Firing patterns and functional roles of different classes of spinal afferents in rectal nerves during colonic migrating motor complexes in mouse colon

2012 ◽  
Vol 303 (3) ◽  
pp. G404-G411 ◽  
Author(s):  
Vladimir P. Zagorodnyuk ◽  
Melinda Kyloh ◽  
Simon J. Brookes ◽  
Sarah J. Nicholas ◽  
Nick J. Spencer

The functional role of the different classes of visceral afferents that innervate the large intestine is poorly understood. Recent evidence suggests that low-threshold, wide-dynamic-range rectal afferents play an important role in the detection and transmission of visceral pain induced by noxious colorectal distension in mice. However, it is not clear which classes of spinal afferents are activated during naturally occurring colonic motor patterns or during intense contractions of the gut smooth muscle. We developed an in vitro colorectum preparation to test how the major classes of rectal afferents are activated during spontaneous colonic migrating motor complex (CMMC) or pharmacologically induced contraction. During CMMCs, circular muscle contractions increased firing in low-threshold, wide-dynamic-range muscular afferents and muscular-mucosal afferents, which generated a mean firing rate of 1.53 ± 0.23 Hz ( n = 8) under isotonic conditions and 2.52 ± 0.36 Hz ( n = 17) under isometric conditions. These low-threshold rectal afferents were reliably activated by low levels of circumferential stretch induced by increases in length (1–2 mm) or load (1–3 g). In a small proportion of cases (5 of 34 units), some low-threshold muscular and muscular-mucosal afferents decreased their firing rate during the peak of the CMMC contractions. High-threshold afferents were never activated during spontaneous CMMC contractions or tonic contractions induced by bethanechol (100 μM). High-threshold rectal afferents were only activated by intense levels of circumferential stretch (10–20 g). These results show that, in the rectal nerves of mice, low-threshold, wide-dynamic-range muscular and muscular-mucosal afferents are excited during contraction of the circular muscle that occurs during spontaneous CMMCs. No activation of high-threshold rectal afferents was detected during CMMCs or intense contractile activity in naïve mouse colorectum.

2016 ◽  
Vol 116 (3) ◽  
pp. 1137-1151 ◽  
Author(s):  
Patrick M. Dougherty ◽  
Jinghong Chen

The input-output and discharge properties of neurons are shaped by both passive and active electrophysiological membrane properties. Whole cell patch-clamp recordings in lamina I–III neurons in an isolated preparation of the whole spinal cord of juvenile rats with attached dorsal roots and dorsal root ganglia were used to further define which of these properties provides the most impactful classification strategy. A total of 95 neurons were recorded in segment L5 and were classified based on the responses to L4 dorsal root stimulation. The results showed that high-threshold and silent neurons had higher membrane resistance and more negative resting membrane potential than low-threshold or wide-dynamic-range neurons. Rheobase in low-threshold and wide-dynamic-range neurons was significantly lower than that of high-threshold or silent neurons. Four types of firing patterns were identified in response to depolarizing current injections. Low-threshold cells most frequently showed a phasic firing pattern characterized by a short initial burst of action potentials, single spiking or irregular firing bursts at the onset of a depolarizing pulse. High-threshold and wide-dynamic-range neurons were characterized by tonic firing with trains of spikes occurring at regular intervals throughout the current pulse. The majority of silent neurons displayed a delayed onset of firing in response to current injection. These results indicate that the passive membrane properties of spinal neurons are tuned to optimize the responses to particular subsets of afferent stimuli.


1989 ◽  
Vol 257 (5) ◽  
pp. H1543-H1550 ◽  
Author(s):  
D. C. Bolser ◽  
M. J. Chandler ◽  
D. W. Garrison ◽  
R. D. Foreman

The responses of thoracic spinal and spinoreticular tract (SRT) neurons to activation of cardiac spinal afferents by injections of bradykinin (BK) and capsaicin (CAP) into the left atrium or pericardial sac were determined in vagotomized cats anesthetized with alpha-chloralose. Activities of spinal and SRT neurons in the T1-T5 spinal cord were recorded extracellularly. All neurons received excitatory somatic and cardiopulmonary sympathetic afferent input. Application of BK and CAP to the heart excited most SRT neurons and many spinal neurons but also inhibited some spinal neurons. The two drugs often affected spinal but not SRT neurons differently. Capsaicin excited high threshold and high threshold inhibitory neurons but not wide-dynamic range spinal neurons. In contrast, BK excited all three categories of spinal and SRT neurons. The differential responses of spinal neurons to intracardiac BK and CAP suggested that these compounds can stimulate functionally different populations of cardiac sympathetic afferents.


