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Volume 17, Number 15,
Issue of August 1, 1997
pp. 5858-5867
Copyright ©1997 Society for Neuroscience
Quantitative Ultrastructural Analysis of Hippocampal
Excitatory Synapses
Thomas Schikorski and
Charles F. Stevens
Molecular Neurobiology Laboratory and Howard Hughes Medical
Institute, The Salk Institute, La Jolla, California 92037
 ABSTRACT
- INTRODUCTION
- MATERIALS AND METHODS
- RESULTS
- DISCUSSION
- FOOTNOTES
- APPENDIX
- REFERENCES
ABSTRACT 
From three-dimensional reconstructions of CA1 excitatory synapses
in the rodent hippocampus and in culture, we have estimated statistical
distributions of active zone and postsynaptic density (PSD) sizes
(average area ~0.04 µm2), the number of active
zones per bouton (usually one), the number of docked vesicles per
active zone (~10), and the total number of vesicles per bouton
(~200), and we have determined relationships between these
quantities, all of which vary from synapse to synapse but are highly
correlated. These measurements have been related to synaptic
physiology. In particular, we propose that the distribution of active
zone areas can account for the distribution of synaptic release
probabilities and that each active zone constitutes a release site as
identified in the standard quantal theory attributable to Katz
(1969) .
Key words:
synaptic vesicle;
active zone;
release;
statistical
distribution;
hippocampus;
release probability
INTRODUCTION
Since the pioneering work of Katz and his
collaborators on synaptic function (summarized in Katz, 1969) and that
of the early electron microscopists on synaptic structure (Palay and
Palade, 1955; Luse, 1956; Wyckoff and Young, 1956), a consistent goal of neurobiologists has been to identify the structural basis for the
entities identified in Katz's theory of synaptic transmission (Katz,
1969). The synaptic vesicle is generally accepted as corresponding to
Katz's quantum, although still without definitive evidence. The number of release sites [Ns in Katz's
(1969) scheme] associated with an axon has been identified with the
total number of releasable vesicles, with the number of boutons, and
with the number of active zones (Zucker, 1973; Jack et al., 1981; Korn
et al., 1981; Neale et al., 1983; Redman and Walmsley, 1983; Walmsley
et al., 1985; Pun et al., 1986; Propst and Ko, 1987; Redman, 1990;
Walmsley, 1991; Pierce and Mendell, 1993; Pierce and Lewin, 1994). A
possible anatomical counterpart of Katz's release probability
p has been subject to less speculation, but several authors
have noted that p might be related to synaptic size (see
Pierce and Lewin, 1994).
With the development of optical techniques to study synaptic
transmission (Betz and Bewick, 1992; Betz et al., 1992) and the extension of these techniques to hippocampal neurons in culture (Ryan
et al., 1993; Ryan and Smith, 1995; Ryan et al., 1996), many synaptic
properties can now be investigated in culture at the level of single
central synapses. Although individual hippocampal synapses differ
greatly from one another with respect to any one of these properties, a
variety of the properties are highly correlated with the release
probability of the synapse (Ryan et al., 1996; Murthy et al., 1997). To
relate results from physiological investigations of synapse populations
to synaptic structure, one must know the statistical distribution of
morphological characteristics. Current statistical information about
hippocampal synapses comes from studies by Harris and Stevens (1989),
Harris et al. (1992), Sorra and Harris (1993), and Harris and Sultan
(1995), but this work has focused almost exclusively on the
postsynaptic side, except for a reconstruction of nine representative
boutons by Harris and Sultan (1995), and has not considered the
structure of synapses in culture. One of the main goals of the research
reported here is to determine the statistical distribution of
presynaptic properties likely to be of physiological relevance for
hippocampal synapses.
We have characterized rodent hippocampal excitatory synapses both in
brain and in culture.
MATERIALS AND METHODS
Terminology
We use "active zone" in the same way as Couteaux (1961) does
and reserve "release site" (sometimes used as a synonym for active zone) for the entity described in Katz's (1969) theory.
"Morphologically docked vesicles" (or simply "docked vesicles")
are those immediately adjacent to the active zone membrane; we
recognize that these vesicles are a superset of the "biochemically"
and "physiologically docked vesicles." "Synapse" (sometimes
called "synaptic junction") is taken to be the unit of active zone,
docked vesicles, and postsynaptic density (PSD); with this terminology
a single bouton might make multiple synapses.
Fixation and embedding
Brain synapses. One adult mouse (strain C57 black 6)
was perfused through the heart under deep Nembutal anesthesia (80 µl/25 gm body weight). A short perfusion with oxygenated saline
[containing (in mM) NaCl 120, KCl 3.5, NaH2PO4 1.25, NaHCO3 26, MgCl2 1.3, and glucose 10, pH 7.2] was followed by a
perfusion with 4% glutaraldehyde in 100 mM phosphate
buffer, pH 7.4, at room temperature (RT). The brain was dissected and
immersed in 4% glutaraldehyde in 100 mM phosphate buffer,
pH 7.4, at RT overnight. Vibratome sections (300 µm) including the
hippocampus were cut and post-fixed in 1% OsO4 at 4°C
for 1 hr. After dehydration in ethanol, the sections were contrasted en
bloc in 0.5% uranyl acetate in 95% ethanol for 1 hr and flat-embedded
in Epon.
Culture synapses. Cells were plated at postnatal day 1 and
grown for 14 d (for culture conditions, see Bekkers and Stevens, 1989). Rat hippocampal cells were immersed in 2% glutaraldehyde in 100 mM phosphate buffer at 4°C for 1 hr, washed in phosphate buffer, and post-fixed in 1% OsO4 at 4°C for 1 hr. Cells
were dehydrated in ethanol, contrasted en bloc in 0.5% uranyl acetate at RT for 50 min, and embedded in Epon.
Embedded vibratome sections were trimmed to blocks including the
stratum (st.) pyramidale, the st. radiatum, and the st. lacunosum moleculare. Both specimens were cut serially at silver. Three series
(magnification 14,000×) at different distances to the stratum pyramidale were photographed from 29 consecutive sections by using a
Jeol 100 CX II electron microscope. For hippocampal neurons in cell
culture, we photographed two series (magnification, 14,000×) from 20 serial sections cut at silver.
Analysis
Electron micrographs were scanned at 600 dpi resolution and
analyzed by using the MetaMorph software (Universal Imaging
Corporation, West Chester, PA). We analyzed 79 asymmetric contacts to
spines of mouse hippocampal CA1 synapses; symmetric synapses or
asymmetric shaft synapses were excluded from our measurements. All
synapses within the selected area were included as long as the active
zone was not cut tangentially as judged from the "smearing" of
membranes. In the case of the hippocampal neurons in cell culture, we
included 21 asymmetric contacts to spines and to dendritic shafts but
excluded symmetric synapses from the analysis. Areas of active zones
and of PSDs and volumes of boutons and of spine heads were measured by
outlining the structure in consecutive sections using the Region Tools
and the measurement function of the MetaMorph software. The final
values were calculated by adding the product of the length or area
times the section thickness (60 nm) for all of the sections in which
the structure appeared. A vesicle was counted as a docked vesicle when
the vesicle membrane was immediately adjacent to the plasma membrane of
the active zone (i.e., when a separation between the vesicular and
plasma membrane was not resolvable). Vesicle diameters were calculated
from the enface areas of vesicles photographed at high power
(72,000×). The diameter was taken as the diameter of a circle with the
same area as the vesicle. Only vesicles that were contained completely
within the 60-nm-thick section were included.
Some very small active zones had a width of  60 nm and thus might
appear in only a single section, and even large active zones that are
traced across multiple sections were reconstructed in a discrete manner
(see Fig. 5). The uncertainties in the active zone contures through a
single section thickness give rise to errors in the area estimate. By
examining upper and lower limiting sizes, we estimate that the error in
any particular area could be as high as 20-30%. We would overestimate
the active zone area in some cases and underestimate it in others, so
these errors would tend to cancel across a population of measurements
for the larger active zones. For the smallest active zones, we probably systematically overestimated their area. However, errors for these zones should be <50%, because, e.g., an active zone that extended only halfway through a section thickness would have a 50% decrease in
the electron density of the active zone membrane and we should have
detected this.
