The Nobel Institute for Neurophysiology, Department of Neuroscience, Karolinska Institute, 171 77 Stockholm, Sweden
![]() |
ABSTRACT |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Aoki, Fumi, Thierry Wannier, and Sten Grillner. Slow Dorsal-Ventral Rhythm Generator in the Lamprey Spinal Cord. J. Neurophysiol. 85: 211-218, 2001. In the isolated lamprey spinal cord, a very slow rhythm (0.03-0.11 Hz), superimposed on fast N-methyl-D-aspartate (NMDA)-induced locomotor activity (0.26-2.98 Hz), could be induced by a blockade of GABAA or glycine receptors or by administration of (1 s, 3 s)-l-aminocyclopentane-1,3-dicarboxylic acid a metabotropic glutamate receptor agonist. Ventral root branches supplying dorsal and ventral myotomes were exposed bilaterally to study the motor pattern in detail. The slow rhythm was expressed in two main forms: 1) a dorsal-ventral reciprocal pattern was the most common (18 of 24 preparations), in which bilateral dorsal branches were synchronous and alternated with the ventral branches, in two additional cases a diagonal dorsal-ventral reciprocal pattern with alternation between the left (or right) dorsal and the right (or left) ventral branches was observed; 2) synchronous bursting in all branches was encountered in four cases. In contrast, the fast locomotor rhythm occurred always in a left-right reciprocal pattern. Thus when the slow rhythm appeared in a dorsal-ventral reciprocal pattern, fast rhythms would simultaneously display left-right alternation. A longitudinal midline section of the spinal cord during ongoing slow bursting abolished the reciprocal pattern between ipsilateral dorsal and ventral branches but a synchronous burst activity could still remain. The fast swimming rhythm did not recover after the midline section. These results suggest that in addition to the network generating the swimming rhythm in the lamprey spinal cord, there is also a network providing slow reciprocal alternation between dorsal and ventral parts of the myotome. During steering, a selective activation of dorsal and ventral myotomes is required and the neural network generating the slow rhythm may represent activity in the spinal machinery used for steering.
![]() |
INTRODUCTION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Bath application of excitatory
amino acids induces fictive swimming activity in the isolated spinal
cord of the lamprey (Brodin et al. 1985; Grillner
et al. 1981
). The basic cellular and network components of the
central pattern generator underlying swimming have been identified
(Grillner et al. 1995
). Basic swimming activity is
always expressed in a left-right reciprocal pattern. For steering behavior in three-dimensional space, however, a differential control of
dorsal and ventral myotomes must be available as well as between left
and right myotomes. Motoneurons supplying the dorsal and ventral parts
of the myotome have different patterns of activation during fictive
locomotion (Wallén et al. 1985
). Pharmacological stimulation of reticulospinal nuclei also activates the dorsal and
ventral branches of the ventral roots differentially (Wannier et
al. 1998
). These studies thus suggest that there are neural mechanisms for the differential control of the dorsal and ventral myotomes.
In the isolated spinal cord, slow fluctuations of the swimming activity
have been observed with apamin (El Manira et al. 1994), bicuculline (Tegnér et al. 1993
), and strychnine
(McPherson et al. 1994
) applications on
N-methyl-D-asparate (NMDA)- or
D-glutamate-induced swimming, and with 5-hydroxytryptamine
(5-HT) on kainate-induced swimming (Schotland and Grillner
1993
). The two rhythms may occur simultaneously in the isolated
spinal cord preparation with the slow rhythm being superimposed on the
faster swimming rhythm. These studies were, however, performed using
whole ventral roots and showed that the slow fluctuation could exhibit
a left-right reciprocal pattern. To determine whether the slow rhythm
occurred in motoneurons supplying both the dorsal and ventral part of
the myotome, the corresponding dorsal and ventral branches of the ventral roots were dissected. The slow bursting (0.03-0.11 Hz) could
display alternating activity between the dorsal and ventral branches,
while the fast locomotor rhythm (0.26-2.98 Hz) only displayed
left-right alternation. The slow rhythm was induced pharmacologically
by, e.g., antagonists of GABAA receptors. A slow
dorsal-ventral reciprocal modulation of the locomotor burst activity
would be expected to make the lamprey modulate its swimming path
sinusoidally in the dorso-ventral plane.
