Targeted therapy of cognitive deficits in fragile X syndrome.

Breaking an impasse in finding mechanism-based therapies of neuropsychiatric disorders requires a strategic shift towards alleviating individual symptoms. Here we present a symptom and circuit-specific approach to rescue deficits of reward learning in Fmr1 knockout mice, a model of Fragile X syndrome (FXS), the most common monogenetic cause of inherited mental disability and autism. We use high-throughput, ecologically-relevant automated tests of cognition and social behavior to assess effectiveness of the circuit-targeted injections of designer nanoparticles, loaded with TIMP metalloproteinase inhibitor 1 protein (TIMP-1). Further, to investigate the impact of our therapeutic strategy on neuronal plasticity we perform long-term potentiation recordings and high-resolution electron microscopy. We show that central amygdala-targeted delivery of TIMP-1 designer nanoparticles reverses impaired cognition in Fmr1 knockouts, while having no impact on deficits of social behavior, hence corroborating symptom-specificity of the proposed approach. Moreover, we elucidate the neural correlates of the highly specific behavioral rescue by showing that the applied therapeutic intervention restores functional synaptic plasticity and ultrastructure of neurons in the central amygdala. Thus, we present a targeted, symptom-specific and mechanism-based strategy to remedy cognitive deficits in Fragile X syndrome.

Ability to share emotions of others as a foundation of social learning.

The natural habitats of most species are far from static, forcing animals to adapt to continuously changing conditions. Perhaps the most efficient strategy addressing this challenge consists of obtaining and acting upon pertinent information from others through social learning. We discuss how animals transfer information via social channels and what are the benefits of such exchanges, playing out on different levels, from theperception of socially delivered information to emotional sharing, manifesting themselves across different taxa of increasing biological complexity. We also discuss how social learning is influenced by different factors including pertinence of information for survival, the complexity of the environment, sex, genetic relatedness, and most notably, the relationship between interacting partners. The results appear to form a consistent picture once we shift our focus from emotional contagion as a prerequisite for empathy onto the role of shared emotions in providing vital information about the environment. From this point of view, we can propose approaches that are the most promising for further investigation of complex social phenomena, including learning from others.

The roots of empathy: Through the lens of rodent models.

Empathy is a phenomenon often considered dependent on higher-order emotional control and an ability to relate to the emotional state of others. It is, by many, attributed only to species having well-developed cortical circuits capable of performing such complex tasks. However, over the years, a wealth of data has been accumulated showing that rodents are capable not only of sharing emotional states of their conspecifics, but also of prosocial behavior driven by such shared experiences. The study of rodent empathic behaviors is only now becoming an independent research field. Relevant animal models allow precise manipulation of neural networks, thereby offering insight into the foundations of empathy in the mammalian brains. Here we review the data on empathic behaviors in rat and mouse models, their neurobiological and neurophysiological correlates, and the factors influencing these behaviors. We discuss how simple rodent models of empathy enhance our understanding of how brain controls empathic behaviors.