Neuronal plasticity changes in the central amygdala and prelimbic cortex network in mice with chronic unpredictable mild stress-induced depression

doi:10.12122/j.issn.1673-4254.2024.11.04

Abstract

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.

Key words: depression, neuroplasticity, amygdala, medial prefrontal cortex

Dongbo LIU, Zewen CHEN, Yun WANG, Xinpeng LI, Pengyu ZHAO, Haoxian ZHENG. Neuronal plasticity changes in the central amygdala and prelimbic cortex network in mice with chronic unpredictable mild stress-induced depression[J]. Journal of Southern Medical University, 2024, 44(11): 2082-2091.

Figures/Tables 7

Fig.1 Effect of chronic unpredictable mild stress (CUMS) on sucrose preference in mice. **P<0.01 vs control group.

Fig.2 Effects of CUMS performance of the mice in open field test.A: Total distance moved.B: Number of crossing grid.C: Number of entries into the central area.D: Time spent in the central area.EPercentage of distance traveled in the central area.F Percentage of time spent in the central area. G Number of rearing. **P<0.01 vs control group.

Fig.3 Effects of CUMS on performance of the mice in forced swimming test. A: Struggling time. B: Swimming time. C: Immobility time. D: Climbing time. **P<0.01 vs control group.

Fig.4 Performance of CUMS and control mice for localization in Morris water maze test. A: Escape latency. B: Path length. C: Average swimming velocity. *P<0.05, **P<0.01, ***P<0.001 vs control group.

Fig.5 Performance of CUMS and control mice for spatial exploration in Morris water maze test. A: Swimming time. B: Percentage of distance within the target quadrant. C: First entry latency into target zone. TQ: Target quadrant. AQ: Adjacent quadrant. OQ: Opposite quadrant. IQ: Irrelevant quadrant. *P<0.05, **P<0.01 vs control group.

Fig.6 Changes of action potential firing patterns of glutamatergic and GABAergic neurons in CeA region of CUMS mice. A: Waveforms of sequential action potentials of glutamatergic neurons in CUMS mice (solid line) and control mice (dotted line). B-D: Effects of CUMS on electrophysiological properties of glutamatergic neurons. E: Waveforms of sequential action potentials of GABAergic neurons in CUMS mice (solid line) and control mice (dotted line). F-H: Effects of CUMS on electrophysiological properties of GABAergic neurons. Vts: Threshold potential; Vr: Resting potential; ARP: Absolute refractory period; ISI: Inter-spike interval. *P<0.05, **P<0.01, ***P<0.001 vs control group.

Fig.7 Changes of action potential firing patterns of glutamatergic and GABAergic neurons in PrL region of CUMS mice. A: Waveforms of sequential action potentials of glutamatergic neurons in CUMS mice (solid line) and control mice (dotted line). B-D: Effects of CUMS on electrophysiological properties of glutamatergic neurons. E: Waveforms of sequential action potentials of GABAergic neurons in CUMS mice (solid line) and control mice (dotted line). F-H: Effects of CUMS on electrophysiological properties of GABAergic neurons. *P<0.05, **P<0.01, ***P<0.001 vs control group.

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