 |
 Previous Article | Next Article 
The Journal of Neuroscience, December 1, 2002, 22(23):10072-10077
BRIEF COMMUNICATION
Heterozygous Knock-Out Mice for Brain-Derived Neurotrophic Factor
Show a Pathway-Specific Impairment of Long-Term Potentiation But
Normal Critical Period for Monocular Deprivation
Alessandro
Bartoletti1, *,
Laura
Cancedda1, *,
Susan W.
Reid2,
Lino
Tessarollo2,
Vittorio
Porciatti3,
Tommaso
Pizzorusso1, 3, and
Lamberto
Maffei1, 3
1 Scuola Normale Superiore, Laboratorio di
Neurobiologia, 56100 Pisa, Italy, 2 Neural Development
Group, Mouse Cancer Genetics Program, National Cancer Institute,
Frederick, Maryland 21701, and 3 Istituto di Neuroscienze
Consiglio Nazionale delle Ricerche, Area Ricerca San Cataldo,
56100 Pisa, Italy
 |
ABSTRACT |
Genetic deletion of a single allele of the
BDNF gene affects hippocampal LTP and causes
several behavioral phenotypes, including deficits in spatial learning.
In the developing visual cortex, overexpression of BDNF accelerates the
time course of the critical period for monocular deprivation (MD), and
exogenous administration of BDNF alters the outcome of MD. We asked
whether reduced levels of BDNF could affect visual cortex plasticity by
studying long-term potentiation (LTP) induction and the effects of MD
in heterozygous BDNF knock-out mice. We found that theta burst
stimulation that induced LTP in the layer IV-III pathway of wild-type
(wt) mice caused only a transient potentiation in BDNF+/ mice, and
that this potentiation vanished in 25 min. In contrast, LTP elicited by
stimulation of the white matter (WM), a form of LTP that can be induced
only during the critical period, occurred normally in wt and BDNF+/
mice. The effects of MD during the critical period were similar in wt
and BDNF+/ mice, indicating that layer IV-evoked, layer III
LTP is not required for ocular dominance plasticity. We then asked
whether reduction of cortical BDNF levels could prolong the critical
period for MD and for the WM-evoked, layer III LTP induction. We found
that in adult BDNF+/ mice, WM-evoked, layer III LTP was not
inducible, and that the critical period for MD terminated normally. We
conclude that deletion of one copy of the BDNF gene
selectively impairs LTP of the layer IV-III pathway but does not alter
ocular dominance plasticity.
Key words:
ocular dominance; neurotrophins; LTP; visual cortex; TrkB; visual deprivation
| |
INTRODUCTION |
Monocular deprivation (MD) during
the critical period causes a loss of responsiveness to the deprived eye
in visual cortical neurons. Although the effects of MD have been widely
studied, knowledge of the molecular mechanisms underlying the plastic
changes induced by MD remains elusive. Evidence has emerged that
neurotrophins regulate ocular dominance (OD) plasticity (McAllister et
al., 1999 ). For instance, intracortical infusion of excess BDNF
disrupts OD columns and counteracts the effects of MD (Cabelli et al., 1995; Galuske et al., 1996; Lodovichi et al., 2000). These actions are
accompanied by a significant alteration of functional properties of
cortical neurons. Recently, the analysis of a transgenic mouse exhibiting a precocious expression of BDNF in the forebrain has shown
that these mice are susceptible to the effects of MD, but that their
critical period terminates precociously (Hanover et al., 1999; Huang et
al., 1999). A precocious cessation of plasticity is also present for
the induction of long-term potentiation (LTP) in the white matter
(WM)-layer III pathway, a form of LTP that can be elicited only during
the critical period for MD (Kirkwood et al., 1995).
Although these experiments strongly suggest a key role for BDNF in
visual cortical plasticity, they do not answer the question of whether
endogenous BDNF is required under physiological circumstances for
cortical plasticity. Experiments using tyrosine kinase receptor B (TrkB)-IgG scavenging molecules have indicated a role for
endogenous TrkB ligands in the development of OD columns (Cabelli et
al., 1997) and in cortical synaptic plasticity (Akaneya et al., 1997; Sermasi et al., 2000). However, these observations do not specifically address the role of BDNF, because TrkB-IgG binds BDNF and NT4 with
equal affinity; NT4 is an important player in visual cortical plasticity because its administration prevents the anatomical and
functional effects of MD (Riddle et al., 1995; Gillespie et al., 2000;
Lodovichi et al., 2000).
