1Department of Anatomy and Neurobiology, Medical College of Ohio, Toledo, Ohio 43614; and 2Department of Psychobiology, University of California Irvine, California 92717
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ABSTRACT |
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Lane, Richard D.,
Rey S. Stojic,
Herbert P. Killackey, and
Robert W. Rhoades.
Source of inappropriate receptive fields in cortical somatotopic maps
from rats that sustained neonatal forelimb removal. Previously
this laboratory demonstrated that forelimb removal at birth in rats
results in the invasion of the cuneate nucleus by sciatic nerve axons
and the development of cuneothalamic cells with receptive fields that
include both the forelimb-stump and the hindlimb. However, unit-cluster
recordings from primary somatosensory cortex (SI) of these animals
revealed few sites in the forelimb-stump representation where responses
to hindlimb stimulation also could be recorded. Recently we reported
that hindlimb inputs to the SI forelimb-stump representation are
suppressed functionally in neonatally amputated rats and that GABAergic
inhibition is involved in this process. The present study was
undertaken to assess the role that intracortical projections from the
SI hindlimb representation may play in the functional reorganization of
the SI forelimb-stump field in these animals. The SI forelimb-stump
representation was mapped during -aminobutyric acid (GABA)-receptor
blockade, both before and after electrolytic destruction of the SI
hindlimb representation. Analysis of eight amputated rats showed that
75.8% of 264 stump recording sites possessed hindlimb receptive fields
before destruction of the SI hindlimb. After the lesions, significantly
fewer sites (13.2% of 197) were responsive to hindlimb stimulation
(P < 0.0001). Electrolytic destruction of the SI
lower-jaw representation in four additional control rats with neonatal
forelimb amputation did not significantly reduce the percentage of
hindlimb-responsive sites in the SI stump field during GABA-receptor
blockade (P = 0.98). Similar results were obtained from
three manipulated rats in which the SI hindlimb representation was
silenced temporarily with a local cobalt chloride injection. Analysis
of response latencies to sciatic nerve stimulation in the hindlimb and
forelimb-stump representations suggested that the intracortical
pathway(s) mediating the hindlimb responses in the forelimb-stump field
may be polysynaptic. The mean latency to sciatic nerve stimulation at
responsive sites in the GABA-receptor blocked SI stump representation
of neonatally amputated rats was significantly longer than that for
recording sites in the hindlimb representation [26.3 ± 8.1 (SD) ms vs. 10.8 ± 2.4 ms, respectively,
P < 0.0001]. These results suggest that hindlimb
input to the SI forelimb-stump representation detected in GABA-blocked
cortices of neonatally forelimb amputated rats originates primarily
from the SI hindlimb representation.
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INTRODUCTION |
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In a previous report, we described an experimental
manipulation (neonatal forelimb removal) in rats that produces a
dramatic reorganization of the dorsal column-medial lemniscal pathway
such that a significant percentage of cuneate nucleus neurons express hindlimb receptive fields in addition to those from the forelimb-stump region (Lane et al. 1995). These hindlimb receptive
fields appear to be suppressed functionally at higher somatosensory
centers because very few can be detected in the primary somatosensory cortex (SI) forelimb-stump representation. The mechanism underlying this suppression appears to involve
-aminobutyric acid (GABA) mediated by both GABAA and GABAB receptors,
because treatment of the cortices with the appropriate GABA antagonists
revealed robust hindlimb receptive fields throughout much of the SI
forelimb-stump representation (Lane et al. 1997
). A
recent study used primarily anatomic methods to examine three possible
sources of this hindlimb input: intracortical connections in SI,
thalamocortical afferents arising from the hindlimb representation of
the ventroposterior lateral nucleus (VPL), and thalamocortical
afferents arising from the forelimb-stump representation of VPL
(Stojic et al. 1998
). The results of that study
indicated that the anatomic arrangement of the thalamocortical and
intracortical fibers in the neonatally amputated rats was normal. These
findings were consistent with the conclusion that the GABA-suppressed
hindlimb inputs to the SI forelimb-stump representation were conveyed
via the thalamocortical neurons in the forelimb-stump representation of
the VPL. This possibility is surprising for two reasons. First,
single-unit recordings from the VPL of neonatally manipulated rats
indicated that a relatively small but significant population of VPL
neurons (19%) express a hindlimb as well as a stump receptive field
(Stojic et al. 1998
). In comparison, more than twice as
many of the SI stump field recording sites (44%) express hindlimb
receptive fields in the GABA-receptor-blocked cortices (Lane et
al. 1997
). Second, a number of studies have implicated
preexisting intracortical connections (Hirsch and Gilbert
1993
; Jenkins et al. 1990
; Li and Waters
1996
; Li et al. 1996
; Smits et al.
