The research proposed here will make quantitative measures of dendrites in descriptive study in aging human ventral cochlear nucleus and in experimental study in rodent entorhinal cortex. These studies are designed to test hypotheses regarding the regulation of dendritic extent in aging brain by events in the local extra-cellular environment: that loss of input promotes dendritic regression, and the death of neurons promotes dendritic proliferation in surviving, neighboring neurons. The human ventral cochlear nucleus presents a model of loss of input from neurons in the spiral ganglion. In the rodent entorhinal cortex death of a selected sub-population of neurons will be produced by suicide transport from the molecular layer of the dentate gyrus to layer II stellate neurons. Dendritic trees of surviving, neighboring superficial pyramidal neurons and layer II stellates (the same class killed) will be quantified. Measures from these experimental brains will be compared to control brains from same age animals to determine whether neuron death produced experimentally promotes dendritic proliferation in surviving neighboring neurons, and whether any effect seen is restricted to the same class of neuron that was killed. Details of the distribution of dendritic trees in entorhinal cortex will be exploited to distinguish between two classes of possible mechanisms: reduced dendritic competition for afferent supply or, elaboration of a neuronotrophic factor. Also in rodent entorhinal cortex we will determine whether the generally accepted dendritic regression produced by lesions of afferent supply becomes more severe in aged animals. This will be explored by making lesions in the nucleus reuniens thalami (a major input to entorhinal cortex) in animals at several ages and determining the effect of this partial deafferentation on dendritic trees as a function of age.
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