scholarly journals Human neuromuscular junction on micro-structured microfluidic devices implemented with a custom micro electrode array (MEA)

Lab on a Chip ◽  
2021 ◽  
Author(s):  
Pauline Duc ◽  
Michel Vignes ◽  
Gérald Hugon ◽  
Audrey Sebban ◽  
Gilles Carnac ◽  
...  

Microfluidic devices were coupled with custom MEA and used for co-culture of human motor neurons and muscles. This allowed to assess human NMJ activity by electrical stimulation of axons and recording of subsequent muscle action potentials.

1978 ◽  
Vol 41 (3) ◽  
pp. 609-620 ◽  
Author(s):  
B. Jahan-Parwar ◽  
S. M. Fredman

1. Intracellular stimulation of individual neurons in the two symmetrical A neuron clusters of the cerebral ganglion evoked contractions of both the foot and parapodia. Electrical stimulation of pedal and parapodial nerves caused antidromic action potentials in A neurons. Units recorded in the nerves followed the driven somatic spike 1:1. This suggests that the A neurons are presumptive pedal and parapodial motor neurons.2. Individual A neurons evoked both bilteral and unilateral contractions of the parapodia or split foot. Contractions in the parapodia were independent of those in the foot. An individual A neuron caused contractions in either the foot or the parapodia, but not both. Sequential transection of parapodial nerves had only a slight effect until a key nerve was cut. The contractions produced by a single A neuron on one side were then abolished. These data suggest that the motor fields of the A neurons are well defined within the foot or the parapodia. 3. Parapodial contractions produced by individual A neurons are not dependent on the excitation of follower motor neurons. Blocking synaptic transmission by the addition of CoCl2 did not eliminate the contractions produced by driving individual A neurons. This is consistent with the A neurons being motor neurons. 4. Intracellular stimulation of individual neurons in the symmetrical B neuron clusters of the cerebral ganglion also evoked pedal and parapodial contractions. Electrical stimulation of the pedal and parapodial nerves elicited antidromic spikes in these neurons. Individual B neurons caused contractions in both the foot and parapodia. This suggests that the B neurons are motor neurons with very large motor fields. 5. Filling the pedal and parapodial nerves with cobalt primarily filled the cell bodies of neurons located in the pedal and pleural ganglia. The somata of A and B neurons were also occasionally filled. This is consistent with the electrophisiological results. 6. Other neurons also evoked parapodial contractions. Intracellular stimulation of neurons in the pedal and pleural ganglia caused parapodial contractions in intact animals. Some of these neurons were excited by stretching the parapodia or touching the tentacles. 7. The B neurons are strongly excited by tactile stimulation of the tentacles. Since they can cause pedal and parapodial contractions they may mediate reflex contractions elicited by tentacular stimulation. Stretching the parapodia only occasionally caused the A neurons to fire. This makes it unlikely that they make a major contribution to pedal and parapodial proprioceptive reflexes. These reflexes are probably controlled by neurons in the pedal and pleural ganglia.


1983 ◽  
Vol 50 (6) ◽  
pp. 1522-1542 ◽  
Author(s):  
E. T. Walters ◽  
J. H. Byrne ◽  
T. J. Carew ◽  
E. R. Kandel

Mechanical, chemical, or electrical stimulation of the tail elicits a short-latency (less than 1 s) tail-withdrawal reflex that is graded with the intensity of the stimulus. The tail-withdrawal reflex is not elicited by stimulation of parts of the body outside of the tail region. Mechanoafferent neurons innervating the tail are located in a small subcluster within a large, homogeneous group of medium-size (40-80 micron) cells on the ventrocaudal (VC) surface of each pleural ganglion. The tail sensory neurons within this large VC cluster are activated by tactile pressure or by electrical stimulation of discrete regions of the tail. They adapt slowly to maintained stimulation and sometimes respond to stimulus offset as well. Both mechanical and electrical stimuli produce responses that are graded with the intensity of the stimulus. Cells in the VC cluster appear to be primary mechanoreceptors because they have axons in peripheral nerves (including nerves innervating the tail), they exhibit action potentials lacking prepotentials in response to tactile stimulation, and these action potentials are still produced by cutaneous stimulation when peripheral and central chemical synaptic transmission is blocked. Stimulation of fields all over the body surface evokes synaptically mediated hyperpolarizing responses in individual mechanoafferent neurons that may represent afferent inhibition. Hyperpolarizing responses lasting many seconds can be produced by brief cutaneous stimuli. The mechanoafferent neurons innervating the tail region make strong monosynaptic connections to tail motor neurons in the ipsilateral pedal ganglion, and through these connections this subpopulation of the VC neurons appears to make a substantial contribution to the short-latency tail-withdrawal reflex. In addition, the combined excitatory receptive fields of these mechanoafferents match the excitatory receptive field of the tail-withdrawal reflex. Mechanoafferent neurons in the VC cluster that have receptive fields on other parts of the body (outside the excitatory receptive field of the tail-withdrawal reflex) have not been observed to make monosynaptic connections to the tail motor neurons. The neurons innervating the tail are reliably found in a discrete region within the larger VC cluster. In addition to this gross somatotopic organization, there is evidence of a finer level of somatotopic organization between the position of the excitatory receptive field on the tail and the position of the cell soma in the tail subcluster.(ABSTRACT TRUNCATED AT 400 WORDS)


