in parallel with the alleviation of behavioral markers of depression, the compound preserves synaptic integrity in neural circuits via modulation of molecular and cellular regulators. It can offer, in this regard, a therapeutic alternative to treat this debilitative pathology.