Fig. 5.
Depiction of 26 active zones, as viewed from
within the bouton, reconstructed from serial sections. The black
bars correspond to the active zone of a single section (thus
the thickness of the bar equals 60 nm), and the
shaded circles indicate the position of docked vesicles.
Note that because the section is approximately twice as thick as the
vesicle diameter, the location of the vesicle within the section is
unknown; all vesicles have been placed in the center of the section for
illustration, but the actual vesicles would not be arranged in the neat
rows as shown here. The point of representing the vesicles here is to
indicate the extent to which areas of the active zone seem to be
unoccupied. Many active zones could be described as round or oval,
although distortions of these idealized forms are common. Two active
zones were perforated. The occupancy of active zones by docked vesicles
varies greatly.
[View Larger Version of this Image (38K GIF file)]
Extracellular volume around a synapse was measured by outlining the
area of the extracellular space. The outlines were contained within
circles, decreasing appropriately in consecutive sections, that
corresponded to a sphere with a radius of 0.5 µm that centered on a
particular reference synapse. We made no corrections for shrinkage
during tissue preparation.
Several synapses were traced with Montage (written by R. Smith,
University of Pennsylvania). Montage data were then rendered using the
Nuages software (B. Geiger), and the volume rendered reconstructions
were imported into AVS (Advanced Visual Systems, Inc.), in which the
object properties (color, viewing angle, and transparency) were edited
and printed.
RESULTS
Figure 1A illustrates a typical
region from a brain section with several synapses that were included in
our study. The active zones and postsynaptic densities are defined by
electron dense material close to the membrane. In addition,
morphologically docked vesicles, a regular synaptic cleft, and
alignment of presynaptic and postsynaptic structures mark the synaptic
region. The active zones and PSDs are indicated by arrows.
Figure 1, B and C, shows representative sections
from a culture.
Fig. 1.
Sample electron micrographs used in our study.
A, Electron micrograph depicting several synapses within
the stratum radiatum in CA1 in the mouse hippocampus. The
arrows indicate the borders of the active zones on the
presynaptic side and of the postsynaptic densities on the spine.
Examples of vesicles that are defined as docked in our study are marked
by arrowheads. B, C,
Electron micrograph showing the ultrastructure of two synapses from a
hippocampal neuron grown in culture. Scale bars: A, 0.5 µm; B, C, 0.25 µm.
[View Larger Version of this Image (119K GIF file)]
We reconstructed the boutons under study from 29 consecutive sections.
An example of a reconstructed bouton is illustrated in Figure
2A for the brain and in Figure
2B for culture. In these illustrations the active
zones and docked vesicles are indicated, but the nondocked vesicles are
omitted for clarity.
Fig. 2.
Three-dimensional reconstructions of synapses from
serial sections. A, Two views of a brain synapse that is
included in our study. The spine head (spine) is
surrounded by two varicosities (axon). One of these
varicosities forms a contact on the spine; the other is located beneath
the spine. The right image presents a view from the
right side of the structure in the left image. The
bouton is transparent for the visualization of the active zone
(red) and the nine docked vesicles
(gray). Nondocked vesicles are, for clarity,
excluded. B, The reconstruction of two shaft synapses
from cultured hippocampal neurons. Both synapses originate from the
same varicosity (axon). The two different shades of
yellow represent the two different dendritic shafts
(dend. I, dend. II). Dend.
II branches at the site of the synapse. The left
and right images depict views of the same structure
rotated by ~30°. The red active zones and their
docked vesicles are visible through the transparent
axon; again nondocked vesicles are excluded for clarity.
[View Larger Version of this Image (107K GIF file)]
We next consider briefly two features of synaptic structure that are
important for interpreting physiological experiments: the distribution
of the sizes of the synaptic vesicles and the diffusion volume for the
neurotransmitter.
Synaptic vesicle numbers and size distribution
For brain synapses, the total number of vesicles per bouton
averaged 270 (SD = 176) with a range from 40 to 801 (for 17 boutons).
We measured the outer diameters of 343 synaptic vesicles that are
(judged from an examination of serial sections) entirely contained
within the 60-nm-thick section. The outer diameters have a Gaussian
distribution (Kolmogorov-Smirnov test, p > 0.2) with
a mean of 35.2 nm, a SD of 3.4 nm, and a coefficient of variation of
0.1. The mean inner diameter is 23 nm, calculated from the outer
diameter by subtracting 6 nm for the thickness of the vesicular membrane.
Neurotransmitter diffusion volume
Because the width of the synaptic cleft in our material averaged
20.0 (SD = 2.8) nm, the average volume of the synaptic cleft calculated from active zone size (see the next section for active zone
and PSD areas) is 0.76 × 10 3
µm3 for the brain. This value, considered a mixing
volume for the released neurotransmitter, is quite arbitrary, however,
because it is calculated on the basis of active zone and PSD areas. The effective diffusion volume to which the neurotransmitter has rapid access could be very much larger. If one defines the "near" volume as the extracellular space within 0.5 µm of the synapse (small molecules diffuse ~0.5 µm in 0.25 msec), the diffusion volume for a
single active zone in the brain was found to be 44 × 103 µm3, ~50 times the
volume of the average synaptic cleft. We return to this issue of mixing
volumes and their significance in Discussion.
Brain active zones
This section presents statistical data on the subcellular
structure, the active zone, that is most intimately involved in neurotransmitter release.
Of the 71 brain boutons, 64 (90%) exhibited only a single active zone,
6 had two active zones (8%), and one had three active zones (2%);
multiple active zones at a single bouton never focused on the same
postsynaptic spine. In culture, 11 of 16 (69%) boutons possessed a
single active zone, and five (31%) had double active zones. These
differences between brain and culture synapses are not statistically
significant, but multiple active zones may actually be more common in
culture than in brain.
In all cases, the active zone closely matches the PSD, as might be
expected. Figure 3A shows a plot of active
zone area as a function of PSD area for 79 active zones in the brain;
the correlation coefficient between these two variables is 0.97. A
corresponding plot for culture synapses is presented in Figure
3B in which the correlation coefficient is 0.974 (for 21 active zones).
Fig. 3.
Correlation of active zone size with PSD
size. A, Scatter plot comparing the sizes of 79 active
zones from mouse brain with their corresponding PSD. The line indicates
the linear regression with a correlation coefficient of 0.97. B, Same comparison of 21 active zones with PSDs from
hippocampal neurons in culture. The correlation coefficient is
0.97.
[View Larger Version of this Image (11K GIF file)]
The active zone area varies over a wide range (coefficient of
variation = 0.56), as does the number of docked vesicles
(coefficient of variation = 0.54). The histogram of active zone
areas (Fig. 4A) is broad with a mean
of 0.039 µm2 and an SD of 0.022 µm2; this histogram is satisfactorily fitted by a
 density function (see Fig. 4 legend). If the average active zone
were a circular disk, its diameter would be 0.22 µm.
Fig. 4.
Comparison of active zone sizes with the
number of docked vesicles for the brain synapses. A,
Frequency distribution of active zone sizes for 79 active zones. The
solid line is a density function
(y = a × ebx, with
a = 3437 and b = 53). Mean = 0.039 µm2; SD = 0.022 µm2. B, Distribution of the number
of docked vesicles for 79 active zones. The solid line
is a density function (y = a × ebx, with
a = 4.98 and b = 0.165).
Mean = 10.3 vesicles per active zone; SD = 5.6. C, Scatter plot of active zone size and corresponding number of docked vesicles. The fitted linear regression is indicated as
a solid line, and the correlation coefficient is 0.927.
[View Larger Version of this Image (21K GIF file)]
Active zone area is linearly related to the volume of the bouton
bearing the active zone. For 17 brain synapses that spanned the range
of bouton volumes, we found that:
where V is the bouton volume
(µm3), and A is the active zone area
(nm2); the correlation coefficient between
V and A is 0.79. The average bouton volume is
0.086 µm3.
Number of docked vesicles per active zone
Like that of the active zone areas, the histogram of the number of
docked vesicles per active zone (Fig. 4B) is broad
with a positive skew and can also be fitted with a density function (see Fig. 4 legend). The mean is 10.3 vesicles per active zone with a
SD of 5.6. For our sample of 79 active zones, the minimum number of
docked vesicles is two, and the maximum is 27.
