Division of Neurobiology, Barrow Neurological Institute, St.
Joseph's Hospital and Medical Center, Phoenix, Arizona 85013
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INTRODUCTION |
Lesion or inactivation of the
lateral cerebellum or its output nucleus, dentate, impairs the ability
to make accurate well-coordinated limb movements (Bastian and
Thach 1995
; Thach et al. 1992). It is generally
assumed that the output of lateral cerebellum exerts its influence on
limb movements by modifying activity in motor cortex via thalamic
connections. However, lesion of the cerebellar receiving area of the
thalamus (Bastian and Thach 1995; Fabre-Thorpe and Levesque 1991; Ranish and Soechting 1976)
has a relatively minor effect on limb movements in comparison with
cerebellar lesion. Therefore it is likely that lateral cerebellum can
influence spinal activity via brain stem connections, and physiological
studies suggest that this is the case (Hames et al.
1981). One of the major brain stem targets of the dentate
nucleus (DN) of the cat is the parvicellular red nucleus (RNp). In this
study, we reexamine the connections of RNp to determine whether these
cells could provide an anatomical basis for the influence of lateral
cerebellum on limb movements.
The mammalian red nucleus (RN) is typically divided into a caudal
magnocellular region (RNm) and a rostral parvicellular region (RNp). It
is generally assumed that these cytoarchitectonic divisions differ also
in connectivity. RNm receives input from the cerebellar interpositus
nucleus and projects to the contralateral spinal cord, whereas RNp
receives input from the cerebellar dentate nucleus and projects to the
ipsilateral inferior olive (Massion 1967). However, in
the cat there is no clear separation between large and small cells in
the RN, and at least some small cells project to the contralateral
spinal cord (Holstege and Tan 1988; Mussen 1927; Pompeiano and Brodal 1957). Could the
spinally projecting cells in RNp connect DN output to the spinal cord
rather than to the inferior olive? In this study, we address this
question by placing injections of wheat germ agglutinin-horseradish
peroxidase (WGA-HRP), a bidirectional tracer, into physiologically
identified regions of the cerebello-rubro-spinal pathway.
Our results demonstrate that most of the cat RNp projects to the
contralateral spinal cord. The spinally projecting cells are largely,
if not entirely, separate from cells projecting to the ipsilateral
inferior olive. Regions of RNp that project to the contralateral spinal
cord receive input from the contralateral cerebellar dentate and a
lateral segment of anterior interpositus. For projections to cervical
cord, RNp favors upper segments, whereas RNm favors lower segments.
The data do not support the prevalent view of RN connectivity and
indicate that the lateral cerebellum can influence limb movements via
spinal connections through RNp. The connections of RNp and its
physiological actions (see Horn et al. 2002) suggest that the pathway influences upper limb musculature more strongly than
distal limb musculature. Dentate may play a role in directing and
stabilizing the limb during reaching and grasping.
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METHODS |
Fourteen male cats (3.5-4.5 kg) were used to trace connections
of the red nucleus. Anesthesia consisted of an initial intramuscular injection of ketamine hydrochloride (8 mg/kg) followed by intravenous doses (10 mg) of pentobarbital sodium. Cats were fastened into a
stereotaxic frame, and a craniotomy and/or laminectomy was performed to
provide access to brain stem and spinal injection sites. After the
tracer injections, wounds were sutured, and the cats were placed on a
heating pad. Anesthesia was maintained with iv infusion of
pentobarbital sodium (2 mg · kg
1
· h1) for the duration of the transport
period (approximately 48 h). During the transport period,
breathing and temperature were monitored, and the airway was cleared
frequently with suction. Prior to perfusion, cats were administered
lethal doses of pentobarbital sodium (>250 mg iv as a rapid bolus).
All procedures were approved by the St. Joseph's Hospital
Institutional Animal Care and Use Committee and were in accordance with
National Institutes of Health guidelines.
Small pressure injections (0.008-0.032 µl) of WGA-HRP (Sigma) were
made at physiologically identified sites. Injection sites were
initially identified using tungsten microelectrodes. The injection
pipettes and the microelectrodes were cross-referenced by using the
same optical zero point. Accuracy of final placement was confirmed by
recording with the injection pipettes. Table 1 summarizes the injection site or sites
for each case.
Perfusion consisted of a saline rinse followed by two liters of freshly
made paraformaldehyde (3-4%, depending on the case) and a series of
10, 20, and 30% sucrose/phosphate buffer solutions (0.1 M, pH 7.4).
Brains were sectioned at 50 µm in either the parasagittal or frontal
planes. Sections were processed with a modified tetramethyl benzidine
(TMB) reaction (Gibson et al. 1984; Mesulam
1982) and then stained with thionin.
The locations of anterogradely labeled terminals and fibers and
retrogradely labeled cell bodies were plotted onto high-resolution digital images using a computerized plotting system (Image Tracer, Translational Technology). The plotting system registered microscope stage position (±1-µm resolution) to the digital image for accurate marking of label location. All plotting was performed under
high-powered (×100) observation using polarized light illumination.
Overlap between the label from two different cases was assessed by
first creating computer images of the sections with the plotted label.
Corresponding sections from the two cases were scaled to the same size
and manually overplotted with the aid of a computer drawing program
(Canvas, Deneba). When the location of label from one case fell within
100 µm of label from the other case, the area was marked as a site of
overlap. For the red nucleus, the location of the caudal and ventral
large cells provided the most reliable alignment between cases.
Stereotaxic coordinates were assigned based on comparison of the
sections with the cat atlas of Berman (1968).
The paraformaldehyde fixation produced severe and variable tissue
shrinkage, so our estimates of cell sizes within RN are not comparable
to those made by previous investigators. However, comparisons between
RN areas within a subject are still meaningful. To measure the size of
spinally projecting cells, high-power brightfield microscopic images
were made of selected regions within the nucleus. Using Image Tracer,
we then marked the retrogradely labeled cells in the image under
darkfield polarized light illumination. The width and length of marked
cell somas were then measured from the brightfield image. Measurements
were orthogonal to each other and made at the points of maximal cell
dimensions. When the section appeared to include the apical dendrite,
an estimate of soma size was extrapolated from cell-wall curvature.
Attempts were made to measure every labeled cell, but in some
instances, cell membranes could not be visualized. The product of each
pair of measurements was used as an estimate of soma area.
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RESULTS |
Projections to the cervical cord
RED NUCLEUS LABELING FROM SPINAL INJECTIONS.
Our first objective was to identify regions of the red nucleus that
project to the cervical spinal cord. A single rubrospinal fiber can
terminate along several segments of the cord (Shinoda et al.
