Leslie Tolbert

Co- Principal Investigator

My laboratory group in the ARL Division of Neurobiology is interested primarily in the development of the nervous system, in particular, how developing nerve cells, or neurons, form the correct circuits during development. We ask our questions in the developing olfactory system of an insect, the moth Manduca sexta, where we have a great deal of flexibility in the surgical and other interventions available to allow tests of hypotheses. The cellular organization of olfactory centers is very similar across species, from insect to human, so we expect our results to have broad applicability.

Much of our focus over the last 15 years has been on elucidating intercellular interactions that lead to the formation of "glomeruli," the sites of processing of inputs about particular odors, in the olfactory lobe of the moth's brain. Now we add to that a new interest in trying to understand how olfactory receptor axons find the correct targets, since -- unlike in other, better understood sensory systems -- there appears to be very preservation of the topography of the receptive surface (epithelium) as the olfactory receptors project into the brain. We use mostly morphological methods (confocal microscopy, electron microscopy) but also use biochemical, molecular biological, patch-clamp, and intracellular recording and dye-filling methods to approach these issues experimentally, both in the animal and in brain slices or dissociated cells from the brain.

Our results to date indicate that glial cells, the so-called "support" cells of the nervous system, play strategic and essential roles in glomerulus formation and in axon targeting. In the realm of mathematical modeling, we have begun to explore the roles of glomerular organization in olfactory function, as a spin-off of our investigations of the role of glial cells in glomerulus development. Anita Rado, in Ph.D. dissertation work done jointly with Dr. Timothy Secomb and me, developed a mathematical model for the diffusion of important ions in the extracellular spaces in and between glomeruli, and related patterns of diffusion to the situation when odor input activates multiple axons in a single glomerulus. Her results suggest that the glial borders that surround individual glomeruli may help to sculpt the patterns of neural activity in response to odor stimulation. Biological experiments suggested by her results and further refinement of the model should elucidate the precise role of the glial cells.

Another issue that will be interesting to explore with mathematical techniques in the future is the neural processing that is carried out in olfactory glomeruli, through analysis of synaptic circuitry and the cable properties of glomerular axons and dendrites. This work has been begun by several people in a collaboration between Drs. Tom Christensen and John Hildebrand and me.