Potentials In Motoneurons Research Articles

The effects of tricaine mesylate on arthropods: crayfish, crab and Drosophila.

Tricaine mesylate, also known as MS-222, was investigated to characterize its effects on sensory neurons, synaptic transmission at the neuromuscular junction, and heart rate in invertebrates. Three species were examined: Drosophila melanogaster, blue crab (Callinectes sapidus), and red swamp crayfish (Procambarus clarkii). Intracellular measures of action potentials in motor neurons of the crayfish demonstrated that MS-222 dampened the amplitude, suggesting that voltage-gated Na + channels are blocked by MS-222. This is likely the mechanism behind the reduced activity measured in sensory neurons and depressed synaptic transmission in all three species as well as reduced cardiac function in the larval Drosophila. To address public access to data, a group effort was used for analysis of given data sets, blind to the experimental design, to gauge analytical accuracy. The determination of a threshold in analysis for measuring extracellular recorded sensory events is critical and is not easily performed with commercial software.

Neuromodulatory Selection of Motor Neuron Recruitment Patterns in a Visuomotor Behavior Increases Speed.

Animals generate locomotion at different speeds to suit their behavioral needs. Spinal circuits generate locomotion at these varying speeds by sequential activation of different spinal interneurons and motor neurons. Larval zebrafish can generate slow swims for prey capture and exploration by activation of secondary motor neurons and much faster and vigorous swims during escape and struggle via additional activation of primary motor neurons. Neuromodulators are known to alter the motor output of spinal circuits, but their precise role in speed regulation is not wellunderstood. Here, in the context of optomotor response (OMR), an innate evoked locomotor behavior, we show that dopamine (DA) provides an additional layer to regulation of swim speed in larval zebrafish. Activation of D1-like receptors increases swim speed during OMR in free-swimming larvae. By analyzing tail bend kinematics in head-restrained larvae, we show that the increase in speed is actuated by larger tail bends. Whole-cell patch-clamp recordings from motor neurons reveal that, during OMR, typically only secondary motor neurons are active, whereas primary motor neurons are quiescent. Activation of D1-like receptors increases intrinsic excitability and excitatory synaptic drive in primary and secondary motor neurons. These actions result in greater recruitment of motor neurons during OMR. Our findings provide an example of neuromodulatory reconfiguration of spinal motor neuron speed modules where members are selectively recruited and motor drive is increased to effect changes in locomotor speed. VIDEO ABSTRACT.

Spatiotemporal correlation of spinal network dynamics underlying spasms in chronic spinalized mice.

Spasms after spinal cord injury (SCI) are debilitating involuntary muscle contractions that have been associated with increased motor neuron excitability and decreased inhibition. However, whether spasms involve activation of premotor spinal excitatory neuronal circuits is unknown. Here we use mouse genetics, electrophysiology, imaging and optogenetics to directly target major classes of spinal interneurons as well as motor neurons during spasms in a mouse model of chronic SCI. We find that assemblies of excitatory spinal interneurons are recruited by sensory input into functional circuits to generate persistent neural activity, which interacts with both the graded expression of plateau potentials in motor neurons to generate spasms, and inhibitory interneurons to curtail them. Our study reveals hitherto unrecognized neuronal mechanisms for the generation of persistent neural activity under pathophysiological conditions, opening up new targets for treatment of muscle spasms after SCI.

Global Gene Expression Analysis of Rodent Motor Neurons Following Spinal Cord Injury Associates Molecular Mechanisms With Development of Postinjury Spasticity