1977), so we maximized the number of labeled rubrospinal cells
by making closely spaced injections across several segments. To
simplify the study, we examined projections only to cervical cord. A
series of WGA-HRP injections were made into the intermediate spinal
gray every 2-3 mm from C3 to
C6 on the right side of the cord (case
CN10, Table 1). Recordings through the injection pipette helped
distinguish cells in the intermediate laminae from the large
motoneurons in the ventral horn.
The frontal sections through the left RN in Fig.
1 were photographed with a combination of
semi-polarized darkfield and transmitted light to visualize both
labeled and unlabeled cells. At the caudal RN pole (Fig. 1, A3.8), the
labeled cells are confined to approximately the dorsal half of the
nucleus. Spinal projections of the RN have a well-recognized topography
(Holstege and Tan 1988; Pompeiano and Brodal
1957; Robinson et al. 1987), and the unlabeled
cells in the ventral half of the nucleus project to lower levels of the
cord. Although the labeled cells vary in size, the high percentage of
large cells identifies this level as the RNm.
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Fig. 1.
Red nucleus (RN) neurons projecting to cervical spinal cord. Frontal
sections illustrating wheat germ agglutinin-horseradish peroxidase
(WGA-HRP)-labeled neurons with polarized darkfield illumination. At
caudal levels (A3.8), predominately large cells in the dorsal half of
the nucleus are labeled. More rostrally (A4.6), a second group of
labeled cells appears dorsal and lateral in the nucleus. Although mixed
in size, the cells are considerably smaller than the caudal-medial
group. Further rostrally (A5.2), the dorsolateral group is prominent,
but the medial group has largely disappeared. Case CN10
(Table 1; Fig. 2). Digitized 35-mm photographs, contrast adjusted
digitally.
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Rostrally (Fig. 1, A4.6), two groups of labeled cells are apparent.
Lying medially and consisting mainly of large cells, one group appears
to be a rostral continuation of RNm. A different group of labeled cells
can be seen lateral to RNm. Although this group contains cells of
various sizes, the cells appear to be smaller than those of the medial group.
Further rostrally (Fig. 1, A5.2) there is no clear RNm, but the smaller
celled lateral group is prominent. In this report, we consider the
rostral lateral group of cells as part of RNp, which is consistent with
their designation in the Berman (1968) cat atlas.
Measurements of cell areas within the groups (see METHODS)
supported our visual impressions. We compared the cells in Fig. 1.
Cells in RNp (lateral group) at A5.2 and A4.6 had median soma areas of
275 and 273 µm2, respectively. Cells in RNm at
A4.6 (medial group) and A3.8 (all cells) had median soma areas of 420 and 418 µm2, respectively. A one-way ANOVA
between groups (Kruskal-Wallis ANOVA on ranks) indicated significant
differences (P < 0.05), so we ran pairwise comparisons
(Dunn's method) between the groups. Comparisons between measurements
of RNm and RNp cells were significantly different (P < 0.05), whereas comparisons within either RNm or RNp were not
significantly different (P > 0.05).
A complete representation of the retrograde labeling from A3.1 to A6.9
for case CN10 is shown in Fig.
2, left. The smaller-celled lateral group becomes prominent at about A4.5 and continues to A5.9.
The medial RNm group extends from the caudal end of the nucleus (A3.1)
to approximately A5.4. The spinal projection from both groups of cells
is almost entirely contralateral. An outline of the labeled RN cells on
the left (contralateral to the injection) has been transposed to the
right to compare locations of cells projecting to the ipsilateral and
contralateral cord. Only a few ipsilateral cells overlap with the
area of contralateral projection (Fig. 2, column 1, right side of
section). Most cells projecting to the ipsilateral cord are located
in the interstitial nucleus of Cajal (ICA), the area between RN
and ICA, and, more rostrally, the Fields of Forel (FF).
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Fig. 2.
RN cervical projection and RN injection sites. Left:
series of frontal sections illustrating labeled cells (black circles)
resulting from injection into right side of spinal segments
C3-C6. A lateral and rostral extension of the
nucleus extends from A4.5-A5.9. An outline (gray) of the labeled cells
contralateral to the injection has been added to the ipsilateral side
(right) to show that very few cells within the RN project to the
ipsilateral cervical cord. A border indicating the ventral edge of the
RN has been added from A3.6 to 5.4. Middle and
right: injection sites of the unilateral case
BRN3 (0.004 µl, 2% WGA-HRP) and the bilateral case
BRN1 (each injection, 0.008 µl, 1% WGA-HRP). Both
injections on the left side covered the rostral-lateral group of
spinally projecting cells. The injection on the right of
BRN1 included only the caudal pole of the nucleus (RNm),
which was not included by either of the left injections. None of the
sites included areas with cells projecting to the ipsilateral cervical
cord. Digital brightfield photographs. Injection sites reacted at the
same strength as other sections.
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TOPOGRAPHY OF RN PROJECTIONS TO THE SPINAL CORD.
The results from the spinal injection case (CN10) indicated
that dorsolateral RN contains smaller cells that project to the contralateral cord. Do the cells in dorsolateral RN terminate at the
same spinal levels as cells in medial RN? We compared the locations of
retrogradely labeled neurons in the RN between cases with injections
restricted to one segment of the cervical cord (Fig.
3). Although the injections sometimes
included fibers in the ventral funiculus (i.e., Fig. 3,
C1), the dorsolateral funiculus, where fibers from RN
travel (Fig. 6), was not included by the injection sites. Therefore
retrogradely labeled cells within the RN were due to pickup by
terminals in the spinal gray and not by fibers of passage.
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Fig. 3.
Injection sites in cervical cord. Injection sites from the single
segment injection cases are shown in brightfield (left)
and in polarized darkfield (right). The injection sites
were mainly in the intermediate laminae (V, VI, VII) of the gray
matter. The C1 injection spread into the ventral funiculus.
Because the rubrospinal tract lies in the dorsolateral funiculus, it is
unlikely that retrogradely labeled cells in RN were due to passing
fiber pickup.
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The C1 injection (Fig.
4, left) labeled cells across
the medial to lateral extent of RN, although the largest number of
labeled cells are in the most lateral section (L3.2). The
C4 injection produced a relatively even
distribution of labeled cells throughout the nucleus. (A replication of
the C4 injection, case C4-2, resulted in the same distribution.) The C6 injection
labeled a large number of cells in the most medial section (L1.4), but
few cells were labeled in the lateral sections. The
C8 injection produced a pattern similar to the
C6 injection.
