Biophysical properties, morphology and mechanisms of communication of olfactory ensheathing cells

LORENA RELA; ANGELIQUE BORDEY; CHARLES A. GREER

Huerta Grande, Córdoba, Argentina

Taller; Taller de Neurociencias; 2008

Taller de Neurociencias

Olfactory ensheathing cells (OECs) are a unique type of glia wrapping the axons of olfactory sensory neurons (OSNs) along their path from the olfactory epithelium to the olfactory bulbs. They can promote axon extension both in cell culture and in animal models of spinal cord injury, thus they seem to provide a permissive environment for axon growth and/or regeneration in the central nervous system.In the olfactory system new sensory neurons are incorporated into the circuits throughout life. We hypothesize that OECs communicate among themselves and with OSNs in order to regulate their incorporation into circuits. With this hypothesis as guide, we began the first characterization of the biophysical, morphological and communication properties of OECs using wholecell voltageclamp recordings in acute slices of mouse olfactory bulb, complementing this approach with immunohistochemistry. Based on their current profiles, OECs are a heterogeneous population. We found both linear profiles and also profiles showing voltageand timedependent currents. Hyperpolarizationactivated inward currents were blocked by 3 mM cesium or 100 (micro)M barium, likely mediated by inwardrectifier potassium channels. Outward currents were partially blocked by 20 mM TEA. We dyefill the cells during recording, revealing a complex morphology in OECs, with fine interdigitations that appear to surround axon bundles and long lamellae that surround groups of axon bundles at a higher structural hierarchy. Some OECs are dyecoupled to 13 other neighboring cells, consistent with the colocalization of OEC markers with connexin43, a known mediator of glial gap junctional coupling.OEC transplants are proposed as a viable therapy to promote axon regeneration and remyelination in the injured central nervous system. However, they seem to better promote axon growth in the olfactory nerve than when transplanted in the spinal cord. Studying them in situ is one way to better understand their properties and mechanisms accounting for this difference. This characterization in normal conditions sets the basis to study the OEC phenotype in conditions of synchronized OSN regeneration after a lesion to the olfactory epithelium, in order to find candidate mechanisms involved in the role of OECs as regulators of circuit formation.