| Abstract No.: | 103 |
| Country: | Canada |
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| Title: | IMAGING THE INTERPLAY BETWEEN SYNAPTOGENESIS AND RETINOTECTAL MAP REFINEMENT |
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| Authors/Affiliations: | 1 Edward S. Ruthazer*;
1 Montreal Neurological Institute, QC, Canada
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| Content: | The development of precise topographic maps in the central nervous system is the result of the activity-dependent refinement of a crude map resulting from molecular axon guidance cues. Over the past half-century considerable evidence has amassed revealing that this process is not purely cell-autonomous, but rather involves complex and dynamic signaling interactions between the innervating axons and the postsynaptic neurons that comprise the target. These interactions remain poorly understood. We have used the retinotectal projection in Xenopus laevis as a model system to probe the underlying molecular signaling mechanisms involved in activity-dependent map refinement and axon remodeling at two levels.
First, because the most direct opportunity for signaling between input and target cells it the formation of direct cell-cell contacts, we have examined how the synaptic adhesion molecule N-Cadherin participates in the stabilization of retinal ganglion cell axon arborizations within the optic tectum. Our results confirm that cadherin signaling contributes to the local structural stability of axonal branches at synaptic junctions.
We also have examined how neural activity patterns drive acute and chronic changes in the target cells, including changes in synaptic efficacy and in the transcriptional profile of these cells. Our results demonstrate that the calcineurin-dependent transcription factor NFAT plays a fundamental role in modifying the receptivity of tectal neuron to activity cues from the retina. We have found that increased activity patterns in the circuit up-regulate calcineurin signaling in tectal neurons, which in turn drives NFAT-mediated transcription that suppresses new synapse formation and branch elaboration. Effectively maintaining a stable balance between ongoing levels of neural activity and dendritic growth and synaptogenesis.
Taken together these data begin to create a model in which rapid local interactions between neurons both drive and are regulated by continual, cell-wide changes in a cell’s transcriptional profile.
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