scholarly journals Induction of a non-rhythmic motor pattern by nitric oxide in hatchling Rana temporaria embryos

2001 ◽  
Vol 204 (7) ◽  
pp. 1307-1317 ◽  
Author(s):  
D.L. McLean ◽  
J.R. McDearmid ◽  
K.T. Sillar

Nitric oxide (NO) is a ubiquitous neuromodulator with a diverse array of functions in a variety of brain regions, but a role for NO in the generation of locomotor activity has yet to be demonstrated. The possibility that NO is involved in the generation of motor activity in embryos of the frog Rana temporaria was investigated using the NO donors S-nitroso-n-acetylpenicillamine (SNAP; 100--500 micromol l(−1)) and diethylamine nitric oxide complex sodium (DEANO; 25--100 micromol l(−1)). Immobilised Rana temporaria embryos generate a non-rhythmic ‘lashing’ motor pattern either spontaneously or in response to dimming of the experimental bath illumination. Bath-applied NO donors triggered a qualitatively similar motor pattern in which non-rhythmic motor bursts were generated contra- and ipsilaterally down the length of the body. The inactive precursor of SNAP, n-acetyl-penicillamine (NAP), at equivalent concentrations did not trigger motor activity. NO donors failed to initiate swimming and had no measurable effects on the parameters of swimming induced by electrical stimulation. Intracellular recordings with potassium-acetate-filled electrodes revealed that the bursts of ventral root discharge induced by NO donors were accompanied by phasic depolarisations in motor neurons. During the inter-burst intervals, periods of substantial membrane hyperpolarization below the normal resting potential were observed, presumably coincident with contralateral ventral root activity. With KCl-filled electrodes, inhibitory potentials were strongly depolarising, suggesting that inhibition was Cl(−)-dependent. The synaptic drive seen in motor neurons after dimming of the illumination was very similar to that induced by the NO donors. NADPH-diaphorase histochemistry identified putative endogenous sources of NO in the central nervous system and the skin. Three populations of bilaterally symmetrical neurons were identified within the brainstem. Some of these neurons had contralateral projections and many had axonal processes that projected to and entered the marginal zones of the spinal cord, suggesting that they were reticulospinal.

1982 ◽  
Vol 99 (1) ◽  
pp. 185-196 ◽  
Author(s):  
J. A. Kahn ◽  
A. Roberts

Rhythmic motor nerve activity was recorded in stage 37/38 Xenopus embryos paralysed with curare. The activity was similar to the swimming motor pattern in the following ways: cycle period (40–125 ms), alternation of activity on either side of a segment, rostro-caudal phase lag. Episodes of rhythmic motor activity could be evoked by stimuli that evoke swimming and inhibited by stimuli that normally inhibit swimming. On this basis we conclude that the swimming motor pattern is generated by a central nervous mechanism and is not dependent on sensory feedback. In addition to the swimming pattern, another pattern of motor activity (‘synchrony’) was sometimes recorded in curarized embryos. In this, the rhythmic bursts on either side of a segment occurred in synchrony, and the rhythm period (20–50 ms) was half that in swimming. This was probably not an artifact of curarization as there were indications of a similar pattern in uncurarized embryos. Its function remains unclear.


2016 ◽  
Vol 311 (5) ◽  
pp. G838-G851 ◽  
Author(s):  
Lara A. Shaylor ◽  
Sung Jin Hwang ◽  
Kenton M. Sanders ◽  
Sean M. Ward

Inhibitory motor neurons regulate several gastric motility patterns including receptive relaxation, gastric peristaltic motor patterns, and pyloric sphincter opening. Nitric oxide (NO) and purines have been identified as likely candidates that mediate inhibitory neural responses. However, the contribution from each neurotransmitter has received little attention in the distal stomach. The aims of this study were to identify the roles played by NO and purines in inhibitory motor responses in the antrums of mice and monkeys. By using wild-type mice and mutants with genetically deleted neural nitric oxide synthase ( Nos1 −/−) and P2Y1 receptors ( P2ry1 −/−) we examined the roles of NO and purines in postjunctional inhibitory responses in the distal stomach and compared these responses to those in primate stomach. Activation of inhibitory motor nerves using electrical field stimulation (EFS) produced frequency-dependent inhibitory junction potentials (IJPs) that produced muscle relaxations in both species. Stimulation of inhibitory nerves during slow waves terminated pacemaker events and associated contractions. In Nos1 −/− mice IJPs and relaxations persisted whereas in P2ry1 −/− mice IJPs were absent but relaxations persisted. In the gastric antrum of the non-human primate model Macaca fascicularis, similar NO and purine neural components contributed to inhibition of gastric motor activity. These data support a role of convergent inhibitory neural responses in the regulation of gastric motor activity across diverse species.


