Generation of Human Motor Units with Functional Neuromuscular Junctions in Microfluidic Devices

AbstractNeuromuscular junctions (NMJs) ensure proper communication between motor neurons and muscle through the release of neurotransmitters. In motor neuron disorders, such as amyotrophic lateral sclerosis (ALS), NMJs degenerate resulting in muscle atrophy, paralysis and respiratory failure. The aim of this study was to establish a versatile and reproducible in vitro model of a human motor unit to study the effect of ALS-causing mutations. Therefore, we generated a co-culture of human induced pluripotent stem cell-derived motor neurons and human primary mesoangioblast-derived myotubes in microfluidic devices. A chemotactic and volumetric gradient facilitated the growth of motor neuron neurites through microgrooves resulting in the interaction with myotubes and the formation of NMJs. We observed that ALS-causing FUS mutations resulted in a reduced neurite outgrowth and in a decreased NMJ number. Interestingly, the selective HDAC6 inhibitor, Tubastatin A, improved the neurite outgrowth and the NMJ morphology of FUS-ALS co-cultures, further prompting HDAC6 inhibition as a potential therapeutic strategy for ALS.

Download Full-text

Discharge patterns in human motor units during fatiguing arm movements

Journal of Applied Physiology ◽

10.1152/jappl.1998.85.5.1684 ◽

1998 ◽

Vol 85 (5) ◽

pp. 1684-1692 ◽

Cited By ~ 39

Author(s):

L. Griffin ◽

S. J. Garland ◽

T. Ivanova

Keyword(s):

Voluntary Movement ◽

Motor Units ◽

Constant Load ◽

Short Isis ◽

Interspike Intervals ◽

Triceps Brachii ◽

Movement Initiation ◽

Human Motor ◽

Discharge Patterns ◽

Human Motor Units

The purpose of this study was to determine whether short interspike intervals (ISIs of <20 ms) would occur naturally during voluntary movement and would increase in number with fatigue. Thirty-four triceps brachii motor units from nine subjects were assessed during a fatigue task consisting of fifty extension and fifty flexion elbow movements against a constant-load opposing extension. Nineteen motor units were recorded from the beginning of the fatigue task; the number of short ISIs was 7.1 ± 4.1% of the total number of ISIs in the first one-third of the task (unfatigued state). This value increased to 11.8 ± 5.9% for the last one-third of the task (fatigued state). Fifteen motor units were recruited during the fatigue task and discharged, with 16.4 ± 6.0% of short ISIs in the fatigued state. For all motor units, the number of short ISIs was positively correlated ( r 2 = 0.85) with the recruitment threshold torque. Short ISIs occurred most frequently at movement initiation but also occurred throughout the movement. These results document the presence of short ISIs during voluntary movement and their increase in number during fatigue.

Download Full-text