The postsynaptic density

doi:10.1016/0166-2236(81)90018-7

Trends in Neurosciences

Volume 4, 1981, Pages 51-53

https://doi.org/10.1016/0166-2236(81)90018-7 Get rights and content

Abstract

Synapses are not only sites of intense physiological activity, but also areas of complex and intriguing morphological specialization. Among the features seen with the electron microscope are a set of structures attached to the junctional membranes of brain synapses. For several years we have been investigating one of the specialized features associated with synaptic junctions, the postsynaptic density (PSD). It is a disc-shaped structure, composed mainly of protein, which is attached to the postsynaptic membrane at synaptic junctions in the brain. Part of our interest in the PSD stems from its location. It seems probable that some of its component molecules, which sit immediately below the site of transmitter release, will prove to be involved in mediating the postsynaptic events ofsynaptic transmission.

References (19)

K. Beaumont et al.
Brain Res.
(1978)
D.J. Grab et al.
J. Biol. Chem.
(1979)
M. Ng et al.
Neurosci.
(1979)
F. Blomberg et al.
J. Cell. Biol.
(1977)
F.E. Bloom et al.
Grab, D. J., Carlin, R. K. and Siekevitz, P. Ann. N.Y. Acad. Sci. (in...
W.B. Huttner et al.
D.T. Kelly et al.
J. Biol. Chem.
(1979)
P.T. Kelly et al.
J. Cell. Biol.
(1978)

There are more references available in the full text version of this article.

Cited by (23)