Although the active zone area and the number of docked vesicles per
active zone both vary greatly from synapse to synapse, these two
quantities are highly correlated as the scatter plot in Figure
4C reveals. The correlation coefficient for brain active zone area and docked vesicles per active zone is 0.927. The average active zone area per docked vesicle is 3.8 × 103 ± 0.93 × 103
µm2 (mean ± SD), which corresponds to one
vesicle per 62 × 62 nm square. The density with which docked
vesicles occupy an active zone (the number of vesicles per area of
active zone), relative to the maximal density observed, is normally
distributed with a mean of 0.67 and a SD of 0.15. Thus the active zones
are, on average, filled to 67% of their observed maximal density.
Active zone shapes
Figure 5 illustrates 26 active zones with 157 docked vesicles (an average of 6 per active zone for this smaller
sample) to indicate the range of active zone sizes and shapes
encountered. In our sample, the largest active zone had a length of 0.8 µm and a width of 0.26 µm, whereas the smallest was 0.12 by 0.06 µm. The positions of synaptic vesicles docked to the active zones are
also illustrated in Figure 5. Note that the placement of the vesicles
seems to be random, an appearance supported by the observation that the
lateral intervesicle distances are approximately exponentially distributed with a characteristic length (measured from the edge of one
vesicle to the edge of its neighbor) of 62.5 nm. Compare this value
with the overall density of one vesicle per 62 nm2.
Precisely how to identify a "functionally docked vesicle" in
electron micrographs is not known. We have used the obvious definition above (close apposition of vesicle and plasma membranes for
morphological docking), but we have also examined the effects of other
definitions on our conclusions. When every vesicle within two vesicle
diameters of the active zone is taken as docked, then the average
number of docked vesicles per active zone increases from 10.3 to 18.8 (approximately twofold, as if vesicles are waiting in line to be
released), whereas the correlation between the active zone area and the
number of docked vesicles remains unaffected (correlation coefficient,
0.929). This positive correlation between the vesicle number and the
active zone size persists even when we take as docked the total number
of vesicles within the terminal (correlation coefficient, 0.79).
Because the active zone area seems to predict the relative size of the
docked pool when docked is defined in various ways, we shall prefer
this measure for calculations that relate to the distribution of docked
vesicles.
Synapses in culture
Because physiological experiments use hippocampal neurons both in
slices and in culture, a comparison of synaptic structure in these two
environments is important. In this section we compare boutons in
culture with the data presented earlier for the brain. Note that our
sample size for culture (16 boutons) is much smaller than that for the
brain because of the much lower density of synapses in culture compared
with that in the brain.
The average area of 21 active zones, reconstructed from 20 consecutive
sections in culture, was 0.027 µm2 with an SD of
0.019 µm2. Our culture sample consisted of 14 active zones that were opposed to spines and 7 active zones that
participated in shaft synapses; when multiple active zones were
present, they did not oppose the same spine. The active zone areas are
not significantly different from those obtained from the mouse brain.
As we found in the brain, the culture active zone area is highly
correlated with the PSD area (correlation coefficient = 0.974;
Fig. 3B) and with the number of docked vesicles; the average
number of docked vesicles is 4.57 (SD = 3.00). The total number of
vesicles per bouton averaged 195 (SD = 154) with a range of 23 to
648. Synapses in culture thus have fewer docked vesicles, although
their active zone area is not significantly less than that for brain
synapses.
Overall, the only statistically significant difference between the
brain and culture synapses is the average number of docked vesicles per
active zone (approximately half for culture). This difference cannot be
attributed to the inclusion of shaft synapses in our sample from
culture because the average number of docked vesicles was the same for
both shaft and spine synapses in culture. Although not statistically
significant, we note that more boutons in culture (21%, or 3 of 14)
have multiple active zones than do boutons in brain (11%, or 7 of
64).
Summary of the quantitative presynaptic data
Table 1 gives a summary of our data both for the
mouse brain synapses and for the rat hippocampal neurons in
culture.
Table 1.
Summary of quantitative presynaptic data
| Presynaptic
data |
Brain |
Cell culture |
|
| Active
zone |
0.039
± 0.022 µm2 |
0.027 ± 0.019 µm2
|
| PSD |
0.043 ± 0.031 µm2 |
0.028
± 0.020 µm2 |
| Docked vesicle number |
10.3
± 5.6 |
4.6 ± 3.0 |
| Area per docked vesicle |
62
× 62 nm |
77 × 77 nm |
| Bouton volume |
0.086
± 0.049 µm3 |
0.122 ± 0.106 µm3
|
| Spine volume |
0.038 ± 0.036 µm3 |
| Total
number of vesicles |
270 ± 176 |
195 ± 154 |
| Outer
vesicle diameter |
35.2 ± 3.4 nm |
|
|
The left column summarizes values for mouse brain synapses as
given in the text. The right column gives corresponding values for rat
hippocampal neurons in culture; some entries do not appear in the text
but are included here for completeness.
|
|
DISCUSSION
The data reported here provide a picture of central synapses as
rather variable structures with certain consistent characteristics. Most boutons possess only a single active zone that, as expected, is
aligned quite precisely with the PSD. Furthermore, a tight relationship
holds between the active zone size and the number of docked vesicles.
But the size and shape of the active zone, the area of the PSD, the
number of docked vesicles per active zone, and the size of the reserve
pool of nondocked vesicles all vary greatly from synapse to
synapse.
Comparison with previous anatomical studies
Although similar statistical studies of presynaptic structure have
not, as far as we are aware, included cortical synapses, our
observations are in good agreement with certain earlier findings for
noncortical synapses. For frog cardiac autonomic synapses (Streichert
and Sargent, 1989), turtle spinal cord synapses on motoneurons (Yeow
and Peterson, 1991), and 1A synapses on mammalian spinal motoneurons
(Pierce and Mendell, 1993), a linear relationship is reported between
bouton volume and both the total number of synaptic vesicles and the
active zone area. Also, spinal synapses exhibit a skewed distribution
of active zone areas with a shape much like the one presented in Figure
4A, although the active zone areas of the spinal
synapses are two and one-half (mammalian) to four (turtle) times those
we find in hippocampus.
Several interesting differences are evident between the hippocampal
boutons and others that have been characterized statistically. The
great majority of hippocampal boutons have only a single active zone,
whereas multiple active zones are common for spinal (an average of 6 active zones per bouton) (Yeow and Peterson, 1991; Pierce and Mendell,
1993), autonomic (~1.5 active zones per bouton) (Streichert and
Sargent, 1989), and thalamic (~3-8 active zones per bouton) (Hamos
et al., 1987) synapses.
Another difference, bouton size, probably accounts for the occurrence
of multiple active zones per bouton in these noncortical synapses and
for the fact that hippocampal active zones are smaller than others. The
volume of the hippocampal boutons is 10-100 times less than the
volumes of the other boutons that have been characterized statistically, and all investigators find a linear relationship between
total active zone area and bouton volume. Because hippocampal synapses
are small, their average active zone size is also small. As Yeow and
Peterson (1991) first noted, active zones rarely exceed an area of 0.4 µm2 (as if larger active zones will not function
properly), so larger boutons seem to add more active zones to conform
to the linear active zone area per bouton volume relationship without
exceeding the upper limit for active zone size. As first reported by
Hamos et al. (1987) and confirmed by the subsequent workers on various synapse types (Streichert and Sargent, 1989; Yeow and Peterson, 1991;
Pierce and Mendell, 1993), the number of active zones is linearly
related to bouton volume. Again, because hippocampal boutons are small,
one would expect to find, as we do, only a single active zone per
bouton if the linear active zone area per bouton volume relationship
extends to cortical neurons. Although they did not perform a formal
quantitative analysis, Peters et al. (1990) also note that the number
of active zones per bouton correlates with bouton size in neocortex so
that larger inhibitory boutons often exhibit multiple active zones
whereas the smaller excitatory synapses generally possess only a single
active zone, as we find for the hippocampus.
