This is the result (so far) of the responses from readers of the newsgroup,
my own Medline searches and the follwoup searches. I have included the
complete references and abstracts. It is about ten printed pages. This is a
highly selective group of references culled from several hundred others
that surfaced during the Medline search. Thanks to all who answered and if
anyone has any other suggestions please forward them my way.
Thomsa
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19. Sanyal S; Hawkins RK; Jansen HG; Zeilmaker GH.
Compensatory synaptic growth in the rod terminals as a sequel to partial
photoreceptor cell loss in the retina of chimaeric mice.
Development, 1992 Mar, 114(3):797-803.
(UI: 92315923)
Abstract: In the retina of chimaeric mice of rd and wild-type genotypic
combination, selective loss of rd/rd photoreceptor cells, after initial
development, leads to a mosaic retina with variable amounts of normal
photoreceptor cells present over the retinal surface. In some of the rod
terminals of these retinas the synaptic complexes with the second order
retinal neurons are seen to contain multiple synaptic ribbons and an
increased number of profiles of the postsynaptic elements. These changes
are observed only in the rod terminals and not in the cone pedicles.
Computer aided three-dimensional reconstruction of the altered synapses
shows that these changes result from an increase in the number of synaptic
sites, characterized by multiplication of the synaptic ribbons and
enlargement of the second order neuronal processes. A quantitative analysis
of such synapses, based on serial electron micrographs, shows that these
are most frequently located in the retinal regions of the chimaeric
individuals that have suffered maximum photoreceptor cell loss. Thus
synaptic growth appears to take place as a reaction to the reduction of
afferent input to the postsynaptic components. These findings demonstrate
persistent synaptic plasticity in the rod terminals of mammalian retina
during the maturational phase of late postnatal development. Compensatory
synaptic growth in the rod terminals, as recorded here, can have important
implications for the maintenance of visual sensitivity in the diseased or
ageing retina.
20. Jansen HG; Sanyal S.
Synaptic plasticity in the rod terminals after partial photoreceptor cell
loss in the heterozygous rds mutant mouse.
Journal of Comparative Neurology, 1992 Feb 1, 316(1):117-25.
(UI: 92242560)
Abstract: In the retina of mice heterozygous for the retinal degeneration slow
gene (rds/+) the photoreceptor cells, both rods and cones, develop abnormal
outer segments but establish normal synaptic contacts. The other retinal
layers also show normal structural organization. Starting from the age of 2
months, a very slow loss of photoreceptor cells progresses throughout life.
As a result, the photoreceptor cell population in the retina of the
affected mice is reduced to less than half at the age of 9-18 months. In
some of the surviving rod terminals during this period, an increase in the
number of synaptic ribbons is recorded. At the same time, the profiles of
processes originating from the second order neurons and participating in
these synapses are also increased in number so that the multiple ribbons
appear as centres of multiple synaptic sites. Morphometric measurements of
the perimeter of the synaptic profiles in rod terminals show a significant
increase in the rds/+ retina over that of the control retina. Observations
based on serial electron microscopy indicate that multiple synaptic sites
are developed while the number of the second order neuronal processes,
entering the terminals, remains unchanged. The frequency of terminals with
multiple synapses in the rds/+ retina increases with progressive
photoreceptor cell loss. Similar changes do not occur in the terminals of
the cones. It is postulated that loss of some rod photoreceptor cells
within a group that is presynaptic to common bipolars or horizontal cells
results in partial deafferentation which in turn stimulates the growth of
the remaining synaptic elements. The possible compensatory effect and
functional significance of such synaptic growth are discussed.
2. Bailey CH; Kandel ER.
Structural changes accompanying memory storage.
Annual Review of Physiology, 1993, 55:397-426.
(UI: 93221111)
Pub type: Journal Article; Review; Review, Academic.
4. Bailey CH; Chen M; Keller F; Kandel ER.
Serotonin-mediated endocytosis of apCAM: an early step of learning-related
synaptic growth in Aplysia.
Science, 1992 May 1, 256(5057):645-9.
(UI: 92263096)
Abstract: The long-term facilitation of synaptic efficacy that is induced by
serotonin in dissociated cell cultures of sensory and motor neurons of
Aplysia is accompanied by the growth of new synaptic connections. This
growth is associated with a down-regulation in the sensory neuron of
Aplysia cell adhesion molecules (apCAMs). To examine the mechanisms of this
down-regulation, thin-section electron microscopy was combined with
immunolabeling by gold-conjugated monoclonal antibodies specific to apCAM.
Within 1 hour, serotonin led to a 50% decrease in the density of
gold-labeled complexes at the surface membrane of the sensory neuron. This
down-regulation was achieved by a heterologous, protein synthesis-dependent
activation of the endosomal pathway, which leads to internalization and
apparent degradation of apCAM. The internalization is particularly
prominent at sites where the processes of the sensory neurons contact one
another and may act there to destabilize process-to-process contacts that
normally inhibit growth. In turn, the endocytic activation may lead to a
redistribution of membrane components to sites where new synapses form.
