| Summary: | <p>Layer 6b (L6b) is the deepest cortical layer, is found in many species and partially derived from subplate. Evolutionary conversation of subplate-derived cells into adulthood and abnormalities in their human homologue, interstitial white matter neurons, in neuropsychiatric disorders suggest functional importance, but their function is currently unknown. It has been shown in somatosensory cortex that subsets of L6b receive long-range intracortical input and project selectively to higher order thalamus. Moreover, L6b subpopulations can be activated by orexin in vitro. Therefore, L6b could play a role in brain state control, potentially via an orexin-gated mechanism.</p>
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<p>In this project, I performed continuous EEG/EMG recordings in freely moving Drd1a-Cre;Snap25<sup>fl/fl</sup>;TdTom, “L6b silenced” mice, in which regulated synaptic vesicle release is selectively ablated from a subset of L6b. Distribution of vigilance states and sleep fragmentation were unchanged, but there was a reduction in theta power during wakefulness and REM, and a reduction in 3-30 Hz frontal EEG power during NREM. After sleep deprivation, EEG slow wave activity dissipated at a lower rate. Silencing L6b also changed in vivo responses to orexin. Orexin A increased maximal wakefulness episodes duration, and this increase was larger in L6b silenced animals. In NREM, orexin A and B increased sleep-wake attempts in both genotypes, and orexin A caused a relative increase in 3-30 Hz frontal EEG spectral power in both genotypes, which extended to 0.5-3.0 Hz only in L6b silenced animals. In an auditory oddball paradigm, I found increased within-paradigm and decreased between-paradigm adaptation in L6b silenced animals, as well as an overall reduction of early peak amplitudes.</p>
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<p>Altogether, the findings in this project demonstrate that L6b has a role in sleep-wake regulation, sleep homeostasis and adaptation, and that there is an interaction between L6b and orexin signalling in vivo. These findings contribute to establishing the role of L6b in brain state control.</p>
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