Download Spontaneous Spike Activity of Spinoreticular Tract Neurons During

ACTIVE SLEEP-RELATED MODULATION OF SPINORETICULAR TRACT NEURONS
Spontaneous Spike Activity of Spinoreticular Tract Neurons
During Sleep and Wakefulness
Peter J. Soja, Walton Pang, Niwat Taepavarapruk, and Shelly A. McErlane
Division of Pharmacology & Toxicology, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, V6T
1Z3, Canada
Abstract: Sleep mentation studies infer that pain sensation in humans may be reduced during active REM sleep. However, to provide a mechanistic explanation for this phenomenon, few, if any neurophysiological studies have been performed at the lumbar level from neurons comprising classical pain pathways during sleep and wakefulness. The spinoreticular tract is one such classical pathway that has been implicated in the
rostral transmission of nociceptive information. The present study was performed to determine if the activity of spinoreticular tract (SRT) neurons is dependent upon behavioral state. Accordingly, extracellular recording techniques were used to monitor the activity of identified SRT neurons in unanesthetized chronic cats during sleep and wakefulness. The ongoing spike activity of SRT neurons was found to be relatively uniform when the states of quiet wakefulness and quiet sleep were compared. However, during active sleep, the majority of the SRT neurons sampled underwent a sustained reduction in spike activity. Marked facilitation of SRT cell activity occurred in a few instances. These data provide
the first unitary evidence supporting earlier evoked potential, psychophysical and clinical studies that ascending sensory information in a classical pain pathway is regulated in a state-dependent fashion.
Key words: Active sleep; dorsal horn; sensory; spinal cord; spinoreticular
INTRODUCTION
difficult to extrapolate from acute experimental preparations on
exactly how or when descending controls act upon SRT neurons
to modulate the rostral transmission of sensory nociceptive information.
Earlier evoked potential studies by Pompeiano and his colleagues suggested that a variety of spinal sensory pathways
whose axons project through the medial leminiscus are regulated
only during the rapid eye movement (REM) portions of active
sleep.14,15 We recently reported that sciatic nerve evoked field
potentials recorded from fibers comprising the SRT and spinothalamic tracts (STT) are reduced throughout the state of active
sleep and can even be abolished during the REM saccades associated with this state.16 These data support the idea that innocuous and nociceptive information conveyed by these ascending
sensory pathways1 may be reduced both tonically and phasically
during the behavioral state of active sleep. However, field
potential experiments of this type are limited in that they do not
distinguish precisely which sensory pathway is specifically regulated. Regulated pathways could include not only the SRT and
STT but also other ascending pathways projecting amongst the
fiber tracts within the ventrolateral reticular formation such as the
spinomesencephalic tract and ventral spinocerebellar tract.
These caveats notwithstanding, the only plausible approach to
evaluate changes in transmission through each of these ascending
sensory pathways is to record single unit activity from antidromically identified spinal cord neurons. The difficulty associated
with this task depends in part on the feasibility of recording a particular type of ascending sensory tract neuron in chronically
instrumented animal preparations.17 In acute anesthetized cats,
SRT neurons are readily located in the upper lumbar segments
within the ventral gray matter lateral as well as ventral to
Clarke’s column DSCT neurons.2,10,18-20 We report herein that the
THE SPINORETICULAR TRACT IS ONE OF SEVERAL
CONSORTIUM SOMATOSENSORY TRACTS INVOLVED IN
THE SENSORI-DISCRIMINATIVE ASPECTS OF PAIN AND
TACTILE PROCESSING.1 Electrophysiological studies performed in acute anesthetized animal preparations have revealed
that SRT neurons respond to intense electrical or natural stimulation of peripheral receptive fields.2-8 For example, studies performed by Ammons et al. and Fields et al. have shown that
spinoreticular tract neurons can be driven by cutaneous nociceptors upon application of intense stimuli (e.g., pinch, or prick to
their peripheral receptive fields).3,9 In addition, high intensity
stimulation of peripheral nerves at intensities capable of recruiting unmyelinated C- fibers also excites SRT neurons in anesthetized animal preparations. Additionally, these forms of SRT
neural excitation by nociceptive stimuli are controlled by
supraspinal influences originating from a variety of sources such
as the nucleus reticularis gigantocellualris and raphe magnus.10,11
In this regard, it has been reported that electrical stimulation of
the NRGc or raphe magnus inhibits the discharge of SRT neurons
responding to noxious stimuli.10,11 With respect to the latter,
studies performed in acute anesthetized animal preparations,
have applied phasic electrical stimulation paradigms to discrete
brainstem centers and demonstrated complex facilitatory or
inhibitory actions on recorded SRT neurons.10-13 However, it is
Accepted for publication November 2000
Address correspondence to: Peter J. Soja, PhD, Faculty of Pharmaceutical
Sciences, The University of British Columbia, 2146 East Mall, Vancouver, BC,
V6T 1Z3 CANADA; Tel: 604-822-2692; Fax: 604-822-4609;
E-mail: [email protected]
SLEEP, Vol. 24, No. 1, 2001
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Active Sleep-related Modulation of Spinoreticular Tract Neurons—Soja et al
Figure 1—Methods used to antidromically identify L3 SRT neurons. The vertical calibration bar to 75µV for EEG, EOG, PGO, and EMG traces. A. Experimental
scheme of lumbar recording and brainstem stimulation sites. B. Oscilloscope trace illustrating SRT neuron spontaneous spike activity and typical signal-to-noise ratio.
