Light deprivation produces a sexual dimorphic effect on neural excitability and depression-like behavior in mice

Light sensory experience plays a crucial role in the regulation of mood, and light deficiency is considered as one important factor potentially leading to depression. Women are twice as likely as men to suffer from depression. However, the physiological mechanism underlying sex differences in the prevalence, incidence and morbidity risk of depression is still poorly understood. The potential causal relationship between sex dimorphic behavioral deficits and altered intrinsic electrophysiological properties of Layer V pyramidal cells (L5PCs) in the motor cortex was investigated using a mouse model with depression-like behavior that was induced by light deprivation. The depression-like behavior was characterized by increased immobility and decreased activity in the forced swimming test and tail suspension test. Compared with male depressive-like mice, light deprivation (LD) induced longer immobile behavior while shorter active behavior in female depressive-like mice, indicating that LD produces a sexual dimorphic effect on depression-like behavior with more severe depressive-like symptoms in females. LD induced lower locomotor activity in female depressive-like mice as evidenced by the significant decrease in pole-climbing and swimming during the anti-static fatigue test and exhaustive swimming test correspondingly. LD also significantly decreased the intrinsic excitability of L5PCs in female depressive-like mice, which may explain the reduced active behavior and locomotor activity of female mice. Collectively, it indicates that LD produces a sexual dimorphic effect on the depression-like behavior, locomotor activity and neural excitability in mice, and may suggest a causal relationship between the more severe depressive conditions and decreased neural excitability of L5PCs in female mice. These divergent findings from male and female depressive-like mice may provide one potential route to the physiological mechanism underlying sex differences in the prevalence of depression at a level of single neurons.