Changes in hippocampal synapses and learning-memory abilities in a streptozotocin-treated rat model and intervention by using fasudil hydrochloride
2012, Neuroscience
Citation Excerpt :
Several functions, including the regulation of adhesion, control of receptor clustering, and regulation of receptor function, have been proposed for this structure (Siekevits, 1985). It is composed of various proteins, including microtubulin, actin, and fibronin; receptors; enzymes; and secondary messenger systems (Matus, 1981). When some of these molecules are phosphorylated (which alters molecule configuration and, in turn, thickness in the PSD), the functional activity of synapses is inevitably affected (Cohen, 1977).
Fasudil hydrochloride (FH), a Rho kinase inhibitor, is used to treat neurological diseases. This study aims to elucidate the anti-dementia role of FH in Alzheimer's disease. Twenty-four Sprague–Dawley rats were randomly divided into four groups: (1) sham-operated group (control), (2) sham-operated followed by FH administration group (sham+FH), (3) streptozotocin (STZ)-treated group (STZ), and (4) STZ treatment followed by FH administration group (STZ+FH). Rats in the STZ and STZ+FH groups received two divided doses of STZ (1.5 mg/kg) intracerebroventricularly on days 1 and 3, whereas control and sham+FH group rats were given citric acid/sodium citrate buffer. Rats in the sham+FH and STZ+FH groups were then treated intraperitoneally with FH (10 mg/kg) for 4 weeks, and rats in the STZ and control groups were treated with saline. Learning and memory were measured using the Morris water maze test. The synaptic ultrastructure in the CA1 region of the hippocampus was observed using electronic microscopy. The expression of synaptophysin (SYP) was measured using real-time polymerase chain reaction and western blot analyses; the expression of p-LIMK2 and p-cofilin were also detected using western blot analysis. The results indicate that STZ induced deficit in learning/memory, decrease in SYP expression, degeneration in synaptic structures, and increase in the expressions of p-LIMK2 and p-cofilin. These changes were reversed by the administration of FH, suggesting that FH has anti-dementia properties that protect synaptic structure and function. FH induced dephosphorylation (inactivation) of LIMK2 and subsequent dephosphorylation (activation) of cofilin, which may be responsible for the amelioration of neuronal synaptic structure and function.
Methylphenidate improves spatial memory of spontaneously hypertensive rats: Evidence in behavioral and ultrastructural changes
2009, Neuroscience Letters
The purpose of this study was to investigate the effects of methylphenidate on the spatial learning and memory ability and synaptic ultrastructure in the hippocamal CA3 region of the spontaneously hypertensive rat, a rat model of attention deficit hyperactivity disorder. The methylphenidate group and model group were respectively administered the drug (10 mg/kg, i.p.) and saline 30 min before place navigation on 6 consecutive days, a control group of Wistar Kyoto rats were administered saline in the same way. Transmission electron microscopic and imaging analyses were then used to detect and analyze any microstructural changes. The performance of the model rats treated with the drug was the best in the probe test. In addition, three parameters including the length of the active zone, the thickness of the postsynaptic density and the synaptic curvature were measured to show the significant synaptic configuration changes in the methylphenidate group in comparison to the model group. Therefore, these ultrastructural changes in the hippocampal CA3 region may be one of the mechanisms by which methylphenidate improves the spatial memory ability of spontaneously hypertensive rats. The Wistar Kyoto rats showed a significantly decreased latency for finding the platform from the second day in spite of a floating characteristic, while in the probe test, their performance was close to that of the model rats. Finally, morphological evidence suggested the model rats to have a cognitive impairment in comparison to the control group and their better performance was possibly due to the physiological hyper-response of WKY in the water maze tasks.
Contributions of dendritic spines and perforated synapses to synaptic plasticity
1990, Brain Research Reviews
The dynamic nature of synaptic connections has presented morphologists with considerable problems which, from a structural perspective, have frustrated the development of ideas on synaptic plasticity. Gradually, however, progress has been made on concepts such as the structural remodelling and turnover of synapses. This has been considerably helped by the recent elaboration of unbiased stereological procedures. The major emphasis of this review is on naturally occurring synaptic plasticity, which is regarded as an ongoing process in the postdevelopmental CNS. The focus of attention are PSs, with their characteristically discontinuous synaptic active zone, since there is mounting evidence that this synaptic type is indicative of synaptic remodelling and turnover in the mature CNS. Since the majority of CNS synapses can only be considered in terms of their relationship to dendritic spines, the contribution of these spines to synaptic plasticity is discussed initially. Changes in the configuration of these spines appears to be crucial for the plasticity, and these can be viewed in terms of the significance of the cytoskeleton, of various dendritic organelles, and also of the biophysical properties of spines. Of the synaptic characteristics that may play a role in synaptic plasticity, the PSD, synaptic curvature, the spinule, coated vesicles, polyribosomes, and the spine apparatus