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.

[1]  M. Murray,et al.  Target regulation of synaptic number in the compressed retinotectal projection of goldfish , 1982, The Journal of comparative neurology.

[2]  A. Smolen.  Postnatal development of ganglionic neurons in the absence of preganglionic input: morphological observations on synapse formation. , 1981, Brain research.

[3]  D. Hillman,et al.  Giant spines and enlarged synapses induced in Purkinje cells by malnutrition , 1980, Brain Research.

[4]  B. Cragg.  Changes in Visual Cortex on First Exposure of Rats to Light: Effect on Synaptic Dimensions , 1967, Nature.

[5]  B. Cragg.  The effects of vision and dark-rearing on the size and density of synapses in the lateral geniculate nucleus measured by electron microscopy. , 1969, Brain research.

[6]  C. Giuli,et al.  A quantitative morphometric study of synapses of rat cerebellar glomeruli during aging , 1980, Mechanisms of Ageing and Development.

[7]  E. Fifková.  The effect of monocular deprivation on the synaptic contacts of the visual cortex. , 1969, Journal of neurobiology.

[8]  B. Cragg.  The development of cortical synapses during starvation in the rat. , 1972, Brain : a journal of neurology.

[9]  E. Weibel.  Stereological Methods. Practical methods for biological morphometry , 1979 .

[10]  D. Hillman,et al.  Marked reorganization of Purkinje cell dendrites and spines in adult rat following vacating of synapses due to deafferentation , 1982, Brain Research.

[11]  C. Cotman,et al.  A new type of lesion-induced synaptogenesis: I. Synaptic turnover in non-denervated zones of the dentate gyrus in young adult rats , 1981, Brain Research.

[12]  E. Bennett,et al.  Quantitative synaptic changes with differential experience in rat brain. , 1971, The International journal of neuroscience.

[13]  Gary Lynch,et al.  An electron microscopic study of lesion-induced synaptogenesis in the dentate gyrus of the adult rat. II. Reappearance of morphologically normal synaptic contacts , 1976, Brain Research.

[14]  E. Fifková.  Changes of axosomatic synapses in the visual cortex of monocularly deprived rats. , 1970, Journal of neurobiology.

[15]  D. Hillman,et al.  Vulnerability of cerebellar development in malnutrition—II. Intrinsic determination of total synaptic area on Purkinje cell spines , 1981, Neuroscience.

[16]  W. Bondareff,et al.  Loss of synapses in the cerebellar cortex of the senescent rat. , 1979, Journal of gerontology.

[17]  Gary Lynch,et al.  An electron microscopic study of lesion-induced synaptogenesis in the dentate gyrus of the adult rat. I. Magnitude and time course of degeneration , 1976, Brain Research.

[18]  C. Sandri,et al.  Ultrastructural effects of 4-aminopyridine on the presynaptic membrane in the rat spinal cord , 1979, Brain Research.

[19]  C. Sandri,et al.  Membrane associated particles of the presynaptic active zone in rat spinal cord. A morphometric analysis , 1977, Brain Research.

[20]  P. Siekevitz,et al.  Form of the postsynaptic density. A serial section study , 1978, The Journal of cell biology.

[21]  G. Vrensen,et al.  The presynaptic grid: A new approach , 1980, Brain Research.

[22]  E. Bennett,et al.  Difference in occipital cortical synapses from environmentally enriched, impoverished, and standard colony rats , 1975, Journal of neuroscience research.

[23]  D. Jones,et al.  Quantitative ultrastructural changes in rat cortical synapses during early-, mid- and late-adulthood , 1982, Brain Research.

[24]  L. Autilio‐Gambetti,et al.  Synapses and malnutrition: quantitative ultrastructural study of rat cerebral cortex. , 1974, Experimental neurology.

[25]  R. Llinás,et al.  Direct analysis of nervous system ultrastructure by computer control of STEM. , 1980, Scanning electron microscopy.

[26]  G. Raisman,et al.  A quantitative ultrastructural and biochemical analysis of the process of reinnervation of the superior cervical ganglion in the adult rat. , 1974, Brain research.

[27]  P. Rakić,et al.  Organization of cerebellar cortex secondary to deficit of granule cells in weaver mutant mice , 1973, The Journal of comparative neurology.

[28]  G. Vrensen,et al.  The postnatal development of the presynaptic grid in the visual cortex of rabbits and the effect of dark-rearing , 1981, Brain Research.

[29]  John D. Pettigrew,et al.  Ultrastructural changes in kitten visual cortex after environmental modification , 1974 .