1991
; Wall 1988
) as well as corticocortical
connections that emerge after peripheral deafferentation
(Darian-Smith and Gilbert 1994
), as key elements in
functional cortical reorganization in both the visual and somatosensory systems. The present experiments were undertaken to test the role of
thalamocortical fibers versus intracortical connections in conveying
hindlimb input to the SI stump representation in the GABA-receptor-blocked cortices of neonatally manipulated rats. Specifically, we examined the consequences of removing the SI hindlimb
representation, a potential source of intracortical input, on the
expression of hindlimb receptive fields in the GABA-receptor-blocked SI
stump field.
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METHODS |
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Neonatal forelimb removal
Pups >12 h old were anesthetized by hypothermia until immobile. The left forelimb was amputated with iridectomy scissors below the shoulder and the brachial artery sealed by electrocautery. The stump was infiltrated with local anesthetic (0.7% bupivacaine), and the skin was closed with cyanoacrylate adhesive. The pups were rewarmed, returned to their mothers, and used in recording experiments when they reached >60 days of age.
Recordings from SI
Standard multiple-unit recording and receptive-field mapping
techniques were used to assess the representation of the body surface
in the SI cortex (Lane et al. 1995, 1997
). Recordings in
animals that sustained neonatal forelimb removals were made from the
right cerebral cortex, contralateral to the amputation. Recordings from
normal animals were made from the right cerebral cortex. Rats initially
were anesthetized with a combination of ketamine (100 mg/kg) and
xylazine (20 mg/kg), the trachea was cannulated, and the left brachial
plexus and sciatic nerves were exposed. The rats were placed in a
stereotaxic head holder and mechanically ventilated. A bipolar
stimulating electrode was placed on the brachial plexus just proximal
to the origin of the median, ulnar, and radial nerves and another was
placed on the sciatic nerve
15 mm distal to the sciatic notch. A
midline incision was made in the scalp, the skull overlying the dorsal
cortex was removed, and the dura was incised and reflected. The surface
of the cortex was photographed at ×44 to record the placement of
microelectrode penetrations. The cortical surface was kept moist by
applying culture medium (Dulbecco's modified essential medium, GIBCO)
warmed to 37°C. Rats were maintained in a state of light anesthesia
for the duration of the recording session with periodic injections of
urethan (200 mg ip).
Unit clusters and occasional single units were recorded with
varnish-coated tungsten microelectrodes (Z = 0.9-1.3
M) and cutaneous receptive fields were defined in the manner
previously described by Rhoades et al. (1993)
and
Lane et al. (1995
, 1997
). Electrode penetrations spaced
~300 µm apart were made in a rectangular array, and multiunit
activity was recorded at depths between 500 and 750 µm (the
approximate depth of lamina IV). Cutaneous receptive fields were mapped
with tactile stimuli delivered with brushes and blunt probes. Response
latencies to brachial plexus or sciatic nerve electrical stimulation
(0.1-ms pulses ranging from 3 to 12 V) were tested at recording sites
characterized as possessing a forelimb-stump or hindlimb receptive
field. Latency values were defined on the oscilloscope traces as the
time between the beginning of the brachial plexus or sciatic nerve
stimulation artifact and the beginning of the cortical response. In
addition to the neonatally manipulated rats, cortical response
latencies to brachial plexus and sciatic nerve electrical stimulation
were measured in two normal rats before and during
-aminobutyric
acid (GABA)-receptor blockade.
