Leslie Tolbert

Leslie Tolbert's picture
Regents' Professor

Telephone: 

(520) 621-6640

Office: 

Gould-Simpson Rm 636

Degree(s): 

A.B. 1973, Harvard University
Ph.D. 1978, Harvard University

 

Tolbert/Oland Lab Group Curriculum vitae  

 

Research Interests: 

 

  • Interactions between neurons and glial cells in the developing nervous system
  • Roles of glial cells in mature neural function
  • Functional organization and plasticity of olfactory systems
  • Use of insect nervous systems as tractable experimental systems that provide broad insights

Research in my laboratory for many years has focused on the development and functional organization of the olfactory system, studied in convenient model organisms, the moth Manduca sexta and, more recently, the fruit fly Drosophila melanogaster.  Our results in several different lines of investigation led us to focus most energetically on exploring the critical roles of glial cells in development.  In recent years, we have expanded our purview to include study of the roles that glia play in supporting and modulating mature neural function as well.

The lab is co-directed by my long-standing colleague and collaborator, Research Professor Lynne Oland.

Development of the olfactory pathway. Over the years, our research has been aimed primarily at elucidating key intercellular interactions during development of the olfactory system. We have been especially interested in the mechanisms underlying the wide-spread phenomenon that sensory neurons guide many aspects of development in their target areas in the brain. Using the olfactory system of Manduca, we found in 1987 that glial cells must be present in order for the axons of olfactory receptor neurons, whose cell bodies are located in the antenna, to induce the formation of synaptic glomeruli in the antennal (olfactory) lobes of the brain.

Much of our work since then has built on the working hypothesis that glial cells act as essential intermediaries in the developmental influence that olfactory axons exert upon their targets - i.e. that glial cells, which are induced by axons to surround developing synaptic glomeruli, form a necessary scaffold within which receptor neurons and target neurons subsequently differentiate their glomerular arbors. We discovered that neuronal activity is not necessary for the formation of a glomerular architecture, so we have focused our attention on cell-surface and extracellular signaling molecules, such as fasciclin II, epidermal growth factor receptors, tenascin, and nitric oxide, that appear to be involved.

We also have studied molecular mechanisms of axon guidance, as we seek to understand how olfactory receptor axons find their correct glomerular targets in the antennal lobe, to produce circuitry that can encode olfactory stimuli. In 1999, we discovered a glia-rich "sorting zone" for axons in the antennal nerve, and, using methods that deplete the developing system of glial cells, we found that those glial cells must be present for sensory axons to sort properly. We continue to use in vitro methods and live-cell video microscopy to explore in detail the interactions between the growth cones of olfactory receptor axons and glia from the sorting zone and from other parts of the olfactory pathway.

Neuron-glia interactions that modulate neuronal function.  In recent years, we have been using Drosophila melanogaster for molecular genetic investigations of neuron-glia interactions that go beyond the interactions we have explored in Manduca. Fundamentally, we are asking how glial cells in the ventral ganglia modulate activity in the neurons that control movement.

Using temperature-sensitive activation of genes that cause cell death, we are studying the effects on motor behavior of killing a particular population of glial cells. Using targeted expression of channel rhodopsins in motor neurons and in neuropil-associated glial cells and whole-cell patch recordings of either cell type, we are monitoring the electrophysiological impacts of each cell type on the other. And at the structural level, we are investigating in detail the anatomical relationships of glial cells to functional compartments of the neuropil and to synapses in that neuropil.  This multi-pronged approach is designed to reveal the roles of glial cells in a “generic” and well-understood neuropil.

In the long run, we will continue to enhance knowledge of the intercellular interactions between developing and mature neurons and glial cells at a structural, functional, and molecular level.  We expect that the knowledge we gain will continue to offer insights into intercellular influences in less accessible mammalian systems.

Selected Publications: 

Gibson NJ, Tolbert LP, Oland LA (2012) Activation of glial FGFRs is essential in glial migration, proliferation, and survival and in glia-neuron signaling during olfactory system development.  PLoS ONE 7(4):e33828.

Oland LA, Tolbert LP (2011) Role of glial cells in neural circuit formation: Insights from research in insects.  Glia 59:1273-1295.

Koussa MA, Tolbert LP, Oland LA (2010) Development of a glial network in the olfactory nerve: role of calcium and neuronal activity.  Neuron Glia Biol. 6:245-261

Oland LA, Gibson NJ, Tolbert LP (2010) Localization of a GABA transporter to glial cells in the developing and adult olfactory pathway of the moth Manduca sexta, J Comp Neurol. 518(6):815-838.

Gibson NJ, Tolbert LP, Oland LA (2009) Roles of specific membrane lipid domains in EGF receptor activation and cell adhesion molecule stabilization in a developing olfactory system, PLoS One. 4(9):e7222.

Oland LA, Biebelhausen JP, Tolbert LP (2008) Glial investment of the adult and developing antennal lobe of Drosophila, J Comp Neurol. 509(5):526-550.

Gibson NJ, Tolbert LP (2006) Activation of epidermal growth factor receptor mediates receptor axon sorting and extension in the developing olfactory system of the moth Manduca sexta, J Comp Neurol. 495(5):554-572.