To directly test the role of endogenous BDNF in visual cortical
plasticity, we used mice with a genetic deletion of the BDNF gene (Lyons et al., 1999). Because BDNF null mutant mice die during the
first few weeks after birth, we used the heterozygous animals that do
not show abnormal mortality. In situ hybridization and RNase
protection analysis reveals that BDNF mRNA expression is decreased in
BDNF heterozygous mice (Linnarsson et al., 1997) (L. Tessarollo,
unpublished observations). These mice present with deficits in feeding
behavior, aggressiveness, and spatial learning (Linnarsson et al.,
1997; but see Montkowski and Holsboer, 1997; Lyons et al., 1999; Kernie
et al., 2000) and show an impaired hippocampal LTP (Korte et al., 1995;
Patterson et al., 1996). Therefore, we have investigated whether the
deletion of a single allele of BDNF could also affect plasticity in the
visual cortex of BDNF+/ mice. We found that BDNF+/ mice have an
impairment in LTP of the layer IV-III pathway but normal WM-evoked,
layer III LTP. OD plasticity either during or after the critical period was unaffected.
| |
MATERIALS AND METHODS |
Animals. BDNF knock-out mice generated in the C57BL/6
genetic background were genotyped by PCR. BDNF+/ and control
wild-type (wt) littermates were electrophysiologically analyzed.
In vitro electrophysiology. Brains were rapidly removed and
immersed in ice-cold cutting solution containing (in
mM): 130 NaCl, 3.1 KCl, 1.0 K2HPO4, 4.0 NaHCO3, 5.0 dextrose, 2.0 MgCl2, 1.0 CaCl2, 10 HEPES,
1.0 ascorbic acid, 0.5 myoinositol, 2 pyruvic acid, and 1 kynurenate, pH 7.3. Slices of visual cortex, 0.35 mm thick, were
obtained using a vibratome (Leica, Nussloch, Germany) and
transferred to a chamber containing cutting solution. The recording
solution was identical to the cutting solution, with the
following differences (in mM): 1.0 MgCl2, 2.0 CaCl2, 0.01 glycine, and no kynurenate. Slices were perfused at a rate of 2 ml/min
with 35°C oxygenated recording solution. Electrical stimulation (100 µsec duration) was delivered with a bipolar concentric stimulating electrode (Frederick Haer Co., Bowdoinham, ME) placed either at the
border between the WM and layer VI or in layer IV. Field potentials in
layer III were recorded by means of a glass micropipette (1-3 M )
filled with NaCl (3 M). Baseline responses were
obtained every 30 sec, with a stimulation intensity that yielded
half-maximal responses. The amplitude of the maximum negative field
potential in layer III was used as a measure of the evoked population
excitatory synaptic current. After achievement of at least a 10 min
stable baseline, theta burst stimulation (TBS) was delivered.
In vivo electrophysiology. Electrophysiological procedures
were performed as described previously (Lodovichi et al., 2000). Briefly, animals were anesthetized with urethane (0.7 ml/kg , i.p., 20% solution in saline), and temperature was maintained at
37°C. A hole was drilled in the skull in correspondence with the binocular portion of the primary visual cortex (area Oc1B) contralateral to the deprived eye, the dura was removed, and a micropipette (1-3 M) filled with NaCl (3 M)
was inserted into the cortex (stereotaxic coordinates, 2.9-3.1 mm from
the central fissure). For each animal, 8-10 cells were recorded in
each of at least three tracks spaced evenly (>100 µm) across the
mediolateral and anteroposterior extent of Oc1B, to avoid sampling
bias. Only cells with a receptive field (RF) within 20° from
the vertical meridian were included in our sample. Cell properties were
determined from peristimulus time histograms (PSTHs) recorded in
response to a computer-generated bar, averaged over at least 20 stimulus presentations. Cells were distributed in Wiesel and Hubel
(1965) OD classes according to the following
criteria: if no response was obtained from the ipsilateral eye, the
unit was classified as 1; if the contralateral peak response (highest
spiking frequency evoked by visual stimulation) was more than 1.3 times
the peak response of the ipsilateral eye, the cell was classified as
2-3. The same criteria were applied for cells in which the ipsilateral eye was exclusively or predominantly driving the cell response; these
cells were classified as 7 or 5-6, respectively. When the peak
response of the dominant eye was less than 1.3 times the response of
the other eye, the cell was classified as 4.
