Heterogeneity and central modulation of feedback reflexes in crayfish motor pool

1992 ◽  
Vol 67 (3) ◽  
pp. 648-663 ◽  
Author(s):  
P. Skorupski ◽  
B. M. Rawat ◽  
B. M. Bush
Keyword(s):  
Motor Activity ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Positive Feedback ◽  
Active State ◽  
Reflex Response ◽  
Chordotonal Organ ◽  
Dependent Manner ◽  
Reflex Effect ◽  
State Dependent

1. Movement of the crayfish thoracocoxal leg joint is monitored by a muscle receptor organ (TCMRO) and a chordotonal organ (TCCO). Both receptors span the joint in parallel but signal opposite directions of leg movement. The TCMRO is innervated by afferents responsive to lengthening, which corresponds to leg remotion, whereas TCCO afferents are responsive to shortening of the chordotonal strand, which corresponds to leg promotion. 2. When both receptors are stimulated in parallel, in an otherwise isolated preparation, reflex responses of coxal promoter and remotor motor neurons occur on both stretch and release. By comparison with experiments where one or the other of these receptors is stimulated selectively, we conclude that reflexes evoked by stretch of the two receptors are due to the TCMRO and reflexes evoked by release are due to the TCCO. 3. Reflexes mediated by these receptors are both state dependent and phase dependent. In preparations that produce patterns of reciprocal motor activity in promotor and remotor motor neurons (the active state), the reflex effect depends on the phase of this centrally generated activity. In preparations that are quiescent, or that produce only tonic motor output (the inactive state), the reflex effect is stable, corresponding to a typical resistance (negative feedback) reflex for both directions of receptor movement. 4. In the active state, coxal promotor motor neurons are both excited and inhibited in a phase-dependent manner by stretching the TCMRO. A subgroup of promotor motor neurons is excited by shortening the TCCO. One subgroup of the antagonistic coxal remotor motor neurons receives phase-dependent excitation from stretch of the TCMRO, whereas a second subgroup receives phase-dependent excitation from shortening the TCCO. 5. There are, therefore, at least two ways in which reflex effects can be modulated. At the level of a single motor neuron, the reflex response can vary in gain, and in some cases in sign, in a manner depending on centrally generated motor activity. In addition, at the level of a pool of synergistic motor neurons, the reflex effect is not uniform; instead, different subgroups of motor neurons display different reflex effects, so that the relative levels of excitability of different motor neuron reflex subgroups can also determine the net reflex effect. 6. Excitation of promotor motor neurons by TCCO shortening and of remotor motor neurons by TCMRO lengthening are positive feedback reflexes. The subgroups of motor neurons in which positive feedback reflexes can be evoked in both promotor and remotor pools are termed group 1.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Functional Analysis of the Sensory Motor Pathway of Resistance Reflex in Crayfish. I. Multisensory Coding and Motor Neuron Monosynaptic Responses

1997 ◽  
Vol 78 (6) ◽  
pp. 3133-3143 ◽  
Author(s):  
Didier Le Ray ◽  
François Clarac ◽  
Daniel Cattaert
Keyword(s):  
Functional Analysis ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Reflex Response ◽  
Chordotonal Organ ◽  
Upward Movement ◽  
Intracellular Recordings ◽  
Motor Pathway ◽  
Sensory Motor