Spinal cord injury leads to severe problems involving impaired motor, sensory, and autonomic functions. After spinal injury there is an initial phase of hyporeflexia followed by hyperreflexia, often referred to as spasticity. Previous studies have suggested a relationship between the reappearance of endogenous plateau potentials in motor neurons and the development of spasticity after spinalization. To unravel the molecular mechanisms underlying the increased excitability of motor neurons and the return of plateau potentials below a spinal cord injury we investigated changes in gene expression in this cell population. We adopted a rat tail-spasticity model with a caudal spinal transection that causes a progressive development of spasticity from its onset after 2 to 3 wk until 2 mo postinjury. Gene expression changes of fluorescently identified tail motor neurons were studied 21 and 60 days postinjury. The motor neurons undergo substantial transcriptional regulation in response to injury. The patterns of differential expression show similarities at both time points, although there are 20% more differentially expressed genes 60 days compared with 21 days postinjury. The study identifies targets of regulation relating to both ion channels and receptors implicated in the endogenous expression of plateaux. The regulation of excitatory and inhibitory signal transduction indicates a shift in the balance toward increased excitability, where the glutamatergic N-methyl-d-aspartate receptor complex together with cholinergic system is up-regulated and the gamma-aminobutyric acid type A receptor system is down-regulated. The genes of the pore-forming proteins Cav1.3 and Nav1.6 were not up-regulated, whereas genes of proteins such as nonpore-forming subunits and intracellular pathways known to modulate receptor and channel trafficking, kinetics, and conductivity showed marked regulation. On the basis of the identified changes in global gene expression in motor neurons, the present investigation opens up for new potential targets for treatment of motor dysfunction following spinal cord injury.

Neurobiology: Venom of Wasps and Initiation of Movements

The ability to initiate movements can be impaired in some brain injuries even though motor actions proceed normally once they are begun. The effects of venom that wasps use in preying upon cockroaches could provide insights into this problem.

Connections Between Thoraco-Coxal Proprioceptive Afferents and Motor Neurons in the Locust

The position of the coxal segment of the locust hind leg relative to the thorax is monitored by a variety of proprioceptors, including three chordotonal organs and a myochordotonal organ. The sensory neurons of two of these proprioceptors, the posterior joint chordotonal organ (pjCO) and the myochordotonal organ (MCO), have axons in the purely sensory metathoracic nerve 2C (N2C). The connections made by these afferents with metathoracic motor neurons innervating thoraco-coxal and wing muscles were investigated by electrical stimulation of N2C and by matching postsynaptic potentials in motor neurons with afferent spikes in N2C. Stretch applied to the anterior rotator muscle of the coxa (M121), with which the MCO is associated, evoked sensory spikes in N2C. Some of the MCO afferent neurons make direct excitatory chemical synaptic connections with motor neurons innervating the thoraco-coxal muscles M121, M126 and M125. Parallel polysynaptic pathways via unidentified interneurons also exist between MCO afferents and these motor neurons. Connections with the common inhibitor 1 neuron and motor neurons innervating the thoraco-coxal muscles M123/4 and wing muscles M113 and M127 are polysynaptic. Afferents of the pjCO also make polysynaptic connections with motor neurons innervating thoraco-coxal and wing muscles, but no evidence for monosynaptic pathways was found.

Plateau potentials in motor neurons in the ventilatory system of the crab

The motor neurons in the crab ventilatory system have previously been considered to be passive output elements in that the generation of bursts of action potentials in these neurons during ventilation was thought to be due to cyclic inhibition and excitation from the interneurons in the ventilatory central pattern generator. This study demonstrates that the large-amplitude depolarization that underlies bursts of action potentials in ventilatory motor neurons is produced by a plateau potential. These motor neurons satisfy a number of the experimental tests that have been proposed for plateau potentials, such as triggering of the burst by a brief depolarization, termination of the burst by a hyperpolarizing input, and an all-or-none suppression of the depolarizing potential by the injection of hyperpolarizing current.

Plasticity in the multifunctional buccal central pattern generator of Helisoma illuminated by the identification of phase 3 interneurons.

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.

An identified glutamatergic interneuron patterns feeding motor activity via both excitation and inhibition.

