Critical periods and Autism Spectrum Disorders, a role for sleep

Abstract

Brain development relies on both experience and genetically defined programs. Time windows where certain brain circuits are particularly receptive to external stimuli, resulting in heightened plasticity, are referred to as "critical periods". Sleep is thought to be essential for normal brain development. Importantly, studies have shown that sleep enhances critical period plasticity and promotes experience-dependent synaptic pruning in the developing mammalian brain. Therefore, normal plasticity during critical periods depends on sleep. Problems falling and staying asleep occur at a higher rate in Autism Spectrum Disorder (ASD) relative to typical development. In this review, we explore the potential link between sleep, critical period plasticity, and ASD. First, we review the importance of critical period plasticity in typical development and the role of sleep in this process. Next, we summarize the evidence linking ASD with deficits in synaptic plasticity in rodent models of high-confidence ASD gene candidates. We then show that the high-confidence rodent models of ASD that show sleep deficits also display plasticity deficits. Given how important sleep is for critical period plasticity, it is essential to understand the connections between synaptic plasticity, sleep, and brain development in ASD. However, studies investigating sleep or plasticity during critical periods in ASD mouse models are lacking. Therefore, we highlight an urgent need to consider developmental trajectory in studies of sleep and plasticity in neurodevelopmental disorders.

Keywords: Autism; Critical periods of development; Sleep; Synaptic plasticity.

Graphical abstract

Fig. 1

The Ocular Dominance Plasticity model. A) In the binocular region of the visual cortex most neurons respond to input from the contralateral eye while very few respond to input from the ipsilateral eye input only. Input from eyes is color coded, red represent left, blue represent right. An example of neuronal activity sampled from the left side will receive most input from the contralateral side (blue). B) Monocular deprivation (MD) results in a shift of response from the non-deprived eye C) Sleep is necessary to consolidate the effects of MD. D) When sleep deprivation (SD) follows MD, the shift in response is not seen. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 2

Summary of biological processes and pathways affected by ASD genes at the intersection of sleep and plasticity. Functional Annotation Enrichment analysis and subsequent clustering of genes in Table 1. Genes highlighted in bold are those for which mutations also affect sleep as outlined in Table 2. KW: KEGG pathway identifier, mmu: Uniprot biological process or molecular function identifier.