Abstract
OBJECTIVE: To explore the relationship between alterations of neural network plasticity and spatial learning and memory functions in mouse models with depression-like behaviors. METHODS: C57Thy1-YFP/GAD67-GFP mice were randomized into control group (with no treatment) and chronic unpredictable mild stress (CUMS) group (n=15) subjected to CUMS for 8 weeks. Depression-like behaviors of the mice were assessed using sucrose preference test, open field test, and forced swimming test, and their spatial learning and memory abilities were evaluated using Morris water maze test. The changes in the firing patterns of different neuronal subtypes were detected in the central nucleus of the amygdala (CeA) and the prelimbic cortex (PrL) using whole-cell patch-clamp technique. RESULTS: Compared with the control mice, CUMS mice showed significantly decreased sucrose preference, total distance moved, number of grid-crossings, entries into the central area, and time spent in the central area in the open field test (P < 0.01). In the forced swimming test, CUMS mice exhibited obviously shortened time of struggling, swimming, and climbing with increased immobility time. In Morris water maze test, CUMS mice showed significantly increased escape latency and path length, decreased percentage of distance and swimming time within the target quadrant, and increased first entry latency into the target zone and swimming time within the opposite quadrant. Exposure to CUMS resulted in significantly enhanced energy barrier and increased absolute refractory period and inter-spike interval of glutamatergic neurons in the CeA and GABAergic neurons in the PrL, while the opposite changes were observed in GABAergic neurons in the CeA and glutamatergic neurons in the PrL. CONCLUSION: CUMS-induced depression may lead to plastic changes in the excitatory and inhibitory neuronal networks within the CeA and PrL to cause impairment of spatial learning and memory abilities in mice.