The OD distribution of each animal was summarized using the
contralateral bias index (CBI) (Gordon and Stryker, 1996), as follows:
CBI = ([(N(1) N(7)] + 1/2[N(2/3) N(5/6)] + N(tot))/2N(tot), where N(tot)
is the total number of recorded cells and N(i) is the number of cells in class i. RF size was assumed to be
the major axis of the area of a visual field eliciting a visual
response higher than baseline discharge +2 SD. The baseline spiking
frequency was measured in the absence of the visual stimulus.
Data from in vitro and in vivo electrophysiology
are reported as averages ± SEM.
| |
RESULTS |
Selective impairment of layer IV-evoked, layer III LTP in
BDNF+/ mice
To explore the role of BDNF in synaptic plasticity of the visual
cortex during the critical period, we studied LTP induction in cortical
slices of heterozygous BDNF+/ mice at postnatal day 21 (P21) to P30.
A stimulating electrode was placed either in layer IV or in the WM;
field potentials were recorded by an electrode positioned in layer III.
Stimulus intensity was adjusted to values that elicited responses of
amplitude approximately half (53 ± 6.3%) of the maximal response
amplitude. Similar half-maximal amplitudes were evoked using equivalent
stimulus intensities in wt and BDNF+/ mice (layer IV, 447 ± 20 µV with a stimulus intensity of 222 ± 31 µA for wt and
427 ± 35 µV with a stimulus intensity of 183 ± 21 µA
for BDNF+/; WM, 469 ± 35 µV with a stimulus intensity of
656 ± 273 µA for wt and 495 ± 43 µV with a stimulus
intensity of 692 ± 139 µA for BDNF+/).
In wt animals, TBS of either layer IV or the WM induced LTP of layer
III responses. The field potential amplitude 25 min after TBS was
115.3 ± 3.1% of the pre-TBS baseline for the layer IV-III pathway and 126.1 ± 6.8% for the WM-layer III pathway (Fig.
1). In contrast, visual cortical slices
taken from BDNF+/ mice showed only a transient potentiation in the
layer IV-III pathway. Indeed, TBS did induce potentiation, but this
potentiation decayed rapidly over time, with synaptic responses
completely returning to the baseline level (101.5 ± 1.9%) within
25 min of induction (Fig. 1C). Typical waveforms recorded at
different times during the experiment in wt and BDNF+/ mice are shown
in Figure 1B,E.
View larger version (27K):
[in this window]
[in a new window]
|
Figure 1.
BDNF+/ mice show impaired layer IV-evoked but
normal WM-evoked layer III LTP. A-C (layers IV-III):
A, Average time course of layer III field
potential amplitude before and after TBS of layer IV in wt mice
(n = 16 slices; 6 mice) and BDNF+/ mice
(n = 10 slices; 6 mice). In contrast to wt animals,
in which LTP persists for at least 30 min, BDNF+/ animals show a fast
decay of response amplitude starting 5 min after TBS and returning to
baseline values within 25 min. B, Average of 10 traces
recorded from a wt and a BDNF+/ slice before, 3 min after TBS
(BDNF+/), and 25 min after TBS. C, Average and
single cases of LTP in wt and BDNF+/ slices 25 min after TBS.
BDNF+/ slices significantly differ from wt, showing no LTP at this
time (t test). D-F (WM-layer III):
D, Average time course of layer III field potential
amplitudes before and after TBS of WM in wt mice (n = 6 slices; 2 mice) and BDNF+/ mice (n = 9 slices; 4 mice). Both experimental groups exhibit an LTP of synaptic
responses after TBS. E, Average of 10 traces recorded
from a wt and a BDNF+/ slice before and 25 min after TBS.