C. Three superimposed oscilloscope traces are presented of an antidromic action potential recorded in L3 spinal cord segment after stimulation of the contralateral,
ventrolateral reticular formation using a single pulse (80 A, 0.2 msec, 1 Hz). D. High-frequency (500 Hz, 2 pulses) train of stimuli. The asterisks in C and D denote
the stimulus onset. Consecutive antidromic responses displayed constant latency-to-onset indicating that the action potential resulted from antidromic activation of
the axon of the recorded unit. E. Single oscilloscope sweeps illustrating a collision between the antidromic and a spontaneous action potential. The sweeps are
aligned by the onset of reticular stimuli (asterisks) as indicated by the dashed vertical line. The lower oscilloscope sweep in E illustrates a collision between an orthodromically activated action potential evoked by stimulation of the reticular formation (0.2 msec, 80 A) and the antidromic spike.
Animals were allowed to fully recover over a three-month
period following these surgical implant procedures during which
time they were gradually trained to accept painless stereotaxic
head and lumbar restraint.22 Animals were loosely wrapped in a
soft canvas bag and subsequently positioned in a heavy duty
Kopf stereotaxic frame. The previously implanted head and
lumbar restraining devices were affixed to the stereotaxic AP bars
by Kopf chronic holding devices (Model 880). Animals were
able to make postural limb adjustments during head and lumbar
restraint. All surgical and chronic restraint procedures reported
complied with (inter) national25,26 and institutional (University of
British Columbia Animal Care Committee) guidelines. Further
details of these implant and restraint procedures were reported
previously.22
activity of individual SRT neurons in the chronic unanesthetized
cat preparation is indeed dependent on behavioral state. These
data may have relevance to psychological studies whereby
reports of experimental or spontaneous pain are diminished or
absent during active sleep. Preliminary results have been reported elsewhere.21
METHODS
Surgical Procedures
Adult cats were prepared for extracellular unit recording of
spinal cord neurons during sleep and waking states using previously established methods.22 Four intact, unanesthetized, chronically instrumented cats were implanted under deep gaseous anesthesia (45-60% N20 in 1.5-2.5% halothane/oxygen mixture) with
head and lumbar restraining devices. Electrodes were also
implanted into the frontal sinus (electroencephalogram [EEG]),
lateral geniculate nucleus of the thalamus (ponto-geniculo-occipital [PGO] wave activity), the orbital plate (electro-oculogram
[EOG]) and neck muscles (electromyogram [EMG]) and were
used for monitoring behavioral states. Through the use of these
electrodes, the animal’s behavioral states of wakefulness, quiet
sleep and active sleep could be determined when spinoreticular
tract neurons were being located and recorded.22-24 In addition to
these electrodes, chronic restraining devices composed of acrylic
resin were fixed to the skull and lower lumbar vertebrae L2-L6.
