Morphogenesis of the Lateral Geniculate Nucleus
Visual Maps and the LGN Receptor in Primates
The Theoretical Biophysics Group has expended a significant amount of effort in direct collaboration with experimentalists. Two such projects connected with neurobiology were studies of the function of visual maps in the cortex and the morphogenesis of the Lateral Geniculate Nucleus (LGN) in primates. An understanding of these systems will allow us to comprehend the formation and function of neural maps, addressing the fundamental issue of how stimuli are interpreted.
Two collaborations in neurobiology, involving two separate experimental laboratories, led to a better understanding of the morphogenesis of so-called brain maps. One project concentrated on the Lateral Geniculate Nucleus (LGN) [1, 2] in primates. The symbiosis of simulation and experiment led to the testing and refinement of a three-dimensional model of LGN morphogenesis. The second collaboration had demonstrated in the first phase that maps in the primary visual cortex of macaque's can be rationalized theoretically. Subsequently, the collaboration performed a thorough critical test of many existing models of visual map formation [3], benchmarking against experimental data provided by our collaborators. Several of the existing models were shown to be inconsistent with the experimental data, although it was not possible to identify a single model which was clearly most consistent.
Ocular Dominance Columns in the Visual Cortex
In collaboration with G. Blasdel, Harvard University, we compared theoretical models and experimental data for the visual cortex. Because of the complexity of map formation, these studies required the use of a CM-5 massively parallel machine. Experimental evidence reveals that the cells in the mammalian visual cortex are preferentially stimulated by one of the two eyes. Furthermore, they respond more strongly to gratings of particular orientation. Cells with similar detection properties are arranged in columns between pia and white matter. Imaging techniques which improve characterization of striate cortex cells have been developed and have led to a refined picture of map organization.
Later work has suggested that the ocular dominance columns are not pre-specified, but instead emerge from an activity-driven self-organizing process. For example, the occlusion of one eye leads to dramatic (semi-reversible) changes in the lateral organization of ocular dominance. Many different theoretical models have been proposed, but the different approaches have rarely been thoroughly compared or tested against experimental data.
We critically evaluated the most prominent and successful of these models using recent data obtained from monkey striate cortex. Although many of the models are based on quite different assumptions, we found that most produced maps which qualitatively resembled the experimental ones [4]. However, several models were inconsistent and could thus be ruled out as sufficient models for macaque map structure and development.
Lateral Geniculate Nucleus of Primates
Even though brain morphology exhibits considerable individuality, there are certain features which are often repeated. The Lateral Geniculate Nucleus (LGN), which is part of the mammalian visual system, has such a repeatable feature --- the correlation (co-localization) of two features in the LGN structure. These features are the presence of cell-free gaps in some of the layers and an extended, abrupt transition from a six-layered to a four-layered laminar structure.
In collaboration with Joseph Malpeli, experimental neurobiologist in the Psychology Department of the University of Illinois, we have tested the hypothesis that optic disk gaps in LGN trigger the laminar transition. We developed and tested a three-dimensional model for LGN morphogenesis which rests on the causal relationship between the optic disk gaps and the laminar transition. We believe this is the first detailed and realistic three-dimensional model of brain morphogenesis.
Our model explains the correlation by positing a causal relationship. The gaps destabilize the propagation of the six-layer pattern, which triggers a transition to the more quickly spreading four-layer pattern. Thus, the resulting boundary between four- and six-layer laminar patterns is caused by the gaps. The shape of the transition surfaces is determined by the different propagation velocities of the four- and six-layer patterns.
This prediction was confirmed using numerical simulations of the model. The experimental data used to develop the model pertained to the macaque primates. Our model suggests the same feature correlation in chimpanzee and human primate species, and is confirmed in three-dimensional reconstruction of human LGN, even though the locations of the optic disk and transition surface are different in all three primates.