When specific comparisons can be made, our findings are generally in
good agreement with previously published observations on hippocampal
synapses. The most comparable study (Harris and Sultan, 1995) found,
for the nine representative boutons they reconstructed, an average of
15.6 vesicles per active zone with a range of 2-36; this compares with
our mean of 10.3 with a range of 2-27 for the brain. The average
bouton volume (0.11 µm3) reported by Harris and
Stevens (1989) also agrees with our value (0.086 µm3).
Physiological implications
Cleft neurotransmitter concentration
The concentration of agonist to which postsynaptic receptors are
exposed is of physiological significance, and order of magnitude calculations are sometimes made by using the volume of a synaptic cleft
and the number of transmitter molecules estimated to be contained
within a single vesicle. For example, Harris and Sultan (1995) provide
estimates from 0.24 to 11 mM for the peak glutamate concentration in the cleft using this procedure (the range results from
variations in synaptic cleft size).
As noted earlier, taking the synaptic cleft volume as the appropriate
one for calculating the peak glutamate concentration is rather
arbitrary. An improved, but still quite approximate, method is to
determine the effective mixing volume with the aid of the
Einstein-Smoluchowski relationship (Einstein, 1926):
where x is the root mean square distance (µm)
traveled in t msec by a molecule with diffusion constant
D (µm2/msec). A typical value for
D, for a molecule the size of glutamate, would be ~0.5
µm2/msec for free diffusion (glutamate binding
would slow diffusion but simultaneously lower concentrations). If one
can estimate a characteristic mixing time, then the characteristic
distance traveled in that time can be obtained from the
Einstein-Smoluchowski relationship; and the accessible volume, that
volume within a characteristic distance, can be determined from
measuring from serial electron micrographs the extracellular space
continuous with the synaptic cleft.
To estimate a characteristic time for this situation, one can consider
the length of time required for glutamate to be released from its
vesicle (Almers and Tse, 1990). For serotoninergic vesicles, the time
constant for this release process is ~0.25 msec (Bruns and Jahn,
1995). The diffusion distance for a characteristic time of 0.25 msec
(assume a diffusion constant of 0.5 × 105
µm2/msec) would be 0.5 µm. The volume associated
with this linear distance is ~44 × 103
µm3, or ~50 times the average volume of a
synaptic cleft, as noted earlier .
If the concentration of glutamate within a vesicle (23 nm inner
diameter, 0.64 × 105
µm3 volume) is taken to be 100 mM
(Burger et al., 1989; Bruns and Jahn, 1995), the peak synaptic cleft
concentration would be ~0.6 mM for glutamate constrained
to remain in the average synaptic cleft itself. The peak cleft
concentration would be 12 µM if the effective mixing
volume is taken to be the contiguous space within 0.5 µm of the
synapse. This estimate 12 µM is much lower than Harris
and Sultan's (1995) value (an average of 2.5 mM for a 100 mM vesicle concentration) because they assumed a larger
vesicle volume and took the mixing volume to be that of the synaptic
cleft.
We have drawn three main conclusions about presynaptic
structure that should relate to neurotransmitter release
mechanisms.
Active zone and release site correspondence
First, we find that the majority of hippocampal boutons in the
brain and in culture exhibit only a single active zone. Thus the study
of single boutons, with minimal stimulation or optical methods, for
example, reduces in effect to the study of single active zones. Because
a single hippocampal bouton normally releases at most a single quantum
of neurotransmitter (Stevens and Wang, 1994, 1995), Katz's (1969)
Ns, the number of release sites, would correspond to the number of active zones (and to the number of boutons). This conclusion is in agreement with earlier proposals (see
Zucker, 1989; Redman, 1990; Korn and Faber, 1991; and Walmsley, 1991).
Although an old idea dating from Zucker (1973), the release site and
active zone identification has not been widely accepted. The main
reasons for this lack of acceptance are uncertainties about the
accuracy with which Katz's Ns could be
determined by the quantal analysis used in the earlier studies. Several
recent investigations (Walmsley, 1991; Pierce and Mendell, 1993;
Rosenmund et al., 1993; Murthy et al., 1997) have confirmed earlier
speculations that release probabilities for a single central axon vary
considerably from site to site, and these studies find that most
synapses have very low release probabilities. Under these
circumstances, quantal analysis is very inaccurate for estimating
Ns because the smallest sampling or systematic
errors are disastrous for determinations of Ns
because the Poisson limit is approached for a significant fraction of
the synapses. The present identification of active zones with release
sites is on firmer ground because quantal analysis was not required for
counting release sites physiologically and because errors arising from
the method of minimal stimulation would overestimate the quantal
content as release probability changes (Stevens and Wang, 1994,
1995).
Docked vesicle pool and releasable pool correspondence
Second, the pool of morphologically docked vesicles averages ~10
and ranges from 2 to 27 in the brain (the range is 1-13 for cultured
synapses), and we propose that these docked vesicles correspond
approximately to the readily releasable pool determined physiologically, an idea put forward recently by Von Gersdorff et al.
(1996) for a ribbon synapse. Although a direct test of this proposal is
required before it can be accepted, the available data support the
identification of the docked vesicles as the releasable pool
(Südhof, 1995). The number of morphologically docked vesicles is
in approximate agreement with the estimates of Stevens and Tsujimoto
(1995), who found a releasable pool size that varied from 8 to 24 quanta for a small sample of cultured hippocampal synapses. L. Dobrunz
and C. F. Stevens (unpublished observations) report an average pool
size of 8.1 ± 0.8 for CA1 neurons in slices, in good agreement
with the morphological estimates here.
The discrepancy between physiological (8-24) and morphological (1-13)
estimates of the releasable pool size in culture could arise in at
least two ways. First, the methods used by Stevens and Tsujimoto (1995)
would tend to undercount boutons and therefore would overestimate the
pool size; the physiological estimate might be too large. Second, the
docked vesicle pool size determined morphologically might underestimate
the actual size of the physiologically docked vesicle pool because of
fixation artifacts; the morphological pool might be too small. Although
one can never be certain about the relationship between electron
micrograph images and the situation that holds for the living cell, we
do not favor the fixation artifact alternative. Smith and Reese (1980)
have reported that gluteraldehyde produces release at the frog
neuromuscular junction, so that fixation might deplete the releasable
pool. But we find that all neurotransmitter release is blocked with a
time constant of ~1 sec in hippocampal cultures without significant
"spontaneous" release produced by the fixative (C. Rosenmund and C. F. Stevens, unpublished observations). Release during fixation should
have been detected because the postsynaptic glutamate receptors are
fixed more slowly than is the release machinery; the postsynaptic
responses to kainate decline approximately four times more slowly than
does evoked release. We therefore have no evidence to suggest that the
releasable pool is significantly depleted by fixation, although we
cannot exclude this possibility.
Docked vesicle pool and release probability correspondence
Third, our determination of the distribution of active zone areas
(and the number of docked vesicles) permits us to test the hypothesis
that release probability is proportional to the number of docked
vesicles (which is proportional to the active zone area). Murthy et al.
(1997) have measured the distribution of release probabilities for a
population of hippocampal boutons, and we can compare this distribution
with the one obtained here if we make the simplest assumption of a
proportionality between active zone area and release probability (see
Appendix for a justification of this assumption). In Figure
6 we have plotted, in cumulative form, the
experimentally derived release probability distribution (Murthy et al.,
1997, their Fig. 2B) and the one predicted from the
distribution of active zone areas (Fig. 4A). The two
distributions (Fig. 6) are not significantly different
(Kolmogorov-Smirnov test, p > 0.2). A single scale
factor relating active zone area to release probability was required
for this match: active zone area (µm2) × 5.75 gives release probability. This value would correspond to a release
probability of ~0.03 per docked vesicle.
Fig. 6.
Comparison of the distribution of the active zone
areas with the release probability. The solid line
represents the release probability of hippocampal CA1 synapses as
measured by Murthy et al. (1997). The dashed line gives
the distribution of release probabilities predicted from the
distribution of active zone areas (Fig. 4A) as
described in Appendix. The theoretical and observed distributions are
not significantly different (Kolmogorov-Smirnov test,
P > 0.2).