1. Previously we demonstrated that glutamate is an important neurotransmitter in the CNS of Helisoma. Exogenous glutamate applied to the buccal ganglia mimicked both the excitatory and inhibitory effects of subunit 2 (S2) of the tripartite central pattern generator (CPG) on S2 postsynaptic motor neurons. Here we identify buccal interneuron B2 as an S2 interneuron by utilizing a combination of electrophysiology, pharmacology, and intracellular staining. In addition, neurons that were electrophysiologically and morphologically characterized as neuron B2 demonstrated antiglutamate immunoreactivity, suggesting that neuron B2 is a source of endogenous glutamate in the buccal ganglia. 2. Depolarization of neuron B2 evoked excitatory postsynaptic potentials in motor neurons excited by S2. The excitatory effects of B2 depolarization and S2 activation were reversibly antagonized by the ionotropic glutamate receptor antagonist 6-cyano-7-nitro-quinoxaline-2,3-dione, similar to the antagonism shown previously for application of exogenous glutamate. Depolarization of neuron B2 also evoked inhibitory postsynaptic potentials in motor neurons inhibited by S2. When such motor neurons were maintained in isolated cell culture, application of exogenous glutamate produced a direct hyperpolarization of the membrane potential. 3. The activity of neuron B2 is necessary for the production of the standard pattern of buccal motor neuron activity, which underlies functional feeding movements. The subunits of the tripartite buccal CPG must be active in the temporal sequence S1-S2-S3 to produce the standard feeding pattern. Rhythmic inhibition from neuron B2 terminated activity in S1 postsynaptic motor neurons and entrained the frequency of activity in S3 postsynaptic motor neurons. Hyperpolarization of neuron B2 disrupted the production of the standard motor pattern by eliminating S2 postsynaptic potentials in identified buccal motor neurons, thereby prolonging S1 activity and disrupting S3 bursting. 4. These data support the hypothesis that S2 neuron B2 is glutamatergic and demonstrate that glutamatergic transmission, and especially inhibition, is fundamental to the production of behaviorally critical motor neuron activity patterns in Helisoma.

Variations in membrane potential of motor neurons during scratch generation

Variations in membrane potential of motor neurons during scratch generation

The effects of stimulating the cerebellar nodulus in the cat on the responses of vestibular neurons

In a first series of experiments, recordings were obtained from cat abducens and trochlear motorneurons and from axons of secondary vestibular neurons terminating in these motor nuclei, and the effects of cerebellar nodulus stimulation on utricular- and canal-evoked responses in these neurons were studied. Ultricular activation of vestibular axons recorded in the ipsilateral VIth and contralateral IVth nuclei was probably monosynaptically inhibited by nodular stimulation provided conditioning-test intervals were in the range between 0–10 ms and the test stimuli were close to threshold intensities. Of the vestibular axons activated by stimulation of the semicircular canal nerves only those evoked by the horizontal canal stimulation and recorded in the ipsilateral VIth nucleus were weakly inhibited. When the vestibular stimuli were strong enough to produce clear field potentials in the motor nuclei and/or postsynaptic potentials in motorneurons, nodular stimulation had practically no effect on their amplitudes. It is concluded that inhibition of vestibuloocular transmission is weak as compared to floccular inhibition studied previously. In a second series of experiments, recordings were obtained from vestibular neurons which were activated antidromically and/or transsynaptically by stimulation of the contralateral fastigial nucleus, and the effects of ipsilateral nodular stimulation on these responses were studied. It was found that nodular stimulation inhibited both antidromic as well as transsynaptic fastigial activations of vestibular neurons. Most of these vestibular neurons were located in the descending vestibular nucleus and received polysynaptic vestibular and spinal inputs. It is concluded that in addition to its weak inhibitory effect on vestibuloocular transmission the nodulus exerts a powerful inhibition on vestibular neurons transmitting vestibular and spinal inputs to cerebellar nuclei and/or cortex. It is suggested that the nodulus controls cerebellar projecting vestibular neurons which carry vestibular and spinal information to the cerebellum. The vestibular, proprioceptive and visual information which is present in the nodulus may aid the role of the nodulus in controlling body posture.

Alterations in the Antidromic Potential of Motor Neurons Following Chromatolysis

Alterations in the Antidromic Potential of Motor Neurons Following Chromatolysis