Participation of glial connexins and BDNF in the postnatal development of olfactory circuits

LUCILA BROCARDO; LUIS ERNESTO ACOSTA; LORENA RELA

Buenos Aires

Congreso; 2nd FALAN Congress; 2016

Federation of Latin American and Caribbean Neuroscience Societies

Olfactory bulb innervation by olfactory sensory neurons (OSNs) refines post-natally and is a BDNF-dependent process. OSNs associate to olfactory ensheathing cells (OECs), specialized glia promoting neurotrophin-dependent axon extension. We propose that glial networks refine simultaneously with neurons and that OEC-released BDNF participates in circuit maturation. Preliminary results show that OEC sensitivity to meclofenamic acid (MFA, gap junction blocker) is comparable at neonate and juvenile stages. MFA-sensitivity is absent in OECs with deletion of the gap junction protein Cx43. Strikingly, OECs show minimal Cx43 expression at P0 and higher levels at P30, suggesting a connexin switch during refinement. To unveil glial modulation of refinement we characterized mice expressing tamoxifen-inducible Cre recombinase regulated by the proteolipid protein promoter (PLP). In the offspring of PLP-Cre mice crossed with the Cre-reporter line tdTomato reported cells were found in OEC-rich regions and expressed OEC markers (S100B and BLBP), resulting selective for OEC gene manipulation. We crossed PLP-Cre mice with BDNF-floxed mice and induced Cre at P0 in the offspring. At the juvenile stage PLP-Cre-;BDNFflox mice had had less tyrosine hydroxylase-positive cells in the bulb when compared with BDNFflox mice, indicating a deficient sensory input in mice with BDNF-deficient OECs. These results suggest that OECs mature with the neuronal circuit and contribute with BDNF for OB maturation.