NYMC Faculty Publications

Positive Emotional Learning Induces Resilience to Depression: A Role for NMDA Receptor-mediated Synaptic Plasticity

Journal Title

Current Neuropharmacology

First Page


Last Page


Document Type


Publication Date



Cell Biology and Anatomy


BACKGROUND: Positive emotions have been shown to induce resilience to depression and anxiety in humans, as well as increase cognitive abilities (learning, memory and problem solving) and improve overall health. In rats, frequency modulated 50-kHz ultrasonic vocalizations (Hedonic 50-kHz USVs) reflect a positive affective state and are best elicited by rough-and-tumble play. METHODS: The effect of positive affect induced by rough-and tumble play was examined on models of depression and learning and memory. The molecular and pharmacological basis of play induced positive affect was also examined. RESULTS: Rough-and-tumble play induced Hedonic 50-kHz USVs, lead to resilience to depression and anxiety, and facilitation of learning and memory. These effects are mediated, in part, by increased NMDAR expression and activation in the medial prefrontal cortex. CONCLUSIONS: We hypothesize that positive affect induces resilience to depression by facilitating NMDAR-dependent synaptic plasticity in the medial prefrontal cortex. Targeting MPFC synaptic plasticity may lead to novel treatments for depression.