Role of NMDA Receptors in Adult-generated Hippocampal Neurons: Implications for Alleviating Depression and Anxiety-like Behaviors

The hippocampus is the brain region critical for learning, memory and emotional regulation. New neurons are continuously produced in the dentate gyrus of the hippocampus throughout adulthood and evidence from animal studies suggest the involvement of adult hippocampal neurogenesis in mental health, particularly in conditions like major depressive disorder (MDD) and memory formation. Selective serotonin reuptake inhibitors (SSRIs), a common class of antidepressants, have been shown to enhance neurogenesis, while disrupted neurogenesis is linked to cognitive impairments and decreased stress resilience in animal studies. Research supports the notion that NMDA receptors are essential in neurogenesis, regulating neuronal plasticity and synaptogenesis. Patients with MDD often exhibit decreased cognitive ability and memory, implicating NMDA receptor involvement. While NMDA receptors are considered potential drug targets for mental illnesses, evidence linking NMDA receptor activity in adult hippocampal neurogenesis (AHN) to mental health is limited, and the mechanisms remain poorly understood. This review aims to summarize recent studies to elucidate the connection between NMDA receptors on adult-born neurons and stress resilience, highlighting their potential as therapeutic targets for depression and anxiety-like behaviors.