[View Larger Version of this Image (14K GIF file)]
Murthy et al. (1997) find that the lower release probability boutons
exhibited the largest amount of paired pulse facilitation. This
observation is in agreement with the finding of Bower and Haberly
(1986) that a class of smaller boutons have greater facilitation. Although the relationship between the number of docked vesicles and
release probability remains to be established at individual synapses,
the data in Figure 6 indicate that the hypothesis is a tenable one.
FOOTNOTES
Received March 25, 1997; revised May 5, 1997; accepted May 19, 1997.
This work was supported by the Howard Hughes Medical Institute, by
National Institutes of Health Grant 5 RO1 NS 12961 (C.F.S.), and by
Deutsche Forschungsgemeinschaft Grant Schi391/1-1 (T.S.). We thank C. Boyer and R. Jacobs for their technical assistance and Dr. T. Bartol,
A. Shrom, and Dr. D. Wild for their help with the three-dimensional
reconstructions.
Correspondence should be addressed to Dr. Charles F. Stevens, Molecular
Neurobiology Laboratory and Howard Hughes Medical Institute, The Salk
Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037.
APPENDIX
To compare our distribution of the active zone sizes (or the
number of docked vesicles) with the physiological data on the distribution of release probabilities (see Fig. 6), we need a mathematical relationship that connects these two quantities. We made
the simplest assumption: release probability is proportional to active
zone area. The purpose of this Appendix is to justify this assumption.
Rosenmund and Stevens (1996) proposed that, for the hippocampal
synapses studied here, release probability is related to the number of
docked vesicles; decreasing the pool of docked vesicles decreases
release probability. Note that here "release probability" is
defined as the probability that a bouton will release neurotransmitter
and is, as will be seen below, distinct from the conditional
probability that an individual vesicle will undergo an exocytotic event
if no other vesicle does so (we call this the "exocytotic
probability").
Stevens and Wang (1994, 1995) find that at most a single vesicle is
released ordinarily by one bouton. This observation, together with the
findings of Stevens and Tsujimoto (1995) and of Rosenmund and Stevens
(1996) who reported that the rate of exocytosis is directly related to
the releasable pool size, is consistent with the following simple
mechanism: when the exocytotic probability is increased, the overall
probability that transmitter will be released is, for short times,
proportional to the number of vesicles available for release; but as
soon as one of the vesicles is successful, this first exocytosis raises
the energy barrier for other vesicles enough that a second exocytotic
event hardly ever takes place. Before the first exocytotic event, then,
release probability depends on all of the docked and cocked vesicles,
but a winner-take-all mechanism limits release to at most one
vesicle.
This view can be formalized as follows: We suppose that a nerve impulse
has arrived at the terminal at time t = 0. Let
f(t) be the probability that no exocytotic event
has occurred up to time t, and call  (t) the
individual vesicle exocytotic rate, the Poisson probability per second
for each vesicle to undergo an exocytotic event. Each vesicle is
assumed to be identical, and we have supposed that release occurs
according to a Poisson process (Barrett and Stevens, 1972). The
equation for the failure probability then is:
where n is the number of vesicles in the readily
releasable pool. The probabilistic exocytotic rate (t)
increases rapidly just after a nerve impulse arrives and then returns
to low levels over several hundred microseconds. The solution to the
above equation is:
We take the period of evoked release from t = 0 to
t = T so that the probability that no
release occurs in response to an arriving nerve impulse is
f(t). The value of the integral is, for a release
period of fixed duration, just a constant a:
The failure probability thus depends exponentially on the number
of vesicles in the releasable
pool f(T) = ena,
and the release probability p is:
For small values of p this last relationship is
approximately:
so release probability is proportional just to the releasable pool
size. In this derivation we assumed that all vesicles had the same
exocytotic probability and that they behaved independently up to the
time that the winner-take-all mechanism operates. Both of these
assumption can be relaxed, and the same exponential relationship between failure probability and pool size results. The value of a might, under more complicated assumptions, differ from
synapse to synapse and can change as the readily releasable pool is
depleted.
REFERENCES
-
Almers W,
Tse FW
(1990)
Transmitter release from synapses: does a preassembled fusion pore initiate exocytosis.
Neuron
4:813-818[Web of Science][Medline].
-
Barrett EF,
Stevens CF
(1972)
The kinetics of transmitter release at the frog neuro-muscular junction.
J Physiol (Lond)
227:691-708[Abstract/Free Full Text].
-
Bekkers JM,
Stevens CF
(1989)
NMDA and non-NMDA receptors are co-localized at individual excitatory synapses in cultured rat hippocampus.
Nature
341:230-233[Medline].
-
Betz WJ,
Bewick GS
(1992)
Optical analysis of synaptic vesicle recycling at the frog neuromuscular junction.
Science
255:200-203[Abstract/Free Full Text].
-
Betz WJ,
Mao F,
Bewick GS
(1992)
Activity-dependent fluorescent staining and destaining of living vertebrate motor nerve terminals.
J Neurosci
12:363-375[Abstract].
-
Bower JM,
Haberly LB
(1986)
Facilitating and nonfacilitating synapses on pyramidal cells: a correlation between physiology and morphology.
Proc Natl Acad Sci USA
83:1115-1119[Abstract/Free Full Text].
-
Bruns D,
Jahn R
(1995)
Real-time measurement of transmitter release from single synaptic vesicles.
Nature
377:62-65[Medline].
-
Burger PM,
Mehl E,
Cameron PL,
Maycox PR,
Baumert M,
Lottspeich F,
DeCamilli P,
Jahn R
(1989)
Synaptic vesicles immunoisolated from rat cerebral cortex contain high levels of glutamate.
Neuron
3:715-720[Web of Science][Medline].
-
Couteaux R
(1961)
Principaux criteres morphologiques et cytochimiques utilisables aujourd'hui pour definir les divers types de synapses.
Actual Neurophysiol
3:145-173.
-
Einstein A
(1926)
On the movement of small particles suspended in a stationary liquid demanded by the molecular-kinetic theory of heat.
In: Investigations on the theory of the Brownian movement (Fürth R,
ed). New York: Dover.
-
Hamos JE,
Van Horn SC,
Raczkowski D,
Sherman SM
(1987)
Synaptic circuits involving an individual retinogeniculate axon in the cat.
J Comp Neurol
259:165-192[Web of Science][Medline].
-
Harris KM,
Stevens JK
(1989)
Dendritic spines of CA1 pyramidal cells in the rat hippocampus: serial electron microscopy with reference to their biophysical characteristics.
J Neurosci
9:2982-2997[Abstract].
-
Harris KM,
Sultan P
(1995)
Variation in the number, location and size of synaptic vesicles provides an anatomical basis for the nonuniform probability of release at hippocampal CA1 synapses.
Neuropharmacology
34:1387-1395[Web of Science][Medline].
-
Harris KM,
Jensen FE,
Tsao B
(1992)
Three-dimensional structure of dendritic spines and synapses in rat hippocampus (CA1) at postnatal day 15 and adult ages: implications for the maturation of synaptic physiology and long-term potentiation.
J Neurosci
12:2685-2705[Abstract].
-
Jack JJB,
Redman SJ,
Wong K
(1981)
The components of synaptic potentials evoked in cat spinal motoneurons by impulses in single group Ia afferents.
J Physiol (Lond)
321:65-96[Abstract/Free Full Text].
-
Katz B
(1969)
In: The release of neural transmitter substances. Liverpool, England: Liverpool University.
-
Korn H,
Faber DS
(1991)
Quantal analysis and synaptic efficacy in the CNS.
Trends Neurosci
14:439-445[Web of Science][Medline].
-
Korn H,
Triller A,
Mallet A,
Faber DS
(1981)
Fluctuating responses at a central synapse: n binomial fit predicts number of stained presynaptic boutons.
Science
213:898-901[Abstract/Free Full Text].
-
Luse SA
(1956)
Electron microscope observations of the central nervous system.
J Biophys Biochem Cytol
2:531-542.[Abstract/Free Full Text]
-
Murthy VN,
Sejnowski TJ,
Stevens CF
(1997)
Heterogenous release properties of visualized individual hippocampal synapses.
Neuron
18:599-612[Web of Science][Medline].