Le Ray, Didier, François Clarac, and Daniel Cattaert. Functional analysis of the sensory motor pathway of resistance reflex in crayfish. I. Multisensory coding and motor neuron monosynaptic responses. J. Neurophysiol. 78: 3133–3143, 1997. An in vitro preparation of the fifth thoracic ganglion of the crayfish was used to study in detail the negative feedback loop involved in the control of passive movements of the leg. Release-sensitive primary afferents of from the coxo-basipodite chordotonal organ (CBCO), a proprioceptor whose strand is released by upward movement of the leg, monosynaptically connect to depressor motor neurons (Dep MNs). Extracellular identification of sensory units from the CBCO neurogram allowed us to determine the global coding of a sine-wave movement, imposed from the most released position of the CBCO strand. Intracellular recordings from sensory terminals (CBTs) and ramp movement stimulations applied to the CBCO strand allowed us to characterize two groups of release-sensitive CBCO fibers. The first group, divided into two subgroups (phasic and phaso-tonic), is characterized by discontinuous firing patterns: phasic CBTs fired exclusively during release movements; phaso-tonic CBTs displayed both a phasic firing and a tonic discharge during the more released plateaus. The second group was continuously firing whatever the movement, with higher frequencies during the release phase of the movement stimulation. All CBTs displayed a marked sensitivity for release movements while only the phaso-tonic ones showed a clear sensitivity to maintained positions. Surprisingly, no pure tonic sensory fibers were encountered. Systematic intracellular recordings from all resistant Dep MNs, performed in high divalent cation saline, allowed us to describe two shapes of monosynaptic resistance reflex responses. A phasic response was characterized by bursts of excitatory postsynaptic potentials (EPSPs) occurring exclusively during CBCO strand release movements. A phaso-tonic response was characterized by a progressive depolarization occurring all along the release phase of the stimulation: during maintained released positions, the amplitude of the sustained depolarization was position dependent; in addition, each release movement produced a phasic burst of EPSPs in the MN. The parallel study of the Dep MN properties failed to point out any correlation between the type of reflex response recorded from the MN and the MN intrinsic properties, which would indicate that the type of MN response is entirely determined by the afferent messages it receives.

Phase-dependent reversal of reflexes mediated by the thoracocoxal muscle receptor organ in the crayfish, Pacifastacus leniusculus

1986 ◽  
Vol 55 (4) ◽  
pp. 689-695 ◽  
Author(s):  
P. Skorupski ◽  
K. T. Sillar
Keyword(s):  
Motor Neurons ◽  
Negative Feedback ◽  
Positive Feedback ◽  
Motor Output ◽  
Dependent Manner ◽  
Muscle Receptor ◽  
Reflex Pathways ◽  
Receptor Organ ◽  
Positive And Negative Feedback ◽  
Central Excitability

Both negative feedback, resistance reflexes and positive feedback, assistance reflexes are mediated by the thoracocoxal muscle receptor organ (TCMRO) in the crayfish, depending on the central excitability of the preparation. In this paper we present evidence that the velocity-sensitive afferent T fiber of the TCMRO may elicit either resistance or assistance reflexes in different preparations. In preparations displaying assistance reflexes, the S and T fibers of the TCMRO exert reciprocal effects on leg motor neurons (MNs). The S fiber excites promotor MNs (negative feedback) and inhibits remotor MNs, the T fiber excites remotor MNs (positive feedback) and inhibits promotor MNs. During reciprocal motor output of promotor and remotor MNs, reflexes mediated by the TCMRO are modulated in a phase-dependent manner. The TCMRO excites promotor MNs during their active phases (negative feedback) but inhibits them during their reciprocal phases. Remotor MNs are excited by the TCMRO during their active phases (positive feedback). It is proposed that depolarizing central inputs that occur in the S and T fibers at opposite phases of the motor output cycle (21) facilitate the output effects of each afferent in alternation, effectively mediating a phase-dependent shift between the effects of one afferent and the other. The implications of central modulation of reflex pathways and the possible functions of positive and negative feedback reflexes during locomotion are discussed.

Synaptic connections between nonspiking afferent neurons and motor neurons underlying phase-dependent reflexes in crayfish

1992 ◽  
Vol 67 (3) ◽  
pp. 664-679 ◽  
Author(s):  
P. Skorupski
Keyword(s):  
Motor Neurons ◽  
Active State ◽  
Synaptic Delay ◽  
Dependent Manner ◽  
Synaptic Connections ◽  
Afferent Neurons ◽  
Motor Patterns ◽  
Dependent Inhibition ◽  
Receptor Organ ◽  
Group 1

1. This paper analyzes the synaptic connections made by nonspiking afferent neurons of the thoracocoxal muscle receptor organ (TCMRO) with basal limb motor neurons in the crayfish. The T fiber, a dynamically sensitive afferent, monosynaptically excites promotor motor neurons. Evidence suggests that both tonic graded chemical transmission and electrical synaptic transmission may be involved, depending on the motor neuron under consideration. 2. In preparations in the active state (spontaneously producing reciprocal motor patterns), the T fiber also inhibits promotor motor neurons in a phase-dependent manner. This inhibitory pathway is probably indirect, because it involves additional synaptic delay. 3. The statically sensitive S fiber also excites promotor motor neurons, but phase-dependent inhibition of promotor motor neurons by the S fiber was not seen. 4. The T fiber excites a subclass of remotor motor neurons (group 1) by a combination of direct chemical input and electrical input. This connection underlies the positive feedback reflex that excites these remotor motor neurons, in a phase-dependent manner, on stretch of the TCMRO during the active state. In inactive preparations, this connection remains subthreshold. 5. Central synaptic outputs of group 1 remotor motor neurons can also inhibit promotor motor neurons. This pathway may contribute to the phase-dependent reflex inhibition of promotor motor neurons that occurs in the active state.

