Synaptic Volume Density

The overall area of the synaptic contact zones present in a defined tissue volume (usually 1 ^m3) accounts for the response capacities of the neural circuitries of a given discrete CNS area. The morphometric term to define such a parameter is surface density (Sv), and, as any other morphological feature of the synaptic junctional areas, it may undergo relevant changes as a consequence of several modulating actions including electrical stimulation, behavioral conditioning, and trophic factors. The Sv value may also be influenced by the intensity and the duration of the stimulus as well as the level of plasticity of the specific CNS zone analyzed (Desmond and Levy, 1986). Over the past two decades, the reliability of the results obtained in estimating the Sv value in different experimental models has been continuously challenged by the progressive advancements in the accuracy of the morphometric methods that are presently applied by computer-assisted image analyzers. Namely, sampling and counting of synapses have been refined repeatedly, both by improved staining methods as well as unbiased procedures, which resulted in a better estimation of the Sv value. Several converging data are now supporting that in a given CNS zone, an adequate-to-function value of Sv is maintained according to the experiential framework of each individual. During the maturation of the CNS, an optimal Sv value is attained through a balance between selective pruning of the redundant synaptic contacts and the reinforcement of those junctional areas that have undergone frequent stimulation and physiological response adaptation (Purves and Lichtman, 1980). Although the adult, fully differentiated CNS retains a high level of plasticity, significant modifications of the experience-stabilized neural circuits do not easily occur since the maintenance of Sv constancy constitutes an important prerequisite to preserve the experience-driven fine tuning of select neuronal networks representing the structural basis of acquired skills (Hillman and Chen, 1984). Memory and learning abilities also rely on adequate Sv values, since an extended network of contacts provides a micro-anatomical structural basis of these important functions. Different physiological mechanisms and biological determinants contribute to maintain constant Sv value by modulating number and size of the synaptic contact zones present in selected CNS areas, and this has led to propose the reasonable assumption of the existence of a close relationship among these three parameters of the synaptic ultrastructure. Namely, although quantitatively measured by independent methodological approaches and analysis procedure, it appears that S and Nv are inversely correlated and that the final outcome of this balance is the Sv value. Thus, while each of these parameters provides specific information on single aspects of synaptic morphology, when taken together per experimental sample, they constitute a reliable index of synaptic plasticity from a morpho-functional point of view. Accordingly, functional decay may result from an imbalance among Nv, S, and Sv leading to altering the maintenance of the synaptic ultrastructural homeostasis. In humans, Sv has been found to be significantly decreased in the old hippocampus, whereas an age-related, not significant reduction of Sv affects the cerebellar cortex. In AD patients a further decrease of Sv occurs only in the hippocampus, probably in connection with the consistent presence in this CNS zone of senile plaques, a typical hallmark of this disease (Bertoni-Freddari et al., 1990, 1996). The Sv decline in physiological aging and AD appears to be due to the numeric loss of contacts (Nv) since the average area (S) of the surviving contacts is significantly enlarged. Although it can reasonably be supported that synaptic enlargement strengthens information processing by the release of more neurotransmitters and the activation of more receptors, this reinforcement of the surviving contacts appears to be less functional than the fine-tuning of the neural networks provided by the higher density of smaller junctional areas typically found in adult individuals.

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Blood Pressure Health

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