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Fig. 4.
Topography of RN projection to cervical cord. Retrogradely labeled RN
cells ( ) illustrated by a series of parasagittal sections with
injections at C1, C4, C6, and
C8 (Fig. 3). The outline in each section indicates the
borders of the RN for that particular section. The nucleus shifts to a
rostral location as it extends laterally. Although the cases indicate a
great deal of overlap, the projection of cells in lateral RN favors
upper cervical levels, whereas the projection from cells in medial RN
favors lower cervical segments. Ventral cells project to lower spinal
segments. The vertical line for each case represents the caudal extent
of the RN at approximately A3.0.
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We compared the location of labeled RN cells from the
C1 and C8 injections in
greater detail (Fig. 5). At caudal levels
(A3-4), there is total overlap between
C1 and C8 projecting cells
with more cells labeled by the C8 injection. At
more rostral levels, the distribution of labeled cells shifts laterally
with proportionately more resulting from the C1
injection. The largest amount of overlap occurs at mid-levels of the
nucleus. The data indicate a modest topography in the cervical spinal
projection of RN. Although all segments seem to receive some input from
the entire RN, more cells in caudal and medial RN (RNm) project to
C6 and C8, whereas more cells in rostral and lateral RN (RNp) project to
C1. The intermediate segments show more even
distributions.
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Fig. 5.
Distribution of RN cells projecting to C1 and
C8. Area graphs show the number of labeled cells at
different lateralities and rostral-caudal levels in the RN.
 , the region projecting to both C1 and
C8. The C1 injection ( ) labeled
cells throughout the RN but labeled more cells in the rostral-lateral
region than the C8 injection ( ).
Conversely, the C8 injection labeled more cells in the
caudal-medial RN.
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SPINAL LABELING FROM RED NUCLEUS INJECTIONS.
To confirm the pattern of RN projections to cervical cord, we made
small injections of WGA-HRP into selected regions of the RN and traced
anterograde labeling in the cord. With anterograde tracing, both the
laminar and segmental distribution of terminations can be determined.
To accurately place the injection sites, we first located the caudal
pole of RN by recording with a tungsten microelectrode and used those
coordinates to calculate the location of the desired injection sites.
In one case (BRN3, Table 1), we placed a single injection in
the rostral RN on the left side 2 mm rostral and 0.5 mm lateral to the
caudal pole. Cells at the injection site fired during forelimb
withdrawal in response to hard pinches of the paw.
The center of the BRN3 injection (Fig. 2, middle)
was located in the lateral RN at A5.0 (reaction product above the
injection resulted from bleeding along the track). The injection site
covered slightly more than the rostral half of the RN. There was little encroachment into the region dorsal and medial to RN that contains cells with ipsilateral spinal projections.
Contralateral to the injection, labeled fibers can be seen in the
dorsolateral funiculus (Fig. 6,
left). Only a few labeled fibers could be found in the
dorsolateral and ventral funiculi on the ipsilateral (left) side, and
only a small amount of terminal label was present on this side. Most of
the ipsilateral label was located in Rexed's lamina VII (Rexed
1954) near the central canal and appeared to result from fibers
crossing at segmental levels.
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Fig. 6.
Spinal terminations of the RN. Left: label resulting
from a large unilateral injection into rostral-lateral RN
(BRN3, Fig. 2). Label is largely confined to the right
(contralateral) side of the cord and is dense at upper cervical
segments. The anterograde label concentrates in Rexed's laminae V, VI,
and VII. Right: label in spinal sections after RNm and
RNp injections in the same animal (BRN1, Fig. 2). The
RNp injection produced label (right side of section) at upper cervical
segments but was nearly absent at lower cervical segments. The RNm
injection (left side) produced label at lower cervical segments but
only diffuse label at upper segments.
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On the contralateral side (right), many labeled fibers could be seen
streaming from the dorsolateral funiculus into the spinal gray, and
terminal label was present in laminae V, VI, and VII. At upper cervical
levels (C1-C4), the
labeled terminals formed a focus in the lateral regions of lamina V and
VI (no label was present in the lateral cervical nucleus). At
C4, the labeled terminals extended deeper into
the dorsal part of lamina VII, and the projection to lamina VII was
pronounced at C7 and
C8.
A gap in labeling can be seen in medial regions of laminae VI and VII;
this gap was most prominent at C7. The gap was
not apparent at C8 (Fig. 6, BRN3).
Below the cervical enlargement (T2 was the lowest
segment examined), the pattern of terminal labeling resembled that seen
at high cervical segments with most of the labeling confined to a
lateral focus in laminae V and VI. While the pattern of labeling was
similar, the density of labeling in the lower cervical and upper
thoracic was significantly lower than at the higher cervical levels. No
terminal label was present in lamina IX (motoneuronal cell groups) at
any level.
COMPARISON OF SPINAL TERMINATIONS OF RNP TO RNM.
The RNp case (BRN3) confirmed a projection to the
contralateral spinal cord. To compare projections of RNm and RNp, we
placed injections in different RN regions on opposite sides in
case BRN1. The bilateral injection allowed us to compare
across sides at spinal levels so the relative density of labeling could
be judged in tissue processed under identical conditions.
Ipsilateral spinal projections from RN could confound bilateral
injections. However, the results from CN10 and
BRN3 indicated that ipsilateral projections from rostral RN
are insignificant. Furthermore, CN10 (Fig. 2) as well as the
other spinal injection cases (6 cases, Table 1) indicated that caudal
RN and immediately surrounding regions do not have a significant
projection to the ipsilateral cervical cord.
The lack of ipsilateral spinal projections from RNm agrees well with
previous studies (McCurdy et al. 1987; Pompeiano
and Brodal 1957; Robinson et al. 1987). One case
(1383 in Holstege 1987) has suggested ipsilateral spinal
projections from RN; however, the injection site for this case included
the region dorsal and medial to rostral RN. Our data (i.e.,
CN10) also indicate an ipsilateral projection from this
region, but it was not included by our RN injections (Fig. 2).
The injection sites were identified as in BRN3 except that
the RNp injection was placed 1.0 mm further rostral to the estimated caudal RN border. Recordings at the injection site revealed responses to tapping or squeezing of the right (contralateral) forelimb, and
cells ventral to the injection site responded to taps and squeezes of
the right hind limb. On the opposite side, we placed an injection at
the caudal pole of the RN.