[30]  Quantitative effects of methylazoxymethanol acetate on purkinje cell dendritic growth , 1978, Brain Research.

[31]  Y. Geinisman,et al.  Loss of synapses in the dentate gyrus of the senescent rat. , 1976, The American journal of anatomy.

[32]  G. Vrensen,et al.  Quantitative aspects of the synaptic organization of the superior colliculus in control and dark-reared rabbits , 1977, Brain Research.

[33]  H. M. Dembitzer,et al.  AN ELECTRON MICROSCOPIC STUDY OF CYCASIN‐INDUCED CEREBELLAR ALTERATIONS , 1972, Journal of neuropathology and experimental neurology.

[34]  G. Vrensen,et al.  Changes in size and shape of synaptic connections after visual training: An ultrastructural approach of synaptic plasticity , 1981, Brain Research.

[35]  D. Jones,et al.  Synaptic junctions in undernourished rat brain—An ultrastructural investigation , 1976, Experimental Neurology.

[36]  R. Llinás,et al.  Neuronal circuit reorganization in mammalian agranular cerebellar cortex. , 1973, Journal of neurobiology.

[37]  W. Greenough,et al.  Effect of environmental complexity on cortical synapses of rats: preliminary results. , 1972, Behavioral biology.

[38]  M. Abercrombie.  Estimation of nuclear population from microtome sections , 1946, The Anatomical record.

[39]  Dean E. Hillman,et al.  Plasticity of the parallel Fiber-Purkinje cell synapse by spine takeover and new synapse formation in the adult rat , 1982, Brain Research.

[40]  J. Altman,et al.  Experimental reorganization of the cerebellar cortex. I. Morphological effects of elimination of all microneurons with prolonged x‐irradiation started at birth , 1972, The Journal of comparative neurology.

[41]  E. Weibel.  Practical methods for biological morphometry , 1979 .

[42]  M. Berry,et al.  The effects of undernutrition on Purkinje cell dendritic growth in the rat , 1978, The Journal of comparative neurology.

[43]  W. Greenough,et al.  Subsynaptic plate perforations: changes with age and experience in the rat. , 1978, Science.

[44]  C. Sotelo.  Permanence and fate of paramembranous synaptic specializations in "mutants" experimental animals. , 1973, Brain research.

[45]  W. Greenough,et al.  Synaptic contact curvature: effects of differential rearing on rat occipital cortex. , 1982, Brain research.

[46]  D. D. De Groot,et al.  The effect of dark rearing and its recovery on synaptic terminals in the visual cortex of rabbits. A quantitative electron microscopic study. , 1974, Brain research.

[47]  C. Cotman,et al.  A new type of lesion-induced synaptogenesis: II. The effect of aging on synaptic turnover in non-denervated zones , 1981, Brain Research.

[48]  D. Jones,et al.  Some effects of undernutrition of synaptic development — a quantitative ultrastructural study , 1976, Brain Research.

[49]  R. Llinás,et al.  Climbing fiber deafferentation: Its action on Purkinje cell dendritic spines , 1975, Brain Research.

[50]  R. Perkins,et al.  The effect of postnatal undernutrition on the development of the mouse Purkinje cell dendritic tree , 1979, Brain Research.

[51]  B. Cragg,et al.  Estimation of the number of synapses in a volume of nervous tissue from counts in thin sections by electron microscopy , 1974, Journal of neurocytology.

[52]  J. Changeux,et al.  Anatomical, physiological and biochemical studies of the cerebellum from Reeler mutant mouse. , 1977, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[53]  D. Woodward,et al.  Malnutrition-induced alterations of developing Purkinje cells , 1977, Experimental Neurology.

[54]  D. Hillman,et al.  Vulnerability of cerebellar development in malnutrition—I. Quantitation of layer volume and neuron numbers , 1981, Neuroscience.

[55]  J. Pysh,et al.  Exercise during development induces an increase in Purkinje cell dendritic tree size. , 1979, Science.

[56]  C. Sotelo.  Anatomical, physiological and biochemical studies of the cerebellum from mutant mice. II. Morphological study of cerebellar cortical neurons and circuits in the weaver mouse , 1975, Brain Research.

[57]  P. Rakić,et al.  Mechanisms of cortical development: a view from mutations in mice. , 1978, Annual review of neuroscience.

[58]  Plasticity of synaptic size with constancy of total synaptic contact area on Purkinje cells in the cerebellum. , 1981, Progress in clinical and biological research.

[59]  W Dames,et al.  Induction and maintenance of free postsynaptic membrane thickenings in the adult superior cervical ganglion , 1979, Journal of neurocytology.