F, Average and single cases of LTP in wt and BDNF+/
slices 25 min after TBS. There is no significant difference between the
two experimental groups (t test). Solid lines
represent prebaseline amplitude. Dashed lines show pre-TBS
peak level.
|
|
In contrast to the decaying potentiation that we found in the layer
IV-III pathway of BDNF+/ mice, TBS delivered to the WM of these mice
was able to induce a long-lasting potentiation (Fig. 1D-F). Figure 1E shows
representative traces taken before and 25 min after TBS, when the
response amplitude was 124.1 ± 4.5% for BDNF+/ mice. These
data indicate that the decrease in BDNF levels causes a significant
deficit in layer IV-evoked, layer III LTP while sparing normal LTP in
the WM-layer III pathway.
OD plasticity during critical period is normal in
BDNF+/ mice
To test the visual cortex plasticity of BDNF+/ mice in
vivo, we evaluated the effect of MD during the critical period
(Fig. 2). We monocularly deprived wt and
BDNF+/ mice for 4-5 d at the peak of sensitivity to MD (P26) (Gordon
and Stryker, 1996). At the end of the deprivation period, we assessed
OD by comparing PSTHs recorded in response to stimulation of either
eye. We found that both groups similarly shifted their OD distributions
toward the nondeprived eye (Fig. 1B,C). To summarize
the OD of each animal, we adopted the CBI, an index that is 0 for
complete ipsilateral dominance and 1 for complete contralateral
dominance (see Materials and Methods). CBIs of the two experimental
groups were equally reduced by MD (Fig. 1D),
demonstrating that there is no difference between wt and BDNF+/ mice
in terms of sensitivity to MD during the critical period. We also
analyzed several functional properties of cortical neurons such as peak
response (wt, 54.9 ± 13.7 spikes/sec; BDNF+/, 65.3 ± 39.3 spikes/sec), peak to baseline (wt, 11 ± 8.3; BDNF+/, 8.6 ± 3.6), and receptive field size (wt, 27.9 ± 4.9°; BDNF+/,
27.7 ± 3°) and found no differences between the two groups (t test). We conclude that the deletion of a single
BDNF allele does not impair the OD plasticity and response
properties of cortical neurons during the critical period.
View larger version (10K):
[in this window]
[in a new window]
|
Figure 2.
OD plasticity during the critical period is
normal in BDNF+/ mice. A, OD distribution of normal wt
mice. The CBI indicates a distribution bias in favor of the
contralateral eye. Brief MD (4-5 d) beginning at P26 induces a strong
OD shift toward the nondeprived eye in P26 MD wt mice
(B) as well as in P26 MD BDNF+/ mice
(C). D, Scatterplot of single
animal CBIs. Left, P26 MD wt mice; right,
P26 MD BDNF+/ mice; shaded region, range of normal
adult wt mice. One-way ANOVA shows a significant difference
(p = 0.012) between the three groups; the
post hoc Tukey test reveals a significant difference
between normal adult and P26 MD wt (p = 0.029) or BDNF+/ (p = 0.006) mice but not
between P26 MD wt and P26 MD BDNF+/ mice.
|
|
Critical period is normal in BDNF+/ mice
Because overexpression of BDNF causes a precocious closure of the
critical period for MD and for induction of WM-evoked, layer III
LTP (Huang et al., 1999), we investigated whether reduction of cortical
BDNF levels was sufficient to prolong the period during which
WM-evoked, layer III LTP can be induced and MD is effective.
WM-evoked, layer III LTP is not present in slices from adult (older
than P63) wt or BDNF+/ mice. Figure
3A shows the average time
course of the response amplitudes before and after TBS. Figure 3C represents the response amplitude change 25 min after TBS
for each experimental slice. The field potential amplitude remained at
pre-TBS levels for both wt (103.6 ± 0.9%) and BDNF+/
(104.3 ± 2.0%) mice. Typical traces for wt and BDNF+/ mice
before and 25 min after TBS are shown in Figure 3B.
View larger version (12K):
[in this window]
[in a new window]
|
Figure 3.