3. Lopez HS; Burger B; Dickstein R; Desmond NL; Levy WB.
Associative synaptic potentiation and depression: quantification of
dissociable modifications in the hippocampal dentate gyrus favors a
particular class of synaptic modification equations.
Synapse, 1990, 5(1):33-47.
(UI: 90141387)
Abstract: This report further characterizes associative long-term synaptic
modification of the ipsilateral and contralateral synapses formed by the
bilateral entorhinal cortical (EC) projection to the dentate gyrus (DG).
The experimental model is the anesthetized hooded rat. The quantitative
results qualify this system as a model for studying the rules of
associative synaptic modification formulated in terms of individual
synapses. Bilateral DG microelectrodes recorded both ipsilateral and
contralateral EC-DG responses before and after brief, high-frequency EC
conditioning stimulation. The weak contralateral pathway received
high-frequency conditioning before, during, or after similar conditioning
of the strong, converging ipsilateral pathway. Statistical analyses
revealed two types of significant, dissociated synaptic modifications,
which depend on the relationship of the ipsilateral and contralateral
afferents. First, contralateral EC-DG responses potentiated or depressed
when the converging ipsilateral responses concurrently either potentiated
or remained unchanged. Second, contralateral EC-DG responses potentiated,
depressed, or showed no change when the collateral ipsilateral responses
concurrently either potentiated or remained unchanged. Correlation and
contingency table analyses indicated that changes in the contralateral
synaptic responses are not well predicted by changes at either neighboring
synapses of the converging ipsilateral pathway or at synapses of the
collateral ipsilateral pathway. The contingencies of associated pre- and
postsynaptic activation determined by the conditioning paradigm, however,
accurately predicted the altered synaptic responses of both ipsilateral and
contralateral EC-DG pathways. The results imply that associative synaptic
modification in the EC-DG system is specific to individual synapses and
requires both appropriate presynaptic and postsynaptic activation. Because
this system provides suitable controls for nonspecific effects of
conditioning stimulation and because modification of neighboring synapses
is dissociable, the EC-DG system can be used to study further those rules
of activity-dependent associative modification that are formulated in terms
of individual synapses. The discussion briefly considers published rules of
synaptic modification, pointing out several rules that are not consistent
with the experimental observations and one that agrees with the present
results.
4. Desmond NL; Levy WB.
Morphological correlates of long-term potentiation imply the modification
of existing synapses, not synaptogenesis, in the hippocampal dentate
gyrus.
Synapse, 1990, 5(2):139-43.
(UI: 90176614)
Abstract: This report evaluates two morphological markers of synaptogenesis
following the induction of long-term potentiation (LTP) in the dentate
gyrus of the anesthetized rat. These two morphological features,
polyribosomes and multiple synaptic contacts, are known to increase in
number with synaptogenesis in the mature hippocampus. The analysis focused
on the middle third of the dentate molecular layer. As shown previously,
this is the region of primary synaptic activation in our
electrophysiological protocol and the region of localized morphological
changes with LTP. Here the incidence of a polyribosome at the base of a
dendritic spine declined 57% with LTP. In addition, the number of multiple
synaptic contacts decreased 18% there with LTP. Both decreases were more
pronounced immediately following conditioning stimulation than at later
intervals. Because both morphological features decrease with LTP but
increase with synaptogenesis, the data do not support the hypothesis that
new synapses form with LTP. Instead, the data add further support to the
view that the strengthening of existing excitatory synapses underlies LTP.
1. Chang FL; Hawrylak N; Greenough WT.
Astrocytic and synaptic response to kindling in hippocampal subfield CA1.
I. Synaptogenesis in response to kindling in vitro.
Brain Research, 1993 Feb 19, 603(2):302-8.
(UI: 93214811)
Abstract: Early morphological events associated with the genesis of
epileptiform activity are essentially unknown, despite significant progress
on morphological correlates of potentially related plastic neural
phenomena. Hippocampal area CA1 shows the capacity to generate epileptiform
bursting activity after certain patterns of electrical stimulation. Using
an in vitro slice kindling preparation, we found increases in the numbers
(areal densities) of shaft and sessile spine synapses in hippocampal
subfield CA1 within minutes following the establishment of stable
afterdischarges. These data strongly suggest that synaptogenesis is
associated with the early stages of epilepsy formation.
2. Hawrylak N; Chang FL; Greenough WT.
Astrocytic and synaptic response to kindling in hippocampal subfield CA1.
II. Synaptogenesis and astrocytic process increases to in vivo kindling.
Brain Research, 1993 Feb 19, 603(2):309-16.
