Juvenile Shank3 KO mice adopt distinct hunting strategies during prey capture learning.

Mice are opportunistic omnivores that readily learn to hunt and eat insects such as crickets. The details of how mice learn these behaviors and how these behaviors may differ in strains with altered neuroplasticity are unclear. We quantified the behavior of juvenile wild type and Shank3 knockout mice as they learned to hunt crickets during the critical period for ocular dominance plasticity. This stage involves heightened cortical plasticity including homeostatic synaptic scaling, which requires Shank3, a glutamatergic synaptic protein that, when mutated, produces Phelan-McDermid syndrome and is often comorbid with autism spectrum disorder (ASD). Both strains showed interest in examining live and dead crickets and learned to hunt. Shank 3 knockout mice took longer to become proficient, and, after 5 days, did not achieve the efficiency of wild type mice in either time-to-capture or distance-to-capture. Shank3 knockout mice also exhibited different characteristics when pursuing crickets that could not be explained by a simple motor deficit. Although both genotypes moved at the same average speed when approaching a cricket, Shank3 KO mice paused more often, did not begin final accelerations toward crickets as early, and did not close the distance gap to the cricket as quickly as wild type mice. These differences in Shank3 KO mice are reminiscent of some behavioral characteristics of individuals with ASD as they perform complex tasks, such as slower action initiation and completion. This paradigm will be useful for exploring the neural circuit mechanisms that underlie these learning and performance differences in monogenic ASD rodent models. Significance Statement During early development, activity-dependent plasticity mechanisms shape brain circuits. Shank3 is a synaptic protein that is mutated in Phelan-McDermid syndrome and is usually comorbid with autism spectrum disorder. Prior research shows that mice deficient in Shank3 exhibit abnormalities in a plasticity mechanism called homeostatic synaptic scaling. Here, we explore whether Shank3 knockout mice can learn to hunt crickets. We find that they can, although they pause more during their hunting and do not accelerate towards the cricket as rapidly. Future studies may be able to trace the neural circuits responsible for these differences, shedding more light on the causes of Phelan-McDermid syndrome and autism.