WM-evoked, layer III LTP is normal in adult
BDNF+/ mice. A, Average time course of layer III field
potential amplitude before and after TBS in wt mivr
(n = 10 slices; 3 mice) and BDNF+/ mice
(n = 10 slices; 4 mice). The field potential
amplitude remained at pre-TBS levels in both experimental groups.
B, Average of 10 traces recorded from a wt and a
BDNF+/ slice before and 25 min after TBS. C, Average
and single cases of LTP in wt and BDNF+/ slices 25 min after TBS.
There is no significant difference between the two experimental groups
(t test). Solid lines represent prebaseline
amplitude. Dashed lines show pre-TBS peak
level.
|
|
To investigate the closure of the critical period for MD in
BDNF+/ mice, we recorded adult mice (older than P51) of both genotypes after 4-5 d of MD (Fig. 4). We
found that both wt and BDNF+/ mice were insensitive to MD, showing no
shift of OD distribution, and we also found CBIs comparable with those
of normal (nondeprived) adult mice. Peak response, peak to baseline,
and receptive field size were also indistinguishable between
monocularly deprived BDNF+/ and wt mice, either deprived or
nondeprived (data not shown; t test). To exclude the
possibility that the critical period could be slightly prolonged, we
assessed the effect of 4-5 d of MD beginning at P35 and P42-P45, when
the critical period is ending. At these ages, MD induced a similar
slight OD shift in both genotypes (Fig. 4D). Two-way
ANOVA on CBIs of all groups (P26, P35, P42-P45, and adults of both
genotypes) showed a significant effect of age (p = 0.004) but no significant effect of genotype and no interaction of
genotype with age. These data indicate that the time course of
the offset of the critical period is normal in BDNF+/ mice.
View larger version (16K):
[in this window]
[in a new window]
|
Figure 4.
The critical period is normal in BDNF+/
mice. A, In adult wt mice (older than P51), MD does not
induce an OD shift. B, In adult BDNF+/ mice
(older than P70), MD is also ineffective in inducing an OD shift.
C, CBIs of single animals. Left, Adult MD
wt mice; right, adult MD BDNF+/ mice; shaded
region, nondeprived mice. No significant difference is present
between the three groups (one-way ANOVA). D,
Developmental regulation of MD effects in wt and BDNF+/ mice. CBIs of
wt and BDNF+/ mice monocularly deprived at different ages (P26, P35,
P42, adult) for 4-5 d are shown. Both genotypes exhibit the same
sensitivity to MD during the critical period, become increasingly less
sensitive to MD at the tail of the critical period, and are completely
insensitive to MD as adults. Two-way ANOVA on CBIs of all groups (P26,
P35, P42, adult; both genotypes) showed a significant effect of age
(p = 0.004) but not of genotype, and no
significant interaction between age and genotype.
|
|
| |
DISCUSSION |
The present study shows that reduction by half of BDNF levels in
heterozygous BDNF mice did not affect the outcome of MD either during
or after the critical period. In contrast, BDNF+/ mice showed
different effects on two forms of cortical LTP. Namely, WM-evoked,
layer III LTP, a form of LTP known to be coregulated with OD plasticity
during the critical period (Kirkwood et al., 1995), was normally
inducible in BDNF+/ mice, whereas layer IV-evoked, layer III LTP was
impaired. WM-evoked, layer III LTP could not be induced in adult wt and
BDNF+/ mice.
LTP deficiency in BDNF+/ mice
The presence of an impairment of layer IV-evoked,
layer III LTP in BDNF+/ mice strengthens the notion that BDNF is a
central player in the mechanisms of synaptic plasticity. Indeed, a
number of experiments have shown an involvement of BDNF in LTP,
primarily in the hippocampus (Kang and Schuman, 1995; Ying et al.,
2002). Moreover, different lines of BDNF knock-out mice generated
independently in different laboratories have shown a severe defect in
hippocampal LTP in both homozygous and heterozygous mice (Korte et al.,
1995; Patterson et al., 1996). It has been suggested that the LTP
impairment present in the hippocampus of BDNF knock-outs is the result
of a more pronounced synaptic fatigue at the level of CA1 synapses during high-frequency tetanic stimulation (Pozzo-Miller et al., 1999).
