Brain-derived neurotrophic factor (BDNF) is widely accepted as being critical for neural and synaptic plasticity throughout the nervous system. Recent work has shown that BDNF in the mesolimbic dopamine (DA) circuit, originating in ventral tegmental area (VTA) DA neurons that project to the nucleus accumbens (NAc), is crucial in the development of depressive-like behaviors following exposure to chronic social defeat stress (CSDS) in mice. While BDNF modulates DA signaling in encoding responses to acute defeat stress, BDNF signaling alone appears responsible for the behavioral effects after CSDS. Very different patterns are seen with another widely used chronic stress paradigm in mice, chronic mild stress (also known as chronic variable or unpredictable stress), where DA signaling but not BDNF signaling is primarily responsible for the behavioral effects observed. This review discusses the molecular, cellular, and circuit basis of this dramatic discrepancy which appears to involve the nature of the stress involved, its severity and duration, as well as its effects on distinct cell types within the VTA-to-NAc mesolimbic circuit.
Key words : BDNF; Dopamine; Social defeat stress; Chronic mild stress; Depression; Animal models; Electrophysiology; Mesolimbic dopamine circuit; Nucleus accumbens; Ventral tegmental area; Individual differences