SLEEP, Vol. 24, No. 1, 2001
Stimulation and Recording Procedures
Glass microelectrodes containing a carbon fiber27 that were
backfilled with 4M NaCl were used to record from L3 spinal cord
neuronal elements using an AC-coupled amplifier (AM-Systems
Model 1800). Amplified signals (1000X, bandpass, 0.3-10 KHz)
were routed to a window discriminator, rate counter (Digitimer,
Inc.), and oscilloscope. Recording electrodes were slowly lowered in tracks beginning 0.2-0.7 mm lateral to the midline of the
L3 spinal cord. Low-intensity search stimuli were applied to a
stimulating electrode (A-M Systems, Cat. # 5755, 5-8 MΩ, AC)
that was stereotaxically positioned (HC: P10, L3.5 to 4.0, H –8.0
19
Active Sleep-related Modulation of Spinoreticular Tract Neurons—Soja et al
to –8.5) in the contralateral ventrolateral reticular formation
immediately below the facial motor nucleus16 in order to “backfire” L3 neurons.
Previous studies performed in acute anesthetized cats have
indicated that spinoreticular neurons are predominantly recorded
in lower thoracic and upper lumbar spinal cord segments at spinal
cord depths corresponding to lamina V and VII,28 dorsolateral
and ventral, respectively, to Clarke’s Column.9,18 Accordingly,
neurons were targeted in this area and well-isolated (signal-tonoise ratios >3.0) cells were systematically checked for ascending axonal projections (Figure 1). Criteria for antidromic activation were similar to those used previously for dorsal spinocerebellar tract (DSCT)22 or trigeminothalamic tract (TGT)24 neurons
and included constant latency spikes evoked by consecutive lowintensity monopolar stimuli (0.2 ms, 0.5 Hz, 100-250 A) the
ability to faithfully follow a short train of high frequency stimuli,
and collision with spontaneous action potentials.22,24
spike amplitude. The average spontaneous firing rate (spikes/s,
Hz) was calculated for each neuron using trains of 500-1000 consecutive spikes. In two cells the firing rate was substantially
reduced during active sleep (see Results). For these neurons, a
minimum of 50 consecutive spikes was used to determine average spontaneous spike rate during active sleep. Data obtained
during quiet wakefulness following active sleep served as control
for comparison with data obtained during quiet sleep, and the
middle portion of active sleep. For spike rate, differences
between control and test (wakefulness, quiet sleep, and active
sleep) states were plotted and analyzed for statistical significance
using a repeated measures ANOVA, (SigmaPlot 2000, SigmaStat,
SPSS Inc.) with α set at 0.05. Spike interval data were also
described using interspike interval histograms (ISIH) and quantified using the following parameters: mean interval (reciprocal of
firing rate), coefficient of dispersion (CD= variance / mean interval) and coefficient of variation (CV = standard deviation / mean
interval).29 Spike rate and ISIH parameters were expressed as
group mean values±SEM.
Data Analyses
A Pentium III microcomputer equipped with spike acquisition
and analysis software (SPIKE 2-v.3-01, 1401plus, Cambridge
Electronic Design, Inc.) was used for quantifying neuronal data.
A subroutine was employed to sort spike templates and verify
that the same SRT neuron was recorded across all behavioral
states. Accepted spikes did not deviate by 15% in peak-to-peak
RESULTS
SRT Neurons, General Properties
Extracellular recordings were obtained from a total of fifteen
antidromically identified SRT neurons located at an average in
situ recording depth of 3,320 microns (range: 2,480-4,500)
Figure 2—Suppression of a spinoreticular tract neuron activity during active sleep. The first four traces depict the behavioral state of the animal, as indicated by the
cortical electroencephalogram (EEG), electro-oculogram (EOG), ponto-geniculo-occipital (PGO) wave, and electromyogram (EMG) activities. Below the four electrophysiological signals, a continuous rate-meter trace represents discharge of the cell during the state of quiet sleep (QS), the transition into and throughout active
sleep (AS) and re-awakening (RW). A sliding average (gray line, binwidth: 30s) is superimposed over the rate histogram trace. Note that spontaneous spike activity
is nearly abolished during the state of active sleep when compared to quiet sleep and re-awakening.
SLEEP, Vol. 24, No. 1, 2001
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Active Sleep-related Modulation of Spinoreticular Tract Neurons—Soja et al
Figure 3—Facilitation of a spinoreticular tract neuron activity during active sleep. The first four traces in represent behavioral state and the bottom trace represents
SRT neuronal activity as indicated in Figure 1. Note that during active sleep, the cell underwent phasic periods of excitation. The sliding average (gray line, bin width:
30s) indicates the overall increased excitability of this cell during active sleep.
below the surface of the spinal cord. Several factors contribute to
the problem of determining the precise in situ spinal laminar
locations of recorded neurons. These include but are not limited
to unavoidable errors associated with obtaining accurate micrometer depth readings from the surface of the spinal cord due to
inherent dead space in pneumatic microdrive apparatus and/or
continuous presence of cerebrospinal fluid on the spinal cord surface. This uncertainty is inevitable despite conscientious efforts
to minimize these factors (see also reference 30).
