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

Abstract

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.

The physiology of play: potential relevance for higher education

“…This plasticity of the brain in adult life is strikingly demonstrated by the observation that rough-and-tumble play facilitates positive emotional learning and induces resilience to depression in late-adolescent (adult) rats (Burgdorf et al, 2017). Interestingly, studies further solidify this concept by demonstrating that for an increased brain plasticity to occur, play with toys used in the experiment must occur with other rats in a playful social interaction as opposed to individually (Burgdorf et al, 2017;Diamond et al, 1987;Diamond, Krech, & Rosenzweig, 1964;Diamond, 1988).…”

“…rat laugher (Liu et al, 2017;Hirsh-Pasek et al, 2009;Whitton, 2018;Yogman et al, 2018). Extraordinarily, rough-and-tumble play in rats (a playful activity in which rats engage well into their adulthood) induces excessive laughter, which can lead to resilience against depression and anxiety, and facilitation of learning and memory (Burgdorf, Colechio, Stanton, & Panksepp, 2017). These effects are mediated, in part, by increased plasticity in the medial prefrontal cortex (Burgdorf et al, 2017;Panksepp, 2005).…”

“…Conversely, increased playful social interactions in rodents have been shown to improve the integration of the pre-frontal cortex for learning complex behaviours like self-regulation and planning (Bell, Pellis, & Kolb, 2010;Pellis & Pellis, 2007;Pellis, Pellis, & Himmler, 2014), and enhance neural plasticity (Himmler, Pellis, & Kolb, 2013). This plasticity of the brain in adult life is strikingly demonstrated by the observation that rough-and-tumble play facilitates positive emotional learning and induces resilience to depression in late-adolescent (adult) rats (Burgdorf et al, 2017). Interestingly, studies further solidify this concept by demonstrating that for an increased brain plasticity to occur, play with toys used in the experiment must occur with other rats in a playful social interaction as opposed to individually (Burgdorf et al, 2017;Diamond et al, 1987;Diamond, Krech, & Rosenzweig, 1964;Diamond, 1988).…”

Reconciling cognitive and affective neuroscience perspectives on the brain basis of emotional experience

“…Also, the neurochemistries of positive social affects, as generated normally by PLAY interactions (Burgdorf et al, 2007), should diminish the psychological pain of depression (Burgdorf et al, 2016(Burgdorf et al, , 2011Panksepp, 2015a;. Likewise, in treatment resistant depression, perhaps an optimal target for DBS therapy would be the enthusiasm/interest generating SEEKING urge (Coenen et al, 2012;Panksepp and Yovell, 2014), another predictions that has been confirmed (Schlaepfer et al, 2013).…”

“…Indeed, because of such ethical concerns, JP decided to devote practically all his research effort for the past three decades to the study of positive emotions, especially animal play and "laughter," and specifically focusing on how such work may help identify new psychiatric treatments (Burgdorf et al, 2016;Panksepp and Wright, 2012;Panksepp and Yovell, 2014;Panksepp, 2016Panksepp, , 2015aWright and Panksepp, 2012;Yovell et al, 2015).…”