Reciprocal relationship between size of postsynaptic densities and their number: constancy in contact area.

Plasticity in the size of postsynaptic membrane specializations (postsynaptic densities) was analyzed by quantitation following lesioning of parallel fiber afferent axons to Purkinje cells in the cerebellum. Double sectioning of parallel fibers in the same folium as well as longitudinal undercutting of the molecular layer to destroy granule cells and their parallel fibers were used to produce various levels of afferent reduction to Purkinje cells. The length of profiles of membrane densities was measured utilizing semi-automated, computer-electron microscopy and the number of synapses was determined from their volume density and changes in volume estimated from cortical thickness. Correlation between the number of synapses on Purkinje cells and their average contacts area revealed a reciprocal relationship throughout a range of 0-67% reductions in parallel fiber synapses. Larger reduction levels had a progressive decrease in average size of contacted postsynaptic densities and an accompanying increase in the number of vacant postsynaptic specializations. Total absence of parallel fibers resulted in nearly all vacant sites on spines (except for a few connections with boutons having irregular shaped vesicles). These vacant sites were, on the average, only half the size of controls but their number was approximately double the control amount. This study confirms that location and size of synapses are not permanent and that plasticity in size of contacts allows reorganization in circuitry to compensate alterations in the number of inputs following a number of perturbations. The finding of a reciprocal relationship indicates that total contact area on Purkinje cells remained relatively constant throughout the entire range of reductions in the number of afferents. A 'constancy principle for total postsynaptic contact area' is envisioned to stabilize functional aspects of circuitry during developmental organization and to direct compensation following reduction in pre- or postsynaptic neurons from environmental effects or attrition in aging. Constancy in target area provides a realm under which the size of individual synapses can be modified as functional adaptations in circuitry even without changes in the number of connections.