Fruit Fly Connectome

Lay Summary: Scientists have now mapped all the neural connections/pathways of a fruit fly (connectome). Why is this important? Fruit fly model is used in autism research, so this advance potentially helps autism research. 

https://www.science.org/doi/10.1126/science.add9330

Fruit Fly Connectome

Before this, there were connectomes for just 3 organisms; roundworm (Caenorhabditis elegans), larval sea squirt (Ciona intestinalis) and larval marine worm (Platynereis dumerilii). These organisms have relatively small brains with several hundred neurons. Mapping larger and more complex brains remained a technical challenge.

Now, the fruit fly's connectome, consisting of more than 3,000 neurons and more than half a million synapses, has been mapped out. The researchers identified 93 different neuron types -  input neurons, output neurons, and interneurons. The team traced the pathways from sensory input neurons to output neurons and found that neural circuits resembled those found in state-of-the-art computer machine learning. Most of the brain’s hub neurons were connected to the learning center, and hubs were more likely than other neurons to form connections to the opposite brain hemisphere. 

The fruit fly connectome provides a starting point for studying the roles of specific neurons and circuits and could inspire new artificial neural networks.

References: The connectome of an insect brain. Winding M, Pedigo BD, Barnes CL, Patsolic HG, Park Y, Kazimiers T, Fushiki A, Andrade IV, Khandelwal A, Valdes-Aleman J, Li F, Randel N, Barsotti E, Correia A, Fetter RD, Hartenstein V, Priebe CE, Vogelstein JT, Cardona A, Zlatic M. Science. 2023 Mar 10;379(6636):eadd9330. doi: 10.1126/science.add9330. Epub 2023 Mar 10. PMID: 36893230.

Why is this advance important for Autism Research

Fruit flies have been used as a model organism for studying autism due to their genetic similarity to humans and their well-understood neurobiology. Researchers have identified several genes in fruit flies that are involved in neural development and function and have been linked to human autism. By manipulating these genes in fruit flies, researchers can study the effects on behavior and neural function and gain insights into the underlying mechanisms of autism. Additionally, fruit flies are relatively easy to work with and have a short lifespan, making them a useful tool for studying the effects of environmental factors on neural development and behavior.

Examples of some of these genes include

1. Shank: This family of scaffold proteins that play important roles in synapse formation and function. Mutations in the human SHANK3 gene have been linked to autism. In fruit flies, mutations in the Shank homolog (dShank) result in defects in synapse formation and behavior that resemble some features of ASDs (1).
2. Neurexin: Family of presynaptic cell-adhesion molecules that interact with postsynaptic proteins such as neuroligins. Mutations in human neurexin genes have been associated with autism. In fruit flies, mutations in the neurexin homolog (dnrx) result in altered synaptic function and social behavior (2).
3. FMR1: gene that encodes a protein called FMRP, which plays a role in synapse function and plasticity. Mutations in the human FMR1 gene cause fragile X syndrome. In fruit flies, mutations in the FMR1 homolog (dfmr1) result in altered synaptic function and behavior that resemble some features of ASDs (3).

(1) Bozdagi, O., Sakurai, T., Papapetrou, D., Wang, X., Dickstein, D. L., Takahashi, N., ... & Buxbaum, J. D. (2010). Haploinsufficiency of the autism-associated Shank3 gene leads to deficits in synaptic function, social interaction, and social communication. Molecular autism, 1(1), 15.
(2) Li, J., Ashley, J., Budnik, V., & Bhat, M. A. (2007). Crucial role of Drosophila neurexin in proper active zone apposition to postsynaptic densities, synaptic growth, and synaptic transmission. Neuron, 55(5), 741-755.
(3) McBride, S. M., Choi, C. H., Wang, Y., Liebelt, D., Braunstein, E., Ferreiro, D., ... & Botas, J. (2005). Pharmacological rescue of synaptic plasticity, courtship behavior, and mushroom body defects in a Drosophila model of fragile X syndrome. Neuron, 45(5), 753-764.