Critical period plasticity underlying complex learning in autism rat models

  • Awarded: 2022
  • Award Type: Targeted: Autism Rat Models Consortium
  • Award #: 901199

During early postnatal development, many neocortical brain areas exhibit “sensitive periods” where circuit refinement is driven by experience, by engaging both Hebbian (correlation-based) and homeostatic forms of plasticity. How these forms of plasticity interact and synergize during normal and aberrant development remains poorly understood. A number of genes strongly associated with autism spectrum disorder (ASD) — including SHANK3 — lead to impairment of one or more of the cellular plasticity mechanisms that underlie homeostatic compensation, leading to the hypothesis that defects in circuit refinement in some monogenic ASDs arise through a failure or inappropriate engagement of homeostatic plasticity.

Here, Gina Turrigiano and colleagues plan to examine this possibility by studying how vision-dependent learning during the classic visual system critical period in Long-Evans rats is impacted by loss of three ASD risk genes: Shank3, Grin2b and Scn2a. Shank3 loss impairs homeostatic plasticity and the ability of visual cortical circuits to recover from sensory deprivation1 and also impairs a complex vision-dependent learned behavior (prey capture) in juvenile rodents2. Turrigiano and colleagues aim to establish the degree to which these deficits generalize to other ASD rat models.

To accomplish this, they plan to combine chronic electrophysiological recordings with behavioral analysis as juvenile rats learn to perform an ethologically relevant and intrinsically motivating behavior (prey capture). They will assess the impact of loss-of-function of Shank3, Grin2b and Scn2a on cellular mechanisms of homeostatic plasticity and determine how this in turn impacts learning and the evolution of activity within the primary visual cortex. Finally, they plan to follow-up on pilot data showing that juvenile rats learn to capture prey more efficiently when they first observe a sibling who is already proficient and determine whether this social transmission of skills is impaired or altered in these monogenic ASD rat models.


1.Tatavarty V. et al. Neuron 106, 769-777 (2020) PubMed
2.GrovesKuhnle C. et al. bioRxiv (2022) Preprint
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