1988 ◽  
Vol 118 (3) ◽  
pp. 471-483 ◽  
Author(s):  
L. M. Voloschin ◽  
E. Décima ◽  
J. H. Tramezzani

ABSTRACT Electrical stimulation of the XIII thoracic nerve (the 'mammary nerve') causes milk ejection and the release of prolactin and other hormones. We have analysed the route of the suckling stimulus at the level of different subgroups of fibres of the teat branch of the XIII thoracic nerve (TBTN), which innervates the nipple and surrounding skin, and assessed the micromorphology of the TBTN in relation to lactation. There were 844 ± 63 and 868 ± 141 (s.e.m.) nerve fibres in the TBTN (85% non-myelinated) in virgin and lactating rats respectively. Non-myelinated fibres were enlarged in lactating rats; the modal value being 0·3–0·4 μm2 for virgin and 0·4–0·5 μm2 for lactating rats (P > 0·001; Kolmogorov–Smirnov test). The modal value for myelinated fibres was 3–6 μm2 in both groups. The compound action potential of the TBTN in response to electrical stimulation showed two early volleys produced by the Aα- and Aδ-subgroups of myelinated fibres (conduction velocity rate of 60 and 14 m/s respectively), and a late third volley originated in non-myelinated fibres ('C') group; conduction velocity rate 1·4 m/s). Before milk ejection the suckling pups caused 'double bursts' of fibre activity in the Aδ fibres of the TBTN. Each 'double burst' consisted of low amplitude action potentials and comprised two multiple discharges (33–37 ms each) separated by a silent period of around 35 ms. The 'double bursts' occurred at a frequency of 3–4/s, were triggered by the stimulation of the nipple and were related to fast cheek movements visible only by watching the pups closely. In contrast, the Aα fibres of the TBTN showed brief bursts of high amplitude potentials before milk ejection. These were triggered by the stimulation of cutaneous receptors during gross slow sucking motions of the pup (jaw movements). Immediately before the triggering of milk ejection the mother was always asleep and a low nerve activity was recorded in the TBTN at this time. When reflex milk ejection occurred, the mother woke and a brisk increase in nerve activity was detected; this decreased when milk ejection was accomplished. In conscious rats the double-burst type of discharges in Aδ fibres was not observed, possibly because this activity cannot be detected by the recording methods currently employed in conscious animals. During milk ejection, action potentials of high amplitude were conveyed in the Aα fibres of the TBTN. During the treading time of the stretch reaction (SR), a brisk increase in activity occurred in larger fibres; during the stretching periods of the SR a burst-type discharge was again observed in slow-conducting afferents; when the pups changed nipple an abrupt increase in activity occurred in larger fibres. In summary, the non-myelinated fibres of the TBTN are increased in diameter during lactation, and the pattern of suckling-evoked nerve activity in myelinated fibres showed that (a) the double burst of Aδ fibres, produced by individual sucks before milk ejection, could be one of the conditions required for the triggering of the reflex, and (b) the nerve activity displayed during milk-ejection action may result, at least in part, from 'non-specific' stimulation of cutaneous receptors. J. Endocr. (1988) 118, 471–483


2000 ◽  
Vol 203 (3) ◽  
pp. 435-445
Author(s):  
M. Wildman

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.


