While neuroscience has made rapid advances with regard to the molecular biology of the brain, the lack of knowledge at more molar levels has sometimes been disarmingly surprising, as in the belated recognition of post-developmental neurogenesis in at least some regions of the adult brain. Our knowledge of the plasticity of nonneural cells in the CNS is even more limited than our knowledge of neuronal plasticity, aside from studies of single gene mutations and pathology. It is clear from our work that astrocytes, oligodendrocytes and vascular tissue exhibit morphological plasticity in response to experience that often quantitatively equals or exceeds the plasticity seen in neuronal measures such as dendritic field dimensions and synapse numbers. We have found, for example, dramatic increases in myelination of the corpus callosum in adult rats exposed to a complex environment. There is abundant evidence that these supporting cells can affect information processing by neurons in significant ways such as modulating synaptic efficacy in response to propagated calcium waves in astrocytes, selectively increasing axonal conduction and altering gene expression patterns in the neurons they envelop. Moreover, while there is controversy regarding post-developmental neurogenesis in regions outside of the dentate gyrus and basal forebrain-olfactory bulb, there is wide agreement that glial and vascular tissue continue to proliferate into adulthood in at least most brain regions in which this has been investigated. Indeed a principal difficulty in demonstrating neurogenesis has been differentiating it from proliferation of glial and vascular tissues. Yet we know very little about proliferation and plasticity of these support tissues and how they might contribute to brain function. This research proposes to examine the effects of experience upon neurogenesis and non-neuronal cells of the cerebral cortex, to sort out regulatory effects upon proliferation and hypertrophy and the neural mechanisms mediating these regulatory effects. The experiential manipulation to be used, exposure to a complex physical and social environment, has dramatic effects on cerebral cortical organization, nearly doubling, for example, vascular volume per neuron, compared to that of rats reared in individual laboratory cages. Studies are proposed to investigate the effects of experience upon the proliferation and modification of oligodendrocytes, astrocytes, microglia and vasculature in the context of experience effects upon the plasticity of neurons and their synapses, using DNA-labeling, protein-impregnating and optical and electron microscopic methods.
Showing the most recent 10 out of 73 publications
