Pal, D. | Search bioRxiv

bioRxiv2018

Differential role of prefrontal and parietal cortices in controlling level of consciousness

There is current controversy regarding the role of prefrontal versus posterior cortices in consciousness. Clinical and correlative data have been used both to support and refute a causal role for prefrontal cortex in the level of consciousness, but a definitive relationship has not been demonstrated. We used anesthetic-induced unconsciousness as a model system to study the effect of cholinergic and noradrenergic stimulation of rat prefrontal and posterior parietal cortices on the level of consciousness. We demonstrate that cholinergic stimulation of prefrontal cortex, but not parietal cortical areas, restored wakefulness in rats despite continuous exposure to sevoflurane anesthesia. Noradrenergic stimulation of the prefrontal or parietal areas did not reverse the anesthetized state. We conclude that cholinergic mechanisms in prefrontal cortex can control the level of consciousness.\n\nOne Sentence SummaryPrefrontal cholinergic stimulation restores consciousness in rats despite continuous exposure to sevoflurane anesthesia

neuroscience↗

bioRxiv2017

Development of migrating entheses involves replacement of progenitor populations

Attachment sites of tendons to bones, called entheses, are essential for proper musculoskeletal function. They are formed embryonically by Sox9+ progenitors and undergo a developmental process that continues into the postnatal period and involves Gli1 lineage cells. During bone elongation, some entheses maintain their relative positions by actively migrating along the bone shaft, while others, located at the bones extremities, remain stationary. Despite their importance, we lack information on the developmental transition from embryonic to mature enthesis and on the relation between Sox9+ progenitors and Gli1 lineage cells. Here, by performing a series of lineage tracing experiments, we identify the onset of Gli1 lineage contribution to different entheses during embryogenesis. We show that Gli1 expression is regulated by SHH signaling during embryonic development, whereas postnatally it is maintained by IHH signaling. Interestingly, we found that unlike in stationary entheses, where Sox9+ cells differentiate into the Gli1 lineage, in migrating entheses the Sox9 lineage is replaced by Gli1 lineage and do not contribute to the mature enthesis. Moreover, we show that these Gli1+ progenitors are pre-specified embryonically to form the different cellular domains of the mature enthesis.\n\nOverall, these findings demonstrate a developmental strategy whereby one progenitor population establishes a simple, embryonic tissue, whereas another population is responsible for its maturation into a complex structure during its migration. Moreover, they suggest that different cell populations may be considered for cell-based therapy of enthesis injuries.

developmental biology↗