-
Neale EA,
Nelson PG,
MacDonald RL,
Christian CN,
Bowers LM
(1983)
Synaptic interactions between mammalian central neurons in cell culture. III. Morphological correlates of quantal synaptic transmission.
J Neurophysiol
49:1459-1468[Abstract/Free Full Text].
-
Palay SL,
Palade GE
(1955)
The fine structure of neurons.
J Biophys Biochem Cytol
1:69-88.[Abstract/Free Full Text]
-
Peters A,
Sethares C,
Harriman KM
(1990)
Different kinds of axon terminals forming symmetric synapses with the cell bodies and initial axon segments of layer II/III pyramidal cells. II. Synaptic junctions.
J Neurocytol
19:584-600[Web of Science][Medline].
-
Pierce JP,
Lewin GR
(1994)
An ultrastructural size principle.
Neuroscience
58:441-446[Web of Science][Medline].
-
Pierce JP,
Mendell LM
(1993)
Quantitative ultrastructure of la boutons in the ventral horn: scaling and positional relationships.
J Neurosci
13:4748-4763[Abstract].
-
Propst JW,
Ko C-P
(1987)
Correlations between active zone ultrastructure and synaptic function studied with freeze-fracture of physiologically identified neuromuscular junctions.
J Neurosci
7:3654-3664[Abstract].
-
Pun RYK,
Neale EA,
Guthrie PB,
Nelson PG
(1986)
Active and inactive central synapses in cell culture.
J Neurophysiol
56:1242-1256[Abstract/Free Full Text].
-
Redman S
(1990)
Quantal analysis of synaptic potentials in neurons of the central nervous system.
Physiol Rev
70:165-198[Free Full Text].
-
Redman S,
Walmsley B
(1983)
Amplitude fluctuations in synaptic potentials evoked in cat spinal motoneurones at identified group Ia synapses.
J Physiol (Lond)
343:135-145[Abstract/Free Full Text].
-
Rosenmund C,
Stevens CF
(1996)
Definition of the readily releasable pool of vesicles at hippocampal synapses.
Neuron
16:1-20[Web of Science][Medline].
-
Rosenmund C,
Clements JD,
Westbrook GL
(1993)
Nonuniform probability of glutamate release at a hippocampal synapse.
Science
262:754-757[Abstract/Free Full Text].
-
Ryan TA,
Smith SJ
(1995)
Vesicle pool mobilization during action potential firing at hippocampal synapses.
Neuron
14:983-989[Web of Science][Medline].
-
Ryan TA,
Reuter H,
Wendland B,
Schweizer FE,
Tsien RW,
Smith SJ
(1993)
The kinetics of synaptic vesicle recycling measured at single presynaptic boutons.
Neuron
11:713-724[Web of Science][Medline].
-
Ryan TA,
Ziv NE,
Smith SJ
(1996)
Potentiation of evoked vesicle turnover at individually resolved synaptic boutons.
Neuron
17:125-134[Web of Science][Medline].
-
Smith JE,
Reese TS
(1980)
Use of aldehyde fixatives to determine the rate of synaptic transmitter release.
J Exp Biol
89:19-29[Abstract/Free Full Text].
-
Sorra KE,
Harris KM
(1993)
Occurrence and three-dimensional structure of multiple synapses between individual radiatum axons and their target pyramidal cells in hippocampal area CA1.
J Neurosci
13:3736-3748[Abstract].
-
Stevens CF,
Tsujimoto T
(1995)
Estimates for the pool size of releasable quanta at a single central synapse and for the time required to refill the pool.
Proc Natl Acad Sci USA
92:846-849[Abstract/Free Full Text].
-
Stevens CF,
Wang Y
(1994)
Changes in reliability of synaptic function as a mechanism for plasticity.
Nature
371:704-707[Medline].
-
Stevens CF,
Wang Y
(1995)
Facilitation and depression at single central synapses.
Neuron
14:795-802[Web of Science][Medline].
-
Streichert LC,
Sargent PB
(1989)
Bouton ultrastructure and synaptic growth in a frog autonomic ganglion.
J Comp Neurol
281:159-168[Web of Science][Medline].
-
Südhof TC
(1995)
The synaptic vesicle cycle: a cascade of protein-protein interactions.
Nature
375:645-653[Medline].
-
Von Gersdorff H,
Vardi E,
Matthews G,
Sterling P
(1996)
Evidence that vesicles on the synaptic ribbon of retinal bipolar neurons can be rapidly released.
Neuron
116:1221-1227.
-
Walmsley B
(1991)
Central synaptic transmission: studies at the connection between primary afferent fibres and dorsal spinocerebellar tract (DSCT) neurones in Clarke's column of the spinal cord.
Prog Neurobiol
36:391-423[Web of Science][Medline].
-
Walmsley B,
Wieniawa-Narkiewicz E,
Nicol MJ
(1985)
The ultrastructural basis for synaptic transmission between primary muscle afferents and neurons in Clarke's column of the cat.
J Neurosci
5:2095-2106[Abstract].
-
Wyckoff RWG,
Young JZ
(1956)
The motoneuron surface.
Proc R Soc Lond [Biol]
144:440-450[Medline].
-
Yeow MBL,
Peterson EH
(1991)
Active zone organization and vesicle content scale with bouton size at a vertebrate central synapse.
J Comp Neurol
307:475-486[Web of Science][Medline].
-
Zucker RS
(1973)
Changes in the statistics of transmitter release during facilitation.
J Physiol (Lond)
229:787-810[Abstract/Free Full Text].
-
Zucker RS
(1989)
Short-term synaptic plasticity.
Ann Rev Neurosci
12:13-31[Web of Science][Medline].
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|
|
|
A. R. Kay and K. Toth
Influence of Location of a Fluorescent Zinc Probe in Brain Slices on Its Response to Synaptic Activation
J Neurophysiol,
March 1, 2006;
95(3):
1949 - 1956.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Virmani, D. Atasoy, and E. T. Kavalali
Synaptic vesicle recycling adapts to chronic changes in activity.
J. Neurosci.,
February 22, 2006;
26(8):
2197 - 2206.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Hvalby, V. Jensen, H.-T. Kao, and S. I. Walaas
Synapsin-regulated synaptic transmission from readily releasable synaptic vesicles in excitatory hippocampal synapses in mice
J. Physiol.,
February 15, 2006;
571(1):
75 - 82.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. L. Moulder and S. Mennerick
Synaptic Vesicles: Turning Reluctance Into Action
Neuroscientist,
February 1, 2006;
12(1):
11 - 15.
[Abstract]
[PDF]
|
|
|
|
|
|
|
C. Zhao, E. M. Teng, R. G. Summers Jr, G.-l. Ming, and F. H. Gage
Distinct Morphological Stages of Dentate Granule Neuron Maturation in the Adult Mouse Hippocampus
J. Neurosci.,
January 4, 2006;
26(1):
3 - 11.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Christie and C. E. Jahr
Multivesicular Release at Schaffer Collateral-CA1 Hippocampal Synapses
J. Neurosci.,
January 4, 2006;
26(1):
210 - 216.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Moretti, J. M. Levenson, F. Battaglia, R. Atkinson, R. Teague, B. Antalffy, D. Armstrong, O. Arancio, J. D. Sweatt, and H. Y. Zoghbi
Learning and Memory and Synaptic Plasticity Are Impaired in a Mouse Model of Rett Syndrome
J. Neurosci.,
January 4, 2006;
26(1):
319 - 327.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Zuber, I. Nikonenko, P. Klauser, D. Muller, and J. Dubochet
The mammalian central nervous synaptic cleft contains a high density of periodically organized complexes
PNAS,
December 27, 2005;
102(52):
19192 - 19197.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. A. Lemke and J. Klingauf
Single Synaptic Vesicle Tracking in Individual Hippocampal Boutons at Rest and during Synaptic Activity
J. Neurosci.,
November 23, 2005;
25(47):
11034 - 11044.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Y. Sun, S. A Lyons, and L. E Dobrunz
Mechanisms of target-cell specific short-term plasticity at Schaffer collateral synapses onto interneurones versus pyramidal cells in juvenile rats
J. Physiol.,
November 1, 2005;
568(3):
815 - 840.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. A. Kushner, Y. Elgersma, G. G. Murphy, D. Jaarsma, G. M. van Woerden, M. R. Hojjati, Y. Cui, J. C. LeBoutillier, D. F. Marrone, E. S. Choi, et al.