(UI: 93214812)
Abstract: Astrocytic glia are important for maintaining synaptic function
during physiological activity. Recent hypotheses concerning epilepsy
suggest a role for astrocytes in the control of neuronal excitability and
in pathogenesis. This report provides morphological evidence that the
periodic electrical stimulation used in the kindling model of epilepsy
induces astrocytic hypertrophy and an increase in shaft synapse density in
the CA1 region of the hippocampus. The Schaffer collateral pathway in the
stratum radiatum of CA1 of five pairs of rats was kindled in vivo. Control
animals received the same number of stimulations at a lower intensity and
frequency. The animals were killed 24-48 h after reaching the criterion of
five generalized seizures, and the brains were examined by electron
microscopy. Kindling produced a 37% and 33% increase in the volume fraction
of astrocytic processes in the middle and distal portions, respectively, of
the s. radiatum in CA1. In the same tissue, the number (areal density) of
shaft synapses was increased 25% in the s. radiatum of animals exhibiting
generalized seizures. On the other hand, the areal density of degenerating
synapses in both kindled and control animals was low and not significantly
different. These results suggest that both synaptogenesis and hypertrophy
of astrocytes contribute to an early stage of epileptogenesis when
degenerative changes of the sort that might induce gliosis were not
prominent in the tissue under study.
di con sho abs 26,29,31,35,41,51,57,65,79,83,87,88,93,97,111,112
26. Lisman JE; Harris KM.
Quantal analysis and synaptic anatomy--integrating two views of
hippocampal plasticity.
Trends in Neurosciences, 1993 Apr, 16(4):141-7.
(UI: 93227289)
Pub type: Journal Article; Review; Review, Tutorial.
Abstract: The excitatory synapses onto CA1 pyramidal cells have become a model
system for understanding the activity-dependent changes in synapses that
underlie learning and memory. Here we examine physiological and anatomical
results that are relevant to understanding the mechanisms of synaptic
transmission and plasticity at these synapses. Three main points are
discussed. First, quantal analysis indicates a large heterogeneity of
postsynaptic efficacies for different synapses on the same cell.
Reconstructions from electron microscopy show that synapse size is also
highly heterogeneous. Reasons for suspecting a relationship between
synaptic size and efficacy are discussed. Second, physiological evidence
indicates that the changes during long-term potentiation are both pre- and
postsynaptic. Similarly, several lines of anatomical evidence suggest that
plasticity affects the structure of both the pre- and postsynaptic
elements. The detailed registration of structures across the synapse and
the physical linkage between pre- and postsynaptic elements suggest a
'structural unit hypothesis' for coordinating pre- and postsynaptic
modifications. Third, quantal analysis indicates that stimulation of a
single axon can release multiple quanta. Anatomical evidence shows that
cell pairs can be connected by multiple synapses, suggesting that multiple
quanta may be released at independent sites. These results raise the
possibility that one component of synaptic plasticity is mediated by
changes in the number of functional synaptic sites.
29. Hawrylak N; Chang FL; Greenough WT.
Astrocytic and synaptic response to kindling in hippocampal subfield CA1.
II. Synaptogenesis and astrocytic process increases to in vivo kindling.
Brain Research, 1993 Feb 19, 603(2):309-16.
(UI: 93214812)
Abstract: Astrocytic glia are important for maintaining synaptic function
during physiological activity. Recent hypotheses concerning epilepsy
suggest a role for astrocytes in the control of neuronal excitability and
in pathogenesis. This report provides morphological evidence that the
periodic electrical stimulation used in the kindling model of epilepsy
induces astrocytic hypertrophy and an increase in shaft synapse density in
the CA1 region of the hippocampus. The Schaffer collateral pathway in the
stratum radiatum of CA1 of five pairs of rats was kindled in vivo. Control
animals received the same number of stimulations at a lower intensity and
frequency. The animals were killed 24-48 h after reaching the criterion of
five generalized seizures, and the brains were examined by electron
microscopy. Kindling produced a 37% and 33% increase in the volume fraction
of astrocytic processes in the middle and distal portions, respectively, of
the s. radiatum in CA1. In the same tissue, the number (areal density) of
shaft synapses was increased 25% in the s. radiatum of animals exhibiting
generalized seizures. On the other hand, the areal density of degenerating
synapses in both kindled and control animals was low and not significantly
different. These results suggest that both synaptogenesis and hypertrophy
of astrocytes contribute to an early stage of epileptogenesis when
degenerative changes of the sort that might induce gliosis were not
prominent in the tissue under study.
31. Scheff SW; Price DA.
Synapse loss in the temporal lobe in Alzheimer's disease.
Annals of Neurology, 1993 Feb, 33(2):190-9.