![]() |
METHODS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The isolated spinal cord of adult lampreys (Petromyzon marius and Ichthyomyzon unicuspis) were used. They were anesthetized with tricaine methane sulfonate (MS-222; 100 mg/l) and dissected in cooled physiological solution. Spinal cord segments were taken from a region between the last gill opening and the dorsal fin. Segments (10-14) from the rostral half of the region close to the gills were usually used. In the beginning of the study with bicuculline and strychnine, segments from the caudal half of this region were also used, but they were less likely to generate the slow rhythm as described in RESULTS. Each ventral root projects out of the spinal canal into its myotome and divides into a dorsal and a ventral branch, which innervate the dorsal and ventral myotome, respectively. Each branch runs on the medial surface of the myotome dorsally or ventrally in the connective tissue between the myosepta. To expose the main trunks of the branches, the spinal cord was dissected together with the notochord and the medial part of the myotomes.
Muscle fibers were carefully removed to expose the dorsal and ventral branches, and the main trunks of the branches were then dissected. After both branches had been exposed bilaterally, the dorsal wall of the spinal canal was removed to expose the spinal cord to the physiological solution. The notochord was cut longitudinally in the midline of the ventral side, making it possible to record from branches on both sides.
The spinal cord was mounted in a silicone elastomer (Sylgard)-lined
chamber with the notochord spread out laterally and continuously perfused with cooled (7-9°C) physiological solution with the
following composition (in mM): 91 NaCl, 2.1 KCl, 2.6 CaCl2, 1.8 MgCl2, 23 NaHCO3, and 4 glucose and bubbled with 95%
O2-5% CO2. The main trunks
of the dorsal and ventral branches on each side were sucked into glass
suction electrodes to record extracellular axonal activity. Ipsilateral
dorsal and ventral branches were recorded either from the same ventral
root or from roots one segment apart. Branches on the left and right
side were located 0-3 segments apart. Bursting activity was induced by
adding NMDA (Tocris Neuramin, UK; 50-200 µM) to the physiological
solution. NMDA (50 µM) was used in most cases. The
GABAA-receptor antagonist, ()-bicuculline
methiodide (Sigma, UK; 10-300 µM), was added during NMDA-induced
swimming activity to induce the slow rhythm. We also investigated the
effects of strychnine nitrate (Kronan, Sweden; 0.1-5 µM) and a
metabotropic glutamate receptor agonist (1 s, 3 s)-l-aminocyclopentane-1,3-dicarboxylic acid (ACPD, Tocris Cookson, UK;
25-300 µM).
In some cases, a midline longitudinal section of the spinal cord was made to study network organization of the slow rhythm. The section of the whole spinal preparation was carried out after the slow rhythm was induced by NMDA and bicuculline, and activity changes were followed for at least 1 h after the section.
The extracellular axonal activity was amplified and filtered (band-pass 300 Hz-1 kHz, Differential AC amplifier Model 1700, A-M Systems). Data were acquired using an A/D converter at sampling rate 2.5 kHz and a 486 PC computer with Axon Instruments software (Digidata 1200 interface and Axotape 2.0, Axon Instruments). Data-Pac II (Run Technologies) was used for further analysis. Spikes exceeding a set threshold were detected and saved as event pulses. We analyzed auto- and cross-correlograms of the bursting branch activity using the event pulses with a bin width of 60 ms and a window of ±30.72 s. To make a correlogram, 2,000 event pulses from the activity in a dorsal branch were used as triggers. The autocorrelogram shows the degree of oscillatory tendency in the branch activity, and the cross-correlogram indicates degree of synchronization and phase relation between the dorsal branch and another branch. We performed fast Fourier transformation (FFT) of the autocorrelogram of the dorsal branch activity to analyze the frequency components of the bursting activity.