The RNm injection (Fig. 2, BRN1, right side) was largely
limited to the caudal 0.5 mm of the RN and did not extend far beyond A4.5. Although the injection was well confined to the borders of the
RN, the entire nucleus was covered at caudal levels. The RNp injection
(Fig. 2, BRN1, left side) was centered in the dorsolateral RN at A5.4. There was essentially no overlap between the corresponding RN areas covered by the two injections. The unilateral RN injection (BRN3) and the RNp injection of BRN1 have
extensive overlap, but the BRN1 injection did not extend as
far caudally as the BRN3 case.
Anterograde labeling of terminals in the spinal cord demonstrated that
RNp and caudal RNm, for the most part, terminate at different levels of
the spinal gray (Fig. 6, right). Due to the decussation of
the rubrospinal tract, label from the RNp is on the right and RNm on
the left. The RNp label was clear at high cervical segments (levels
above C3 were densely labeled but were not
photographed prior to fading) and focused in the lateral parts of
laminae V and VI. As in the BRN3 case, a gap in labeling is seen in the medial regions of laminae V and VI. Unlike the
BRN3 case, the density of label decreased at levels caudal
to C4 and was essentially absent at
C7 and C8. We believe this
difference can be attributed to the more rostral position of the
BRN1 RNp injection.
The RNm injection labeled many fibers in the dorsolateral funiculus
(Fig. 6, BRN1, left side of sections) but produced only a
small amount of label in the spinal gray at upper cervical levels. The
label that did exist was focused medial to the location of label from
RNp in central regions of laminae VI and VII (Fig. 6, BRN1,
C3 and C4, left side).
Below C4 the amount of label present in the
spinal gray increased rapidly and showed a peak in density at
C7. At C7 the label was
evenly distributed across lamina VI and the dorsal regions of lamina
VII. The C7 label from caudal RN included the
area left bare in the BRN3 case. The label at the higher
cervical segments also appeared to fill the gap in the RNp projections.
RNm and RNp appear to project to different areas of the spinal gray in
the same cervical segment. At C8 the density of
the labeling dropped, but a substantial amount was still present in the
central portions of laminae VI and VII.
The RNm injection also produced a small amount of label in the
dorsolateral motoneuronal pools (lamina IX) at C8
(barely visible in Fig. 6). Neither of the RNp injections led to label
in motoneuronal pools. Below the cervical enlargement (segments down to
T3 were processed), a moderate density of
labeling was present in the central portions of laminae V, VI, and VII.
To gain a more representative comparison of the label between sides for
BRN1, digital photographs were analyzed using Adobe Photoshop. A pixel intensity and color range was set to select label in
polarized light darkfield images. The number of selected pixels within
the spinal gray served as an estimate of the area of anterograde label.
The same pixel selection template was used for all sections, and counts
from three to six sections at each segment were averaged. Reaction
strength varied between sections, so the comparison was made as a ratio
of the pixel count between sides as well as by the absolute count.
Between C1 and C3 the pixel
count was higher on the side corresponding to the RNp injection (Fig.
7, top). The ratio was highest at C1 with approximately three to four times as
many selected pixels on the RNp side. At C4, the
pixel count was approximately equal between sides. Below
C4, the count was greater on the side corresponding to the RNm injection, and the ratio peaked at
C7-C8 with approximately
10 times as much label resulting from the RNm injection as from the RNp
injection.
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Fig. 7.
Measures of spinal label from the RN injections. Sections from
C1 to T3 were measured from the dual injection
case BRN1. Top: the ratio of label
measured from the same spinal sections that minimizes variation due to
differences in reaction strength between sections. The ratio favored
label from the RNp injection at higher segments and favored the label
from the RNm injection at lower segments. Bottom: the
average number of pixels measured at the different segments. The RNp
injection produced high levels of label in the upper cervical cord and
progressively lower levels in lower segments. The RNm injection had a
peak at C7 and progressively lower levels moving up and
down the cord. Error bars ±1 SD.
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The RNp injection produced a relatively steady decrease in count with
spinal level (Fig. 7, bottom). The highest level was found
at C1 and the lowest at T3.
The RNm injection produced a low count at C1 that
rapidly increased to a peak at C7 and then declined to a low number by T3.
The anterograde results are in good agreement with the retrograde
results. Large cells at the caudal pole of the nucleus have a
projection to laminae VI and VII at all cervical levels, but the
projection is denser at lower segments. Smaller cells in the rostral
pole of RN project mainly to laminae V, VI, and VII at upper cervical segments.
SPINAL VERSUS OLIVARY PROJECTIONS.
Traditionally, RNp has been thought to transmit information from the
dentate nucleus of the cerebellum to the principle subnucleus of the
ipsilateral inferior olive. Because both our retrograde and anterograde
studies indicated that a substantial portion of the cat RNp projects to
the contralateral spinal cord, could the same cells provide input to
the inferior olive (IO)? The BRN3 injection produced some
anterograde label in the ipsilateral IO (mostly in the dorsal lamella
of the principal olive), but the BRN1 injections produced no
visible label in the IO. Therefore it is likely that spinally
projecting and olivary projecting cells in RNp are largely from
different populations of neurons.
To determine the location of RN cells projecting to the IO, we made
injections centered on the dorsal lamella of the principle subnucleus
of the inferior olive (PO). Several studies have indicated that the
dorsal lamella receives input from the RN and surrounding regions
(Edwards 1972; Holstege and Tan 1988;
Walberg 1956). Two injections separated by 1 mm in the
A-P plane were placed into the dorsal lamella. At both injection sites,
hard squeezes to the limbs elicited discharge of the olivary neurons.
Cells in the layer dorsal to the injection sites responded to light
cutaneous stimulation of the forelimb, which is characteristic of the
rostral dorsal accessory olive (Gellman et al. 1983).
The spread of the injections included all divisions of the rostral half
of the IO but there was relatively little spread into the overlying
reticular formation (Fig. 8A).
Except for the rostral tip, the injection site covered the rostral half
of the IO (Fig. 8B).
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Fig. 8.
Inferior olive WGA-HRP injection. A: frontal section
through center of injections (CN11, Table 1). Injections
were centered on the dorsal lamella of the principle olive (PO) but
spread to the other subnuclei. Spread beyond the inferior olive (IO)
was relatively limited. B: parasagittal reconstruction
of the injections indicates that most of the rostral half of the IO was
included. - - - in A indicates plane of section in
B, and - - - in B indicates plane of
section in A. DAO, dorsal accessory olive; MAO, medial
accessory olive.
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Frontal sections from the olivary injection case (Fig.
