Difference between revisions of "Wiring The Brain"

From Q-Bio Seminar Series
Jump to: navigation, search
 
Line 10: Line 10:
  
 
;Abstract:
 
;Abstract:
:The highly ordered wiring of retinal ganglion cell (RGC) neurons in the retina to neurons in the superior colliculus of the midbrain has long served as the dominant experimental system for the analysis of topographic neural maps. These maps are comprised of axonal connections in which the positional coordinates of a set of input neurons are mapped onto the corresponding coordinates of their targets. They are a feature of nearly all sensory modalities, including sight, touch, sound, taste and smell, and are seen throughout the nervous system. We describe a quantitative model for the development of one arm of the retinocollicular (retinotectal) map: the wiring of the nasal-temporal axis of the retina to the posterior-anterior axis of the SC. The model is based RGC-RGC competition that is governed by comparisons of the signaling intensity experienced by retinal ganglion cells expressing differing levels of EphA receptor protein-tyrosine kinases, whose expression is exponentially graded across the nasal-temporal axis of the retina. These comparisons are made using ratios of, rather than absolute differences in, EphA signaling intensity. Molecular genetic experiments, exploiting a combination of EphA receptor knock-in and knock-out mice, confirm the salient predictions of this 'Relative Signaling' model, and demonstrate that it both describes and predicts topographic mapping.  
+
:In order for us to see, each retinal ganglion cell (RGC) neuron, which corresponds to a pixel in snapshots of the world that our retina takes many times a second, needs to be connected to the rest of our brain in a regular, reproducible fashion. That is, to preserve the information about the relative position of each pixel, this neural wiring must honor locality: two nearby RGC must connect to two nearby neurons in the area of the brain knows as the superior colliculus (SC). Such wiring arrangements are called ''topographic maps'', and they are a feature of nearly all sensory modalities, including sight, touch, sound, taste and smell, and are seen throughout the nervous system. How do these maps form in embryonic development? How do neurons from the retina, which are clonal copies of each other, figure out where they are in the retina and hence which of the neurons in SC they should connect to? While the entire picture is still unclear, some details have started to emerge following Prof. Lemke's laboratory research on one aspect of this mapping, namely: how do the RCG know their precise position in the retina along its vertical axis? The solution is a certain molecule, called EphA receptor protein-tyrosine kinase, which is being produced by each of the cells. Due to a competition among the RCGs, the concentration of this molecule varies across the retinal vertical axis, informing the cells of their position and instructing them where in the SC they should connect to in a robust fashion. To verify this hypothesis, Prof. Lemke's laboratory has exploited molecular genetic experiments, creating mutant mice with too many or too few EphA receptor molecules, and the RCG competition theory was able to predict the effects of such changes on the topographic map formation.
 +
 
  
 
[[image:lemke.jpg|Prof. Greg Lemke]]
 
[[image:lemke.jpg|Prof. Greg Lemke]]

Latest revision as of 10:20, 6 July 2009

By Prof. Greg Lemke, Head of Molecular Neurobiology Laboratory, The Salk Institute

July 21, 2009

Santa Fe Complex

For us to be able to see, specific cells in our retinas must be connected in a regular fashion to specific cells in our brains. How does the brain achieve it? How does it reproducibly wire its billions of nerve cells together during embryonic development? This lectures describes how the visual system uses variable abundances of a set of receptors - called EPH proteins - to connect the eye to the brain in a regular, reproducible fashion that allows us to see.

Prof. Lemke will be introduced by Dr. Ilya Nemenman, Staff Scientist, Los Alamos National Laboratory.

Abstract
In order for us to see, each retinal ganglion cell (RGC) neuron, which corresponds to a pixel in snapshots of the world that our retina takes many times a second, needs to be connected to the rest of our brain in a regular, reproducible fashion. That is, to preserve the information about the relative position of each pixel, this neural wiring must honor locality: two nearby RGC must connect to two nearby neurons in the area of the brain knows as the superior colliculus (SC). Such wiring arrangements are called topographic maps, and they are a feature of nearly all sensory modalities, including sight, touch, sound, taste and smell, and are seen throughout the nervous system. How do these maps form in embryonic development? How do neurons from the retina, which are clonal copies of each other, figure out where they are in the retina and hence which of the neurons in SC they should connect to? While the entire picture is still unclear, some details have started to emerge following Prof. Lemke's laboratory research on one aspect of this mapping, namely: how do the RCG know their precise position in the retina along its vertical axis? The solution is a certain molecule, called EphA receptor protein-tyrosine kinase, which is being produced by each of the cells. Due to a competition among the RCGs, the concentration of this molecule varies across the retinal vertical axis, informing the cells of their position and instructing them where in the SC they should connect to in a robust fashion. To verify this hypothesis, Prof. Lemke's laboratory has exploited molecular genetic experiments, creating mutant mice with too many or too few EphA receptor molecules, and the RCG competition theory was able to predict the effects of such changes on the topographic map formation.


File:Lemke.jpg

Back to The q-bio Public Lectures main page.

Personal tools