![]() |
RESULTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Bicuculline induces a slow rhythm
Figure 1A shows NMDA-induced fictive locomotion in a preparation subjected to bicuculline with recordings from dorsal and ventral branches of the dorsal roots bilaterally. A fast burst activity (around 1.6 Hz) is modulated by a slower rhythm (0.05 Hz) occurring simultaneously in the left and right dorsal branch and alternating with increased activity in the ventral branches. The fast locomotor rhythm alternated between left and right side (Fig. 1A, inset). In 24 of 27 preparations, application of bicuculline induced a slow rhythm that was superimposed on the fast NMDA-induced rhythm. The slow rhythm started to appear at a bicuculline concentration 30-50 µM (Fig. 2C) and continued as the concentration was increased up to 200-300 µM. When the two rhythms appeared simultaneously, the frequency of the slow oscillation ranged from 0.03 to 0.11 Hz, whereas the fast swimming rhythm ranged from 0.26 to 2.98 Hz. The most common pattern induced by bicuculline was the dorsal-ventral reciprocal pattern (Fig. 1, A and C), which was observed in 18 of 24 preparations. A diagonal reciprocal pattern that is reciprocal between the left dorsal and right ventral branches or vice versa, was induced in two preparations. A pattern in which the slow rhythm was synchronized in all four branches was observed in four preparations but in this case without a concurrent fast rhythm (Fig. 1B). There was no difference in the frequency range of these three patterns (Fig. 1C).
|
|
In 8 of 18 preparations a slow rhythm was present before bicuculline application. This NMDA-induced slow rhythm usually occurred in a left-right reciprocal pattern, but with bicuculline (n = 18), the slow rhythm became somewhat faster and changed into a dorsal-ventral reciprocal pattern superimposed on the faster left-right reciprocal activity.
Dorsal-ventral reciprocal pattern
Figure 2A, 1 and 2, shows the transformation of the bursts pattern when bicuculline was added. The locomotor rhythm became significantly faster, while the slow rhythm became superimposed on the faster burst pattern. This is very evident in the two ventral branches which are modulated in phase. The cross-correlogram in Fig. 2B2 (see METHODS) compares the activity in the left and right dorsal branches. Clearly the slow activity occurs in phase while the fast activity (left-right) is reciprocal (see Fig. 2B, inset). Figure 2B1 shows in a corresponding way that the ipsilateral dorsal and ventral branches are reciprocal with regard to the slow rhythm but in phase with regard to the fast locomotor rhythm. In the power spectra of Fig. 2C, it is shown that the slow rhythm becomes more prominent with increasing bicuculline levels, while the locomotor rhythm shows a progressively increasing frequency.
In 2 of 24 preparations, a slow alternating pattern was observed between one dorsal branch and a contralateral ventral branch that is a diagonal reciprocal pattern. Figure 3B1 shows a clear diagonal cross-correlogram, whereas the corresponding correlogram in Fig. 3B2 for the ipsilateral branches show no correlation (compare also Fig. 3A). This diagonal reciprocal pattern may either represent a partial expression of a general dorsal-ventral reciprocal pattern (Fig. 1A2) or a separate mode of coordination.
|
Rostrocaudal distribution of the dorsal-ventral slow rhythm generator
All experiments were carried out on spinal cord segments from a
region caudal to the gill and rostral to the dorsal fin (segment 12~15-50~60) to exclude fin motoneuron activity, which is in
antiphase to myotomal motoneuron activity (Buchanan and Cohen
1982). We tested the likelihood of inducing the dorsal-ventral
reciprocal pattern of the slow rhythm in different parts of the spinal
cord by dividing it into a rostral and a caudal half. The
dorsal-ventral reciprocal pattern was elicited by bicuculline in 17 of
19 preparations taken from the rostral half, whereas it only occurred
in 1 of 4 from the caudal part (
2 test with
Yate's correction,
2 = 4.73, P < 0.05). The
results indicate that the rostral part of the spinal cord (segments
12-30) close to the gill is more readily activated into a slow
dorsal-ventral reciprocal pattern as compared with the caudal part.