Mean antidromic latencies taken from the beginning of the
stimulus artifact to the initiation of the action potential measured
3.2 ms ± 0.5, (range: 2.1-4.4) at threshold (mean: 106 µA±7,
range: 20-230) stimulus intensities. The mean conduction velocities were estimated at 86.8 m/s±15.5 (range: 60.2-120m/s).
Each neuron displayed constant latency antidromic spikes with
no jitter, faithfully followed short high frequency (500Hz) stimulus trains and demonstrated collision between antidromically
propagated and spontaneously occurring action potentials
(Figure 1). For all cells, antidromic spikes were evoked from the
contralateral reticular formation. In our recording experiments, it
was not possible to test for bilateral projections of recorded cells
due to space constraints involving positioning of stereotaxic
hardware. The animals never displayed any signs of discomfort
such as EEG desynchronization, hissing, or vocalization during
these identification procedures.
SRT neurons recorded in the L3 spinal segment of the chronic unanesthetized cat preparation display moderate rates of sponSLEEP, Vol. 24, No. 1, 2001
taneous spike activity, which, as reported below, was dependent
on the animal’s behavioral state. An example of the spontaneous
firing rate of an antidromically identified SRT neuron is shown in
Figure 1B. SRT neurons also displayed broad cutaneous receptive fields encompassing the animal’s ipsilateral flank, proximal
tail, and hind limb areas. Most SRT neurons recorded in the
unanesthetized cat displayed phasic robust burst discharge to
innocuous forms of receptive field stimuli such as air puff
induced hair movement, and light stroking of cutaneous receptive
fields. Stroking and air puff were induced using a hand held soft
camel hair brush or glass pipette fitted with a bulb. Such stimuli
do not provide for quantifiable data as reliably as mechanically
controlled forms of stimulation (e.g., reference 23). In several
cases, oligosynaptic responses could also be recorded following
low-intensity stimulation of the sciatic nerve. These and other
data involving mechanically controlled forms of stimulation are
currently in progress and will be described in detail elsewhere.
Spontaneous Spike Activity During Wakefulness, Quiet
Sleep, and Active Sleep
The state of quiet wakefulness was characterized by a desynchronized cortical EEG pattern, tonic EMG activity, sparse or no
PGO and EOG activity, and little or no postural movements
(Figures 2, 3). During quiet wakefulness, the average spontaneous discharge rate of all 15 SRT neurons measured 21.1
spikes/s±3.9 (range: 4.7-58.9). The state of quiet sleep differs
21
Active Sleep-related Modulation of Spinoreticular Tract Neurons—Soja et al
Figure 4—Bar graphs summarizing the direction and magnitude of change in spike activity for 15 SRT neurons recorded across the sleep or wake cycle. Y axis represents facilitation or suppression during active sleep when compared to quiet wakefulness. Each bar represents the relative change for each SRT neuron.
from quiet wakefulness principally by the presence of a large
amplitude synchronized slow-wave EEG pattern, a relatively
moderate level of EMG activity, and little or no EOG and PGO
wave activity (Figures 2, 3). The group mean spontaneous spike
rate for the same SRT neurons measured 19.1 spikes/s±3.5
(range: 5.2-41.4) and did not significantly differ from values
obtained during quiet wakefulness, (p>0.05).
The state of active sleep is hallmarked by EEG desynchrony,
muscle atonia, robust PGO wave activity, and EOG activity
(Figures 2, 3). During this state, the ongoing spike activity of all
SRT neurons was reduced to 14.7 spikes/s±3.1 (p<0.05, range:
0.5-38). When compared to the state of quiet wakefulness, this
corresponds to a 31% decrease in SRT neuronal activity. During
active sleep, there was a greater than 25% decrease in spike rate
in eight cells and an increase in two cells. Examples of suppression and facilitation of SRT neuron spike activity during active
sleep are illustrated in Figures 2 and 3, respectively. Note that for
each example, the change in firing rate occurs only during active
sleep. Figure 4 illustrates the relative change in cellular activity
during active sleep for each cell.
