Balia, M. | Search bioRxiv

bioRxiv2023

Cadherins orchestrate specific patterns of perisomatic inhibition onto distinct pyramidal cell populations

In the mammalian neocortex, excitatory pyramidal cells are assembled into distinct subnetworks, which project to different brain areas. GABAergic interneurons were long thought to connect promiscuously and extensively to pyramidal neurons, but recent evidence supports the existence of a cell type-specific inhibitory connectome. How and when interneurons establish such a precise connectivity pattern among intermingled populations of excitatory neurons remains enigmatic. Here, we investigated the molecular rules shaping cell type- and input-specific inhibitory connectivity in different Layer 5 (L5) pyramidal cell populations. We found that neighboring L5 intra- (L5 IT) and extra-telencephalic (L5 ET) neurons receive different combinations of inhibitory perisomatic inputs from Parvalbumin- (PV+) and Cholecystokynine-positive (CCK+) basket cells. We also identified Cdh12 and Cdh13, two cadherin superfamily members, as critical mediators of L5 pyramidal cell type-specific inhibitory connectivity. Our data revealed a minimal overlap between L5 IT and L5 ET presynaptic inhibitory networks, and suggests that different populations PV+ basket cells innervate distinct L5 pyramidal cell types. Altogether, our work unravels the contribution of cadherins in shaping cortical interneuron wiring and provides new insights into the development of inhibitory microcircuits.

neuroscience↗

bioRxiv2022

A population of gray matter oligodendrocytes directly associates with the vasculature

Oligodendrocyte lineage cells interact with the vasculature in the gray matter. Physical and functional interactions between blood vessels and oligodendrocyte precursor cells play an essential role in both the developing and adult brain. Oligodendrocyte precursor cells have been shown to migrate along the vasculature and subsequently detach from it during their differentiation to oligodendrocytes. However, the association of mature oligodendrocytes with blood vessels has been noted since the discovery of this glial cell type almost a century ago and this interaction remains poorly explored. Here, we systematically investigated the extent of mature oligodendrocyte interaction with the vasculature in mouse. We found that ~17% of oligodendrocytes were in contact with blood vessels in cortex, hippocampus and cerebellum. Contacts were made mainly with capillaries and sparsely with larger arterioles or venules. By combining light and serial electron microscopy, we demonstrated that oligodendrocytes are in direct contact with the vascular basement membrane, raising the possibility of direct signaling pathways and metabolite exchange with endothelial cells. During experimental remyelination in the adult, oligodendrocytes were regenerated and associated with blood vessels in the same proportion compared to control cortex, suggesting a homeostatic regulation of the vasculature-associated oligodendrocyte population. Based on the frequent and close association with blood vessels, we propose that vasculature-associated oligodendrocytes should be considered as an integral part of the vasculature microenvironment. This particular location could underlie specific functions of vasculature-associated oligodendrocytes, while contributing to the vulnerability of mature oligodendrocytes in neurological diseases.

neuroscience↗