9, CN11) were matched to those
of the C3-C6 injection
case (Fig. 9, CN10) to compare the distributions of
retrogradely labeled cells. The olivary injection resulted in no
labeled cells in the caudal half of the RN. In the rostral half, a few
olivary projecting cells were located in medial portions of the
nucleus. However, most cells projecting to the olive are found in cell
groups surrounding and including parts of the central gray (i.e.,
nucleus Darkschewitsch, ND) and ventral regions of the pretectal
nuclei.
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Fig. 9.
Limited overlap of olivary and spinally projecting cells.
Left: cells () labeled after a
C3-C6 spinal injection (case CN10,
Fig. 2). Middle: cells labeled after the IO injection
(Fig. 5). Right: areas of potential overlap of olivary
and spinally projecting cells. An outline of the RN projection to the
contralateral cord has been included in the enlarged series. The
largest potential for overlap occurs at A5.4 but is modest even at this
level. FF, fields of Forel; FR, fasciculus retroflexus; ICA,
interstitial nucleus of Cajal; ND, nucleus Darkshewitsch; PTA, anterior
pretectal nucleus; PTP, posterior pretectal nucleus.
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The largest area of overlap between spinally and olivary projecting
cells occurs at A5.4, where some cells in the mid-region of RN were
labeled by the IO injection (Fig. 9, right). These cells
probably account for the label seen in the dorsal lamella for case
BRN3 because that injection site included mid-RN at this level. For most levels, however, there is no overlap between olivary and spinally projecting cells. The spinally projecting area of RNp
appears to have little or no projection to rostral IO.
Sources of input to the red nucleus
LABELED CELLS IN THE CEREBELLAR NUCLEI.
The retrograde labeling from the RN injections allowed us to compare
inputs to RNp and RNm. The heaviest source of input to the RN arises
from the deep cerebellar nuclei. Both dentate and interpositus provide
input to RN. The injection into the caudal pole of RNm labeled a large
number of cells in posterior interpositus (NIP) and the medial
two-thirds of anterior interpositus (NIA) but few cells in DN or
lateral NIA (Fig. 10,
right). In contrast, the RNp injections labeled cells in
lateral NIA and DN (Fig. 10, left and middle).
The mutually exclusive areas of label demonstrate the topographic
nature of the cerebellar projection and indicate that passing fiber
pickup was minimal at the injection sites. Fibers terminating in RNp
pass through RNm (Figs. 11D
and 13B), and fibers terminating in RNm continue through
rostral RN to terminate in the thalamus. Pick-up by these fibers would
have produced overlap of labeled areas in the cerebellar nuclei.
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Fig. 10.
Cerebellar input to RNm and RNp. Series of frontal sections through
interpositus and dentate indicating the locations of retrogradely
labeled cells resulting from the RN injections (BRN3 and
BRN1). For comparison, the plots from the RNm injection
(case BRN1, right) have been flipped so that all nuclear
outlines are in the same orientation, and the medial nucleus is not
represented because it contained no labeled cells. Additionally, the
area labeled by the RNm injection has been shaded on the plots from the
RNp injection cases. The RNp injections labeled cells in rostral and
medial dentate (DN) and lateral anterior interpositus (NIA). The RNm
injection labeled cells throughout the medial regions of NIA and
posterior interpositus (NIP). There is little overlap between nuclear
regions projecting to RNm and RNp.
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Fig. 11.
Dentate injection site and inferior olive connections.
A: parasagittal section illustrating an injection into
medial DN (case CN9). - - -, area tentatively
identified as lateral NIA; the dorsal edge of the injection spread
slightly into this area. B: parasagittal section
illustrating label in IO following injection shown in A.
Label is confined to the ventral lamella of the PO and the vlo, no
label was apparent in rDAO. Panels are digitized 35-mm photographs.
B was photographed using polarized darkfield
illumination and has been digitally enhanced to visualize cellular
grouping and label. Enhancements were applied to the entire tissue
section.
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The RNp injections (BRN3 and BRN1, Fig. 2,
left) produced similar patterns of retrogradely labeled
cells in the cerebellar nuclei (Fig. 10, left and
middle). However, the BRN3 injection, which
included a larger portion of RN (Fig. 2) and used 2% rather than 1%
WGA-HRP, labeled a higher number of cells. At rostral levels, labeled
cells were mainly located in the dentate nucleus (DN, Fig. 10, P7.9,
left and middle). More caudally, labeled cells were numerous in the lateral parts of anterior interpositus (NIA) and
medial DN. The RNp injections labeled only a few cells in NIP, and
caudal lateral regions of DN were sparsely labeled.
PROJECTIONS FROM DENTATE TO RN.
We confirmed the retrograde results from RN injections with anterograde
labeling from three cerebellar nuclear injections. One case
(CN9) was sectioned in the parasagittal plane, so that the
large cells in caudal RN could be used for accurate rostral-caudal alignment between cases. The DN injection (Fig. 11A) was
centered in medial ventral DN, although dorsal spread may have included a small ventral region of dorsolateral NIA. The injection did not
encroach on NIP.
Because the IO has a precise topographic relationship with the
cerebellar nuclei (Groenewegen et al. 1979;
Tolbert et al. 1976), labeling in IO provides a method
for estimating effective pickup at cerebellar nuclear injection sites.
The DN has reciprocal connections with the principle division of the
contralateral IO (PO), whereas NIA has reciprocal connections with the
contralateral rostral dorsal accessory division (rDAO).
The olivary label in case CN9 indicated that the effective
injection site did not include NIA because no label was present in
rDAO. The presence of label in the lamellae of the PO indicated that
the DN was included by the injection. The parasagittal section in Fig.
11B illustrates anterograde label in the ventral lamella and
vlo (but not in rDAO) from the CN9 injection.
For comparison with the anterograde label in RN, an additional spinal
injection case (SC12) was sectioned in the parasagittal plane. We placed injections of 1% WGA-HRP every 2 mm from
C1 to mid C5 (Table 1). In
rostral and lateral regions of the RN, cells labeled from the spinal
injections overlapped with anterograde label from the DN injection. The
cells projecting to the cervical cord lie in the dorsal rostral part of
the RN (Fig. 12A), which matches the anterograde label from the DN (Fig. 12B).
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Fig. 12.
Inputs to RNp. Parasagittal sections (L2.6) comparing spinally
projecting cells in RNp (A) with anterograde label from
dentate (B) and zona incerta (C). Each
section is illustrated with polarized darkfield illumination
(left) to illustrate label and brightfield illumination
(right) to illustrate cellular grouping.
A: the cervical injections labeled small- and
medium-sized cells in rostral and dorsal RN. B: terminal
label from medial dentate is restricted to rostral and dorsal RN.
