The experiments in this application will assess the role of afferent activity in the development of vibrissa-related neurons in the ventral posteromedial nucleus (VPM) of the rat's thalamus. The guiding hypothesis for all of the experiments is that afferent activity in general and a subset of that activity, patterned activity (activity that distinguishes distinct subsets of afferents from each other), may have very different effects upon the development of target neurons.l We suggest that all afferent activity may promote both survival and elaboration of axonal and dendritic arbors for a given population of neurons. Conversely, patterned afferent activity may be required for competition among the axons of the neurons in question at their target and it may promote cell death and the retraction of axonal and perhaps also dendritic arbors. We will test this hypothesis by manipulating the afferent activity to VPM neurons. We will reduce all afferent activity to these cells by application of tetrodotoxin (TTX) to the infraorbital nerve (the trigeminal branch that supplies the vibrissa follicles) for the first 3 weeks of life. We will reduce only patterned afferent activity by simply gluing the shafts of the mystacial vibrissae together for this same period. We will assess the effects of these manipulations by: 1) counting VPM cells, 2) determining the receptive field characteristics and dendritic morphology of VPM neurons via intracellular recording and horseradish peroxidase (HRP) injection, and 3) reconstructing the cortical axon arbors of VPM cells labeled by small thalamic deposits of Phaseolus vulgaris leucoagglutinin. If the effects of patterned afferent activity upon a population of nerve cells are a function of that activity's role in competition among the axons of the neurons in question at their target, it should be possible to mimic the effects of a loss patterned afferent input to VPM cells by blocking the activity of their axons in cortex. We will accomplish this by applying TTX to the somatosensory cortex for the first 3 weeks of life and then assessing the dependent variables listed above. In a final series of studies, we will use simple cell counting and anterograde and retrograde transport of Di-I to determine both the number of VPM cells and morphological properties of these neurons and their axons in newborn rats. This will define the status of this portion of the somatosensory system at the time when we initiate our manipulations. The establishment of this """"""""baseline"""""""" will aid interpreting the results of the studies outlined in the preceding paragraphs.
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