Analyses of interspike interval histograms (ISIH) across all
SRT neurons revealed that the pattern of spike firing was relatively constant during quiet wakefulness and quiet sleep.
Individual interspike interval distributions of SRT neuronal activity constructed during quiet sleep and wakefulness were leptokurtic, and positively skewed (Figure 5). Indeed, they closely
resembled those corresponding to the same behavioral states
from a previous study of dorsal spinocerebellar tract neurons.30
In the present study, this was confirmed by measuring no significant difference in the group mean values for coefficient of dispersion (CD) and variation (CV) of interspike intervals when
quiet wakefulness was compared with quiet sleep (p>0.05;
CDQUIET WAKEFULNESS: 0.05±0.01, range: 0.003-0.14; CDQUIET SLEEP:
SLEEP, Vol. 24, No. 1, 2001
0.08 ± 0.03, range: 0.007-0.42; CVQUIET WAKEFULNESS: 0.96±0.21,
range: 0.39-3.25; CVQUIET SLEEP: 0.75±0.08, range: 0.27-1.33).
Moreover, the group mean interspike intervals did not differ
(p>0.05). However, during active sleep, ISIH distributions were
broader and markedly asymmetric due to considerably fewer
SRT action potentials during this state (Figure 5). Accordingly,
there was a significant increase in the CD and CV values by factors of 4.2 and 1.7, respectively (p<0.05; CDACTIVE SLEEP:
0.21±0.04, range: 0.01-0.54; CVACTIVE SLEEP: 1.27±0.16, range:
0.75-3.25). Predictably, when compared to quiet wakefulness, the
group mean interspike interval during active sleep was also
increased by a factor of 1.4 (p<0.05).
During active sleep, rapid eye movement (REM) saccades
often occurred in conjunction with a burst of PGO waves and
were further associated with complex changes in SRT neuron
spike activity. An example of both facilitation and suppression of
SRT neuron activity around REM saccade events is illustrated in
Figure 3. In this particular example, the firing rate of the cell was
facilitated during active sleep. Further details of the modulation
of SRT neuron spike activity REM saccades will be reported elsewhere.
DISCUSSION
The present study utilized conventional extracellular recording methods in the chronic unanesthetized cat to monitor the
spike discharge of antidromically identified SRT neurons during
states of sleep and wakefulness
SRT neurons recorded in the present study were antidromically activated using discrete microstimuli applied to the ventrolateral reticular formation. Backfired SRT neurons had a mean
axonal conduction velocity (86.8 m/s) similar to that of DSCT
neurons (81.1 m/s) and were recorded somewhat deeper to DSCT
22
Active Sleep-related Modulation of Spinoreticular Tract Neurons—Soja et al
Figure 5—Interspike interval histograms (ISIHs) for an SRT neuron recorded during wakefulness, quiet sleep, and active sleep. Each ISIH was constructed from 1000
consecutive spikes. Compared with wakefulness and quiet sleep, ISIHs constructed during and AS are reduced in amplitude and skewed to the right. This reduction
in amplitude is due to the reduced firing rate while the skewing of the ISIH is a result of longer pauses in the firing pattern. Above each ISIH is the median interval,
and coefficients of dispersion (CD) and variation (CV) describing the interspike intervals in each ISIH. The increased coefficient of variation in active sleep as compared with wakefulness or quiet sleep further confirms the irregular pattern of spike discharge during active sleep. Spike train patterns over 2 s epochs derived from
each behavioral state are also shown.