As illustrated in Fig. 1
(experiment 1), the SI forelimb-stump and hindlimb
representations in cortex were mapped with multiunit recording
electrodes as described in the preceding text (map A). In
four cases, the SI lower-jaw representation was mapped in addition to
the forelimb-stump and hindlimb fields. After the initial mapping was
completed, 30 µl of a GABA-receptor-blocker solution containing equal
parts of 50 µM bicuculline methiodide and 50 µM phaclofen (both
supplied by Research Biochemicals International) was applied to the
surface of the cortex as previously described (Lane et al.
1997). After a delay of ~15 min, the stump region was
remapped (map B) in the manner described earlier. Between 30 and 50 sites in the forelimb-stump representation were tested during
each mapping, and the same sites were retested after the addition of
the GABA-receptor blockers. The percentage of forelimb-stump sites with
hindlimb receptive fields was determined for each animal under each
recording condition. After completion of the second map, either the SI
hindlimb (n = 8) or lower-jaw (n = 4)
representation was lesioned electrolytically. These representations
were destroyed by making multiple penetrations with a metal electrode
~300 µm apart through the first 800 µm of the cortex while
maintaining a constant 4 V DC. The completeness of the lesion was
determined later by examining cytochrome oxidase (CO) stained sections
of the cortices. The GABA-receptor blockers then were reapplied to the
cortex as before, and the forelimb-stump representation was remapped a
third time (map C). In several experiments, a recording
electrode was positioned near the center of the stump representation
and left undisturbed during the subsequent treatments. At the end of
the mapping experiment, the animal was given a lethal dose of carbon
dioxide and perfused with heparinized saline followed by 4%
paraformaldehyde dissolved in sodium phosphate buffer (pH 7.4). The
cortex was removed, flattened, and cut into 50-µm sections. Sections
were stained for CO by the method of Wong-Riley (1979)
.
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Temporary inactivation of the SI hindlimb representation with cobalt chloride
In another series of experiments (Fig. 1, experiment 2), the stump and hindlimb representations of three neonatally amputated rats were mapped before and after treatment with the GABA blockers (map A). For the remainder of the experiment, a recording electrode was positioned near the center of the SI forelimb-stump representation at a location (site 1) that was responsive to both stump and hindlimb tactile stimulation. A second recording electrode was positioned in the SI hindlimb representation at a location (site 2) that was responsive to hindlimb tactile stimulation. After characterizing the receptive fields at sites 1 and 2 (trace series 1), a saline solution containing 0.2 µl of cobalt chloride (30 mM) was injected into each of six sites in the SI hindlimb representation. After confirming that the cobalt chloride injections suppressed the sensory responses to hindlimb stimulation at site 2, the responses to tactile stimulation recorded at site 1 were evaluated (trace series 2). Once activity had returned to the hindlimb representation as assayed at site 2, the responses recorded at site 1 were reevaluated (trace series 3). GABA-receptor blockade was maintained throughout the latter part of the experiment. At the end of the recording session, rats were killed with carbon dioxide, perfused, and the cortices processed for CO staining as described earlier.
Statistical analysis
An analysis of variance (ANOVA) was used to test for significant differences between the percentages of sites with hindlimb receptive fields in the forelimb-stump representation under the various conditions described in the previous section and to compare the differences in forelimb-stump and hindlimb latency times measured under these conditions. When the ANOVA demonstrated significant (P < 0.05) between-group differences, a Scheffe test was performed to identify experimental groups with significantly different means. In two cases, specific latencies were compared using Student's t-test.
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RESULTS |
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Effects of lesioning the hindlimb or lower-jaw representations on expression of hindlimb receptive fields in the stump representation of neonatally amputated rats
The organization of the stump and hindlimb representations within
SI in two adult rats that sustained neonatal forelimb amputation are
shown in Fig. 2, A and
E. Within the stump representation, few sites responded to
hindlimb stimulation. Of 271 sites that responded to stimulation of the
stump in eight neonatally manipulated rats, only 3.7%
(n = 10, Fig. 2, ) also could be activated by stimulation of the hindlimb (Fig.