Midline longitudinal section of the spinal cord
To investigate if the neural network responsible for the slow oscillation involves both sides of the spinal cord, a midline longitudinal section of the spinal cord was made in 6 preparations. Before the midline section, the slow rhythm was induced by bicuculline application on NMDA-induced swimming activity. The dorsal-ventral reciprocal pattern of the slow rhythm was induced in five of six preparations, with the synchronous pattern being induced in the remaining preparation. The ventral root activity was almost abolished directly after the operation, but traces of a slow rhythm recovered in 9 of 12 hemicords (from 6 preparations) within 5 min (Table 1, Fig. 4A2). The efferent discharge in Fig. 4A2 appears to be continuous but it is actually modulated in a slow fashion. The autocorrelograms of the dorsal and ventral branches (Fig. 4B, 1 and 2) show that there is a slow rhythmic activity while the cross-correlogram shows that the dorsal and ventral branches are in phase (Fig. 4B3). However, the dorsal-ventral reciprocal pattern between the ipsilateral branches, which was present before the midline section (Fig. 4A1), never recovered in any preparation. The slow rhythm in ipsilateral branches became synchronous without a phase difference in five hemicords. In the remainder, the pattern became disorganized. In two cases, different slow frequencies were observed in dorsal and ventral branches, and in two cases, a slow rhythm remained only in one branch. There was no consistent change in the frequency of the slow rhythm after the hemisection of the spinal cord (Fig. 4C). In contrast to the slow rhythm, the swimming rhythm did not recover in any preparations up to 60 min after the section. These results suggest that a slow rhythm can be generated independently in dorsal and ventral branches or be synchronized after a midline section but that a reciprocally organized dorsal-ventral activity may depend on a bilateral organization.
|
|
Other potential slow rhythm inducers
STRYCHNINE.
If the glycine receptor antagonist strychnine (5 µM) is introduced
during fictive locomotion, the frequency of locomotor activity increases progressively to become disrupted (Grillner and
Wallén 1980). A partial glycine blockade by
strychnine may result in synchronous locomotor bursts on both sides of
the spinal cord (Cohen and Harris-Warrick 1984
;
Hagervik and McClellan 1994
). Strychnine may also induce
a slow activity pattern (McPherson et al. 1994
),
although it was not investigated how this pattern was represented in
dorsal and ventral branches of the ventral root. In the present study,
strychnine (0.1-5 µM) induced a slow dorsal-ventral reciprocal
pattern in two of three preparations (Fig.
5A2), and a diagonal
reciprocal pattern in the third preparation. The left-right alternation
in Fig. 5A1 was abolished after strychnine. The
cross-correlogram for the motor pattern in Fig. 5A2 is
characteristic of the dorsal-ventral reciprocal pattern with a central
trough of the slow oscillation between ipsilateral branches (Fig.
5B1) and a central peak between the left and right dorsal
branches (Fig. 5B2). The fast swimming rhythm was not
clearly discernible in the strychnine-induced slow rhythm (Fig.
5A2) compared with that in the bicuculline-induced slow
rhythm (see Figs. 1A and 2A2). The power spectra
for this preparation show that the slow rhythm started to appear at a
strychnine concentration of 0.5 µM (Fig. 5C). The
frequency range of this slow rhythm was the same as that induced by
bicuculline (0.05-0.10 Hz). The fast swimming rhythm was disrupted by
strychnine in all three preparations.
|
ACPD.
The metabotropic glutamate receptor agonist ACPD is known to induce a
slow oscillatory activity in rat hippocampus (Aniksztejn et al.
1995; Cherubini et al. 1991
; Taylor et
al. 1995
) and to affect locomotor circuitry in the lamprey
spinal cord (Krieger et al. 1994
, 1998
). We investigated
the effect of ACPD (25-200 µM) on the induction of the slow rhythm;
when it was applied on NMDA-induced swimming (Fig.
6A2), a slow rhythm was
induced in a dorsal-ventral reciprocal pattern in two of three
preparations. As with the bicuculline-induced slow rhythm, the
ACPD-induced slow rhythm was superimposed on a fast swimming rhythm
(Fig. 6A2). The cross-correlograms (Fig. 6B,
1 and 2) for the recordings in Fig.
6A2 show that there is a slow dorsal-ventral reciprocal
pattern and a fast left-right reciprocal pattern. The power spectra in Fig. 6C show that the slow rhythm is represented with a
prominent peak at 50 µM ACPD, while the faster rhythm is present at 0 µM ACPD and progressively increases in frequency with increasing ACPD
concentration.
|
![]() |
DISCUSSION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The results show that bicuculline, strychnine, and ACPD induce a slow rhythm when applied independently on NMDA-evoked activity. The slow rhythm had three patterns: a dorsal-ventral reciprocal, a diagonal reciprocal, and a synchronous pattern, with the dorsal-ventral pattern being the most common. It is noteworthy that the fast locomotor and the slow rhythms could occur simultaneously in different combinations.