In our experiments, we did not find deficits of the response to the TBS
used for LTP induction (data not shown). It is possible that either the
defect is present in a minority of synapses in the visual cortex or
that our TBS is a less challenging stimulation with respect to tetanic stimulation.
Previous studies have shown that BDNF is a powerful
regulator of LTP and long-term depression plasticity in the developing visual cortex either in vitro or in vivo (Akaneya
et al., 1996, 1997; Huber et al., 1998; Sermasi et al., 2000; Jiang et
al., 2001). However, none of these studies has addressed the issue of a
selective role of BDNF in LTP of different intracortical pathways. Our
study indicates that endogenous BDNF differentially regulates the
synaptic plasticity of cortical circuits. Indeed, although LTP could be
readily induced by WM stimulation, layer IV-evoked, layer III responses
potentiated only transiently after TBS in BDNF+/ mice. This selective
impairment of layer IV-evoked, layer III LTP suggests that TBS
stimulation of layer IV, but not of WM, activates mechanisms that are
strongly dependent on BDNF for the stabilization of LTP. Although the
nature of these mechanisms is still unknown, the deficit in layer
IV-evoked, layer III LTP present in BDNF+/ mice is not sufficient to
alter OD plasticity in vivo. Indeed, BDNF+/ mice exhibited
a normal OD shift after MD during the critical period. Thus, BDNF
heterozygous mice represent an example in which an OD shift is caused
by MD even if LTP of the layer IV-layer III pathway is impaired,
suggesting that this form of synaptic plasticity is not a good model
for mechanistic studies of OD plasticity.
Normal OD plasticity in BDNF+/ mice
OD plasticity was normal in BDNF heterozygous mice
during, at the end of, and after cessation of the critical period,
demonstrating a normal maturation of the molecular mechanisms
responsible for OD plasticity in BDNF+/ mice. Functional properties
of visual cortical neurons were also indistinguishable among the two
genotypes. Overall, our in vivo data show that heterozygous
BDNF mice exhibit a haplosufficient phenotype for visual cortical
development. This differs from other aspects of BDNF function, such as
its regulation of feeding behavior, aggressiveness (Lyons et al., 1999;
Kernie et al., 2000), and spatial learning (Linnarsson et al., 1997; but see Montkowski and Holsboer, 1997). Indeed, all of these behaviors are affected in BDNF+/ mice. The lack of deficits in OD plasticity in
the BDNF+/ mice is surprising considering the data showing that BDNF
is an important factor in the cellular mechanisms underlying the
developmental plasticity of OD. The exogenous supply of BDNF disrupts
OD columns in kittens (Cabelli et al., 1995) and alters the outcome of
MD in rats and kittens (Galuske et al., 1996; Lodovichi et al., 2000).
The application of TrkB-IgG also affects the anatomical segregation of
OD columns in kittens (Cabelli et al., 1997). However, at least some of
the effects of TrkB-IgG could be attributable to their action on NT4,
which is also bound by TrkB-IgG. NT4 regulates OD plasticity, because
its application counteracts the effects of MD in various species
(Riddle et al., 1995; Gillespie et al., 2000; Lodovichi et al., 2000).
Therefore, it is possible that in BDNF+/ mice the endogenous levels
of NT4 are able to compensate for the reduction in BDNF, resulting in a
normal phenotype with respect to visual cortical plasticity.
Alternatively, BDNF cortical levels, although reduced, are still
sufficient for normal plasticity of the visual cortex.
Analyzing various forms of plasticity in heterozygous
BDNF+/ mice, we have shown that the reduction of endogenous BDNF
affects one form of cortical LTP but does not impair OD plasticity. The generation of conditional cortical knock-outs of BDNF is needed to
understand whether the complete elimination of the endogenous BDNF can
have a more general effect on the developmental plasticity of the
visual cortex.
| |
FOOTNOTES |
Received April 12, 2002; revised Sept. 19, 2002; accepted Sept. 26, 2002.
*
A.B. and L.C. contributed equally to this paper.
