Synaptic inhibition is the mechanistic backbone of a suite of cortical functions, not the least of which are maintaining network stability and modulating neuronal gain. In cortical models with a single inhibitory neuron class, network stabilization and gain control work in opposition to one another – meaning high gain coincides with low stability and vice versa. It is now clear that cortical inhibition is diverse, with molecularly distinguished cell classes having distinct positions within the cortical circuit. We analyze circuit models with pyramidal neurons (E) as well as parvalbumin (PV) and somatostatin (SOM) expressing interneurons. We show how, in E – PV – SOM recurrently connected networks, SOM-mediated modulation can lead to simultaneous increases in neuronal gain and network stability. Our work exposes how the impact of a modulation mediated by SOM neurons depends critically on circuit connectivity and the network state.

Olfactory ensheathing cells (OECs) are unique glial cells found in both central and peripheral nervous systems where they support continuous axonal outgrowth of olfactory sensory neurons to their targets. Previously, we reported that following severe spinal cord injury, OECs transplanted near the injury site modify the inhibitory glial scar and facilitate axon regeneration past the scar border and into the lesion. To better understand the mechanisms underlying the reparative properties of OECs, we used single-cell RNA-sequencing of OECs from adult rats to study their gene expression programs. Our analyses revealed five diverse OEC subtypes, each expressing novel marker genes and pathways indicative of progenitor, axonal regeneration, secreted molecules, or microglia-like functions. We found substantial overlap of OEC genes with those of Schwann cells, but also with microglia, astrocytes, and oligodendrocytes. We confirmed established markers on cultured OECs, and localized select top genes of OEC subtypes in olfactory bulb tissue. We also show that OECs secrete Reelin and Connective tissue growth factor, extracellular matrix molecules which are important for neural repair and axonal outgrowth. Our results support that OECs are a unique hybrid glia, some with progenitor characteristics, and that their gene expression patterns indicate functions related to wound healing, injury repair, and axonal regeneration.