Labeled fibers course through caudal regions of RN. C:
terminal label from zona incerta injection (Fig. 12B) is
heaviest in the rostral half of RN, although a strip of labeled
terminals extends caudally along the ventral border of the nucleus.
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The pattern of overlap through the RN between the dentate projection
and the spinally projecting cells (Fig.
13C) indicates that most of
the rostral-lateral region of RN that projects to the cervical cord
receives input from medial DN. Only medial RN (L1.1-1.9) contains a
large number of cells projecting to cervical cord that are not included
in the terminal area of the CN9 injection.
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Fig. 13.
Dentate input to RN. Matched parasagittal sections illustrating
overlap of dentate terminals (A) with cells projecting
to cervical cord (B). A: labeled
terminals (small crosses) from a medial dentate injection (Fig.
11A, case CN9). In all plots, the
outlines indicate the borders of the RN for the individual sections.
The vertical line for each case represents the caudal extent of the RN
at approximately A3.0. B: labeled cells (black circles)
following a series of spinal injections from C1 to
C5 (case SC12). C: overlap
areas (gray) between A and B. The overlap
is located in the rostral-lateral RN. Only medial sections (L1.0-1.5)
contain a large number of spinally projecting cells that do not overlap
with dentate terminals.
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Two additional injections of the cerbellar nuclei confirmed the
retrograde results. The two injections (CN12 bilateral) were slightly different from the CN9 injection in that one was
centered more laterally in dentate whereas the other injection was
centered more medially in dentate and included some of lateral NIA. The amount of rDAO label in each case corresponded with the amount of NIA
included in the injection site. The lateral dentate injection led to
label in the lateral junction of the lamellae of the PO but none in
rDAO. The medial dentate/lateral NIA injection labeled the ventral
lamella of the PO as well as rostral and medial rDAO. The anterograde
label from the lateral dentate injection overlapped with the labeled
cells from the spinal injection case (CN10, Fig. 2) in the
lateral areas of the RN cells in sections A4.5 to A5.9. The overlap
from the medial dentate/NIA injection extended further caudally and
covered lateral RN from A3.6 to A5.9.
BRAIN STEM INPUTS.
Connections of the RN have been described in detail (Edwards
1972; Robinson et al. 1987), but the current
injections into RN revealed some differences between RNm and RNp
connections that have not been well described. Although the cerebellar
nuclei provide the largest input to both RNm and RNp, our
retrograde results indicate that RNp receives significant input from
additional brain stem areas. The largest input arises from the ZI and
FF. The RNp also has extensive reciprocal connections with the ventral
half of the anterior pretectal nucleus and with a region of the central tegmental field dorsal to RNp. The connections with the central tegmental field are probably analogous to those that have been described for the rat (Cadusseau and Roger 1992;
Roger and Cadusseau 1987). A rather diffuse connection
may exist with the mesencephalic tegmentum contralateral to the
injection site. Although all of these inputs require verification
with anterograde tracing, we were particularly interested in the large
ZI input because this nucleus might provide a pathway allowing basal
gangliar activity access to brain stem and spinal levels.
The BRN3 injection into RNp produced a dense focus of
labeled cells in the medial part of ZI where it fuses with FF (Fig. 14A). A less dense layer of
labeled cells trails laterally in the dorsal half of ZI. In all areas,
the appearance of the label also suggests the presence of anterograde
label, indicating a bidirectional connection with RN.
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Fig. 14.
RN input from zona incerta (ZI) and fields of Forel (FF).
A: polarized darkfield photograph of ZI shows labeled
cells throughout the medial-lateral extent of the nucleus after RNp
injection. B: frontal sections through ZI and FF show
locations of labeled cells () after RNp injection cases
(BRN3 and BRN1). - - -, the laterality
of the section shown in C (L5.2). C:
parasagittal section shows the ZI injection site that produced heavy
terminal labeling in RNp (Fig. 10C).
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Both RNp injections (BRN3, BRN1) labeled cells in ZI and FF
(Fig. 14B). In case BRN3, RN projections from
ZI/FF were mainly ipsilateral, with a small contralateral component.
The ZI/FF labeling from the dual RN injection (BRN1) was
essentially the same as from the unilateral RNp injection
(BRN3), suggesting that RNm is not likely to be a major
component of the connection with ZI/FF.
To verify the ZI input to RN, we placed a WGA-HRP injection into ZI
(case ZI1). The injection site (Fig.
15C) spread dorsally into
the thalamus and ventrally into the subthalamic nucleus (not visible in
the photograph, Fig. 14C). However, neither of these areas
contained retrogradely labeled cells after RN injections, so it is
unlikely that label in RN was confounded by injection site spread.
Anterograde label from the ZI injection (Fig. 12C) overlaps
with terminal label from DN as well as with cells retrogradely labeled
from cervical cord. RNm was unlabeled except for a strip along its
ventral border. In more medial sections, the strip of label included
the caudal as well as ventral borders of the nucleus but most of RNm
was unlabeled. ZI apparently has a widespread input to RNp but a
restricted input to the ventral and caudal borders of RNm. A
significant number of retrogradely labeled cells were present in
lateral RNp (and surrounding regions), thereby supporting the
bidirectional nature of this connection.
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Fig. 15.
Major elements of the cerebello-rubro-spinal pathways to cervical cord.
Two pathways from the cerebellar nuclei are shown. In one pathway,
lateral cerebellum (dentate/lateral NIA, light gray) projects to
rostral-lateral RNp, which then projects to the upper cervical cord.
This pathway converges with input from ZI and FF. In the other pathway,
output from medial NIA and NIP (black) projects to the medial-caudal
RNm, which then projects to intermediate spinal regions and motoneurons
at C8. The spinal projection is heaviest at lower cervical.
The darker gray indicates areas of potential overlap in RN and spinal
cord.
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The ZI injection retrogradely labeled cells in the entopeduncular
nucleus (the feline equivalent of GPi), so it is possible that ZI
provides an interface between basal gangliar output and RNp. However,
this connection needs verification because the entopeduncular label may
have resulted from fibers of passage. In addition to this potential
indirect entopeduncular input to RNp, a small number of entopeduncular
cells were retrogradely labeled following the BRN3
injection. Therefore RN probably has a minor direct input from the
entopeduncular nucleus, and a larger indirect input via ZI (and
adjoining FF). Using autoradiography, Nauta (1979) also found evidence for a small, direct entopeduncular projection to RN and
acknowledged the possibility that ZI and FF receive entopeduncular input.
BRAIN STEM TARGETS.
