Over the last 60 years we have seen a significant rise in metabolic disease, especially type 2 diabetes. In the same period, the emergence of electricity and artificial lighting has allowed our behavioural cycles to be independent of external patterns of sunlight.This has led to a corresponding increase in sleep deprivation, estimated to be about 1 hour per night, as well as circadian misalignment (living against the clock). Evidence from experimental animals as well as controlled human subjects have shown that sleep deprivation and circadian misalignment can both directly drive metabolic dysfunction, causing diabetes. However, the precise mechanism by which these processes contribute to insulin resistance remains poorly understood. In this article, we will review the new literature in the field and propose a model attempting to reconcile the experimental observations made. We believe our model will serve as a useful point of reference to understand how metabolic dysfunction can emerge from sleep or circadian rhythm disruptions, providing new directions for research and therapy.

Subplate neurons (SPNs) are thought to play a role in nascent sensory processing in neocortex. To better understand how heterogeneity within this population relates to emergent function, we investigated the synaptic connectivity of Lpar1-EGFP SPNs through the first postnatal week in whisker somatosensory cortex (S1BF). These SPNs comprise of two morphological subtypes: fusiform SPNs with local axons, and pyramidal SPNs with axons that extend through the marginal zone. The former receive translaminar synaptic input up until the emergence of the whisker barrels; a timepoint coincident with significant cell death. In contrast, pyramidal SPNs receive local input from the subplate at early ages but then – during the later time window, acquire input from overlying cortex. Combined electrical and optogenetic activation of thalamic afferents identified that Lpar1-EGFP SPNs receive sparse thalamic innervation. These data reveal components of the postnatal network that interpret sparse thalamic input to direct the emergent columnar structure of S1BF.

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