3A, AVG bar). Figure 2,
B and F, shows the stump representations from the
same animals during application of bicuculline and phaclofen. There was
a large increase in the number of sites (
) within the stump
representation at which responses could be evoked by stimulation of the
hindlimb. Of 264 sites that responded to stimulation of the stump
during GABA-receptor blockade, 75.8% (n = 200) also
could be activated by stimulation of the hindlimb (Fig. 3A;
P < 0.001 vs. the unblocked cortices of these same
rats).
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The hindlimb input to the SI stump representation revealed by GABA-receptor blockade was reduced markedly by electrolytic lesions of the SI hindlimb representation (Figs. 2, C and D, and 3A). The electrophysiological effect of the hindlimb lesion is demonstrated best by recordings collected at a site near the center of the stump representation before GABA-receptor blockade, during GABA-receptor blockade, and after lesioning the SI hindlimb region while maintaining the GABA-receptor blockade (Fig. 4). Before blockade there are distinct responses to stump electrical and tactile stimulation (Fig. 4, series 1, traces 1 and 3, respectively) but no detectable cortical response to stimulation of the hindlimb (Fig. 4, series 1, traces 2 and 4). During GABA blockade, a robust hindlimb response appeared (Fig. 4, series 2, traces 2 and 4). However, this hindlimb response became undetectable after the SI hindlimb representation was lesioned (Fig. 4, series 3, traces 2 and 4). A total of 197 recording sites in the SI stump representation that were previously hindlimb-responsive were assessed after the lesions. Of these, only 13.2% (n = 26) still possessed hindlimb responsivity after lesions of the S1 hindlimb region (Fig. 3A, AVG bar). All of these sites remained responsive to stump stimulation after the lesioning of the hindlimb representation. Although the effect of hindlimb lesions on the percent of sites possessing hindlimb responsivity varied among individual animals, no correlation was apparent between this value and the completeness of the hindlimb lesion as seen on the CO-stained cortical sections (see Fig. 2D for example of lesions).
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In a series of control experiments, 116 sites were evaluated in four manipulated rats; 65.5% (n = 76) displayed hindlimb receptive fields in stump recording sites during GABA-receptor blockade. After electrolytic lesions of the lower-jaw representation, 64.3% (72 of 112) still possessed hindlimb responsiveness (Fig. 3, AVG bars, P = 0.98 compared with prelesioned stump with GABA-receptor blockade). Figure 2, E-H, shows the maps and lesions from one of these animals. Figure 5 shows the traces from the stump representation from one of these control animals. In this case, the lower-jaw representation was lesioned and the postlesion traces are shown in series 3. Note that the hindlimb response in the GABA-receptor-blocked cortex is still present after lesioning the lower-jaw representation (Fig. 5, series 3, traces 2 and 4).
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Temporary inactivation of the SI hindlimb representation with cobalt chloride
The role of the cortical hindlimb representation in the functional reorganization of the stump field was evaluated further by reversible inactivation of the hindlimb response with cobalt chloride. (Figs. 6 and 7). Figure 7A shows the traces obtained from the recording electrode positioned in the stump representation at site 1, whereas Fig. 7B presents the traces obtained from the electrode located at site 2 in the hindlimb representation. Before the cobalt chloride treatment, the GABA-receptor-blocked stump site showed robust responses to both forelimb and hindlimb stimulation (Fig. 7A, series 1). During cobalt chloride treatment of the hindlimb representation, the neuronal responses evoked by the stimulation of the hindlimb disappeared in both the hindlimb representation (Fig. 7B, series 2, traces 2 and 4) as well as in the SI stump representation (Fig. 7A, series 2, traces 2 and 4). After the cobalt chloride effect had worn off, as indicated by the return of the hindlimb responsivity in the hindlimb representation (Fig. 7B, series 3, traces 2 and 4), the hindlimb responsivity also had returned to the stump representation as shown in Fig. 7A (series 3, traces 2 and 4). The borders of the mapped hindlimb and stump representations, the positions of the two recording sites, and the cobalt chloride injection sites in the hindlimb representation were verified by the CO pattern obtained from tangential sections of this brain (Fig. 6).