(UI: 93167765)
Abstract: The temporal lobe is a well-documented area showing neuropathological
and neurochemical changes in Alzheimer's disease (AD). Autopsy tissue was
obtained from the superior temporal (Brodmann area 22) and the middle
temporal (Brodmann area 21) regions of the cortex from patients with AD (n
= 10; postmortem time < 13 hr) and age-matched control subjects (n = 10;
postmortem time < 13 hr). Ultrastructural examination of the tissue
revealed a highly significant AD-related decline in synaptic numbers in
lamina III and V in both the superior and the middle temporal gyrus. Both
normal control and AD tissue samples demonstrated a significant negative
correlation between the number of synapses and the synapse size, as indexed
by the length of the postsynaptic density. This change in synaptic size
appears to compensate for the loss of synaptic numbers when viewed in terms
of total synaptic contact area. Although the AD tissue showed an average
30% decline in synaptic numbers, the total synaptic contact area remained
largely unchanged in both regions of the cortex. There were no significant
correlations with age, postmortem time, or number of plaques observed in
these areas. The loss of synaptic contacts in AD does not appear to be
isolated to a particular cortical region or lamina.
35. Masliah E; Mallory M; Hansen L; DeTeresa R; Terry RD.
Quantitative synaptic alterations in the human neocortex during normal
aging.
Neurology, 1993 Jan, 43(1):192-7.
(UI: 93140991)
Abstract: We quantified the synaptic population density in the frontal cortex
of 25 individuals without dementia 16 to 98 years old, using sections
double-immunolabeled for beta/A4 amyloid and for synaptophysin, and found a
significant inverse correlation between the presynaptic terminal (PT)
counts and age (r = -0.7, p < 0.001). Individuals older than 60 years had
an average 20% decrease in PT density compared with individuals younger
than 60 years. There were no significant correlations between the age and
the number of beta/A4 amyloid-positive plaques or between synaptic density
and the number of amyloid plaques. Further analysis of the digitized serial
optical images showed focal areas of synapse loss and distended
synaptophysin-containing boutons in the mature plaques of the normal aged
cases. However, we found no microscopic changes in the synaptic content
inside and outside the diffuse plaques. We suggest that a loss of synaptic
input in the neocortex is an age-dependent factor that contributes to the
overall synaptic loss in Alzheimer's disease, but that this might be
largely independent of the beta/A4-amyloid deposition.
51. Keller A; Arissian K; Asanuma H.
Synaptic proliferation in the motor cortex of adult cats after long-term
thalamic stimulation.
Journal of Neurophysiology, 1992 Jul, 68(1):295-308.
(UI: 92389016)
Abstract: 1. One of the hypotheses for information storage in the CNS
postulates the induction of structural changes in synaptic circuits. This
postulate predicts that behavioral experiences produce changes in neural
activity that subsequently induce synaptogenesis in the mature CNS.
Available data indicate that the establishment of engrams for novel motor
acts may involve alterations of synaptic interactions within the primary
motor cortex. The present study examines the hypothesis that patterns of
synaptic circuitry and of synaptic activation are rearranged after enhanced
neural activity in pathways projecting to the motor cortex. 2. Electrodes
implanted in the ventroposterolateral (VPL) nucleus of the thalamus were
used for long-term stimulation (20 microA, 4 days) of afferents to the
motor cortex in freely behaving, adult cats. This stimulation primarily
affected corticocortical inputs from the somatosensory cortex (area 2) to
area 4 gamma of the motor cortex. Electron microscopy and stereological
procedures were used to compare the numerical density (Nv) of various types
of synapses in layers II/III of the stimulated (experimental) motor cortex
with the Nv of the corresponding synapses in the contralateral (control)
hemisphere. 3. Long-term stimulation produced a significant increase
(25.6%) in synaptic Nv in experimental motor cortex. This increase was due
primarily to an increase in the Nv of asymmetrical synapses with dendritic
spines. The numbers of symmetrical synapses, and of asymmetrical synapses
with dendritic shafts, were not affected by long-term stimulation. 4.
Synaptic active zones [calculated by measuring the lengths of postsynaptic
densities (PSDs)] were significantly longer in experimental motor cortex.
Lengthening of PSDs occurred selectively in asymmetrical synapses with
dendritic shafts (28% increase). 5. The Nv of synapses having perforations
in their PSDs (perforated synapses) was significantly higher in
experimental hemispheres. Also increased was the incidence of
synapse-associated polyribosomes, which are most commonly found at the base
of dendritic spines. An increase in the number of perforated synapses and
of polyribosomes are both morphological hallmarks of synaptogenesis. 6. The
percentages of synapses having different curvatures (i.e., presynaptically
concave, convex, or flat) were similar in experimental and in control motor
cortex.(ABSTRACT TRUNCATED AT 400 WORDS)
57. Kadota T; Mizote M; Hori M; Fujita M; Kadota K.
Synaptic vesicle increase correlated to potentiation of transmission at
the synapse of the cat superior cervical ganglion in vivo.
Journal of Electron Microscopy, 1992 Feb, 41(1):37-45.