Dynamics of Neurons Controlling Movements of a Locust Hind Leg II. Flexor Tibiae Motor Neurons

1997 ◽  
Vol 77 (4) ◽  
pp. 1731-1746 ◽  
Author(s):  
Philip L. Newland ◽  
Yasuhiro Kondoh
Keyword(s):  
Motor Neuron ◽  
Motor Neurons ◽  
High Frequency ◽  
Cutoff Frequency ◽  
Second Order ◽  
Chordotonal Organ ◽  
Linear Component ◽  
Response Dynamics ◽  
First Order ◽  
Frequency Components

Newland, Philip L. and Yasuhiro Kondoh. Dynamics of neurons controlling movements of a locust hind leg. II. Flexor tibiae motor neurons. J. Neurophysiol. 77: 1731–1746, 1997. Imposed movements of a proprioceptor that monitors the relative position of the tibia about the femur, the femorotibial chordotonal organ (FeCO), evoke resistance reflexes in the motor neurons that control the movements of the tibia of the locust. The response dynamics of one pool of motor neurons, the flexor tibiae motor neurons, which are located in three groups (anterior, lateral, and posterior), have been analyzed by the Wiener kernel method. First- and second-order kernels that represent the linear and nonlinear responses, respectively, were computed by a cross-correlation between the intracellularly recorded synaptic responses in the motor neurons and the white noise stimulus applied to the FeCO, and were used to define the input-output characteristics of the motor neurons. The posterior fast, intermediate, and slow and the anterior fast and intermediate flexor tibiae motor neurons had biphasic first-order kernels with initial negative phases, indicating that they are velocity sensitive. The falling phases of the kernels had distinct shoulders, indicating that the responses of the motor neurons also had delayed low-pass components, i.e., position sensitivity. The anterior slow flexor motor neuron had a monophasic, low-passed, first-order kernel, indicating that it is position sensitive. The linear component of the motor neuron responses, predicted by convolving the first-order kernels with the stimulus signal, strongly resembled the actual response, whereas the second-order nonlinear component was small, particularly at >10 Hz. The power spectra of the fast motor neurons showed that they had the highest cutoff frequencies (at >8 Hz), whereas the slow flexor motor neurons had a gradual roll-off at 1 Hz. The intermediate flexor motor neuron had an intermediate cutoff frequency of ∼2–3 Hz. The linear responses of the flexor motor neurons could be decomposed into low- and high-frequency components. The high-frequency components (>10 Hz) were velocity dependent and linear, whereas the low-frequency components (<10 Hz) were position dependent and nonlinear. The nonlinearity was a signal compression (or half-wave rectification). The results show that although the flexor motor neurons receive many common inputs during FeCO stimulation, each individual has specific dynamic response properties. The responses of the motor neurons are fractionated so that a given individual within the pool will respond best to position, whereas others will respond better to velocity. Likewise, some motor neurons respond best at low frequencies, whereas others respond best at higher frequencies of stimulation.

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

1996 ◽  
Vol 75 (2) ◽  
pp. 561-574 ◽  
Author(s):  
E. M. Quinlan ◽  
A. D. Murphy
Keyword(s):  
Motor Activity ◽  
Motor Neuron ◽  
Central Pattern Generator ◽  
Motor Neurons ◽  
Motor Pattern ◽  
Pattern Generator ◽  
Neuron Activity ◽  
Phase 2 ◽  
Phase 3 ◽  
Standard Pattern

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.

scholarly journals A directional 3D neurite outgrowth model for studying motor axon biology and disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xandor M. Spijkers ◽  
Svetlana Pasteuning-Vuhman ◽  
Jennifa C. Dorleijn ◽  
Paul Vulto ◽  
Nienke R. Wevers ◽  
...  
Keyword(s):  
Motor Neuron ◽  
Motor Neurons ◽  
Microtiter Plate ◽  
Axonal Guidance ◽  
Immunofluorescent Staining ◽  
Axonal Outgrowth ◽  
Dependent Manner ◽  
Laboratory Equipment ◽  
Motor Neuron Diseases ◽  
Adjacent Layer