This work was supported by the Cofinanziamento Ministero Istruzione
Università e Ricerca, Consiglio Nazionale delle Ricerche targeted project in Biotechnology SP-5, Progetto Strategico Neuroscienze.
Correspondence should be addressed to Dr. Tommaso Pizzorusso, Scuola
Normale Superiore, Istituto Neuroscienze Consiglio Nazionale delle
Ricerche, via Moruzzi, 1, 56100 Pisa, Italy. E-mail:
tommaso{at}in.pi.cnr.it.
| |
REFERENCES |
-
Akaneya Y,
Tsumoto T,
Hatanaka H
(1996)
Brain-derived neurotrophic factor blocks long-term depression in rat visual cortex.
J Neurophysiol
76:4198-4201[Abstract/Free Full Text].
-
Akaneya Y,
Tsumoto T,
Kinoshita S,
Hatanaka H
(1997)
Brain-derived neurotrophic factor enhances long-term potentiation in rat visual cortex.
J Neurosci
17:6707-6716[Abstract/Free Full Text].
-
Cabelli RJ,
Hohn A,
Shatz CJ
(1995)
Inhibition of ocular dominance column formation by infusion of NT-4/5 or BDNF.
Science
267:1662-1666[Abstract/Free Full Text].
-
Cabelli RJ,
Shelton DL,
Segal RA,
Shatz CJ
(1997)
Blockade of endogenous ligands of trkB inhibits formation of ocular dominance columns.
Neuron
19:63-76[ISI][Medline].
-
Galuske RA,
Kim DS,
Castren E,
Thoenen H,
Singer W
(1996)
Brain-derived neurotrophic factor reversed experience-dependent synaptic modifications in kitten visual cortex.
Eur J Neurosci
8:1554-1559[ISI][Medline].
-
Gillespie DC,
Crair MC,
Stryker MP
(2000)
Neurotrophin-4/5 alters responses and blocks the effect of monocular deprivation in cat visual cortex during the critical period.
J Neurosci
20:9174-9186[Abstract/Free Full Text].
-
Gordon JA,
Stryker MP
(1996)
Experience-dependent plasticity of binocular responses in the primary visual cortex of the mouse.
J Neurosci
16:3274-3286[Abstract/Free Full Text].
-
Hanover JL,
Huang ZJ,
Tonegawa S,
Stryker MP
(1999)
Brain-derived neurotrophic factor overexpression induces precocious critical period in mouse visual cortex.
J Neurosci
19:RC40[Abstract/Free Full Text](1-5).
-
Huang ZJ,
Kirkwood A,
Pizzorusso T,
Porciatti V,
Morales B,
Bear MF,
Maffei L,
Tonegawa S
(1999)
BDNF regulates the maturation of inhibition and the critical period of plasticity in mouse visual cortex.
Cell
98:739-755[ISI][Medline].
-
Huber KM,
Sawtell NB,
Bear MF
(1998)
Brain-derived neurotrophic factor alters the synaptic modification threshold in visual cortex.
Neuropharmacology
37:571-579[ISI][Medline].
-
Jiang B,
Akaneya Y,
Ohshima M,
Ichisaka S,
Hata Y,
Tsumoto T
(2001)
Brain-derived neurotrophic factor induces long-lasting potentiation of synaptic transmission in visual cortex in vivo in young rats, but not in the adult.
Eur J Neurosci
14:1219-1228[ISI][Medline].
-
Kang H,
Schuman EM
(1995)
Long-lasting neurotrophin-induced enhancement of synaptic transmission in the adult hippocampus.
Science
267:1658-1662[Abstract/Free Full Text].
-
Kernie SG,
Liebl DJ,
Parada LF
(2000)
BDNF regulates eating behavior and locomotor activity in mice.
EMBO J
19:1290-1300[ISI][Medline].
-
Kirkwood A,
Lee HK,
Bear MF
(1995)
Co-regulation of long-term potentiation and experience-dependent synaptic plasticity in visual cortex by age and experience.
Nature
375:328-331[Medline].
-
Korte M,
Carroll P,
Wolf E,
Brem G,
Thoenen H,
Bonhoeffer T
(1995)
Hippocampal long-term potentiation is impaired in mice lacking brain-derived neurotrophic factor.