(UI: 92317845)
Abstract: Changes in the pattern, number and size of synaptic vesicles during
transmitter release were examined in the synapses of the cat superior
cervical ganglion (SCG) in vivo in relation to alteration in the amplitude
of postganglionic compound action potential (PGP). Stimulation of the
preganglionic nerve fibers at 10 Hz caused an increase in the mean
amplitude of PGP. It became augmented by approximately 30% compared to
control 10-30 sec after starting the stimulation, and then gradually
declined to reach a plateau after 4-6 min. This level, about 20% higher in
value than control, was sustained until the end of 30 min of stimulation.
The nerve terminal was divided into two areas to examine topographically
the numerical changes in synaptic vesicles (SVs): zone I on the presynaptic
membrane encircled with a diameter equivalent to the active zone length,
and zone II occupying the remaining area outside zone I. The synaptic
vesicle density in zone I (vesicle number/microns 2) was 96.9 +/- 4.8 (mean
+/- S.E.M.) in the unstimulated control ganglia and 128.8 +/- 9.4 (mean +/-
S.E.M.) in the ganglia stimulated for 10-30 sec, which was 30% higher in
value than control. Then, it decreased slightly reaching a plateau, 20%
higher in value than control. The diameter distribution of the SVs showed
that their diameters in zone I (56.6 nm mean) were larger than those (51.6
nm mean) in zone II, and that prolonged stimulation induced smaller
vesicles in both areas. The results showed that the increase in SV number
in zone I correlated well with the elevation of PGP.(ABSTRACT TRUNCATED AT
250 WORDS)
65. Terry RD; Masliah E; Salmon DP; Butters N; DeTeresa R; Hill R; Hansen LA;
Katzman R.
Physical basis of cognitive alterations in Alzheimer's disease: synapse
loss is the major correlate of cognitive impairment.
Annals of Neurology, 1991 Oct, 30(4):572-80.
(UI: 92161745)
Abstract: We present here both linear regressions and multivariate analyses
correlating three global neuropsychological tests with a number of
structural and neurochemical measurements performed on a prospective series
of 15 patients with Alzheimer's disease and 9 neuropathologically normal
subjects. The statistical data show only weak correlations between
psychometric indices and plaques and tangles, but the density of
neocortical synapses measured by a new immunocytochemical/densitometric
technique reveals very powerful correlations with all three psychological
assays. Multivariate analysis by stepwise regression produced a model
including midfrontal and inferior parietal synapse density, plus inferior
parietal plaque counts with a correlation coefficient of 0.96 for Mattis's
Dementia Rating Scale. Plaque density contributed only 26% of that
strength.
83. Bailey CH; Chen M.
Morphological aspects of synaptic plasticity in Aplysia. An anatomical
substrate for long-term memory.
Annals of the New York Academy of Sciences, 1991, 627:181-96.
(UI: 91353944)
Pub type: Journal Article; Review; Review, Tutorial.
Abstract: The morphological basis of long-term sensitization of the
gill-and-siphon withdrawal reflex in Aplysia was explored by examining the
structure of identified sensory neuron synapses in control and behaviorally
modified animals. Following long-term training, sensitized animals
displayed an increase in the number of sensory neuron synapses compared to
control animals. The relative permanence of these structural changes and
their similarity in time course to the behavioral duration of sensitization
suggest a role for synapse number changes during long-term memory.
87. Grabs D; Voss J; Schuster T; Wenzel J; Krug M.
Heterosynaptic changes in number and shape of the transmission zones of
axo-spino-dendritic synapses in the central nervous system following
long-term potentiation.
Journal fur Hirnforschung, 1991, 32(5):541-5.
(UI: 92251124)
Abstract: Regarding the hippocampal formation and especially the external two
thirds of it's dentate molecular layer a lot of possible morphological
changes after long-term potentiation (LTP) have been described in
literature. The present morphometric-stereological study of
axo-spino-dendritic synapses from the inner third of the molecular layer
was done under the aspect of heterosynaptic influences following LTP. We
were looking for differences in the number of transmission zones, in the
total length of the transmission zone and in the qualitative shape of the
single transmission membrane. Because of the hierarchical link of the three
analytic levels (test-group, animal, synapse), for statistical
interpretation we used the analysis of variance with two-way hierarchical
classification. We detected large differences between the single synapses
but not significant differences between the 3 groups (passive control,
active control, LTP-group). Our quantitative studies showed the same
results also in the middle third of the molecular layer (Grabs et al.
1991). Pure morphological studies should be done under selective staining
of specified population of synapses to differ in stimulated and
non-stimulated synapses. Only with the help of selective staining in the
area of the synapses possible differences between the groups may be found.
88. Smith PF; de Waele C; Vidal PP; Darlington CL.
Excitatory amino acid receptors in normal and abnormal vestibular
function.
Molecular Neurobiology, 1991, 5(2-4):369-87.
(UI: 92368518)
Pub type: Journal Article; Review; Review, Tutorial.
Abstract: Although excitatory amino acid (EAA) receptors have been investigated
extensively in the limbic system and neocortex, less is known of the
function of EAA receptors in the brainstem. A number of biochemical and
electrophysiological studies suggest that the synapse between the
ipsilateral vestibular (VIIIth) nerve and the brainstem vestibular nucleus
(VN) is mediated by an EAA acting predominantly on kainate or
alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors.
