Related Experiment Video
Updated: Jun 21, 2026
10:45
Levator Auris Longus Preparation for Examination of Mammalian Neuromuscular Transmission Under Voltage Clamp Conditions
Published on: May 5, 2018
The vesicular acetylcholine transporter is required for neuromuscular development and function.
Braulio M de Castro1, Xavier De Jaeger, Cristina Martins-Silva
1Molecular Brain Research Group, Robarts Research Institute, University of Western Ontario, P.O. Box 5015, 100 Perth Drive, London, Ontario N6A 5K8, Canada.
Molecular and Cellular Biology
|July 29, 2009
Summary
The vesicular acetylcholine (ACh) transporter (VAChT) is vital for life, as VAChT knockout mice die shortly after birth. VAChT deficiency severely impacts neuromuscular junction development and ACh release.
Area of Science:
- Neuroscience
- Molecular Biology
- Developmental Biology
Background:
- The vesicular acetylcholine (ACh) transporter (VAChT) is crucial for storing ACh in synaptic vesicles.
- VAChT-independent ACh release is implicated in developmental processes.
Purpose of the Study:
- To investigate the physiological role of VAChT and VAChT-independent ACh release.
- To determine the necessity of VAChT for survival and neuromuscular junction development.
Main Methods:
- Generation of VAChT knockout mice.
- Electrophysiological recordings at the skeletal-neuromuscular junction.
- Biochemical analysis of ACh and related proteins.
Main Results:
- Homozygous VAChT knockout mice exhibit embryonic lethality.
- Synaptosomes from knockout mice show impaired depolarization-induced ACh release.
- Neuromuscular junctions in knockout mice display abnormal development, including increased motoneuron and nerve terminal numbers, abnormal sprouting, and muscle necrosis.
- Despite increased ACh synthesis markers, spontaneous miniature end-plate potentials are reduced in amplitude and frequency.
Conclusions:
- VAChT-mediated ACh storage is essential for survival.
- VAChT is critical for normal motor neuron development and neuromuscular junction formation.
- Disruption of VAChT function leads to severe developmental defects mimicking ACh synthesis deficiencies.
Related Concept Videos
01:23Cholinergic Neurons: Neurotransmission
Cholinergic neurotransmission involves the synthesis and the release of acetylcholine (ACh) in order to transmit nerve impulses across the synapse. The process begins with the synthesis of acetyl CoA, a precursor for ACh, from ATP, acetate, and coenzyme A in the mitochondria. Choline, another vital precursor, is transported inside the neuron through choline transporters, including high-affinity choline transporter CHT1, low-affinity choline transporter CTL1, and lower-affinity choline...
01:26Chemical Synapses
Chemical synapses are specialized sites between two neurons or between a neuron and a non-neuronal cell like a muscle, glandular or sensory cell.
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
01:26Chemical Synapses
Chemical synapses are specialized sites between two neurons or between a neuron and a non-neuronal cell like a muscle, glandular or sensory cell.
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
01:29Neuromuscular Junction And Blockade
The site of chemical communication between a motor neuron and a muscle fiber is called the neuromuscular junction (NMJ). The end of the motor neuron at the NMJ divides into a cluster of synaptic end bulbs. The cytoplasm of these bulbs consists of synaptic vesicles enclosing acetylcholine molecules, the principal neurotransmitter released at the NMJ. The region opposite the synaptic bulb that ends in the muscle fiber is called the motor end plate, which has acetylcholine receptors. Within the...
01:19The Neuromuscular Junction
The nervous system consists of complex motor neuron circuits, including upper motor neurons originating from the cerebral cortex and lower motor neurons starting in the spinal cord, coordinating both voluntary and involuntary movements. Among these, somatic motor neurons activate skeletal muscles and are classified into alpha, beta, and gamma types. Alpha neurons are vital for voluntary movement coordination, while gamma neurons adjust muscle spindle sensitivity, and the function of beta...
01:26Fusion of Secretory Vesicles with the Plasma Membrane
Proteins and neurotransmitters in secretory vesicles can be released from a cell upon vesicle docking, priming, and fusion with the plasma membrane. Vesicles are docked and primed in preparation for the quick exocytosis of their contents in response to a stimulus. The fusion process is mainly carried out by a SNAP Receptor or SNARE complex, consisting of synaptobrevin, syntaxin-1, and SNAP-25.
In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or...
In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or...