2006 ◽  
Vol 95 (5) ◽  
pp. 3154-3163 ◽  
Author(s):  
S. A. Kautz ◽  
C. Patten ◽  
R. R. Neptune

Recent investigation in persons with clinically complete spinal cord injury has revealed that locomotor activity in one limb can activate rhythmic locomotor activity in the opposite limb. Although our previous research has demonstrated profound influences of the nonparetic limb on paretic limb motor activity poststroke, the potency of interlimb pathways for increasing recruitment of the paretic limb motor pattern is unknown. This experiment tested whether there is an increased propensity for rhythmic motor activity in one limb (pedaling limb) to induce rhythmic motor activity in the opposite limb (test limb) in persons poststroke. Forty-nine subjects with chronic poststroke hemiparesis and twenty controls pedaled against a constant mechanical load with their pedaling leg while we recorded EMG and pedal forces from the test leg. For the experimental conditions, subjects were instructed to either pedal with their test leg (bilateral pedaling) or rest their test leg while it was either stationary or moved anti-phased (unilateral pedaling). In persons poststroke, unilateral pedaling activated a complete pattern of rhythmic alternating muscle activity in the nonpedaling, test leg. This effect was most clearly demonstrated in the most severely impaired individuals. In most of the control subjects, unilateral pedaling activated some muscles in the nonpedaling leg weakly, if at all. We propose that, ipsilateral excitatory pathways associated with contralateral pedaling in control subjects are increasingly up-regulated in both legs in persons with hemiparesis as a function of increased hemiparetic severity. This enhancement of interlimb pathways may be of functional importance since contralateral pedaling induced a complete motor pattern of similar amplitude to the bilateral pattern in both the paretic and nonparetic leg of the subjects with severe hemiparesis.


1998 ◽  
Vol 79 (1) ◽  
pp. 361-370 ◽  
Author(s):  
Sylvie Baudoux ◽  
Carsten Duch ◽  
Oliver T. Morris

Baudoux, Sylvie, Carsten Duch, and Oliver T. Morris. Coupling of efferent neuromodulatory neurons to rhythmical leg motor activity in the locust. J. Neurophysiol. 79: 361–370, 1998. The spike activity of neuromodulatory dorsal unpaired median (DUM) neurons was analyzed during a pilocarpine-induced motor pattern in the locust. Paired intracellular recordings were made from these octopaminergic neurons during rhythmic activity in hindleg motor neurons evoked by applying pilocarpine to an isolated metathoracic ganglion. This motor pattern is characterized by two alternating phases: a levator phase, during which levator, flexor, and common inhibitor motor neurons spike, and a depressor phase, during which depressor and extensor motor neurons spike. Three different subpopulations of efferent DUM neurons could be distinguished during this rhythmical motor pattern according to their characteristic spike output. DUM 1 neurons, which in the intact animal do not innervate muscles involved in leg movements, showed no change apart from a general increase in spike frequency. DUM 3 and DUM 3,4 neurons produced the most variable activity but received frequent and sometimes pronounced hyperpolarizations that were often common to both recorded neurons. DUM 5 and DUM 3,4,5 neurons innervate muscles of the hindleg and showed rhythmical excitation leading to bursts of spikes during rhythmic activity of the motor neurons, which innervate these same muscles. Sometimes the motor output was coordinated across both sides of the ganglion so that there was alternating activity between levators of both sides. In these cases, the spikes of DUM 5 and DUM 3,4,5 neurons and the hyperpolarization of DUM 3 and DUM 3,4 neurons occurred at particular phases in the motor pattern. Our data demonstrate a central coupling of specific types of DUM neurons to a rhythmical motor pattern. Changes in the spike output of these particular efferent DUM neurons parallel changes in the motor output. The spike activity of DUM neurons thus may be controlled by the same circuits that determine the action of the motor neurons. Functional implications for real walking are discussed.