AbstractWe report a method to generate a 3D motor neuron model with segregated and directed axonal outgrowth. iPSC-derived motor neurons are cultured in extracellular matrix gel in a microfluidic platform. Neurons extend their axons into an adjacent layer of gel, whereas dendrites and soma remain predominantly in the somal compartment, as verified by immunofluorescent staining. Axonal outgrowth could be precisely quantified and was shown to respond to the chemotherapeutic drug vincristine in a highly reproducible dose-dependent manner. The model was shown susceptible to excitotoxicity upon exposure with excess glutamate and showed formation of stress granules upon excess glutamate or sodium arsenite exposure, mimicking processes common in motor neuron diseases. Importantly, outgrowing axons could be attracted and repelled through a gradient of axonal guidance cues, such as semaphorins. The platform comprises 40 chips arranged underneath a microtiter plate providing both throughput and compatibility to standard laboratory equipment. The model will thus prove ideal for studying axonal biology and disease, drug discovery and regenerative medicine.

Octopamine induces steady-state reflex reversal in crayfish thoracic ganglia

1996 ◽  
Vol 76 (1) ◽  
pp. 93-108 ◽  
Author(s):  
P. Skorupski
Keyword(s):  
Spontaneous Activity ◽  
Motor Neurons ◽  
Motor Output ◽  
Reflex Response ◽  
Neuron Activity ◽  
Chordotonal Organ ◽  
Nerve Activity ◽  
Group 2 ◽  
Stimulation Of ◽  
Group 1

1. This paper investigates the effect of octopamine on spontaneous and reflex motor output of crayfish leg motor neurons. Octopamine modulated spontaneous activity, both rhythmic and tonic, and dramatically modulated the pattern of reflex motor output elicited by stimulating identified proprioceptors of the basal limb. 2. Spontaneous reciprocal motor patterns, involving alternating bursts of promotor and remotor motor neuron activity, were reversibly abolished by octopamine. The threshold concentration for this effect was approximately 1 microM. 3. At concentrations greater than approximately 10 microM octopamine inhibited spontaneous promotor nerve activity in both bursting and nonbursting preparations. In some experiments promotor inhibition was correlated with the induction of tonic remotor nerve activity. The EC50 for complete inhibition of promotor nerve activity by octopamine was 20-30 microM. 4. Reflexes mediated by two basal limb proprioceptors, the thoracocoxal muscle receptor organ (TCMRO; which signals leg promotion) and the thoracocoxal chordotonal organ (TCCO; which signals leg remotion) were analyzed in a number of promotor and remotor motor neurons. In both cases assistance reflexes (excitation of promotors by the TCCO and remotors by the TCMRO) were restricted to subgroups of the motor pool. Among remotor motor neurons, the first two units recruited during bursts of spontaneous activity were members of the assistance reflex group (group 1). A third unit, sometimes recruited during more intense spontaneous bursts, was excited by TCCO stimulation and was therefore a member of the resistance reflex group (group 2). Other resistance group remotors were also excited by the TCCO, but this input normally remained subthreshold. 5. Stimulation of the TCCO afferent nerve elicited excitatory postsynaptic potentials (EPSPs) in group 2 (resistance group) remotor motor neurons at a latency compatible with a monosynaptic connection. The same stimulation excited group 1 (assistance group) promotor motor neurons, but at a greater and more variable latency. Thus the remotor resistance reflex from the TCCO is probably monosynaptic, but the promotor assistance reflex, also elicited by TCCO stimulation, is likely to be di- or polysynaptic. Assistance group (group 1) remotor motor neurons are inhibited by mechanical stimulation of the TCCO, or electrical stimulation of its nerve. 6. Octopamine had selective effects on individual remotor units. First, assistance group remotor motor neurons were affected in two ways. One unit was inhibited, so that reflex spiking in response to TCMRO stimulation was abolished. A second unit was not inhibited, but its reflex response mode changed, so that instead of responding to TCMRO input with an assistance reflex, it responded to TCCO input with a resistance reflex. Second, among motor neurons that normally respond to TCCO input with resistance reflexes, these responses were enhanced by octopamine. 7. Promotor motor neurons were inhibited by octopamine and reflex responses were also affected selectively. Responses to TCCO input (assistance reflexes) were abolished; whereas, responses to TCMRO input (resistance reflexes) were relatively less affected. 8. Intracellular recordings revealed that the majority of remotor motor neurons depolarized in the presence of octopamine. In preparations where these could be classified on the basis of TCMRO/ TCCO inputs, all were identified as group 2 (resistance group). A minority of remotor motor neurons were hyperpolarized by octopamine. All of these were identified as group 1 (assistance group), with strong TCMRO input. 9. The majority of promotor motor neurons were depolarized by octopamine. This depolarization was nevertheless inhibitory since it reversed slightly positive to rest and was associated with a substantial fall in inp