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Comparison of forelimb-stump and hindlimb latencies in normal and manipulated rats
The responses evoked by sciatic nerve stimulation at recording sites in the SI stump representation had very long latencies compared with both responses to stimulation of this nerve in the hindlimb representation and response to brachial plexus stimulation in the stump field. The average latency to sciatic nerve stimulation in the SI hindlimb representation measured in two normal animals was 12.7 ± 1.4 (SD) ms (n = 40) whereas that measured in seven neonatally amputated animals was significantly (P < 0.0001, Student's t-test for independent samples) shorter (10.5 ± 2.0 ms, n = 74). Application of the GABA-receptor blockers to the cortex did not have a significant effect on these values (13.3 ± 1.8 ms and 10.8 ± 2.4 ms, respectively) (see Fig. 8, A, B, and G). The average latencies to brachial plexus stimulation in the forelimb representation in normal rats with and without GABA-receptor blockade (9.4 ± 1.6 ms, n = 122 and 10.3 ± 2.1 ms, n = 120, respectively) were similar to the latencies measured under comparable conditions in the stump representation of neonatally manipulated rats (10.0 ± 2.2 ms, n = 78 and 9.6 ± 2.7 ms, n = 77, respectively; Fig. 8, C, D, and G). The average latency (26.3 ± 8.1 ms, n = 169) measured in the GABA-receptor-blocked stump cortex of neonatally amputated rats in response to sciatic nerve stimulation was significantly (P < 0.0001) longer than many of the previously listed values (Fig. 8, E and G). The average latency of those sites (n = 22) in the GABA-receptor-blocked stump representation that maintained hindlimb responsivity after lesion of the hindlimb representation was 19.1 ± 7.8 ms (Fig. 8F). This latency was not significantly different from that for the same sites before the lesion (19.5 ± 5.6 ms, P = 0.750, paired Student's t-test).
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DISCUSSION |
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The results of the present study indicate that the hindlimb input to the SI forelimb-stump representation detected in GABA-receptor-blocked cortices of neonatally forelimb amputated rats reaches this site via a pathway that includes the SI hindlimb representation. However, before considering these results further, several important technical limitations of our approach must be considered.
Technical limitations
The present study used multiple electrolytic lesions to
destroy the SI hindlimb representation. It is possible that these lesions produced nonspecific effects (e.g., ischemia), which altered the properties of SI forelimb-stump neurons. However, the fact that SI
lower-jaw representation lesions had no effect on these cells argues
against nonspecific effects producing the observed changes. This view
was supported further by the observation that reversible silencing of
the SI hindlimb cortex by chemical means (CoCl2) produced a
similar effect at the stump recording sites. Regarding the
CoCl2 experiments, it should be noted that the effects observed were measured at a single pair of sites in the forelimb-stump and hindlimb representations and not across multiple sites in the
forelimb-stump representation as was the case in the lesion study.
Measuring the electrophysiological effects at a single site in the
hindlimb representation leaves open the possibility that the
CoCl2 injections did not silence all of the hindlimb cortex. Mooney et al. (1992) observed that a single
25-nl injection of 10 mM CoCl2 in the superior colliculus
of a hamster silenced the surrounding tissue to a distance of 150 µm.
Taking into account the higher concentration and larger volume of
CoCl2 injected and assuming a linear relationship between
the dose and area of influence, an area within ~700 µm of each
injection site would be silenced in the present study. The combined
area of influence of the four CoCl2 injections in the SI
hindlimb representation should have silenced virtually the entire
hindlimb representation. Most importantly, determination of the extent
of the hindlimb representation silenced would be important had we not
seen an effect of our CoCl2 injections. This was not the
case.
