Imitative and contagious behaviors in animals and their potential roles in the study of neurodevelopmental disorders.

Social learning in the forms of imitative and contagious behaviors are essential for learning abilities and social interaction. However, children with neurodevelopmental disorders and intellectual disabilities show impairments in these behaviors, which profoundly affect their communication skills and cognitive functions. Although these deficits are well studied in humans, pre-clinical animal model assessments of imitative and contagious behavioral deficits are limited. Here, we first define various forms of social learning as well as their developmental and evolutionary significance in humans. We also explore the impact of imitative and contagious behavioral deficits in several neurodevelopmental disorders associated with autistic-like symptoms. Second, we highlight imitative and contagious behaviors observed in nonhuman primates and other social animals commonly used as models for neurodevelopmental disorders. Lastly, we conceptualize these behaviors in the contexts of mirror neuron activity, learning, and empathy, which are highly debated topics. Taken together, this review furthers the understanding of imitative and contagious behaviors. We hope to prompt and guide future behavioral studies in animal models of neurodevelopmental disorders.

Synaptic inputs to broad thorny ganglion cells in macaque retina.

In primates, broad thorny retinal ganglion cells are highly sensitive to small, moving stimuli. They have tortuous, fine dendrites with many short, spine-like branches that occupy three contiguous strata in the middle of the inner plexiform layer. The neural circuits that generate their responses to moving stimuli are not well-understood, and that was the goal of this study. A connectome from central macaque retina was generated by serial block-face scanning electron microscopy, a broad thorny cell was reconstructed, and its synaptic inputs were analyzed. It received fewer than 2% of its inputs from both ON and OFF types of bipolar cells; the vast majority of its inputs were from amacrine cells. The presynaptic amacrine cells were reconstructed, and seven types were identified based on their characteristic morphology. Two types of narrow-field cells, knotty bistratified Type 1 and wavy multistratified Type 2, were identified. Two types of medium-field amacrine cells, ON starburst and spiny, were also presynaptic to the broad thorny cell. Three types of wide-field amacrine cells, wiry Type 2, stellate wavy, and semilunar Type 2, also made synapses onto the broad thorny cell. Physiological experiments using a macaque retinal preparation in vitro confirmed that broad thorny cells received robust excitatory input from both the ON and the OFF pathways. Given the paucity of bipolar cell inputs, it is likely that amacrine cells provided much of the excitatory input, in addition to inhibitory input.

The mouse model of fragile X syndrome exhibits deficits in contagious itch behavior.

Individuals with autism spectrum disorders (ASDs) imitate observed behavior less than age-matched and typically developing peers, resulting in deterred learning ability and social interaction. However, this deficit lacks preclinical assessment tools. A previous study has shown that mice exhibit contagious itch behavior while viewing a scratching demonstrator mouse, as opposed to an ambulating demonstrator mouse, but whether autism mouse models imitate observed scratching behavior remains unknown. Here, we investigated contagious itch behavior in the mouse model of fragile X syndrome (FXS), a common form of inherited intellectual disabilities with a high risk for ASDs. We found that the mouse model of FXS shows deficits in contagious itch behavior. Our findings can be used as a new preclinical assessment tool for measuring imitative deficits in the study of neurodevelopmental disorders including FXS.

Nanoparticle delivery of CRISPR into the brain rescues a mouse model of fragile X syndrome from exaggerated repetitive behaviours.

Technologies that can safely edit genes in the brains of adult animals may revolutionize the treatment of neurological diseases and the understanding of brain function. Here, we demonstrate that intracranial injection of CRISPR-Gold, a nonviral delivery vehicle for the CRISPR-Cas9 ribonucleoprotein, can edit genes in the brains of adult mice in multiple mouse models. CRISPR-Gold can deliver both Cas9 and Cpf1 ribonucleoproteins, and can edit all of the major cell types in the brain, including neurons, astrocytes and microglia, with undetectable levels of toxicity at the doses used. We also show that CRISPR-Gold designed to target the metabotropic glutamate receptor 5 (mGluR5) gene can efficiently reduce local mGluR5 levels in the striatum after an intracranial injection. The effect can also rescue mice from the exaggerated repetitive behaviours caused by fragile X syndrome, a common single-gene form of autism spectrum disorders. CRISPR-Gold may significantly accelerate the development of brain-targeted therapeutics and enable the rapid development of focal brain-knockout animal models.