HIPPOCAMPAL REGULATION OF THE SURVIVAL AND MORPHOLOGICAL DEVELOPMENT OF LOCUS-CERULEUS NEURONS IN DISSOCIATED CELL-CULTURE

The influence of target structures on neural development, originally d escribed for the peripheral nervous system, has more recently been inv estigated in the central nervous system. We sought to determine whethe r targets regulate the development of the locus coeruleus, with its di ffuse and complex projections in marked contrast to the simpler neural circuits of the peripheral nervous system. Dissociated locus coeruleu s cells were grown alone or with the hippocampus in serum-free, chemic ally defined medium that minimized non-neuronal growth. Coculture with the hippocampus resulted in a significant increase in locus coeruleus tyrosine hydroxylase activity. Elevated tyrosine hydroxylase activity was accompanied by a commensurate increase in the number of tyrosine hydroxylase-immunoreactive cells, suggesting hippocampal enhancement o f locus coeruleus survival. Furthermore, when hippocampal cells were a dded to locus coeruleus dissociates at zero time, or after two days, t yrosine hydroxylase-positive cell number was increased only by hippoca mpal cells added initially, suggesting that the target does indeed fos ter survival. The apparent target enhancement of locus coeruleus survi val seems to be selective since total protein and total neuron number, estimated with neuron-specific enolase immunocytochemistry, were not affected by the hippocampus. Coculture with the hippocampus also incre ased the length and complexity of locus coeruleus cell processes. Neit her the increase in tyrosine hydroxylase cell number nor the changes i n morphology could be attributed to nonspecific effects of the increas ed cell density in cocultures. Our observations thus suggest that the target hippocampus influences the survival and neurite elaboration of afferent locus coeruleus neurons.