bioRxiv Science⌕ Search

Biology subjects

Groleau, M.

Publications and source records attributed to Groleau, M..

3 recordsLinked to original sources

Rapid Vascular Activation Precedes Immune Cell Infiltration Following Corneal Alkali Burn

Under homeostatic conditions, the cornea is avascular and contains few immune cells, but this changes rapidly following injury. Although the long-term consequences of corneal damage are well characterized, the earliest vascular and immune responses remain poorly understood. Here, we used a murine corneal alkali-burn model to examine limbal vascular activation and leukocyte recruitment immediately and at 2, 6, and 24 hours after injury. Limbal blood vessels underwent immediate dilation; however, vascular leakage into the corneal stroma occurred only in males. Lymphatic capillaries rapidly formed directed extensions toward the injury without significantly increasing their total vascular area, with males exhibiting longer extensions than females. Fluorescent dextran uptake provided evidence that these lymphatic vessels were functionally engaged in early tracer drainage. Despite pronounced vascular activation, early recruitment of neutrophils, monocytes, dendritic cells, macrophages, T cells, B cells, and natural killer cells remained limited. Thus, limbal blood and lymphatic vessels initiate the earliest response to corneal alkali injury before substantial leukocyte infiltration. These findings reveal sex-dependent differences in vascular permeability and lymphatic remodeling and identify the limbal vasculature as an early regulator of corneal inflammation and tissue repair.

pathology↗

Mesoscopic cortical network reorganization during recovery of partial optic nerve injury in GCaMP6s mice

As the residual vision following a traumatic optic nerve injury can spontaneously recover over time, we explored the plasticity of cortical networks during the early post-optic nerve crush (ONC) phase. Using in vivo wide-field calcium imaging on awake Thy1-GCaMP6s mice, we characterized resting state and evoked cortical activity before, during, and 30 days after ONC. The recovery of monocular visual acuity and depth perception was evaluated at the same time points. Cortical responses to an LED flash decreased in the contralateral hemisphere in the primary visual cortex and in the secondary visual areas following the ONC, but was partially rescued between 3 and 5 days post-ONC, remaining stable thereafter. The connectivity between visual and non-visual regions was disorganized after the crush, as shown by a decorrelation, but correlated activity was restored 30 days after the injury. The number of surviving retinal ganglion cells dramatically dropped and remained low. At the behavioral level, the ONC resulted in visual acuity loss on the injured side and an increase in visual acuity with the non-injured eye. In conclusion, our results show a reorganization of connectivity between visual and associative cortical areas after an ONC, which is indicative of spontaneous cortical plasticity.

neuroscience↗

p75 Neurotrophin Receptor Regulates the Timing of the Maturation of Cortical Parvalbumin Cell Connectivity and Promotes Ocular Dominance Plasticity in Adult Visual Cortex.

By virtue of their extensive axonal arborisation and perisomatic synaptic targeting, cortical inhibitory Parvalbumin (PV) cells strongly regulate principal cell output and plasticity. An interesting aspect of PV cell connectivity is its prolonged maturation time course, which is completed only by end of adolescence. The p75 neurotrophin receptor (p75NTR) regulates a wide range of cellular function, including apoptosis, neuronal process remodeling and synaptic plasticity, however its role on cortical circuit development is still not well understood, mainly because localizing p75NTR expression with cellular and temporal resolution has, so far, been challenging.\n\nUsing RNAscope and a modified version of the Proximity Ligation Assay (PLA), we show that p75NTR mRNA and protein are expressed in cortical PV cells in the postnatal and adult brain. Further, p75NTR expression in PV cells decreases between postnatal day (P)14 and P26, at a time when PV cell synapse numbers increase dramatically. Conditional knockout of p75NTR in single PV neurons in cortical organotypic cultures and in PV cell networks in vivo leads to precocious formation of PV cell perisomatic innervation and perineural nets around PV cell somata, suggesting that p75NTR expression controls the timing of the maturation of PV cell connectivity in the adolescent cortex.\n\nRemarkably, we found that p75NTR is still expressed, albeit at low level, in PV cells in adult cortex. Interestingly, activation of p75NTR onto PV cells in adult visual cortex in vivo is sufficient to destabilize their connectivity and to reintroduce juvenile-like cortical plasticity following monocular deprivation. Altogether, our results show that p75NTR activation dynamically regulates PV cell connectivity, and represents a novel tool to foster brain plasticity in adults.

neuroscience↗