Our aim is to understand the mechanisms operating during pattern formation in the trigeminal (V) system. One mechanism thought to be important in this process is neuronal activity. However, recent experiments funded by this grant showed that blockade of cortical activity has no appreciable effect upon normal thalamocortical pattern formation. In view of previous findings from other systems, these results are quite surprising.
The aim of the studies proposed in this renewal application is to determine the reason for this apparent difference between the conditions necessary for the normal development of the rat's V neuraxis and neuronal connections in many portions of the brains of this and other species. Our working hypothesis is that neuronal activity plays little role in V pattern formation in the rat because the normal ontogeny of this system occurs when activity levels are very low and thus incapable of influencing refinement of projections. It therefore follows that abnormally increased activity should alter V thalamocortical development and that normal activity may play a substantial role in the refinement of V cortico-cortical connections which develop at postnatal ages when levels of patterned activity are considerably higher. We will carry out four types of experiments to test this hypothesis: 1) We will directly assess levels and patterns of neuronal activity in the developing V system by recording from V ganglion cells and from neurons in V nucleus principalis (PrV), the ventral posteromedial thalamus (VPM), and primary somatosensory cortex (S-1) in unanesthetized in vivo preparations. With the exception of limited data from anesthetized animals and a small number of in vitro studies, we have no information that addresses this question in any portion of the developing V system. 2) We will employ intracellular recording from in vitro preparations to determine the ages at which ascending functional connections are made at each level of the V neuraxis. 3) We will interfere with activity in the developing V system by induction of abnormal patterns rather than blockade. We will create foci of abnormal activity by placement of penicillin-impregnated, slow-release polymer implants in the developing cortex. If activity is capable of modifying pattern formation, the experimental induction of foci of high and correlated activity should alter thalamocortical development. 4) We will assess the effects of activity blockade upon the development of cortico-cortical pathways that mature postnatally when levels of patterned activity in the developing cortex more closely approximate those observed in adult animals. Here, TTX implants will be used to silence cortex, and development of the callosal and associational projections of the primary somatosensory cortex will be evaluated using both anterograde and retrograde tracing techniques.
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