1996 ◽  
Vol 75 (2) ◽  
pp. 561-574 ◽  
Author(s):  
E. M. Quinlan ◽  
A. D. Murphy

1. The mechanism for generating diverse patterns of buccal motor neuron activity was explored in the multifunctional central pattern generator (CPG) of Helisoma. The standard pattern of motor neuron activity, which results in typical feeding behavior, consists of three distinct phases of buccal motor neuron activity. We have previously identified CPG interneurons that control the motor neuron activity during phases 1 and 2 of the standard pattern. Here we identify a pair of interneurons responsible for buccal motor neuron activity during phase 3, and examine the variability in the interactions between this third subunit and other subunits of the CPG. 2. During the production of the standard pattern, phase 3 excitation in many buccal motor neurons follows a prominent phase 2 inhibitory postsynaptic potential. Therefore phase 3 excitation was previously attributed to postinhibitory rebound (PIR) in these motor neurons. Two classes of observations indicated that PIR was insufficient to account for phase 3 activity, necessitating phase 3 interneurons. 1) A subset of identified buccal neurons is inhibited during phase 3 by discrete synaptic input. 2) Other identified buccal neurons display discrete excitation during both phases 2 and 3. 3. A bilaterally symmetrical pair of CPG interneurons, named N3a, was identified and characterized as the source of phase 3 postsynaptic potentials in motor neurons. During phase 3 of the standard motor pattern, interneuron N3a generated bursts of action potentials. Stimulation of N3a, in quiescent preparations, evoked a depolarization in motor neurons that are excited during phase 3 and a hyperpolarization in motor neurons that are inhibited during phase 3. Hyperpolarization of N3a during patterned motor activity eliminated both phase 3 excitation and inhibition. Physiological and morphological characterization of interneuron N3a is provided to invite comparisons with possible homologues in other gastropod feeding CPGs. 4. These data support a model proposed for the organization of the tripartite buccal CPG. According to the model, each of the three phases of buccal motor neuron activity is controlled by discrete subsets of pattern-generating interneurons called subunit 1 (S1), subunit 2 (S2), and subunit 3 (S3). The standard pattern of buccal motor neuron activity underlying feeding is mediated by an S1-S2-S3 sequence of CPG subunit activity. However, a number of "nonstandard" patterns of buccal motor activity were observed. In particular, S2 and S3 activity can occur independently or be linked sequentially in rhythmic patterns other than the standard feeding pattern. Simultaneous recordings of S3 interneuron N3a with effector neurons indicated that N3a can account for phase-3-like postsynaptic potentials (PSPs) in nonstandard patterns. The variety of patterns of buccal motor neuron activity indicates that each CPG subunit can be active in the absence of, or in concert with, activity in any other subunit. 5. To explore how CPG activity may be regulated to generate a particular motor pattern from the CPG's full repertoire, we applied the neuromodulator serotonin. Serotonin initiated and sustained the production of an S2-S3 pattern of activity, in part by enhancing PIR in S3 interneuron N3a after the termination of phase 2 inhibition.


Vaccines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 94
Author(s):  
Joel Mintz ◽  
Anastasia Vedenko ◽  
Omar Rosete ◽  
Khushi Shah ◽  
Gabriella Goldstein ◽  
...  

Nitric oxide (NO) is a short-lived, ubiquitous signaling molecule that affects numerous critical functions in the body. There are markedly conflicting findings in the literature regarding the bimodal effects of NO in carcinogenesis and tumor progression, which has important consequences for treatment. Several preclinical and clinical studies have suggested that both pro- and antitumorigenic effects of NO depend on multiple aspects, including, but not limited to, tissue of generation, the level of production, the oxidative/reductive (redox) environment in which this radical is generated, the presence or absence of NO transduction elements, and the tumor microenvironment. Generally, there are four major categories of NO-based anticancer therapies: NO donors, phosphodiesterase inhibitors (PDE-i), soluble guanylyl cyclase (sGC) activators, and immunomodulators. Of these, NO donors are well studied, well characterized, and also the most promising. In this study, we review the current knowledge in this area, with an emphasis placed on the role of NO as an anticancer therapy and dysregulated molecular interactions during the evolution of cancer, highlighting the strategies that may aid in the targeting of cancer.