2005 ◽  
Vol 22 (2) ◽  
pp. 227-243 ◽  
Author(s):  
Tatiana Y. Kostrominova ◽  
Douglas E. Dow ◽  
Robert G. Dennis ◽  
Richard A. Miller ◽  
John A. Faulkner

Loss of innervation in skeletal muscles leads to degeneration, atrophy, and loss of force. These dramatic changes are reflected in modifications of the mRNA expression of a large number of genes. Our goal was to clarify the broad spectrum of molecular events associated with long-term denervation of skeletal muscles. A microarray study compared gene expression profiles of 2-mo denervated and control extensor digitorum longus (EDL) muscles from 6-mo-old rats. The study identified 121 genes with increased and 7 genes with decreased mRNA expression. The expression of 107 of these genes had not been identified previously as changed after denervation. Many of the genes identified were genes that are highly expressed in skeletal muscles during embryonic development, downregulated in adults, and upregulated after denervation of muscle fibers. Electrical stimulation of denervated muscles preserved muscle mass and maximal force at levels similar to those in the control muscles. To understand the processes underlying the effect of electrical stimulation on denervated skeletal muscles, mRNA and protein expression of a number of genes, identified by the microarray study, was compared. The hypothesis was that loss of nerve action potentials and muscle contractions after denervation play the major roles in upregulation of gene expression in skeletal muscles. With electrical stimulation of denervated muscles, the expression levels for these genes were significantly downregulated, consistent with the hypothesis that loss of action potentials and/or contractions contribute to the alterations in gene expression in denervated skeletal muscles.


2014 ◽  
Vol 151 (1_suppl) ◽  
pp. P71-P72
Author(s):  
Morgan R. Bliss ◽  
Heather Wark ◽  
Daniel McDonnall ◽  
Marshall E. Smith

Spine ◽  
2000 ◽  
Vol 25 (4) ◽  
pp. 411-417 ◽  
Author(s):  
Yuzuru Takahashi ◽  
Jiro Hirayama ◽  
Yoshio Nakajima ◽  
Seiji Ohtori ◽  
Kazuhisa Takahashi

2000 ◽  
Vol 83 (4) ◽  
pp. 2145-2162 ◽  
Author(s):  
Ralph E. Beitel ◽  
Russell L. Snyder ◽  
Christoph E. Schreiner ◽  
Marcia W. Raggio ◽  
Patricia A. Leake

Cochlear prostheses for electrical stimulation of the auditory nerve (“electrical hearing”) can provide auditory capacity for profoundly deaf adults and children, including in many cases a restored ability to perceive speech without visual cues. A fundamental challenge in auditory neuroscience is to understand the neural and perceptual mechanisms that make rehabilitation of hearing possible in these deaf humans. We have developed a feline behavioral model that allows us to study behavioral and physiological variables in the same deaf animals. Cats deafened by injection of ototoxic antibiotics were implanted with either a monopolar round window electrode or a multichannel scala tympani electrode array. To evaluate the effects of perceptually significant electrical stimulation of the auditory nerve on the central auditory system, an animal was trained to avoid a mild electrocutaneous shock when biphasic current pulses (0.2 ms/phase) were delivered to its implanted cochlea. Psychophysical detection thresholds and electrical auditory brain stem response (EABR) thresholds were estimated in each cat. At the conclusion of behavioral testing, acute physiological experiments were conducted, and threshold responses were recorded for single neurons and multineuronal clusters in the central nucleus of the inferior colliculus (ICC) and the primary auditory cortex (A1). Behavioral and neurophysiological thresholds were evaluated with reference to cochlear histopathology in the same deaf cats. The results of the present study include: 1) in the cats implanted with a scala tympani electrode array, the lowest ICC and A1 neural thresholds were virtually identical to the behavioral thresholds for intracochlear bipolar stimulation; 2) behavioral thresholds were lower than ICC and A1 neural thresholds in each of the cats implanted with a monopolar round window electrode; 3) EABR thresholds were higher than behavioral thresholds in all of the cats (mean difference = 6.5 dB); and 4) the cumulative number of action potentials for a sample of ICC neurons increased monotonically as a function of the amplitude and the number of stimulating biphasic pulses. This physiological result suggests that the output from the ICC may be integrated spatially across neurons and temporally integrated across pulses when the auditory nerve array is stimulated with a train of biphasic current pulses. Because behavioral thresholds were lower and reaction times were faster at a pulse rate of 30 pps compared with a pulse rate of 2 pps, spatial-temporal integration in the central auditory system was presumably reflected in psychophysical performance.


Sign in / Sign up

Export Citation Format

Share Document