We propose to examine, in detail, the role of activity in development of axonal projections in two locales of the mouse brain. The whisker related portion of the principal trigeminal nucleus (nVp) and the somatosensory cortex (barrelfield) will be studied. Methods for demonstrating patterns of afferent termination based on anterograde axonal transport of those based on correlative histochemistry for axonal endings will be used to show the patterns of inputs from whiskers to the brainstem and for the thalamus to the cortex in early postnatal life. These patterns will be characterized qualitatively and quantitatively. Sequences of development in the two regions of the brain after four types of manipulation will be compared with the normal development in the two brain regions. Specifically we will examine the response to: 1) damage to the whiskers in the periphery. 2) Protection from degeneration after whisker lesions with exogenous NGF. 3) Changes with suppression of neural activity of application of the sodium channel blocker tetrodotoxin (TTX) to the periphery and the brain; 4) Alteration with chronic blockade of the NMDA glutamate receptors; and 5) Modifications in animals with chronic sensory deprivation produced by whisker clipping. Our hypothesis is that the patterns of normal development in two parts of the brain require patterned activity to develop normally. The experiments, which interfere with the activity in different groups of peripheral and central axons should uncover altered projections by their pattern and magnitude will shed light on the role of activity in development.
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