Another limitation of our methods is that they did not provide information as to the source of the residual hindlimb responsive sites in the GABA-receptor-blocked forelimb-stump representation of the amputated rats after the SI hindlimb field was destroyed. Two possible sources of these remaining inputs are small regions of the SI hindlimb representation that survived the lesions and cortically projecting VPL neurons. The first possibility seems unlikely because the percentage of surviving hindlimb responsive sites in the stump representation of individual rats did not correlate with the extent of undamaged cortex in the SI hindlimb representation as observed on CO-stained sections (data not shown). In fact, in one case (269, see Fig. 3A), CO-stained sections revealed that the SI hindlimb representation was destroyed completely by electrolytic lesioning (not shown). The complete removal of the SI hindlimb area in this case did not result in the total elimination of all hindlimb responsive sites within the forelimb-stump representation. Therefore it is likely that the small percentage of hindlimb response sites that remain after SI hindlimb lesioning or inactivation are derived from another source within the forelimb-stump sensory pathway, in particular, the VPL nucleus.
The possibility that the surviving hindlimb responsive sites (13.2% of
all stump recording sites) received their input directly from VPL
neurons is supported by the fact that a comparable percentage of
stump-responsive VPL neurons (19% as reported by Stojic et al.
1998) also possess hindlimb receptive fields. Furthermore, the
average response latency to sciatic nerve stimulation measured at the
surviving hindlimb responsive sites in the forelimb-stump representation (19.1 ± 7.8 ms) after lesioning or inactivation is
consistent with the average latency to sciatic nerve stimulation measured in a small sample of VPL neurons (24 ± 8.7 ms,
n = 12) (Stojic et al. 1998
).
Role of intracortical neurons in cortical reorganization
Intracortical neurons appear to play a major role in transmitting
the hindlimb receptive-field information from the SI hindlimb representation to the stump representation. Previous work has indicated
that intracortical reorganization may be responsible for substantial
rearrangements of adult cortical representations in response to injury
(e.g., Darian-Smith and Gilbert 1994; Das and
Gilbert 1995
; Doetsch et al. 1988
; Jacobs
and Donoghue 1991
; Pons et al. 1991
). However,
the intracortical reorganization apparent in the present study appears
to differ from that described in previous reports. We (Stojic et
al. 1998
) have been unable to detect any significant anatomic
evidence of direct connections between the SI hindlimb and stump
representations in neonatally amputated rats. Our results thus suggest
that a polysynaptic intracortical pathway, perhaps involving
dysgranular cortex, may underlie the functional reorganization observed
in our experiments. It is possible that neonatal forelimb amputation
simply increases the effectiveness of existing polysynaptic connections
between the hindlimb and stump representations. Evidence of significant
hindlimb inputs to the SI forelimb field of normal rats has been
reported in an earlier study from this lab (Lane et al.
1997
). Before GABA-receptor blockade, 2.7% of all SI forelimb
recording sites express hindlimb inputs, and this value increases to
11.7% under GABA blockade. This suggests that neonatal forelimb
amputation may act by enhancing the normal expression of inappropriate
inputs in the SI forelimb-stump representation.
Support for a polysynaptic pathway between the SI hindlimb and stump
representations comes from the long latency values measured in the
GABA-receptor blocked stump representation in response to sciatic nerve
stimulation (Fig. 8E). The average response latency to
sciatic-nerve stimulation in hindlimb cortex of neonatally amputated
rats is 11 ms, whereas that in the stump representation is 26 ms. This
large time interval would allow multiple intracortical neurons to be
present in the pathway between the hindlimb and stump representation.
It is worth noting that the very long latencies of hindlimb-response
neurons in the cortical stump representation are consistent with those
reported for neurons with altered receptive fields in other studies.
Faggin et al. (1997) recently reported that in response
to mechanical stimulation of facial whiskers, the average latency of
unmasked sensory responses in the somatosensory cortices of rats that
received subcutaneous injections of lidocaine was 19.6 ms.