Modulation of Presynaptic Plasticity and Learning by the H-ras/Extracellular Signal-Regulated Kinase/Synapsin I Signaling Pathway
J. Neurosci.,
October 19, 2005;
25(42):
9721 - 9734.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. D. Micheva and S. J. Smith
Strong Effects of Subphysiological Temperature on the Function and Plasticity of Mammalian Presynaptic Terminals
J. Neurosci.,
August 17, 2005;
25(33):
7481 - 7488.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P.-Y. Pan, Q. Cai, L. Lin, P.-H. Lu, S. Duan, and Z.-H. Sheng
SNAP-29-mediated Modulation of Synaptic Transmission in Cultured Hippocampal Neurons
J. Biol. Chem.,
July 8, 2005;
280(27):
25769 - 25779.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. R. Wilson, J. Kang, E. V. Hueske, T. Leung, H. Varoqui, J. G. Murnick, J. D. Erickson, and G. Liu
Presynaptic Regulation of Quantal Size by the Vesicular Glutamate Transporter VGLUT1
J. Neurosci.,
June 29, 2005;
25(26):
6221 - 6234.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Wang and M. W. Quick
Trafficking of the Plasma Membrane {gamma}-Aminobutyric Acid Transporter GAT1: SIZE AND RATES OF AN ACUTELY RECYCLING POOL
J. Biol. Chem.,
May 13, 2005;
280(19):
18703 - 18709.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Kuromi and Y. Kidokoro
Exocytosis and Endocytosis of Synaptic Vesicles and Functional Roles of Vesicle Pools: Lessons from the Drosophila Neuromuscular Junction
Neuroscientist,
April 1, 2005;
11(2):
138 - 147.
[Abstract]
[PDF]
|
|
|
|
|
|
|
A. G. Millar, R. S. Zucker, G. C. R. Ellis-Davies, M. P. Charlton, and H. L. Atwood
Calcium Sensitivity of Neurotransmitter Release Differs at Phasic and Tonic Synapses
J. Neurosci.,
March 23, 2005;
25(12):
3113 - 3125.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. A. Richards, J. Bai, and E. R. Chapman
Two modes of exocytosis at hippocampal synapses revealed by rate of FM1-43 efflux from individual vesicles
J. Cell Biol.,
March 14, 2005;
168(6):
929 - 939.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Hilfiker, F. Benfenati, F. Doussau, A. C. Nairn, A. J. Czernik, G. J. Augustine, and P. Greengard
Structural Domains Involved in the Regulation of Transmitter Release by Synapsins
J. Neurosci.,
March 9, 2005;
25(10):
2658 - 2669.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. M. Young Jr.
Proteolysis of SNARE proteins alters facilitation and depression in a specific way
PNAS,
February 15, 2005;
102(7):
2614 - 2619.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. A. Ledoux and C. S. Woolley
Evidence That Disinhibition Is Associated with a Decrease in Number of Vesicles Available for Release at Inhibitory Synapses
J. Neurosci.,
January 26, 2005;
25(4):
971 - 976.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. A. Biro, N. B. Holderith, and Z. Nusser
Quantal Size Is Independent of the Release Probability at Hippocampal Excitatory Synapses
J. Neurosci.,
January 5, 2005;
25(1):
223 - 232.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Gitler, Y. Takagishi, J. Feng, Y. Ren, R. M. Rodriguiz, W. C. Wetsel, P. Greengard, and G. J. Augustine
Different Presynaptic Roles of Synapsins at Excitatory and Inhibitory Synapses
J. Neurosci.,
December 15, 2004;
24(50):
11368 - 11380.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Raghavachari and J. E. Lisman
Properties of Quantal Transmission at CA1 Synapses
J Neurophysiol,
October 1, 2004;
92(4):
2456 - 2467.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Rohrbough, E. Rushton, L. Palanker, E. Woodruff, H. J. G. Matthies, U. Acharya, J. K. Acharya, and K. Broadie
Ceramidase Regulates Synaptic Vesicle Exocytosis and Trafficking
J. Neurosci.,
September 8, 2004;
24(36):
7789 - 7803.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. R. Deweese and A. M. Zador
Shared and Private Variability in the Auditory Cortex
J Neurophysiol,
September 1, 2004;
92(3):
1840 - 1855.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. C. Angulo, A. S. Kozlov, S. Charpak, and E. Audinat
Glutamate Released from Glial Cells Synchronizes Neuronal Activity in the Hippocampus
J. Neurosci.,
August 4, 2004;
24(31):
6920 - 6927.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Wallace and M. F. Bear
A Morphological Correlate of Synaptic Scaling in Visual Cortex
J. Neurosci.,
August 4, 2004;
24(31):
6928 - 6938.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Scimemi, A. Fine, D. M. Kullmann, and D. A. Rusakov
NR2B-Containing Receptors Mediate Cross Talk among Hippocampal Synapses
J. Neurosci.,
May 19, 2004;
24(20):
4767 - 4777.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. L. Voronin and E. Cherubini
'Deaf, mute and whispering' silent synapses: their role in synaptic plasticity
J. Physiol.,
May 15, 2004;
557(1):
3 - 12.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. M. Wojcik, J. S. Rhee, E. Herzog, A. Sigler, R. Jahn, S. Takamori, N. Brose, and C. Rosenmund
An essential role for vesicular glutamate transporter 1 (VGLUT1) in postnatal development and control of quantal size
PNAS,
May 4, 2004;
101(18):
7158 - 7163.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. A. Nimchinsky, R. Yasuda, T. G. Oertner, and K. Svoboda
The Number of Glutamate Receptors Opened by Synaptic Stimulation in Single Hippocampal Spines
J. Neurosci.,
February 25, 2004;
24(8):
2054 - 2064.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. G. Mozhayeva, M. F. Matos, X. Liu, and E. T. Kavalali
Minimum Essential Factors Required for Vesicle Mobilization at Hippocampal Synapses
J. Neurosci.,
February 18, 2004;
24(7):
1680 - 1688.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. W. Ordway
Quantal size fits central synaptic depression
PNAS,
January 27, 2004;
101(4):
907 - 908.
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Chen, N. C. Harata, and R. W. Tsien
From the Cover: Paired-pulse depression of unitary quantal amplitude at single hippocampal synapses
PNAS,
January 27, 2004;
101(4):
1063 - 1068.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. XU-FRIEDMAN and W. G. REGEHR
Structural Contributions to Short-Term Synaptic Plasticity
Physiol Rev,
January 1, 2004;
84(1):
69 - 85.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Momiyama, R A. Silver, M. Hausser, T. Notomi, Y. Wu, R. Shigemoto, and S. G Cull-Candy
The density of AMPA receptors activated by a transmitter quantum at the climbing fibre-Purkinje cell synapse in immature rats
J. Physiol.,
May 15, 2003;
549(1):
75 - 92.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. M. Franks, C. F. Stevens, and T. J. Sejnowski
Independent Sources of Quantal Variability at Single Glutamatergic Synapses
J. Neurosci.,
April 15, 2003;
23(8):
3186 - 3195.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Conti and J. Lisman
The high variance of AMPA receptor- and NMDA receptor-mediated responses at single hippocampal synapses: Evidence for multiquantal release
PNAS,
April 15, 2003;
100(8):
4885 - 4890.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. HU and B. DAVLETOV
SNAREs and control of synaptic release probabilities
FASEB J,
February 1, 2003;
17(2):
130 - 135.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Zhao and M. Klein
Modulation of the Readily Releasable Pool of Transmitter and of Excitation-Secretion Coupling by Activity and by Serotonin at Aplysia Sensorimotor Synapses in Culture
J. Neurosci.,
December 15, 2002;
22(24):
10671 - 10679.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. J. Tyler, S. P. Perrett, and L. D. Pozzo-Miller
The Role of Neurotrophins in Neurotransmitter Release
Neuroscientist,
December 1, 2002;
8(6):
524 - 531.