Anterograde labeling from the RN injections revealed no new brain stem
projections, but it did provide additional detail about the topography
of known projections. The sensory trigeminal nucleus, facial nucleus
and spinal trigeminal nucleus were labeled by the RNp injection of case
BRN1 but not by the RNm injection. Label in the lateral
reticular nucleus and main cuneate was present after injections into
either the RNm or RNp.
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DISCUSSION |
Although many of the details that we report in this paper have
been demonstrated or suggested by previous studies, our results are the
first to identify and describe the connections of a spinally projecting
region of the cat RNp. We demonstrate that the region of RNp projecting
to the cord is large and has different connectivity than either RNm or
the olivary-projecting region of RNp. For the cervical cord,
projections of RNp favor upper segments, whereas those from RNm favor
lower segments. Although both RNp and RNm receive major inputs from the
cerebellar nuclei, the input to RNp originates from lateral NIA and
medial DN, whereas input to RNm originates from medial NIA and NIP.
Additionally, the spinally projecting region of RNp receives a large
input from ZI and FF, whereas RNm receives a highly restricted input
from these nuclei. The anatomical differences are likely to reflect
functional differences between subregions of the RN.
Other studies have reported small cells in rostral RN projecting to the
contralateral spinal cord (Holstege and Tan 1988; Mussen 1927; Pompeiano and Brodal 1957).
However, our data indicate that the cells do not mix with cells
projecting to IO but rather form a large homogeneous region. The
spinally projecting region of RNp appears to be more extensive in our
study, but this is probably because we made a number of closely spaced
WGA-HRP injections in upper cervical segments. The closely spaced
injections would result in more tracer pickup by the extensively
branched RN axons (Shinoda et al. 1977, 1988), and RNp
terminates most heavily at upper segments, especially
C1. Previous studies of RN spinal projections would not have identified cells projecting selectively to upper cervical segments because they either sectioned the tract or injected tracers at spinal levels caudal to C1.
Our results indicate that the RNp populations projecting to the
spinal cord and the IO are almost entirely separate, which is in good
agreement with previous studies (Huisman et al. 1982; Spence and Saint-Cyr 1988). The mesencephalic input to
the IO in the cat arises from a complex of nuclei that includes only a
restricted rostral and medial portion of RNp (Onodera
1984; Saint-Cyr and Courville 1981;
Walberg and Nordby 1981). The separation of olivary and
spinally projecting neurons supports the suggestion by Holstege
and Tan (1988) that RNp be divided into subregions. However,
projection targets are just one possible basis for subdividing RN.
Equally important considerations are the source of inputs to the subregions.
Using degeneration techniques, Voogd (1964) identified a
dorsolateral region about midway along the rostral caudal extent of the
RN that receives input from the cerebellar dentate nucleus. Our data
support his observation and also identify this as a spinally projecting
region of RN. These neurons may mediate the short latency activation of
spinal neurons following stimulation of the dentate nucleus in the
decerebrate cat (Hames et al. 1981).
Based on spinal connections, the smaller cells in lateral RN could be
grouped with RNm. However, based on cerebellar input, they would be
grouped with RNp because RNp has traditionally been considered a
recipient of dentate input. We chose to group the lateral spinally
projecting cells with RNp, which is consistent with the Berman
(1968) cat atlas (see horizontal plates).
Figure 15 summarizes the major input-output relations of spinally
projecting regions of the RN. The figure shows two different pathways
from the cerebellum. The first pathway (light gray) starts from a strip
that includes lateral NIA and medial DN. The rostral-lateral RN
receives this projection as well as one from ZI and FF and then
projects to the lateral areas of the upper cervical cord. The second
pathway (black) originates in medial NIA and then projects to the
caudal-medial RN. Cells in this area of RN project to the lower
cervical segments including motoneurons at C8.
The topography consists of two pathways with an intermediate
overlapping region (dark gray). Alternatively, the cerebellar nuclei
from lateral to medial could map to the cervical cord from rostral to
caudal in a continuum.
COMPARISONS BETWEEN SPECIES.
Parvicellular RN projects to the spinal cord in species other than cat.
The most intensively studied species has been the rat (see
Ruigrok and Cella 1995 for review). As in the cat, the rat RN is not sharply divided into magnocellular and parvicellular regions (Reid et al. 1975a,b), and at least some of the
parvicellular neurons project to the spinal cord (Huisman et al.
1981, 1983; Shieh et al. 1983). Additionally,
the rat RNp does not supply input to the inferior olive (Ruigrok
et al. 1993; Rutherford et al. 1984).
Dorsolateral regions of the rat RNp receive input from caudal regions
of the cerebellar lateral (dentate) nucleus (Angaut and Cicirata
1988; Ruigrok et al. 1993; Teune et al.
2000). Therefore a large portion of the rat RNp receives input
from the cerebellar lateral nucleus, has little or no projection to the
IO, and has, at least, some projection to the spinal cord. It appears
that the connections are similar, perhaps identical, to the connections of the spinally projecting region of the cat RNp.
The RN of the North American opossum is organized much like the cat and
rat. There is no distinct parvicellular division of the opossum red
nucleus (King et al. 1971; Martin et al.
1974), and the cells projecting to the IO lie rostral and
medial in the RN (Martin et al. 1983). As in the cat,
there is only a small region of spatial overlap between the olivary and
spinally projecting cells. Even in this overlap region, the populations
are distinct because very few cells project to both the spinal cord and
IO (Martin et al. 1983).
Studies in monkey indicate spinal terminations similar to the cat,
including direct connections to motorneuronal pools that innervate
muscles that move the digits (Holstege et al. 1988; Ralston et al. 1988). Early studies using degeneration
tracing techniques identified small- and medium-sized cells in or near lateral RN projecting to the contralateral spinal cord (Kuypers and Lawrence 1967; Poirier and Bouvier 1966);
however, HRP tracing studies failed to demonstrate this population
(Castiglioni et al. 1978; Kneisley et al.
1978). More recently, Burman et al. (2000) used
WGA-HRP to confirm the existence of smaller cells dorsolateral to the
RN that project to the contralateral cord. It seems likely that these
smaller cells are analogous to spinally projecting RNp cells of the cat.
In the human RN, there are few large cells, so most of the nucleus is
presumed to be parvicellular and therefore olivary projecting (Massion 1967). However, as Pompeiano and Brodal
(1957) pointed out, if many spinally projecting cells in the
human are small, the spinal projection may be greatly underestimated.
Degeneration studies following brain stem lesions in human infants
support this suggestion (Papez and Stottler 1940). The
authors conclude that most of the rubrospinal fibers in the human arise
from small cells caudal and lateral in the nucleus. Such a projection
fits well with the data from the degeneration studies in the monkey as
well as with the data from our study.