1994 ◽  
Vol 72 (6) ◽  
pp. 2590-2597 ◽  
Author(s):  
J. W. Leem ◽  
B. H. Lee ◽  
W. D. Willis ◽  
J. M. Chung

1. A set of 11 cutaneous stimuli defined previously to differentiate among different types of cutaneous sensory receptors in the rat hindpaw was also effective in differentially activating second-order sensory neurons in the dorsal horn and the gracile nucleus of rats. 2. All sampled units were responsive to more than 1 of the 11 stimuli. However, none responded to innocuous warming or cooling stimuli. Therefore further analysis was restricted to responses to nine of the selected stimuli. 3. Cluster analysis of the responses to nine selected innocuous and noxious mechanical stimuli and noxious thermal stimuli yielded seven classes that seemed functionally distinct from each other: a class of high-threshold neurons, three classes of convergent (wide dynamic range) neurons, a class of a mixture of poorly responsive neurons and neurons receiving Pacinian inputs, and two classes of low-threshold neurons. 4. High-threshold neurons responded predominantly to noxious mechanical and thermal stimuli and presumably received an input from both mechanically and thermally sensitive nociceptors. These cells were located in the dorsal horn, and some were spinothalamic tract cells. Wide dynamic range neurons were excited by innocuous and noxious stimuli, but better by noxious stimuli. These classes of cells were either in the dorsal horn (some were spinothalamic tract cells) or in the nucleus gracilis.(ABSTRACT TRUNCATED AT 250 WORDS)


2001 ◽  
Vol 16 (26) ◽  
pp. 1667-1670
Author(s):  
◽  
YUQIAN MA

L3 + C is a branch experiment on L3 magnet spectrometer, which is located on the ring of LEP accelerator at CERN. To take the advantage of L3 muon chambers in its low threshold, wide dynamic range and high resolution, the momentum of cosmic ray muons in the range of 15–2000 GeV/c at a shallow depth of 30 m of molasse can be measured precisely. Since 1998, a scintillator detector system, a new fast trigger and DAQ system, and a small air shower array had been established for study the CR muon events independently. Up to August 2000, 8 billion muons and 25 million air shower events had been recorded. The first results for CR muon spectrum and the charge ratio etc. had been obtained.


2004 ◽  
Vol 91 (1) ◽  
pp. 213-222 ◽  
Author(s):  
Donald A. Simone ◽  
Xijing Zhang ◽  
Jun Li ◽  
Jun-Ming Zhang ◽  
Christopher N. Honda ◽  
...  

We investigated the role of mechanosensitive spinothalamic tract (STT) neurons in mediating 1) the itch evoked by intradermal injection of histamine, 2) the enhanced sense of itch evoked by innocuous stroking (alloknesis), and 3) the enhanced pain evoked by punctate stimulation (hyperalgesia) of the skin surrounding the injection site. Responses to intradermal injections of histamine and capsaicin were compared in STT neurons recorded in either the superficial or the deep dorsal horn of the anesthetized monkey. Each neuron was identified by antidromic activation from the ventral posterior lateral nucleus of thalamus and classified by its initial responses to mechanical stimuli as wide dynamic range (WDR) or high-threshold (HT). Approximately half of the WDRs and one of the HTs responded weakly to histamine, some with a duration > 5 min, the maximal time allotted. WDRs but not HTs exhibited a significant increase in response to punctate stimulation after histamine consistent with their possible role in mediating histamine-induced hyperalgesia. Neither type of neuron exhibited significant changes in response to stroking, consistent with their unlikely role in mediating alloknesis. Furthermore, nearly all STT neurons exhibited vigorous and persistent responses to capsaicin, after which they became sensitized to stroking and to punctate stimulation. We conclude that the STT neurons in our sample are more likely to contribute to pain, allodynia, and hyperalgesia than to itch and alloknesis.


1979 ◽  
Vol 42 (5) ◽  
pp. 1370-1389 ◽  
Author(s):  
D. R. Kenshalo ◽  
R. B. Leonard ◽  
J. M. Chung ◽  
W. D. Willis