Modulation of spontaneous and reflex activity of crayfish leg motor neurons by octopamine and serotonin

1996 ◽  
Vol 76 (5) ◽  
pp. 3535-3549 ◽  
Author(s):  
M. D. Gill ◽  
P. Skorupski
Keyword(s):  
Motor Neurons ◽  
Stance Phase ◽  
Opposite Effect ◽  
Reflex Response ◽  
Chordotonal Organ ◽  
Inhibitory Effects ◽  
Nerve Activity ◽  
Reflex Responses ◽  
High Concentrations ◽  
Serotonergic Modulation

1. We compared the effects of octopamine and serotonin on the activity of crayfish leg motor neurons in an isolated preparation of the 4th thoracic ganglion. Spontaneous activity of leg promotor (swing phase in a forward walking crayfish) and remotor (stance phase) motor neurons consisted either of continuous promotor activity (with the remotor nerve silent) or alternating bursts of promotor and remotor activity. Octopamine and serotonin, at high concentrations (< or = 100 and < or = 20 microM, respectively), abolished spontaneous promotor activity and rhythmic bursting (if ongoing). Both amines induced tonic remotor nerve activity, but each amine activated different identified remotor motor neurons. 2. Reflex responses of remotor motor neurons to stimulation of thoracocoxal (TC) joint proprioceptors were modulated by octopamine and serotonin in characteristic ways. The muscle receptor (TCMRO) that signals joint remotion excited a subset of remotor motor neurons in an assistance reflex. The chordotonal organ (TCCO) that signals joint promotion excited different remotor motor neurons in a resistance reflex. Octopamine abolished assistance reflexes and facilitated resistance reflexes. One assistance group unit was inhibited, whereas reflex reversal was induced in another: this unit was now excited in a resistance reflex, rather than in an assistance reflex. The responses of resistance group remotor units were enhanced. Serotonin had the opposite effect on assistance group remotors: one unit was excited and generated a stronger assistance reflex. The effect of serotonin on resistance group remotor units was similar (but quantitatively different) to that of octopamine. 3. Both octopamine and serotonin modulated spontaneous motor output at concentrations below those required to inhibit promotor nerve activity. Rhythmic promotor and remotor bursting was abolished, and replaced with continuous promotor activity, by serotonin at 1 microM and octopamine at 1–10 microM. In nonbursting preparations, promotor activity could be excited (instead of inhibited) by either amine at lower concentrations. 4. Octopaminergic inhibition of spontaneous promotor activity was antagonized by mianserin (10 microM). Phentolamine at the same concentration was less effective as an antagonist. Serotonergic inhibition of promotor activity was not blocked by mianserin. Mianserin also antagonized inhibitory, but not excitatory, effects of octopamine on remotor reflex responses. Serotonergic modulation of these reflexes was not affected. 5. An intersegmental difference was found in aminergic inhibition of promotor nerve activity. Whereas the effect (at the higher concentrations used) was inhibition of promotor activity from T4, simultaneous recordings from promotor nerves of the more rostral ganglia T3 and T2 showed either promotor excitation, or inhibition that was significantly weaker than in T4. This may relate to the known postural effects of these amines in intact crayfish and lobsters. 6. We conclude that octopamine and serotonin are modulators of segmental reflexes in the crayfish walking system. Each amine “assembles” a unique remotor nerve reflex response from different combinations of remotor units. In the case of octopamine, inhibitory effects are mediated by a mianserin-sensitive receptor, whereas excitatory effects are mediated by a mianserin-insensitive receptor.