Two rhythms with different patterns
In the isolated lamprey spinal cord, a slow rhythm superimposed on
the swimming rhythm has been observed following the application of 5-HT
on kainate-evoked swimming (Schotland and Grillner 1993) and on NMDA-evoked swimming with apamin (El Manira et al.
1994
), bicuculline (Tegnér et al. 1993
),
and strychnine (McPherson et al. 1994
). In these
studies, whole ventral roots were recorded and a dorsal-ventral
organization could thus not be studied. In the present study, the slow
rhythm was predominantly organized in a dorsal-ventral reciprocal
pattern, while the swimming rhythm always displayed a left-right
reciprocal pattern. The present study is the first to report that the
slow and fast rhythms occur simultaneously in different combinations in
the isolated spinal cord.
Slow rhythm generator
The simultaneous existence of two independent rhythms with
different left-right and dorsal-ventral reciprocal patterns of activity
suggests that there are two distinct rhythm generating networks in the
lamprey spinal cord. This is supported by the observation that the slow
rhythm, but not the fast locomotor-related rhythm, could recover after
a longitudinal midline section of the spinal cord. Buchanan et
al. (1995) also reported that a complete midline section
abolished the swimming rhythm in lamprey. Hemispinal cords can,
however, be made to produce brief episodes of fast rhythmic burst
activity after a glycinergic blockade (Grillner et al.
1986
), and a fast bilaterally synchronous pattern can be observed in the intact cord after a partial strychnine blockade (Cohen and Harris-Warrick 1984
).
The presence of two superimposed rhythms has been reported previously
in the isolated spinal cord or isolated spinal cord-hindlimb preparation in the neonatal rat and mouse (Cazalets et al.
1990; Hernandez et al. 1991
). In these
preparations, the slow burst activity was alternating between
ipsilateral antagonistic muscles, suggesting that there are neural
mechanisms in the rodent spinal cord that can induce an ipsilateral
slow reciprocal pattern. Bracci et al. (1996a
,b
)
reported slow rhythmic bursting (0.03 Hz) with a left-right synchronous
pattern induced by coapplication of bicuculline and strychnine to the
isolated rat spinal cord. The burst activity had an intraburst
oscillating structure, which was abolished by ventral quadrant
isolation of the spinal cord, whereas the slow burst activity remained.
These results may suggest that there are discrete networks also for the
slow burst generation and the fast intraburst oscillation in the rat
spinal cord.
In the present study, with a spinal midline longitudinal section, the reciprocal pattern of the slow rhythm between the ipsilateral dorsal and ventral branches was disrupted and changed to a synchronous pattern. This result suggests that there are discrete slow oscillators for the dorsal and ventral myotomes that may depend on an excitatory coupling. A bilateral organization appears to be necessary to induce a reciprocal pattern between dorsal and ventral oscillators. The occurrence of a diagonal reciprocal pattern of the slow rhythm suggests that the reciprocity between dorsal and ventral oscillators may be organized preferentially by a diagonal coupling.
The present results are compatible with a conceptual model (Fig.
7A), consisting of separate
slow oscillator networks controlling dorsal and ventral myotomes on
each side. The slow oscillators can be coupled in three ways: a
diagonal reciprocal inhibitory, an ipsilateral excitatory, and a
contralateral mutual excitatory coupling. By changing the strength of
these couplings (for instance by descending signals from the brain
stem), the three patterns observed in the present study could be
produced. The contralateral excitatory coupling would make the dorsal
oscillators synchronous. When the ipsilateral excitatory coupling is
weak, a dorsal-ventral reciprocal motor pattern may occur (Fig.
7B). When all excitatory couplings are weak in comparison
with the diagonal inhibitory couplings, a diagonal reciprocal pattern
may arise involving only two oscillators (Fig. 7C). When the
ipsi- and contralateral excitatory couplings are relatively strong as
compared with the diagonal inhibitory coupling, all oscillators may
become synchronous (Fig. 7D). Finally, if the contralateral
excitatory coupling is weak, the network can generate a left-right
reciprocal pattern (Fig. 7E). Ekeberg et al.