1. The responses of primate spinothalamic tract cells innervating the glabrous skin of the foot to noxious thermal stimuli have been examined. 2. Of the 41 cells studied, 98% responded to noxious thermal stimuli. Heating the cutaneous receptive field with a series of stimuli from 35 to 43, 47, and 50 degrees C produced a graded increase in discharge rate. The responses were characterized by an onset, which occurred after the temperature change had either slowed or stopped, an acceleration in the discharge up to a peak, and then an adaptation to a new base-line level. The time constants of adaptation were faster than those reported for C polymodal nociceptors. 3. No systematic differences were found in the responses to noxious thermal stimuli of cells with wide dynamic range receptive fields and of cells with narrow dynamic range, high-threshold receptive fields. There were also no differences in the responses of cells located in the marginal zone and of cells located in the neck of the dorsal horn. 4. The relationship between peak frequency and final skin temperature with a 30 s stimulus duration can best be described by a power function with an exponent of 2.1. An increase in the stimulus duration to 120 s resulted in an increase in the exponent of the power function to 3.2. 5. Repetition of the series of 30-s heat stimuli resulted in an increase in peak frequency, total impulse count, and background activity. Repetition of stimuli having a duration of 120 s produced an increase in the peak frequency at 43 and 45 degrees C, a smaller increase at 47 degrees C, and a decrease at 50 degrees C. Background activity was increased by the lower temperature stimuli, but was decreased following higher temperature stimuli. 6. In six additional cells, the skin was heated with three consecutive presentations at each temperature level (43, 45, 47, and 50 degrees C) for 30 s. No change was observed in the peak frequencies of the responses to successive stimuli of the same intensity. However, the exponent of the power function relating the average peak frequency for the six cells to changes in skin temperature was 3.9. This exponent was larger than that seen when two series of graded heat stimuli of 120 s duration were used, indicating more sensitization despite the fact the total time of exposure to noxious heat was less. 7. A role for both high-threshold and wide dynamic range spinothalamic cells in transmitting nociceptive information to the diencephalon is postulated.


1995 ◽  
Vol 74 (4) ◽  
pp. 1549-1562 ◽  
Author(s):  
J. F. Herrero ◽  
P. M. Headley

1. To compare the responsiveness of lumbar spinal neurons to peripheral sensory stimuli under normal physiological conditions and under halothane anesthesia, we performed a study in sheep that were prepared chronically. This permitted recordings to be made in the same animals either when they were awake and free from recent surgery, drugs, and training and only partially restrained or when they were anesthetized with halothane. 2. We recorded 261 units in dorsal and ventral horns under conscious conditions. Of these, 19% had no detectable receptive field (RF) and 44% had responses dominated by proprioceptive inputs; these units were not investigated in detail. The remaining 96 neurons (37%) had clearly defined cutaneous RFs. Of these, most (72%) had wide-dynamic-range (WDR; convergent, multireceptive) properties, 19% were low-threshold mechanoreceptive (LTMR), and 9% were high-threshold mechanoreceptive (HTMR). These units with cutaneous RFs were investigated in greater detail. 3. The spontaneous activity under these awake conditions was low (< 4 spikes/s) for nearly all units in all three categories. The mechanical threshold of the most sensitive (central) part of the cutaneous RF was assessed with von Frey bristles. Thresholds were < 5 mN for all LTMR neurons, < 1-30 mN for WDR neurons, and > 80 mN for HTMR neurons. The size of the low-threshold cutaneous RFs was significantly larger for WDR neurons (mean 46 cm2) and HTMR neurons (45 cm2) than for LTMR neurons (24 cm2). The RFs were distributed all over the ipsilateral hindlimb. Large RFs were mostly proximal, whereas small RFs were distributed relatively evenly over the limb. 4. Recordings were made from a further 165 units while the animals were under halothane anesthesia. With 86 neurons having cutaneous peripheral RFs, the proportions having LTMR, HTMR, or WDR characteristics were very similar to those in awake animals. Under halothane the ongoing activity of WDR units was slightly (but significantly) less. The threshold to von Frey bristle stimulation was significantly higher only for WDR units, in both dorsal and ventral horns. The mean size of cutaneous RFs was significantly larger in all classes of units recorded under halothane anesthesia. For WDR units this was true for cells in both dorsal and ventral horns. This effect on mean values was due to a larger proportion of units with very large fields under anesthesia, particularly in the dorsal horn. 5. Comparison of the data from conscious animals with published results of acute experiments indicates that acute recording conditions do not distort the relative distribution and resting characteristics of these three functional categories of lumbar spinal neurons as much as might have been expected. 6. Halothane does not have major effects on the resting sensory responsiveness of spinal neurons with cutaneous RFs. The increase in RF area, which contrasts with most results from acute studies, is likely to be due to a dampening of descending inhibitory control mechanisms.


