Studies on fruit flies are shedding light on the complex neural coordination of movements, enhancing our understanding of motor neuron functionality.
Scientists are developing a wiring diagram of the motor circuits in fruit flies’ central nervous system that control their muscles. This diagram, which is called a connectome, has already provided insights into the complex coordination between the nerves controlling leg and wing movements.
Complexity in Simple Creatures
While fruit flies seem like simple creatures, the researchers said their motor system contains “an unexpected level of complexity.”
“A typical fly motor neuron receives thousands of synapses from hundreds of presynaptic premotor neurons,” the scientists observed. “This number is on par with the scale of synaptic integration in pyramidal cells of the rodent cortex.”
New Studies on Motor Coordination
Two new papers published in the scientific journal Nature have revealed the latest findings in this area, advancing our understanding of how the central nervous system in animals coordinates individual muscles to facilitate a variety of behaviors.
Animation of the anatomical reconstruction of various nervous system structures involved in take-off and flight in a female fruit fly.
Motor Neuron Efficiency and Adaptability
Fruit flies use their legs for numerous activities such as leaping, walking, grooming, fighting, and courtship. They can also adapt their gait to navigate terrains like house plants, walls, damp surfaces, ceilings – and even insect-scale treadmills.
All such movements, from postural reflexes that enable a fly to hold its position steady, to traversing obstacles or changing flight direction, originate through electrical signals from motor neurons. These signals are conducted through threadlike projections from the motor neuron to stimulate muscles.
A fly’s six legs are managed by just 60 to 70 motor neurons, the researchers pointed out. In a cat, they noted, about 600 motor neurons supply a single feline calf muscle. Only 29 motor neurons govern the power and steering muscles of a fruit fly wing. In comparison, a hummingbird’s pectoral muscle is supplied by 2,000 motor neurons.
Although the fly’s motor neurons are few, it performs remarkable aerial and terrestrial feats.
Wiring Logic of Premotor Circuits
The scientists explained that motor units are composed of a single motor neuron and the muscle fibers that it can excite. Various motor units, activated in different combinations and sequences, collaborate to achieve a myriad of movement behaviors.
The scientists in the two studies were interested in the wiring logic of premotor circuits. They wanted to understand how a fly’s nervous system coordinates motor units to accomplish varied tasks.
Detailed Mapping and Synaptic Architecture
One of the studies employed automated tools, machine learning, cell-type annotation, and electron microscopy to identify 14,600 neuronal cell bodies and about 45 million synapses (signal-transmission junctions) in the ventral nerve cord of a female fruit fly. The ventral nerve cord in flies is analogous to the spinal cord in vertebrates. The scientists subsequently applied deep learning to automatically reconstruct the anatomy of the neurons and their connections throughout the female fly.
Motor Neurons and Muscle Activation in Flight
The researchers used sophisticated methods to map the muscles targeted by leg and wing motor neurons. They determined which motor neurons in the female adult nerve cord connectome connect to individual muscles in the front leg and wing. From there, they created an atlas of the circuits that coordinate the fly’s leg and wing movements during take-off and flight motor initiation.
To get into the air, the fly’s middle legs extend to jump and its front legs flex for departure. This is very roughly like a taxiing airliner retracting its wheels after leaving the ground or a wading heron tucking its spindly legs to keep them out of the way as it rushes into the sky.
The scientists also found that some muscle fibers in adult flies are innervated by several motor neurons. This also occurs in the larval stage of the fruit fly and locusts. While some mammals have multiple innervations of nerve fibers as newborns, these usually disappear by adulthood.
Multiple innervations might offer more flexibility and explain why an insect’s limbs can operate with precision despite having so few motor neurons.
Functional and Evolutionary Insights from Fly Connectomics
The scientists also examined the fly’s wing motor system, which has roughly three sections grouped by function: powering the wing flapping, steering the insect, and adjusting wing motion.
The investigation of the connectivity of the premotor neurons enabled the researchers to compare the organization of premotor circuits for two types of limbs. The leg and the wing in fruit flies each have a distinct evolution and biomechanics.
Implications and Future Directions of Connectome Research
Connectomes are allowing scientists to produce new theories on how neural circuits function, and to debunk some false notions. The scientists mentioned that the recent community effort to develop the fruit fly connectome has led to one of the first synapse-level wiring diagrams for any limbed animal. They hope that additional connectomes will allow researchers to compare neural wiring across individuals. The anticipated reconstruction of a male fruit fly central nerve cord might illuminate differences between sexes.
References:
“Connectomic reconstruction of a female Drosophila ventral nerve cord” by Anthony Azevedo, Ellen Lesser, Jasper S. Phelps, Brandon Mark, Leila Elabbady, Sumiya Kuroda, Anne Sustar, Anthony Moussa, Avinash Khandelwal, Chris J. Dallmann, Sweta Agrawal, Su-Yee J. Lee, Brandon Pratt, Andrew Cook, Kyobi Skutt-Kakaria, Stephan Gerhard, Ran Lu, Nico Kemnitz, Kisuk Lee, Akhilesh Halageri, Manuel Castro, Dodam Ih, Jay Gager, Marwan Tammam, Sven Dorkenwald, Forrest Collman, Casey Schneider-Mizell, Derrick Brittain, Chris S. Jordan, Michael Dickinson, Alexandra Pacureanu, H. Sebastian Seung, Thomas Macrina, Wei-Chung Allen Lee and John C. Tuthill, 26 June 2024, Nature.
DOI: 10.1038/s41586-024-07389-x
“Synaptic architecture of leg and wing premotor control networks in Drosophila” by Ellen Lesser, Anthony W. Azevedo, Jasper S. Phelps, Leila Elabbady, Andrew Cook, Durafshan Sakeena Syed, Brandon Mark, Sumiya Kuroda, Anne Sustar, Anthony Moussa, Chris J. Dallmann, Sweta Agrawal, Su-Yee J. Lee, Brandon Pratt, Kyobi Skutt-Kakaria, Stephan Gerhard, Ran Lu, Nico Kemnitz, Kisuk Lee, Akhilesh Halageri, Manuel Castro, Dodam Ih, Jay Gager, Marwan Tammam, Sven Dorkenwald, Forrest Collman, Casey Schneider-Mizell, Derrick Brittain, Chris S. Jordan, Thomas Macrina, Michael Dickinson, Wei-Chung Allen Lee and John C. Tuthill, 26 June 2024, Nature.
DOI: 10.1038/s41586-024-07600-z
The research was supported by a Searle Scholar Award, Klingenstein-Simons Fellowship, Pew Biomedical Scholar Award, McKnight Scholar Award, Sloan Research Fellowship, New York Stem Cell Foundation, University of Washington Innovation Award, Genise Goldenson Award, National Institutes of Health Grants U19NS104655, RO1MH177808.