[Abstract]
[PDF]
|
|
|
|
|
|
|
S. Karunanithi, L. Marin, K. Wong, and H. L. Atwood
Quantal Size and Variation Determined by Vesicle Size in Normal and Mutant Drosophila Glutamatergic Synapses
J. Neurosci.,
December 1, 2002;
22(23):
10267 - 10276.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. G. Millar, H. Bradacs, M. P. Charlton, and H. L. Atwood
Inverse Relationship between Release Probability and Readily Releasable Vesicles in Depressing and Facilitating Synapses
J. Neurosci.,
November 15, 2002;
22(22):
9661 - 9667.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. F. Wesseling and D. C. Lo
Limit on the Role of Activity in Controlling the Release-Ready Supply of Synaptic Vesicles
J. Neurosci.,
November 15, 2002;
22(22):
9708 - 9720.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. E. Cabin, K. Shimazu, D. Murphy, N. B. Cole, W. Gottschalk, K. L. McIlwain, B. Orrison, A. Chen, C. E. Ellis, R. Paylor, et al.
Synaptic Vesicle Depletion Correlates with Attenuated Synaptic Responses to Prolonged Repetitive Stimulation in Mice Lacking alpha -Synuclein
J. Neurosci.,
October 15, 2002;
22(20):
8797 - 8807.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Abenavoli, L. Forti, M. Bossi, A. Bergamaschi, A. Villa, and A. Malgaroli
Multimodal Quantal Release at Individual Hippocampal Synapses: Evidence for No Lateral Inhibition
J. Neurosci.,
August 1, 2002;
22(15):
6336 - 6346.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Pennuto, D. Dunlap, A. Contestabile, F. Benfenati, and F. Valtorta
Fluorescence Resonance Energy Transfer Detection of Synaptophysin I and Vesicle-associated Membrane Protein 2 Interactions during Exocytosis from Single Live Synapses
Mol. Biol. Cell,
August 1, 2002;
13(8):
2706 - 2717.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Waters and S. J Smith
Vesicle pool partitioning influences presynaptic diversity and weighting in rat hippocampal synapses
J. Physiol.,
June 15, 2002;
541(3):
811 - 823.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. H Brager, M. Capogna, and S. M Thompson
Short-term synaptic plasticity, simulation of nerve terminal dynamics, and the effects of protein kinase C activation in rat hippocampus
J. Physiol.,
June 1, 2002;
541(2):
545 - 559.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. M. G. Shepherd, M. Raastad, and P. Andersen
General and variable features of varicosity spacing along unmyelinated axons in the hippocampus and cerebellum
PNAS,
April 30, 2002;
99(9):
6340 - 6345.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F.-M. Lu and K. Kuba
Synchronous and Asynchronous Exocytosis Induced by Subthreshold High K+ at Cs+-Loaded Terminals of Rat Hippocampal Neurons
J Neurophysiol,
March 1, 2002;
87(3):
1222 - 1233.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Sara, M. G. Mozhayeva, X. Liu, and E. T. Kavalali
Fast Vesicle Recycling Supports Neurotransmission during Sustained Stimulation at Hippocampal Synapses
J. Neurosci.,
March 1, 2002;
22(5):
1608 - 1617.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. G. Mozhayeva, Y. Sara, X. Liu, and E. T. Kavalali
Development of Vesicle Pools during Maturation of Hippocampal Synapses
J. Neurosci.,
February 1, 2002;
22(3):
654 - 665.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Scheuss, R. Schneggenburger, and E. Neher
Separation of Presynaptic and Postsynaptic Contributions to Depression by Covariance Analysis of Successive EPSCs at the Calyx of Held Synapse
J. Neurosci.,
February 1, 2002;
22(3):
728 - 739.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. W. Hopf, J. Waters, S. Mehta, and S. J. Smith
Stability and Plasticity of Developing Synapses in Hippocampal Neuronal Cultures
J. Neurosci.,
February 1, 2002;
22(3):
775 - 781.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. S. Diamond
Neuronal Glutamate Transporters Limit Activation of NMDA Receptors by Neurotransmitter Spillover on CA1 Pyramidal Cells
J. Neurosci.,
November 1, 2001;
21(21):
8328 - 8338.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. C. Meyer, E. Neher, and R. Schneggenburger
Estimation of Quantal Size and Number of Functional Active Zones at the Calyx of Held Synapse by Nonstationary EPSC Variance Analysis
J. Neurosci.,
October 15, 2001;
21(20):
7889 - 7900.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A.G. M. Leenders, F. H. L. da Silva, W. E.J.M. Ghijsen, and M. Verhage
Rab3A Is Involved in Transport of Synaptic Vesicles to the Active Zone in Mouse Brain Nerve Terminals
Mol. Biol. Cell,
October 1, 2001;
12(10):
3095 - 3102.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Xu-Friedman, K. M. Harris, and W. G. Regehr
Three-Dimensional Comparison of Ultrastructural Characteristics at Depressing and Facilitating Synapses onto Cerebellar Purkinje Cells
J. Neurosci.,
September 1, 2001;
21(17):
6666 - 6672.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Pamidimukkala and M. Hay
Frequency dependence of endocytosis in aortic baroreceptor neurons and role of group III mGluRs
Am J Physiol Heart Circ Physiol,
July 1, 2001;
281(1):
H387 - H395.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. J. Tyler and L. D. Pozzo-Miller
BDNF Enhances Quantal Neurotransmitter Release and Increases the Number of Docked Vesicles at the Active Zones of Hippocampal Excitatory Synapses
J. Neurosci.,
June 15, 2001;
21(12):
4249 - 4258.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. R. Mellor and A. D. Randall
Synaptically Released Neurotransmitter Fails to Desensitize Postsynaptic GABAA Receptors in Cerebellar Cultures
J Neurophysiol,
May 1, 2001;
85(5):
1847 - 1857.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Hanse and B. Gustafsson
Vesicle release probability and pre-primed pool at glutamatergic synapses in area CA1 of the rat neonatal hippocampus
J. Physiol.,
March 1, 2001;
531(2):
481 - 493.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. M. Ullian, S. K. Sapperstein, K. S. Christopherson, and B. A. Barres
Control of Synapse Number by Glia
Science,
January 26, 2001;
291(5504):
657 - 661.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
K. C. Rowland, N. K. Irby, and G. A. Spirou
Specialized Synapse-Associated Structures within the Calyx of Held
J. Neurosci.,
December 15, 2000;
20(24):
9135 - 9144.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. E. Kriebel, B. Keller, J. Holsapple, G. Q. Fox, and G. D. Pappas
Porocytosis: Fusion Pore Array Secretion of Neurotransmitter
Neuroscientist,
December 1, 2000;
6(6):
422 - 427.
[Abstract]
[PDF]
|
|
|
|
|
|
|
V. Matveev and X.-J. Wang
Differential Short-term Synaptic Plasticity and Transmission of Complex Spike Trains: to Depress or to Facilitate?
Cereb Cortex,
November 1, 2000;
10(11):
1143 - 1153.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Waters and S. J Smith
Phorbol Esters Potentiate Evoked and Spontaneous Release by Different Presynaptic Mechanisms
J. Neurosci.,
November 1, 2000;
20(21):
7863 - 7870.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. R. Cottrell, G. R. Dube, C. Egles, and G. Liu
Distribution, Density, and Clustering of Functional Glutamate Receptors Before and After Synaptogenesis in Hippocampal Neurons
J Neurophysiol,
September 1, 2000;
84(3):
1573 - 1587.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Oleskevich and B. Walmsley
Phosphorylation regulates spontaneous and evoked transmitter release at a giant terminal in the rat auditory brainstem
J. Physiol.,
July 15, 2000;
526(2):
349 - 357.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C Auger and A Marty
Quantal currents at single-site central synapses
J. Physiol.,
July 1, 2000;
526(1):
3 - 11.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. D. Murphy, S. M. Rueter, J. Q. Trojanowski, and V. M.-Y. Lee
Synucleins Are Developmentally Expressed, and alpha -Synuclein Regulates the Size of the Presynaptic Vesicular Pool in Primary Hippocampal Neurons
J. Neurosci.,
May 1, 2000;
20(9):
3214 - 3220.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