2000 ◽  
Vol 84 (3) ◽  
pp. 1180-1185 ◽  
Author(s):  
Xijing Zhang ◽  
Christopher N. Honda ◽  
Glenn J. Giesler

Percutaneous upper cervical cordotomy continues to be performed on patients suffering from several types of severe chronic pain. It is believed that the operation is effective because it cuts the spinothalamic tract (STT), a primary pathway carrying nociceptive information from the spinal cord to the brain in humans. In recent years, there has been controversy regarding the location of STT axons within the spinal cord. The aim of this study was to determine the locations of STT axons within the spinal cord white matter of C2 segment in monkeys using methods of antidromic activation. Twenty lumbar STT cells were isolated. Eleven were classified as wide dynamic range neurons, six as high-threshold cells, and three as low-threshold cells. Eleven STT neurons were recorded in the deep dorsal horn and nine in superficial dorsal horn. The axons of the examined neurons were located at antidromic low-threshold points (<30 μA) within the contralateral lateral funiculus of C2. All low-threshold points were located ventral to the denticulate ligament, within the lateral half of the ventral lateral funiculus (VLF). None were found in the dorsal half of the lateral funiculus. The present findings support our previous suggestion that STT axons migrate ventrally as they ascend the length of the spinal cord. Also, the present findings indicate that surgical cordotomies that interrupt the VLF in C2 likely disrupt the entire lumbar STT.


1987 ◽  
Vol 58 (3) ◽  
pp. 480-495 ◽  
Author(s):  
W. S. Ammons

Spinoreticular (SRT) and spinothalamic (STT) neurons were studied for responses to renal and somatic stimuli in 34 cats that were anesthetized with alpha-chloralose. SRT cells were antidromically activated from the medial medullary reticular formation near the gigantocellular tegmental field contralateral (35 cells), ipsilateral (15 cells), or both contralateral and ipsilateral (11 cells) to the recording site. Collision tests showed that activation from two electrodes resulted from stimulation of separate axonal branches and not from current spread. Twenty STT cells were activated from the spinothalamic tract just medial to the medial geniculate nucleus. SRT cells were located in laminae I, V, VII, and VIII of the T12-L2 segments. Most cells were located in lamina VII. STT cells were found in laminae I, V, and VII. The axons of 12 SRT cells were located in the ventrolateral or ventral quadrants of the upper cervical spinal cord. Antidromic conduction velocities of SRT cells averaged 48.7 +/- 3.7 m/s. No differences in conduction velocity were found between cells projecting to different reticular sites. In addition conduction velocity did not vary with the type of somatic or renal input. Antidromic conduction velocities of STT cells averaged 46.4 +/- 4.7 m/s. Renal nerve stimulation excited 58 and inhibited 3 SRT cells. All 20 STT cells were excited. Thirty SRT cells were excited only by A-delta input, 26 received both A-delta- and C-fiber inputs, and 2 cells received only C-fiber input. Ten STT cells received A-delta input only and 10 received both A-delta- and C-fiber inputs. All cells with renal input also received somatic input. Thirty-six SRT cells (59%) were classified as high threshold, 12 (20%) as wide dynamic range, and 10 (16%) as deep. Ten STT cells were classified as high threshold and 10 as wide dynamic range. Somatic receptive fields of STT cells were usually simple and invariably included the left flank region, although many of the fields extended to the left hindlimb or abdomen. Eighteen of the 20 were restricted to the ipsilateral side. In contrast, somatic receptive fields of SRT cells were primarily bilateral (71%). While all but two receptive fields included the left flank area, most extended to one or both hindlimbs, the abdomen, or the right flank. Inhibitory receptive fields were found for 33% of the SRT cells and 20% of the STT cells.(ABSTRACT TRUNCATED AT 400 WORDS)


2001 ◽  
Vol 85 (4) ◽  
pp. 1777-1781 ◽  
Author(s):  
R. H. Westgaard ◽  
C. J. De Luca

The firing pattern of low-threshold motor units was examined in the human trapezius and first dorsal interosseous (FDI) muscles during slowly augmenting, low-amplitude contractions that were intended to mimic contractile activity in postural muscles. The motor unit activity was detected with a special needle electrode and was analyzed with the assistance of computer algorithms. The surface electromyographic (EMG) signal was recorded. Its root-mean-square (RMS) value was calculated and presented to the subject who used it to regulate the muscle force level. In the trapezius, there was minimal, if any, firing rate modulation of early recruited motor units during slow contractions (≤1% EMGmax/s), and later recruited motor units consistently presented higher peak firing rates. As the force rate of the contraction increased (3% EMGmax/s), the firing rates of the motor units in the trapezius approached an orderly hierarchical pattern with the earliest recruited motor units having the greatest firing rate. In contrast, and as reported previously, the firing rates of all motor units in the FDI always presented the previously reported hierarchical “onion-skin” pattern. We conclude that the low-threshold motor units in the postural trapezius muscle, that is the motor units that are most often called on to activate the muscle in postural activities, have different control features in slow and fast contractions. More detailed analysis revealed that, in the low force-rate contractions of the trapezius, recruitment of new motor units inhibited the firing rate of active motor units, providing an explanation for the depressed firing rate of the low-threshold motor units. We speculate that Renshaw cell inhibition contributes to the observed deviation of the low-threshold motor units from the hierarchical onion-skin pattern.


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