(1995) have proposed a similar cross-oscillator hypothesis for
generating turning movements in three-dimensional space using the swim
rhythm generators.
|
Mechanisms for the slow oscillator and pattern generator
The slow rhythm with a dorsal-ventral reciprocal pattern is
distinctly different from the left-right alternating locomotion. When a
slow left-right alternation occurs (Brodin and Grillner 1985), it is not possible to know whether it represents a very slow activity in the locomotor networks or activity in the current "slow" network. If we restrict the discussion to the dorsal-ventral reciprocal slow pattern, it may be induced by a blockade with strychnine blocking glycine receptors and bicuculline-methiodide blocking GABAA receptors and apamin-sensitive
KCa channels and also by agonists of metabotropic
glutamate receptors (mGluRs; ACPD). These agents thus release the slow
dorsal-ventral reciprocal pattern, observed here for the first time. At
present, the neural mechanisms that are utilized by the different
agonists-antagonists to induce the slow rhythm are not yet elucidated.
However, it is likely that inhibitory inputs to spinal GABAergic
neurons could produce an effect analogous to bicuculline, and the
5-HT-systems could reduce the efficiency of KCa
channels as does apamin. Previous studies recording whole ventral roots
have reported that a variety of agents may induce a slow left-right
alternation concurrently with a fast alternation in lamprey
(McPherson et al. 1994
; Schotland and Grillner
1993
), tadpole (Reith and Sillar 1998
), and the
neonatal rat (Bracci et al. 1996a
).
The activation of the mGluRs by ACPD induces a slow rhythm. In the
lamprey spinal cord, presynaptic inhibitory modulation of
reticulospinal EPSPs in gray matter neurons is mediated by mGluRs
(Krieger et al. 1996), and a modulation of the lamprey spinal locomotor network has been demonstrated (Krieger et al. 1998
). In hippocampal CA3 neurons of neonatal and mature rats, ACPD also induced persistent slow oscillations (Aniksztejn et al. 1995
; Cherubini et al. 1991
;
Taylor et al. 1995
) suggested to involve presynaptic
mGluRs (Aniksztejn et al. 1995
). A presynaptic modulation of GABAergic synapses by mGluR agonists has also been reported (Hayashi et al. 1993
; Kaba et al.
1994
; Llano and Marty 1995
; Poncer et al.
1995
) and spontaneous inhibitory postsynaptic currents recorded
in Purkinje cells had a tendency to cluster in bursts in the presence
of ACPD (Llano and Marty 1995
).
Steering behavior and the slow rhythm
Lamprey swimming is always performed as a lateral undulation. This
lateral undulatory swimming is maintained even during steering behavior
in the sagittal plane. The present study shows that the network
producing the slow rhythm can differentially control dorsal and ventral
myotomes and thus suggests one possible mechanism that may affect the
swimming in a vertical direction. The dorsal-ventral reciprocal pattern
of the slow rhythm was more readily induced in the rostral part of the
spinal cord, compatible with the observation that a sharp downward turn
was accomplished by a ventral flexion of the rostral part of the body
(Ullén et al. 1995). For natural steering
behavior, descending control from reticulospinal neurons (Ullén et al. 1998
) plays an important role.
Pharmacological microstimulation of the reticular formation could
elicit differential swimming activity in dorsal and ventral branches of
the ventral roots, as well as on the left and right side
(Wannier et al. 1998
). Thus descending systems activated
by visual or other sensory inputs may utilize interneurons of the slow
network to accomplish steering in the dorso-ventral plane. Under
natural behavior, the lamprey may not always swim in a straight line
but slowly vary its depth up and down in a sinusoidal fashion as would
be produced by the dorsal-ventral reciprocal pattern documented here.
This type of behavior occurs in fish that like to increase the chances
of detecting olfactory cues in water. If so, the lamprey may utilize
the slow rhythm for this purpose.
![]() |
ACKNOWLEDGMENTS |
---|
We are grateful to Dr. David Parker for valuable comments on the manuscript and to H. Axegren and M. Bredmyr for technical assistance.
This work was supported by the Swedish Medical Research Council (Project 3026), Karolinska Institutets fonder and "gästforskaranslag" to F. Aoki, the Janggen-Pöhn Stiftung, the Wenner-Gren Foundation to T. Wannier, and the Wallenberg Foundation.
Present address of T. Wannier: Institut de Physiology, Rue du Musee 5, 1700 Fribourg, Switzerland.
![]() |
FOOTNOTES |
---|
Address for reprint requests: S. Grillner (E-mail: Sten.Grillner{at}neuro.ki.se).
Received 4 August 1999; accepted in final form 21 September 2000.
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|