Schroeder et al. (1995)
observed that in response to
electrical stimulation of the forearm skin, a similar long latency of
~30 ms for peak current flow for the nondominant radial nerve input
to area 3b in squirrel monkey versus 12 ms for the dominant ulnar and
median nerve inputs. Ebner and Armstrong-James (1990)
observed that the center receptive field of layer IV cells in the SI
vibrissae representation of rats has a latency of 7-10 ms in response
to whisker deflection, but the surround receptive field has a latency
of 15-40 ms in response to adjacent whisker deflection. Like the
hindlimb responses in the stump representation of neonatally amputated
rats, the surround receptive field for vibrissae sensitive neurons
depends on intracortical connections (Armstrong-James et al.
1989
; Fox 1994
).
The present results raise the question: why do the neonatally amputated
rats possess a physiological demonstrable connection between the SI
hindlimb and the SI stump representation that is silenced by GABAergic
neurons? Perhaps this phenomenon is a result of alterations in the
pattern of intracortical connections in response to the nerve injury
and/or the associated change in afferent input caused by the neonatal
forelimb amputation. In the visual system, sensitivity of the
architecture of intracortical fibers to changes in visual experience
during postnatal development has been observed in cat striate cortex
(Callaway and Katz 1991; Lowel and Singer
1992
; Lubke and Albus 1992
; Luhmann et
al. 1986
; Price and Blakemore 1985
). In the
somatosensory system, infraorbital nerve lesion on postnatal day 7, after the whisker pattern is established, produces a drastic reduction
in intracortical projections within the mouse barrel cortex
(McCasland et al. 1992
). This indicates that the normal
murine pattern of intracortical connections is dependent on sensory
input. In contrast, Rhoades et al. (1996)
found that
neither silencing of cortical synaptic activity or transection of the
infraorbital nerve on postnatal day 7 (after thalamocortical afferent
patterns are established) has an effect on the pattern of
vibrissae-related intracortical projections within rat SI. However,
infraorbital nerve section on day of birth, before the establishment of
the thalamocortical afferent pattern in the cortex, profoundly affects
the patterning of intracortical connections. On the basis of these
studies, one would expect that limb amputation on the day of birth
would produce changes in the patterns of both thalamocortical and
intracortical fibers within the rat SI stump representation, and this
may well be the case. Unfortunately, these studies do not tell us what
changes to expect between two physically separated representations, the
hindlimb and stump.
Assuming the presumptive excitatory hindlimb to stump representation
pathway is established early in postnatal development, the GABAergic
inhibitory system, which appears to develop more slowly than the
excitatory system (Micheva and Beaulieu 1997), could,
via Hebbian mechanisms (Hebb 1949
), suppress this
connection in the stump region due to its lack of synchrony with the
more abundant stump responsive afferents in this region. However,
unlike other systems in which Hebbian mechanisms have been proposed to explain development and/or plasticity of connections (Hubel et al. 1977
; Shatz and Stryker 1978
; Wiesel
and Hubel 1970
), the suppression of hindlimb information in the
stump representation does not appear to involve a loss or retraction of
the pathway, which can support expression of functional reorganization.
Rather it appears that hindlimb inputs to the stump field can make a significant number of effective synaptic connections, but these connections are suppressed functionally through GABA-inhibitory mechanisms. Thus the preferential expression of stump inputs over hindlimb information may result not only from the competition between
the two groups of excitatory inputs in a classical Hebbian fashion.
Instead, the suppression of hindlimb inputs may involve the stump
afferents' ability to effectively steer the development of inhibitory
circuits within the stump field to permit the expression of stump
inputs over the more inappropriate hindlimb inputs. What factors that
would permit the development of this inhibition remain, as of yet,
unclear and require further investigation.
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ACKNOWLEDGMENTS |
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This work was supported by National Institutes of Health Grants NS-28888 and DE-07734.
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FOOTNOTES |
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Address for reprint requests: R. D. Lane, Dept. of Anatomy and Neurobiology, Medical College of Ohio, Toledo, OH 43614.
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 2 June 1998; accepted in final form 14 October 1998.
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REFERENCES |
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