neurons in the L3 spinal gray matter.30 However, the mean axonal conduction velocity of SRT neurons in the present study is
reported to be approximately two times faster than SRT neurons
recorded more dorsolaterally in the spinal gray matter of acute
anesthetized animal preparations17-19 and likely reflects different
classes of SRT neurons in the spinal gray.1 While both SRT and
DSCT neurons display robust and regular spike activity during
SLEEP, Vol. 24, No. 1, 2001
the state of wakefulness and quiet sleep, SRT neurons recorded in
the acute, paralyzed and anesthetized animal preparation exhibit
much lower (1-8 spikes/s) spontaneous firing rates than those
reported in the present study, presumably due to the direct suppressant actions of anesthetic agents such as α-chloralose.31,32
The principal finding of the present study is that SRT neuronal
activity is dependent on behavioral state. The direction, magni23
Active Sleep-related Modulation of Spinoreticular Tract Neurons—Soja et al
tude and pattern of state dependent modulation are similar to that
which occurs for Clarke’s Column DSCT neurons recorded in the
L3 segment.33 These data may provide a cellular correlate to our
previous evoked potential studies where sciatic nerve-evoked
field responses recorded from the SRT fiber tract were reduced or
even abolished during the state of active sleep.16
Given the well established evidence that the SRT is a major
sensory channel conveying tactile and pain information to higher
brain centers,1,9,18,19,34 our data also provide a neurophysiological
basis for clinical observations that thermal pain sensations, per
se, may be dampened during sleep when compared to wakefulness35 (see also reference 36). The present study imposed strict
ethical constraints whereby the responsiveness of SRT neurons to
peripherally applied forms of noxious stimuli could not be undertaken. Hence it was not possible to verify that the sample of SRT
neurons we recorded from actually relay nociceptive information
suprapsinally. However, given that L3 SRT neurons recorded in
acute anesthetized animals respond to nociceptive stimulation of
their peripheral receptive fields, it is likely that certain SRT cells
recorded in the present study were nociceptive. The ability to
obtain stable recordings of individual SRT neurons located in the
upper lumbar segments in the chronic cat preparation across
behavioral states, such as sleep and wakefulness, will further
enhance opportunities for investigating the interactions between
sleep and pain without the confounding distorting suppression
caused by general anesthetics32 and/or recent surgery.37
Additional unit recording studies of SRT and other spinal projection (e.g., spinothalamic tract, neurons driven submaximally by
specific receptors such as thermoreceptor and/or hair mechanoreceptors during the sleep/wake cycle) are required to corroborate
these35 and other findings.38,39 Indeed, other lines of evidence
suggest that during active sleep sensory gating of small vs. large
diameter input occurs at higher neuraxial levels, in particular, the
trigeminal sensory nuclear complex.24,40
Neurotransmitters released from afferent terminals onto
spinal projection neurons include substance P and glutamate.
Both agents are known to exert potent postsynaptic excitations of
spinal cord sensory tract neurons.41-43 SRT neurons may be subjected to state-dependent modulatory influences that counteract
the actions of primary afferent neurotransmitters. In this regard,
we recently reported that the glutamate-evoked responses of SRT
neurons were reduced during the state of active sleep when compared to quiet sleep or wakefulness.44 Hence it is possible that
the reduction of sensory transmission through the SRT during
active sleep is partly dependent on direct postsynaptic inhibition
of L3 cells. However, the pharmacological basis for reduced
glutamate responsiveness of SRT neurons during active sleep is
not known. Another mechanism for reduced SRT neuron activity during active sleep may include the induction via higher brain
centers of presynaptic mechanisms regulating transmitter release
at synapses between primary afferent and recorded SRT neurons.45 Such processes could also occur at synapses upstream
such as between SRT axon terminals and recipient third order
reticular formation cells.17,46
In this relatively small sample of SRT neurons recorded to
date, inhibition was the predominant effect observed during
active sleep. A few cells were also markedly facilitated.
Facilitation of spike activity may arise as a result of disinhibitory processes and/or direct postsynaptic excitatory drives to SRT
neurons. The possibility remains that further sampling of (venSLEEP, Vol. 24, No. 1, 2001
tral vs. dorsolateral) SRT neurons during wakefulness vs. active
sleep may yield clearly distinct subclasses (i.e., facilitated and/or
inhibited SRT neurons). Indeed, antecedent experiments performed in the acute anesthetized animal preparation have demonstrated distinct supraspinal facilitatory and inhibitory influences
on SRT neurons following phasic electrical stimulation of the
medullary reticular core.5
In summary, the results of the present study imply that ongoing sensory transmission conveyed to higher brain centers via the
SRT may be regulated in a state-dependent fashion. Multiple
mechanisms may be engaged at spinal and supraspinal sites to
afford suppression (and facilitation) of synaptic transmission
including pain through this sensory pathway.
ACKNOWLEDGMENTS
This work was supported by a grant from the U.S. National
Institutes of Health (NS 34716). W. Pang was supported by
Pharmaceutical Manufacturer’s Association of Canada/Medical
Research Council of Canada (PMAC/MRC) Studentship in
Pharmacy. N. Taepavapruk was supported by a Thai Government
Graduate Fellowship.
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Active Sleep-related Modulation of Spinoreticular Tract Neurons—Soja et al