Proc Natl Acad Sci USA
92:8856-8860[Abstract/Free Full Text].
-
Linnarsson S,
Bjorklund A,
Ernfors P
(1997)
Learning deficit in BDNF mutant mice.
Eur J Neurosci
9:2581-2587[ISI][Medline].
-
Lodovichi C,
Berardi N,
Pizzorusso T,
Maffei L
(2000)
Effects of neurotrophins on cortical plasticity: same or different?
J Neurosci
20:2155-2165[Abstract/Free Full Text].
-
Lyons WE,
Mamounas LA,
Ricaurte GA,
Coppola V,
Reid SW,
Bora SH,
Wihler C,
Koliatsos VE,
Tessarollo L
(1999)
Brain-derived neurotrophic factor-deficient mice develop aggressiveness and hyperphagia in conjunction with brain serotonergic abnormalities.
Proc Natl Acad Sci USA
96:15239-15244[Abstract/Free Full Text].
-
McAllister AK,
Katz LC,
Lo DC
(1999)
Neurotrophins and synaptic plasticity.
Annu Rev Neurosci
22:295-318[ISI][Medline].
-
Montkowski A,
Holsboer F
(1997)
Intact spatial learning and memory in transgenic mice with reduced BDNF.
NeuroReport
8:779-782[ISI][Medline].
-
Patterson SL,
Abel T,
Deuel TA,
Martin KC,
Rose JC,
Kandel ER
(1996)
Recombinant BDNF rescues deficits in basal synaptic transmission and hippocampal LTP in BDNF knockout mice.
Neuron
16:1137-1145[ISI][Medline].
-
Pozzo-Miller LD,
Gottschalk W,
Zhang L,
McDermott K,
Du J,
Gopalakrishnan R,
Oho C,
Sheng ZH,
Lu B
(1999)
Impairments in high-frequency transmission, synaptic vesicle docking, and synaptic protein distribution in the hippocampus of BDNF knock-out mice.
J Neurosci
19:4972-4983[Abstract/Free Full Text].
-
Riddle DR,
Lo DC,
Katz LC
(1995)
NT-4-mediated rescue of lateral geniculate neurons from effects of monocular deprivation.
Nature
378:189-191[Medline].
-
Sermasi E,
Margotti E,
Cattaneo A,
Domenici L
(2000)
TrkB signalling controls LTP but not LTD expression in the developing rat visual cortex.
Eur J Neurosci
12:1411-1419[Medline].
-
Wiesel TN,
Hubel DH
(1965)
Comparison of the effects of unilateral and bilateral eye closure on cortical unit responses in kittens.
J Neurophysiol
28:1029-1040[Free Full Text].
-
Ying SW,
Futter M,
Rosenblum K,
Webber MJ,
Hunt SP,
Bliss TV,
Bramham CR
(2002)
Brain-derived neurotrophic factor induces long-term potentiation in intact adult hippocampus: requirement for ERK activation coupled to CREB and upregulation of Arc synthesis.
J Neurosci
22:1532-1540[Abstract/Free Full Text].
Copyright © 2002 Society for Neuroscience 0270-6474/02/222310072-06$05.00/0
This article has been cited by other articles:
|
|
|
|
 
I. Abidin, U. T. Eysel, V. Lessmann, and T. Mittmann
Impaired GABAergic inhibition in the visual cortex of brain-derived neurotrophic factor heterozygous knockout mice
J. Physiol.,
April 1, 2008;
586(7):
1885 - 1901.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Kolarow, T. Brigadski, and V. Lessmann
Postsynaptic Secretion of BDNF and NT-3 from Hippocampal Neurons Depends on Calcium Calmodulin Kinase II Signaling and Proceeds via Delayed Fusion Pore Opening
J. Neurosci.,
September 26, 2007;
27(39):
10350 - 10364.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Genoud, G. W. Knott, K. Sakata, B. Lu, and E. Welker
Altered Synapse Formation in the Adult Somatosensory Cortex of Brain-Derived Neurotrophic Factor Heterozygote Mice
J. Neurosci.,
March 10, 2004;
24(10):
2394 - 2400.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
TOP
ABSTRACT
INTRODUCTION