Motor Control of Aimed Limb Movements in an Insect

2008 ◽  
Vol 99 (2) ◽  
pp. 484-499 ◽  
Author(s):  
Keri L. Page ◽  
Jure Zakotnik ◽  
Volker Dürr ◽  
Thomas Matheson
Keyword(s):  
Motor Activity ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Large Amplitude ◽  
The Body ◽  
Movement Direction ◽  
Joint Movement ◽  
Skeletal System ◽  
Limb Movements ◽  
Co Activation

Limb movements that are aimed toward tactile stimuli of the body provide a powerful paradigm with which to study the transformation of motor activity into context-dependent action. We relate the activity of excitatory motor neurons of the locust femoro-tibial joint to the consequent kinematics of hind leg movements made during aimed scratching. There is posture-dependence of motor neuron activity, which is stronger in large amplitude (putative fast) than in small (putative slow and intermediate) motor neurons. We relate this posture dependency to biomechanical aspects of the musculo-skeletal system and explain the occurrence of passive tibial movements that occur in the absence of agonistic motor activity. There is little recorded co-activation of antagonistic tibial extensor and flexor motor neurons, and there is differential recruitment of proximal and distal flexor motor neurons. Large-amplitude motor neurons are often recruited soon after a switch in joint movement direction. Motor bursts containing large-amplitude spikes exhibit high spike rates of small-amplitude motor neurons. The fast extensor tibiae neuron, when recruited, exhibits a pattern of activity quite different to that seen during kicking, jumping, or righting: there is no co-activation of flexor motor neurons and no full tibial flexion. Changes in femoro-tibial joint angle and angular velocity are most strongly dependent on variations in the number of motor neuron spikes and the duration of motor bursts rather than on firing frequency. Our data demonstrate how aimed scratching movements result from interactions between biomechanical features of the musculo-skeletal system and patterns of motor neuron recruitment.

scholarly journals Bioengineered model of the human motor unit with physiologically functional neuromuscular junctions

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rowan P. Rimington ◽  
Jacob W. Fleming ◽  
Andrew J. Capel ◽  
Patrick C. Wheeler ◽  
Mark P. Lewis
Keyword(s):  
Neuromuscular Junction ◽  
Motor Neuron ◽  
Motor Unit ◽  
Motor Nerve ◽  
Motor Units ◽  
Extracellular Matrices ◽  
Synaptic Membrane ◽  
Type I ◽  
Dependent Manner ◽  
Human Motor

AbstractInvestigations of the human neuromuscular junction (NMJ) have predominately utilised experimental animals, model organisms, or monolayer cell cultures that fail to represent the physiological complexity of the synapse. Consequently, there remains a paucity of data regarding the development of the human NMJ and a lack of systems that enable investigation of the motor unit. This work addresses this need, providing the methodologies to bioengineer 3D models of the human motor unit. Spheroid culture of iPSC derived motor neuron progenitors augmented the transcription of OLIG2, ISLET1 and SMI32 motor neuron mRNAs ~ 400, ~ 150 and ~ 200-fold respectively compared to monolayer equivalents. Axon projections of adhered spheroids exceeded 1000 μm in monolayer, with transcription of SMI32 and VACHT mRNAs further enhanced by addition to 3D extracellular matrices in a type I collagen concentration dependent manner. Bioengineered skeletal muscles produced functional tetanic and twitch profiles, demonstrated increased acetylcholine receptor (AChR) clustering and transcription of MUSK and LRP4 mRNAs, indicating enhanced organisation of the post-synaptic membrane. The number of motor neuron spheroids, or motor pool, required to functionally innervate 3D muscle tissues was then determined, generating functional human NMJs that evidence pre- and post-synaptic membrane and motor nerve axon co-localisation. Spontaneous firing was significantly elevated in 3D motor units, confirmed to be driven by the motor nerve via antagonistic inhibition of the AChR. Functional analysis outlined decreased time to peak twitch and half relaxation times, indicating enhanced physiology of excitation contraction coupling in innervated motor units. Our findings provide the methods to maximise the maturity of both iPSC motor neurons and primary human skeletal muscle, utilising cell type specific extracellular matrices and developmental timelines to bioengineer the human motor unit for the study of neuromuscular junction physiology.

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