1986 ◽  
Vol 55 (4) ◽  
pp. 678-688 ◽  
Author(s):  
K. T. Sillar ◽  
P. Skorupski

A preparation is described in which the thoracic ganglia of the crayfish are isolated together with the thoracocoxal muscle receptor organ (TCMRO) of the fourth leg. This preparation allows intracellular analysis of both centrally generated and reflex activity in leg motor neurons (MNs). The isolated thoracic ganglia can spontaneously generate a rhythmic motor pattern resembling that used during forward walking (Fig. 4). This involves the reciprocal activity of promotor and remotor MNs, with levator MNs firing in phase with promotor bursts. Stretch of the TCMRO in quiescent preparations evokes a resistance reflex in promotor MNs (Fig. 6). In more active preparations the response is variable and often becomes an assistance reflex, with excitation of remotor MNs on stretch (Fig. 7). When rhythmic motor patterns occur, the neuropilar processes of the S and T fibers receive central inputs that are strongly correlated with the oscillatory drive to the MNs and probably have the same origin (Figs. 8 and 9). Central inputs to the S and T fibers occur in opposite phases within a cycle of rhythmic motor output. The S fiber is depolarized in phase with promotor MNs and the T fiber in phase with remotor activity. The input to the T fiber is shown to be a chemical synaptic drive that has a reversal potential approximately 14 mV more depolarized than the fiber's resting membrane potential. This input substantially modulates the amplitude and waveform of passively propagated receptor potentials generated by TCMRO stretch (Fig. 11). It is argued that the central inputs to the TCMRO afferents will modulate proprioceptive feedback resulting from voluntary movements.


Molecules ◽  
2019 ◽  
Vol 24 (13) ◽  
pp. 2470 ◽  
Author(s):  
Tanya Sahyoun ◽  
Axelle Arrault ◽  
Raphaël Schneider

Nitric oxide (NO) is naturally synthesized in the human body and presents many beneficial biological effects; in particular on the cardiovascular system. Recently; many researchers tried to develop external sources to increase the NO level in the body; for example by using amidoximes and oximes which can be oxidized in vivo and release NO. In this review; the classical methods and most recent advances for the synthesis of both amidoximes and oximes are presented first. The isomers of amidoximes and oximes and their stabilities will also be described; (Z)-amidoximes and (Z)-oximes being usually the most energetically favorable isomers. This manuscript details also the biomimetic and biological pathways involved in the oxidation of amidoximes and oximes. The key role played by cytochrome P450 or other dihydronicotinamide-adenine dinucleotide phosphate (NADPH)-dependent reductase pathways is demonstrated. Finally, amidoximes and oximes exhibit important effects on the relaxation of both aortic and tracheal rings alongside with other effects as the decrease of the arterial pressure and of the thrombi formation


1987 ◽  
Vol 133 (1) ◽  
pp. 111-120 ◽  
Author(s):  
F. Delcomyn

1. Rhythmic motor activity may be recorded in the legs of cockroaches during the execution of several different types of behaviour that involve leg movements. It was examined in detail during searching and walking. 2. During walking, motor activity always consisted of a series of bursts separated by silent periods. During searching, it was usually continual, but modulated in frequency. 3. Sometimes, the motor pattern recorded from a searching leg was burst-like rather than modulated. In these cases, it could nevertheless be reliably distinguished from the motor pattern recorded during walking by a simple analysis of the burst pattern. 4. An analysis of the motor pattern recorded during righting indicated that this pattern was more like that for walking than that for searching. Therefore, searching is not simply walking that lacks certain periodic sensory input due to leg contact with the ground. 5. It is concluded that walking and searching can be reliably distinguished from one another on the basis of an analysis of a record of motor activity in a single leg muscle only. An ability to distinguish between similar types of behaviour on the basis of the motor pattern may prove useful in a variety of experiments.


2003 ◽  
Vol 66 (1) ◽  
pp. 83-93 ◽  
Author(s):  
Jian-wen He ◽  
Kazuho Hirata ◽  
Songyan Wang ◽  
Masaru Kawabuchi

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