In addition, there is electrophysiological evidence that input from the
contralateral vestibular nerve via the contralateral VN is partially
mediated by N-methyl-D-aspartate (NMDA) receptors. Input to the VN from the
spinal cord may also be partially mediated by NMDA receptors. All of the
electrophysiological studies conducted so far have used in vitro
preparations, and it is possible that denervation of the VN during the
preparation of an explant or slice causes changes in EAA receptor function.
Nonetheless, these results suggest that EAA receptors may be important in
many different parts of the vestibular reflex pathways. Studies of the
peripheral vestibular system have also shown that EAAs are involved in
transmission between the receptor hair cells and the vestibular nerve
fibers. A number of recent studies in the area of vestibular plasticity
have reported that antagonists for the NMDA receptor subtype disrupt the
behavioral recovery that occurs following unilateral deafferentation of the
vestibular nerve fibers (vestibular compensation). It has been suggested
that vestibular compensation may be owing to an upregulation or increased
affinity of NMDA receptors in the VN ipsilateral to the peripheral
deafferentation; however; at present, there is no clear evidence to support
this hypothesis.
93. Black JE; Isaacs KR; Anderson BJ; Alcantara AA; Greenough WT.
Learning causes synaptogenesis, whereas motor activity causes
angiogenesis, in cerebellar cortex of adult rats.
Proceedings of the National Academy of Sciences of the United States of
America, 1990 Jul, 87(14):5568-72.
(UI: 90319153)
Abstract: The role of the cerebellar cortex in motor learning was investigated
by comparing the paramedian lobule of adult rats given difficult acrobatic
training to that of rats that had been given extensive physical exercise or
had been inactive. The paramedian lobule is activated during limb movements
used in both acrobatic training and physical exercise. Acrobatic animals
had greater numbers of synapses per Purkinje cell than animals from the
exercise or inactive groups. No significant difference in synapse number or
size between the exercised and inactive groups was found. This indicates
that motor learning required of the acrobatic animals, and not repetitive
use of synapses during physical exercise, generates new synapses in
cerebellar cortex. In contrast, exercise animals had a greater density of
blood vessels in the molecular layer than did either the acrobatic or
inactive animals, suggesting that increased synaptic activity elicited
compensatory angiogenesis.
97. DeKosky ST; Scheff SW.
Synapse loss in frontal cortex biopsies in Alzheimer's disease:
correlation with cognitive severity.
Annals of Neurology, 1990 May, 27(5):457-64.
(UI: 90297544)
Abstract: Ultrastructural studies of biopsied cortical tissue from the right
frontal lobe of 8 patients with mild to moderate Alzheimer's disease (AD)
revealed that the number of synapses in lamina III of Brodmann's area 9 was
significantly decreased when compared with the number in age-matched
control brains (n = 9; postmortem time, less than 13 hours). Further
decline in synaptic number was seen in age-matched autopsied AD specimens.
In the AD brains there was significant enlargement of the mean apposition
length, which correlated with degree of synapse loss; as synapse density
declined, synapse size increased. The enlargement of synapses, coupled with
the decrease in synaptic number, allowed the total synaptic contact area
per unit volume to remain stable in the patients who underwent biopsy. In
autopsied subjects who had AD, there was no further enlargement of mean
synaptic contact area. There was a significant correlation between synapse
counts and scores on the Mini-Mental State examination in the patients who
underwent biopsy. Lower mental status scores were associated with greater
loss of synapses. Choline acetyltransferase activity was significantly
decreased in the biopsied group and declined further in the autopsied
specimens of AD. There was no relationship between choline
acetyltransferase activity and scores on the Mini-Mental State examination
or synapse number. There is evidence of neural plasticity in the AD
neuropil; synaptic contact size increased in patients who had biopsy and
possibly compensated for the numerical loss of synapses. But by end stage
of the disease, the ability of the cortex to compensate was exceeded and
both synapse number and synaptic contact area declined.(ABSTRACT TRUNCATED
AT 250 WORDS)
111. Nelson PG; Fields RD; Yu C; Neale EA.
Mechanisms involved in activity-dependent synapse formation in mammalian
central nervous system cell cultures.
Journal of Neurobiology, 1990 Jan, 21(1):138-56.
(UI: 90203884)
Abstract: Differences in neuronal activity produced by electrical stimulation
lead to competition between synapses from sensory afferents converging on a
common spinal cord neuron. Studies were performed on neurons dissociated
from the mouse spinal cord and grown in culture dishes with three
compartments. Synaptic efficacy from stimulated afferents was increased
compared with unstimulated convergents, and the number of functional
connections was increased by stimulation compared with control cultures.
