Molecular Cytoarchitecture of Central Visual Areas

Hockfield, Susan

Abstract

The acquisition of mature, differentiated neuronal properties takes place over an extended period. Some of the very last events in neuronal development occur during a circumscribed period in postnatal life, called the critical period, when the mature set of synapses between neurons is selected and the adult anatomical and physiological properties of neurons are acquired. In the visual system of cats and primates the selection of the appropriate set of synapses is governed, at least in part, by visuallY-evoked neuronal activity. The mature set of synapses established during the critical period are, under normal conditions, subject to little reorganization in the adult, So, for example, if a human infant receives aberrant visual input due to uncorrected congenital cataracts or strabismus, normal vision will never be achieved. Our experiments have explored the possibility that the change in neuronal phenotype from an immature, plastic state to a mature, less plastic state is mediated by changes in protein expression. We have identified a neuronal cell surface proteoglycan, recognized by monoclonal antibody Cat- 301, that is first detected late in development. In several cases we have been able to demonstrate that mature levels of expression of the Cat-301. proteoglycan are achieved at the close of the critical period for the acquisition of mature anatomical and physiological properties. This suggests that the Cat-301 proteoglycan may be involved in stabilizing the mature set of synaptic connections. Understanding the cellular and molecular mechanisms by which mature synaptic structure is stabilized could provide an avenue by which manipulation of these mechanisms might aid in recovery from neurological or ophthalmological diseases or injury. The major goal of this project is to use molecular differences among neurons to gain insight into the organization and development of mammalian central visual areas.
The specific aims toward this goal are: l. To examine the spatial and temporal patterns of expression of cell-surface associated proteoglycans to determine if distinct surface associated proteoglycans are expressed by different neuronal subsets in an activity- dependent manner. 2. To study the postnatal development of the human LGN and visual cortex using Cat-301 and antibodies to other chondroitin sulfate proteoglycans to investigate the timing of the close of the critical period for human visual function. 3. To investigate the function of the Cat-30l proteoglycan to test whether this protein might play a role in stabilizing the mature synaptic structure of neurons. 4. To clone the gene for the Cat-30l proteoglycan from rat, cat and human to further our understanding of the structure, function, and regulation of the Cat-301 protein and to identify related activity-dependent proteins that may be expressed by other functional classes of visual system neurons.