FETAL NGF AUGMENTATION PRESERVES EXCESS TRIGEMINAL GANGLION-CELLS ANDINTERRUPTS WHISKER-RELATED PATTERN-FORMATION

In the developing nervous system, precisely patterned connections resu lt from mechanisms that remodel initially diffuse connections. For exa mple, ocular dominance column formation depends upon activity-based co mpetitive interactions. In the developing trigeminal(V) somatosensory system, injury to afferent inputs prevents somatotopic pattern formati on; however, afferent impulse blockade does not. What establishes cent ral V patterns remains unclear. As a first step in assessing the role of neurotrophins in naturally occurring death of V ganglion cells and whisker-related pattern formation, the consequences of prenatal NGF in jections were evaluated. Fetal rats given NGF on both embryonic day (E ) 15 and E18 had 36% more V ganglion cells than normal and lacked whis ker-related patterns in the V brainstem complex at birth and through p ostnatal day 3, as determined by cytochrome oxidase histochemistry. Ra ts injected with NGF on E16 or on E18, or with vehicle had normal gang lion cell numbers and brainstem patterns. Animals injected with antibo dies to NGF or an NGF receptor had reduced ganglion cell numbers and n ormal brainstem patterns. These findings suggest that naturally occurr ing cell death in the V ganglion is neurotrophically regulated and tha t this process impacts upon somatotopic pattern formation in the V bra instem complex. Results of anterograde tracing experiments in NGF-augm ented animals suggest that pattern disruptions are due to an absence o f whisker-related patterning in the central projections of V ganglion cells. Moreover, single primary afferent collaterals labeled by Neurob iotin injections in the V ganglion did not have widespread or unusuall y complex arbors. Thus, NGF may affect V pattern formation by preservi ng or inducing projections to brainstem regions that normally come to lack such projections, such as the spaces normally demarcating neighbo ring whisker primary afferent projections.