Blocking NMDA channel activation with 100 microM APV in medium containing
1.8 mM calcium inhibited this synaptic plasticity, but plasticity was not
blocked by APV in medium in which the calcium concentration was elevated to
3 mM. These experiments support the view that electrical activity
differentially influences processes that cause a persistent decrease in
synaptic efficacy or lead to synapse elimination and those that increase
synaptic strength or lead to synapse augmentation. We interpret our results
in terms of a model in which these antagonistic mechanisms are both
regulated via changes in calcium levels and second messengers that are
modulated by electrical activity. A significant portion of the
activity-related calcium influx relevant to synaptic plasticity passes
through the NMDA channel, but other sources of calcium are involved. In
particular, competitive elimination of synapses appears to occur during
blockade of NMDA channels if the extracellular concentration of calcium is
elevated moderately. The outcome of competition between the two
calcium-dependent but antagonistic processes may depend either on their
differential sensitivity to intracellular calcium concentration or separate
specificities to NMDA and non-NMDA receptor-linked mechanisms.
112. Scheff SW; DeKosky ST; Price DA.
Quantitative assessment of cortical synaptic density in Alzheimer's
disease.
Neurobiology of Aging, 1990 Jan-Feb, 11(1):29-37.
(UI: 90221028)
Abstract: Significant progress has been made over the last decade in
delineating the neuropathological and neurochemical changes in the brains
of patients with Alzheimer's disease (AD). Less well studied are the actual
synaptic connections of affected areas of the brain, such as the cerebral
cortex. Because the final common pathway for neurotransmission involves
synaptic integrity, we quantitatively assessed synaptic number and synapse
size in lamina III and V of human frontal cortex (Brodmann area 9) in
patients with AD and age-matched controls. Samples were also matched for
postmortem interval, and artifacts associated with postmortem change were
eliminated. We found a significant decrease in synaptic number per unit
volume in both lamina, more marked in lamina III (-42%) than V (-29%). In
both normal controls and AD brains, there was a negative correlation
between synapse number and synapse size as indexed by the length of the
postsynaptic density (PSD); cortical samples with fewer synapses had larger
synapse size. This appeared to be a compensatory response, rather than a
selective loss of small synapses, since the total amount of synaptic
contact area per unit volume did not decline in lamina V (despite a 29%
loss of synapses); in lamina III it was reduced 11% despite a 42% loss of
synapses. The loss of synapses in AD is widespread and significant in
frontal cortex; there is observable compensation by enlargement of synaptic
size. This compensatory effort is overcome by the continuing loss of
synapses in areas most affected by the degeneration.
MED-> quit
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/tmp_mnt/hosts/ursa/u/chimento 31 } mv XtermLog.a6792 synapse.num.refs
/tmp_mnt/hosts/ursa/u/chimento 32 } ls sysnaps*
No match
/tmp_mnt/hosts/ursa/u/chimento 33 } ls syns apse*
synapse.model synapse.num.refs
/tmp_mnt/hosts/ursa/u/chimento 34 } ls *refs
prejac.refs synapse.num.refs
retina.synapse.refs vest.nuc.refs
/tmp_mnt/hosts/ursa/u/chimento 35 } print synasp pse.num.refs retina.synapse.refs
request id is hp4-424 (2 file(s))
/tmp_mnt/hosts/ursa/u/chimento 36 } inc
Incorporating new mail into inbox...
286+ 12/29 Alan Saul Re: changes in synaptic number<<In article <3ds7
/tmp_mnt/hosts/ursa/u/chimento 37 } show
(Message inbox:286)
-- using template mhl.format --
From: saul+ at pitt.edu (Alan Saul)
To: chimento at ursa.arc.nasa.gov (Thomas Chimento)
Date: Thu, 29 Dec 1994 11:33:08 -0500
Subject: Re: changes in synaptic number
In article <3ds70e$isk at news.arc.nasa.gov>, chimento at ursa.arc.nasa.gov
(Thomas Chimento) wrote:
> I have been looking for references on changes in the number of synaptic
> connections resulting from an alteration in the input or environment of an
> organism. I have done all the Medline searches under synaptic plasticity
> and read numerous review articles on synapses, but I am unable to find an
> example of anatomical, quantitative changes in the number of synaptic
> sites anywhere in the nervous system caused by changing the input to that
> part of the nervous system. I am not toaking about dendritic spine numbers,
> but the synaptic sites within existing neurons.
>> The reason I am searching for this information is that our experiments in
> the vestibular endorgan have demonstrated a change in the number of
> synaptic sites within hair cells when the gravitational environment is
> altered. In a hypergravity environment produced on a 24' centrifuge (2-g)
> the number of synaptic sites decreases whereas an opposite effect occurs
> when the animals (rats) are placed in microgravity aboard the Space
> Shuttle. I am hesitant to state that this is the only such case
> demonstrated, but have not been able to find any others. Any help would be
> greatly appreciated. Suggestions of key words for a search, books,
> articles, or specific investigators names all would be very helpful.
