Initial anatomical and physiological studies suggested that sensory information relayed from the periphery by the thalamus is serially processed in primary sensory cortical areas. It is thought to propagate from layer 4 (L4) up to L2/3 and down to L5, which constitutes the main output of the cortex. However, more recent experiments point toward the existence of a direct processing of thalamic input by L5 neurons. Therefore, the role of L2/3 neurons in the sensory processing operated by L5 neurons is now highly debated. Using cell type-specific and reversible optogenetic manipulations in the somatosensory cortex of both anesthetized and awake mice, we demonstrate that L2/3 pyramidal neurons play a major role in amplifying sensory-evoked responses in L5 neurons. The amplification effect scales with the velocity of the sensory stimulus, indicating that L2/3 pyramidal neurons implement gain control in deep-layer neurons.

This study investigated whether four single nucleotide polymorphisms (SNPs) moderated caffeine effects on vigilance and performance in a double-blind and crossover total sleep deprivation (TSD) protocol in 37 subjects. In caffeine (2 × 2.5 mg/kg/24 h) or placebo-controlled condition, subjects performed a psychomotor vigilance test (PVT) and reported sleepiness every six hours (Karolinska sleepiness scale (KSS)) during TSD. EEG was also analyzed during the 09:15 PVT. Carriers of the TNF-α SNP A allele appear to be more sensitive than homozygote G/G genotype to an attenuating effect of caffeine on PVT lapses during sleep deprivation only because they seem more degraded, but they do not perform better as a result. The A allele carriers of COMT were also more degraded and sensitive to caffeine than G/G genotype after 20 h of sleep deprivation, but not after 26 and 32 h. Regarding PVT reaction time, ADORA2A influences the TSD effect but not caffeine, and PER3 modulates only the caffeine effect. Higher EEG theta activity related to sleep deprivation was observed in mutated TNF-α, PER3, and COMT carriers, in the placebo condition particularly. In conclusion, there are genetic influences on neurobehavioral impairments related to TSD that appear to be attenuated by caffeine administration. (NCT03859882).