Gap junctions in the developing olfactory system

LORENA RELA; CHARLES A. GREER

Huerta Grande, Córdoba, Argentina

Taller; Taller de Neurociencias; 2006

Taller de Neurociencias

The study of developing sensory systems is one means to understand how the synaptic specificity and neuron anatomy are attained in neural circuits. In the vertebrate olfactory system, olfactory sensory neurons (OSNs) project a single dendrite to the surface of the olfactory epithelium. Each seems to express a specific odorant receptor that makes it respond to particular odorants. OSNs project their axons to the olfactory bulb (OB) synapsing onto mitral cells (MCs) on neuropil structures (glomeruli). MCs typically extend a primary apical dendrite to a single glomerulus, secondary basal dendrites that make reciprocal synapses with inhibitory interneurons and one axon to higher order brain regions. OSNs expressing the same receptor molecule converge in the same glomeruli suggesting that glomeruli are the functional units for odor coding. It has been shown that MCs projecting their primary dendrites to the same glomerulus are electrically coupled through gap junctions formed by Connexin36 (Cx36). It is not known how this glomerulus-specific coupling is developed. Gap junctions are abundant in the brain during postnatal development, but in the adult are confined to specific groups of neurons. It has been suggested that the maturation of glutamatergic neurotransmission is necessary for the developmental gap junction uncoupling and Cx36 downregulation in the rat hypothalamus. To study the development of the glomerulus-specific coupling between MCs and the putative role of the NMDA receptor in regulating this process we propose: 1) to assess whether the glomerulus-specific coupling results as a specific elimination of a widespread electrical coupling analyzing the dye transfer and electrical coupling among MCs in slices of mouse OB during postnatal development; 2) to analyze the subcellular localization of Cx36 in MCs at different ages using a Cx36 specific antibody on sections from the OB of transgenic mice expressing a fluorescent marker in a subpopulation of MCs; 3) to test for the possible role of NMDA receptor signaling in the development of the coupling between MCs; we propose a) to analyze the dye transfer and electrical coupling among MCs in developing mice chronically treated with NMDA receptor blockers, and b) to analyze the dye transfer between MCs in primary cultures of mouse OB in the presence or absence of NMDA receptor blockers.