Without looking things up myself, the best I can do is provide a couple
names that I think show something like alterations of synaptic densities
(among other things) in response to stimulation or deprivation.
Levy and Desmond did lots of this sort of thing a few years back (80s?) in
hippocampus.
Beaulieu and Collonier looked at visual cortex ultrastructure in enriched
and deprived environments.
And of course there is lots of work on neuromuscular junctional changes,
e.g. Changeux.
[7m--More--[m[K
--
Alan Saul
saul+ at pitt.edu
/tmp_mnt/hosts/ursa/u/chimento 38 } repl
[1;1H[m[45;1H[?1h"/hosts/ursa/u/chimento/Mail/drafts/16" 42 lines, 2145 characters [K[H[2JTo: saul+ at pitt.edu (Alan Saul)[H
Subject: Re: changes in synaptic number
In-reply-to: Your message of Thu, 29 Dec 94 11:33:08 EST.[4;14H<199412291633.LAA19543 at post-ofc02.srv.cis.pitt.edu>
--------
In article <3ds70e$isk at news.arc.nasa.gov>, chimento at ursa.arc.nasa.gov
(Thomas Chimento) wrote:
> I have been looking for references on changes in the number of synaptic
> connections resulting from an alteration in the input or environment of an
> organism. I have done all the Medline searches under synaptic plasticity
> and read numerous review articles on synapses, but I am unable to find an
> example of anatomical, quantitative changes in the number of synaptic
> sites anywhere in the nervous system caused by changing the input to that
> part of the nervous system. I am not toaking about dendritic spine numbers,
> but the synaptic sites within existing neurons.
>> The reason I am searching for this information is that our experiments in
> the vestibular endorgan have demonstrated a change in the number of
> synaptic sites within hair cells when the gravitational environment is
> altered. In a hypergravity environment produced on a 24' centrifuge (2-g)
> the number of synaptic sites decreases whereas an opposite effect occurs
> when the animals (rats) are placed in microgravity aboard the Space
> Shuttle. I am hesitant to state that this is the only such case
> demonstrated, but have not been able to find any others. Any help would be
> greatly appreciated. Suggestions of key words for a search, books,
> articles, or specific investigators names all would be very helpful.
Without looking things up myself, the best I can do is provide a couple
names that I think show something like alterations of synaptic densities
(among other things) in response to stimulation or deprivation.
Levy and Desmond did lots of this sort of thing a few years back (80s?) in
hippocampus.
Beaulieu and Collonier looked at visual cortex ultrastructure in enriched
and deprived environments.
And of course there is lots of work on neuromuscular junctional changes,
e.g. Changeux.
--
Alan Saul
saul+ at pitt.edu
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[K[@T[@h[@o[@m[@a[@s
[K[14B:r footer"footer" 16 lines, 833 characters [H[2JWithout looking things up myself, the best I can do is provide a couple[H
names that I think show something like alterations of synaptic densities
(among other things) in response to stimulation or deprivation.
Levy and Desmond did lots of this sort of thing a few years back (80s?) in
hippocampus.
Beaulieu and Collonier looked at visual cortex ultrastructure in enriched
and deprived environments.
And of course there is lots of work on neuromuscular junctional changes,
e.g. Changeux.
--
Alan Saul
saul+ at pitt.edu
Thanks for the clues. I'll check the names. I think that a lot of what
these investigators found related to increases in spine number. I am trying
to find increases in synaptic connections without changes in the overall
anatomy of the cell. Thanks again.
Thomas
********************************************************************
* Thomas C. Chimento Ph.D. Phone: 415-604-0376 (and Voice Mail)*
### ## ### ##### ### Fax: 415-604-3954[17C*
#### ## ## ## ### ## ##[38C*
## #### ## ## ### ## ## chimento at neuron.arc.nasa.gov *
## ### ## ## ##### ## ##[38C*
* Biocomputation Center[42C*
* MS 239-11[54C*
* Moffett Field, CA 94035-1000[34C*
*+*+*+*+*+*+*+*+*+*+*+*+*+*+*+*+*+*+*+*+*+*+*+*+*+*+*+*+*+*+*+*+*+**
* My thoughts, only my thoughts, and nothing but my thoughts. *
********************************************************************
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********************************************************************
* Thomas C. Chimento Ph.D. Phone: 415-604-0376 (and Voice Mail)*
### ## ### ##### ### Fax: 415-604-3954[17C*
#### ## ## ## ### ## ##[38C*
## #### ## ## ### ## ## chimento at neuron.arc.nasa.gov *
## ### ## ## ##### ## ##[38C*
* Biocomputation Center[42C*
* MS 239-11[54C*
* Moffett Field, CA 94035-1000[34C*
*+*+*+*+*+*+*+*+*+*+*+*+*+*+*+*+*+*+*+*+*+*+*+*+*+*+*+*+*+*+*+*+*+**
* My thoughts, only my thoughts, and nothing but my thoughts. *
********************************************************************
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