Synaptic remodelling during development and maturation: Junction differentiation and splitting as a mechanism for modifying connectivity

doi:10.1016/0165-3806(84)90084-1

Developmental Brain Research

Volume 13, Issue 1, March 1984, Pages 125-137

https://doi.org/10.1016/0165-3806(84)90084-1 Get rights and content

Abstract

Morphological variation of the synaptic active zone during later development and maturation (15–224 days) has been studied in the molecular layer of the rat occipital cortex. Both E-PTA stained and osmicated tissue have been used.

In the E-PTA stained material the degree of specialization of the presynaptic thickening is directly related to junction length. Junctions with well-developed dense projections (Types A and B) are longest and continue to increase in length with maturation, suggesting that active remodelling of the synaptic apposition is an ongoing process. The presence of perforated junctions, possessing two or more regions with specializations of different maturity and different curvature, raises the possibility that these junctions may arise by the addition and differentiation of new paramembranous material at an existing junction.

In osmicated tissue, presynaptic terminals possessing multiple active zones have been quantitated. The maturational increase in number of simple perforated junctions (Type 1), is paralleled by a smaller increase in the number of multiple perforated junctions (Type 2). A spine apparatus is frequently observed in these perforated terminals, suggesting that it is intimately involved in the reorganization. The direction of curvature of the closely apposed junctions is predominantly negative (indenting the postsynaptic process). Other types of arrangement, with separate postsynaptic processes, are described (Types 3–5), and micrographs suggestive of sequential stages in pre- and postsynaptic terminal splitting are presented. The total length of the postsynaptic thickening of perforated terminals is twice the mean synaptic length of non-perforated terminals, again suggestive that duplication of the active zone may have occurred.

Division of existing synaptic terminals by duplication and subsequent splitting would readily account for the increased dendritic spinal numbers seen in Golgi preparations of animals raised under enriched conditions. This would be a straight-forward mechanism by which reinforcement of neuronal connections could occur in response to use.

References (44)

A.M. Adinolfi
The organization of paramembranous densities during postnatal maturation of synaptic junctions in the cerebral cortex
Exp. Neurol.
(1972)
G.K. Aghajanian et al.
The formation of synaptic junctions in developing rat brain — a quantitative EM study
Brain Res.
(1967)
S.J. Buell et al.
Quantitative evidence for selective dendritic growth in normal human ageing but not in senile dementia
Brain Res.
(1981)
M.B. Bunge et al.
The onset of synapse formation in spinal cord cultures as studied by electron microscopy
Brain Res.
(1967)
B.G. Cragg
The development of synapses in kitten visual cortex during visual deprivation
Exp. Neurol.
(1975)
S.E. Dyson et al.
Quantitation of terminal parameters and their interrelationships in maturing central synapses: a perspective for experimental studies
Brain Res.
(1980)
L. Ganz et al.
The selective effect of visual deprivation on receptive field shape determined neurophysiologically
Exp. Neurol.
(1968)
W.T. Greenough et al.
Pattern of dendritic branching in occipital cortex of rats reared in complex environments
Exp. Neurol.
(1973)
R.L. Holloway
Dendritic branching: some preliminary results of training and complexity in rat visual cortex
Brain Res.
(1966)
J.S. Lund et al.
The effects of varying periods of visual deprivation on synaptogenesis in the superior colliculus of the rat
Brain Res.
(1972)

M.A. Matthews et al.

Electron microscopy of the development of synaptic patterns in the ventrobasal complex of the rat

Brain Res.

(1977)

L. Muller et al.

The postnatal development of the presynaptic grid in the visual cortex of rabbits and the effects of dark-rearing

Brain Res.

(1981)

G. Raisman

Neuronal plasticity in the septal nuclei of the adult rat

Brain Res.

(1969)

L.T. Rutledge et al.

Morphological changes in pyramidal cells of mammalian neocortex associated with increased use

Exp. Neurol.

(1974)

M.L. Schwartz et al.

Long-lasting behavioural and dendritic spine deficits in the monocularly deprived albino rat

Exp. Neurol.

(1980)

D.N. Spinelli et al.

Early experience effect on dendritic branching in normally reared kittens

Exp. Neurol.

(1980)

S.B. Tarrant et al.

Postsynaptic membrane and spine apparatus: proximity in dendritic spines

Neurosci. Lett.

(1979)

H.B.M. Uylings et al.

Effects of differential environments on plasticity of dendrites of cortical pyramidal neurons in adult rats

Exp. Neurol.

(1978)

G. Vrensen et al.

The presynaptic grid: a new approach

Brain Res.

(1980)

G. Vrensen et al.

Changes in size and shape of synaptic connections after visual training: an ultrastructural approach of synaptic plasticity

Brain Res.

(1981)

R.W. West et al.

Effect of environmental complexity on cortical synapses of rats: preliminary results

Behav. Biol.

(1972)

M. Armstrong-James et al.

Quantitative studies of postnatal changes in synapses in rat superficial motor cerebral cortex

Z. Zellforsch.

(1970)

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^∗: Present address: Department of Anatomy, University of Otago, P.O. Box 913, Dunedin, New Zealand

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Research reportSynaptic remodelling during development and maturation: Junction differentiation and splitting as a mechanism for modifying connectivity

Abstract

Exp. Neurol.

Brain Res.

Brain Res.

Brain Res.

Exp. Neurol.

Brain Res.

Exp. Neurol.

Exp. Neurol.

Brain Res.

Brain Res.

Brain Res.

Brain Res.

Brain Res.

Exp. Neurol.

Exp. Neurol.

Exp. Neurol.

Neurosci. Lett.

Exp. Neurol.

Brain Res.

Brain Res.

Behav. Biol.

Quantitative studies of postnatal changes in synapses in rat superficial motor cerebral cortex

Z. Zellforsch.

Research report
Synaptic remodelling during development and maturation: Junction differentiation and splitting as a mechanism for modifying connectivity