It is likely that species differences in RN connections are not as
large as previously supposed. All of the aforementioned species have
large cells projecting to the contralateral spinal cord that receive
input from interpositus. All have small cells in the rostral medial
part of the nucleus that project to the ipsilateral IO. Finally, we
would like to suggest that all have a lateral area consisting of
smaller cells that project to the contralateral cord and receive input
from DN.
The greatest confusion about RN connections may be the result of a lack
of correspondence between similarly named regions. In the monkey, the
area identified as RNp is probably confined to the olivary projecting
region of RNp. In the rat and cat, the area identified as RNp includes
both olivary and spinally projecting regions.
FUNCTIONAL IMPLICATIONS.
Most RN output projects to interneurons, but, in some instances, the
RST terminates among motoneurons. Probably the strongest motoneuronal
projection is to the facial nucleus (Courville 1966; Holstege et al. 1984; Robinson et al.
1987). Both of our RNp injections but not the RNm injection
produced anterograde label in the facial nucleus. Inactivation of RN
blocks the expression of a classically conditioned eye-blink response
(Chapman et al. 1990) as does inactivation of
interpositus (Yeo et al. 1985), so it appears that RNp
provides lateral interpositus with a pathway to the facial nucleus.
The involvement of lateral NIA with facial movements agrees well with
its olivary connections. Medial regions of the rDAO project to lateral
NIA, which, in turn, projects to dorsolateral RN (Daniel et al.
1987; Gibson et al. 1987; Robinson et al.
1987). Cells in medial rDAO (and the adjoining medial portion
of the ventral lamella of the PO) respond to stimulation of the face and head (Gellman et al. 1983; Weiss et al.
1993) and receive input from the trigeminal nucleus
(Berkley and Hand 1978). The trigeminal nucleus also
connects to a caudal region of dorsolateral RN (Robinson et al.
1987). Therefore RNp is likely to be involved in facial movements.
The only clear RN projection to spinal motor pools is to lateral pools
at C8 (Fujito et al. 1991;
Holstege 1987; McCurdy et al. 1987;
Robinson et al. 1987). Our data indicate that RNm is the
source of C8 motoneuronal terminations. Although
the projection to motor pools is small in comparison to projections to
spinal interneurons, many studies have indicated that the RNm and
interpositus are especially important for the control of digit
movements (Gibson et al. 1985, 1994; Jarratt and
Hyland 1999; Martin et al. 1993; Mason et
al. 1998; Mewes and Cheney 1991; Sybirska
and Gorska 1980; van Kan and McCurdy 2001;
van Kan et al. 1994; Whishaw and Gorny
1996). Positioning of the digits appears to be an important function of RNm and interpositus.
Despite the focus of RNm on digit control, inactivation and lesion
studies (Bracha et al. 1999; Gibson et al.
1994; Lawrence and Kuypers 1968; Martin
et al. 1993; Schrimsher and Reier 1993; Sybirska and Gorska 1980) indicate that the RN
influences proximal as well as distal limb musculature [although
Levesque and Fabre-Thorpe (1990) report minimal deficits
in reaching with chemical lesions of the RN]. The RNp projection to
upper cervical levels suggests that this region may be important for
proximal limb control. Recordings at the RNp injection sites indicated
that the cells discharge during withdrawal of the forelimb, and the
retrograde labeling indicated that they receive input from the
cerebellar nuclei which interconnect with the lamellae of the PO. Cells
in the PO respond to stimulation of the limbs (Gellman et al.
1983), and it is likely that RNp and DN form a second
cerebello-spinal circuit involved in limb movement control. The
findings reported in the accompanying paper (Horn et al.
2002) indicate that the output from RNp does have a strong
influence on musculature of the shoulder.
RNp terminations at C1-C2
could be involved in the control of head movements because motor
neurons at these levels innervate neck muscles (Gordon and
Richmond 1991; Kitamura and Richmond 1994).
However, RNp terminations favor lateral interneuronal regions, which
project to motoneurons at other spinal levels. Interneuronal regions of
C1-C2 receive input from
many descending motor systems (Gibson et al. 1998;
Holstege and Kuypers 1982), including the tecto-spinal
pathway (Cowie and Holstege 1992; Huerta and
Harting 1982), which has been implicated in limb movement
control (Werner et al. 1997). This region of
interneurons may integrate a number of inputs important for orienting a
variety of body parts such as the head, limbs, and trunk. Propriospinal
interneurons at C3-C4 are
likely to be involved in limb control (Illert et al.
1977) and interrupting propriospinal connections from these
segments does produce deficits in reaching (Alstermark et al.
1981).
Inactivation of the monkey cerebellar nuclei can also affect limb
guidance, although there is some debate about which regions of the
nuclei are critical. Both dentate (Thach et al. 1992)
and NIP inactivation (Mason et al. 1998) have been
reported to disrupt reach accuracy. If the topography of cerebellar
projections to RN is similar between cat and monkey, injections into
NIP might also affect DN cells projecting to RNp. Alternatively, both
NIP and DN might be important for reach accuracy. Posterior
interpositus projects to the medial border of the cat RN
(Robinson et al. 1987), and our data demonstrate that
cells in medial regions of RN project to all cervical levels. Therefore
NIP may play an integrative role influencing activity in both proximal
and distal musculature during limb movements. Dentate may focus more on
proximal musculature, but deficits in either system could produce
inaccuracy during reaching.
Humans with lesions of the lateral cerebellum reach inaccurately. In
fact, lesions of the lateral cerebellum disrupt reach accuracy more
than lesions of the thalamus, which suggests that dentate output
projects to areas important for reaching without passing through
thalamus (Bastian and Thach 1995). It is tempting to
speculate that the small-celled lateral region of human RN (Papez and Stottler 1940) allows dentate output to
influence activity of the upper cervical cord.
Testing of the previous speculation will require a great deal of
additional research. At least for the cat, it is likely that the spinal
projections of RNp and RNm serve different roles in the control of limb
movements
it would be surprising if this were not also the case for
other mammalian species.
This work was supported by National Institute of Neurological
Disorders and Stroke Grants NS-36820 to A. R. Gibson and NS-10726 to M. Pong.
Address for reprint requests: M. Pong, BNI-Neurobiology, St.
Joseph's Hospital and Medical Center, 350 W. Thomas Rd., Phoenix, AZ
85013 (E-mail: mpong{at}chw.edu).
TOP
ABSTRACT
INTRODUCTION