have all been implicated. Each of these is assessed. Especial emphasis is placed on PSs because of their ever-increasing significance in discussions of synaptic plasticity. The possibility of their being artefacts is dismissed on a number of grounds, including consideration of the results of serial section studies. Various roles, other than one in synaptic plasticity have been put forward in discussing PSs. Although relevant to synaptic plasticity, these include a role in increasing synaptic efficacy, as a more permanent type of synaptic connection, or as a route for the intercellular exchange of metabolites or membrane components. The consideration of many estimates of synaptic density, and of PS frequency, have proved misleading, since studies have reported diverse and sometimes low figures. A recent reassessment of PS frequency, using unbiased stereological procedures, has provided evidence that in some brain regions PSs may account for up to 40% of all synapses. All ideas that have been put forward to date regarding the role of PSs are examined, with particular attention being devoted to the major models of Nieto-Sampedro and co-workers, Carlin and Siekevitz, and Dyson and Jones. New ideas based on recent analysis of quantitative data and of 3-dimensional reconstructions of PSs are discussed. According to these, PSs constitute a separate, and more enduring, component of the synaptic population than NPSs, and have a major role in the maintenance of synaptic efficacy in the mature CNS.
Dendritic RNA and postsynaptic density formation in chick cerebellar synaptogenesis
1988, Neuroscience
In order to investigate the ribosomal origin of the postsynaptic densities during chick cerebellar maturation, a new procedure for synaptosomal preparation was implemented. Samples from embryonic chick cerebellar cortex, from 14 to 20 days of development and young adult chicks, were initially mechanically dissociated after treatment with 1.25% trypsin for 10 min; with this procedure we were able to obtain a dendritic suspension from which an enriched synaptosomal fraction was prepared in a discontinuous Ficoll-sucrose gradient. RNA and protein values determined from the synaptosomal fractions showed the following variations: from 46.3 ng RNA/mg of wet weight at day 14 to 616.7 ng RNA/mg of wet weight at day 18; in young adult chicks, the average was 242 ng RNA/mg of wet weight. RNA/protein ratio varied from 78.9 μg RNA/mg protein at day 16 to 329.8 μg RNA/mg protein at day 18; in the young adult chick, this ratio decreased to 68.4 μg RNA/mg protein.
The highest value of RNA was obtained at day 18 of chick embryo development coinciding with the maximum period of synaptic formation and consequently of the PSDs. These results seem to reinforce the hypothesis of the ribosomal origin of the PSDs.
Postsynaptic density visualized by whole mount electron microscopy
1986, Neuroscience Research
Detergent-unextractable structures of synaptic plasma membrane of rat cerebrum were observed by whole mount electron microscopy. The globular structures were identified as postsynaptic densities (PSDs) from several criteria and appeared to consist of folded strings, to which a number of other molecules might be attached. Some of the globular structures were attached with subsynaptic webs. The structures contained a number of finely striated small strips (10–20 nm wide, 60–100 nm long), parts of which were peeled off from PSD cytoskeletal base by N-lauroyl sarcosinate.
Anatomical distribution and characteristics of [<sup>3</sup>H]muscimol high affinity binding sites in the dorsolateral pontine tegmentum of the rat brain
1985, Neurochemistry International
The pharmacological characterization and fine anatomical distribution of [³H]muscimol high affinity binding sites in the dorsolateral pontine tegmentum (region of locus coeruleus) of the rat was established using biochemical and autoradiographic techniques. On crude synaptosomal membranes obtained from microsamples of locus coeruleus, as well as on frozen sections of the dorsolateral pontine tegmentum, [³H]muscimol binding was saturable, displaced by 80–90% with 10⁻⁵ M GABA or 5·10⁻⁴ M (+) bicuculline, but unchanged in the presence of 10⁻⁴ M nipecotic acid. Analysis of the saturation curve suggested the existence of one population of high affinity binding sites with K_d = 10.5 nM, B_max = 2.15 pmol/mg of crude synaptosomal membrane proteins, and K_d = 14.3 nM, B_max = 0.36 pmol/mg proteins on frozen tissue sections.
Autoradiographic data on ³H ultrofilms evidenced low densities of sites in this region compared to cerebellum or cortex as stated by previous authors. The highest densities of sites were observed in nuclei locus coeruleus and cuneiform, and in central grey. Dorsal and ventral parabrachial, ventral tegmental, motor trigeminal and superior vestibular nuclei exhibited slightly lower densities of sites, and brachium conjunctivum and medial longitudinal fasciculus presented no binding sites. In addition, light microscopy autoradiographic observations revealed [³H]muscimol binding sites between the structures previously quoted. In the locus coeruleus, [³H]muscimol binding sites were not strictly superimposed with cell bodies. These data are discussed in relation with the distribution of GABAergic terminals in the various areas of the dorso-lateral pontine tegmentum.

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^∗: Andrew Matus is a group leader at the Friedrich-Miescher-Institut, P.O. Box 273, 4002 Basel, Switzerland.

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Trends in Neurosciences

ReviewThe postsynaptic density

Abstract

Brain Res.

J. Biol. Chem.

Neurosci.

J. Cell. Biol.

J. Biol. Chem.

J. Cell. Biol.

Review
The postsynaptic density