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#Drosophila

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Sometimes one stops to just look at the data. And the software user interface. They are beautiful.

We are looking at a cross section of the #Drosophila larval brain, near the brain commissure, where hundreds of neurons (magenta: their reconstructed skeletons) cross from one brain hemisphere to the other. To the right, a 3D rendering of multiple neurons, a pair of which cross the midline in a U-shaped bend.

Our CATMAID software is web-based, in other words it's just a website that accesses remote data. I credit it's sleek design to @herrsaalfeld – author of the early, "Ice Age" CATMAID and its blue tones – who at some point in his life studied "medieninformatik" and has always had a penchant for art.

See our images and fly neurons here, kindly hosted by the #VirtualFlyBrain :
l1em.catmaid.virtualflybrain.o

How time flies! Or as we say in the #drosophila community:

"time's fun when you're having flies"

Anywho, I can't believe it's already ten years since I described the scholarly infrastructure of my dreams and we are still nowhere close:

bjoern.brembs.net/2015/04/what

I admit it does take a healthy dose of denial to still remain optimistic, when you've been around for that long. 😆

Replied in thread

@futurebird One key difference in the moth vs. the fruit fly:

"larvae trained at third instar still showed odor aversion after two molts, as fifth instars, but did not avoid the odor as adults, consistent with the idea that post-metamorphic recall involves regions of the brain that are not produced until later in larval development."

journals.plos.org/plosone/arti

... whereas fly larvae don't develop further brain regions during larval life.

journals.plos.orgRetention of Memory through Metamorphosis: Can a Moth Remember What It Learned As a Caterpillar?Insects that undergo complete metamorphosis experience enormous changes in both morphology and lifestyle. The current study examines whether larval experience can persist through pupation into adulthood in Lepidoptera, and assesses two possible mechanisms that could underlie such behavior: exposure of emerging adults to chemicals from the larval environment, or associative learning transferred to adulthood via maintenance of intact synaptic connections. Fifth instar Manduca sexta caterpillars received an electrical shock associatively paired with a specific odor in order to create a conditioned odor aversion, and were assayed for learning in a Y choice apparatus as larvae and again as adult moths. We show that larvae learned to avoid the training odor, and that this aversion was still present in the adults. The adult aversion did not result from carryover of chemicals from the larval environment, as neither applying odorants to naïve pupae nor washing the pupae of trained caterpillars resulted in a change in behavior. In addition, we report that larvae trained at third instar still showed odor aversion after two molts, as fifth instars, but did not avoid the odor as adults, consistent with the idea that post-metamorphic recall involves regions of the brain that are not produced until later in larval development. The present study, the first to demonstrate conclusively that associative memory survives metamorphosis in Lepidoptera, provokes intriguing new questions about the organization and persistence of the central nervous system during metamorphosis. Our results have both ecological and evolutionary implications, as retention of memory through metamorphosis could influence host choice by polyphagous insects, shape habitat selection, and lead to eventual sympatric speciation.

Whole adult fly brain connectome for FAFB (female adult fly brain) – last year in preprint form, today as an immersive feature in Nature.

140,000 neurons, over 50 million synapses – organised into over 8,000 cell types. (VNC not included.)

nature.com/immersive/d42859-02

The whole connectome: Dorkenwald et al. 2024 (Seung, Murthy) nature.com/articles/s41586-024

Cell types: Schlegel et al. 2024 (Jefferis) nature.com/articles/s41586-024 by @uni_matrix

Network statistics: Lin et al. 2024 (Murthy) nature.com/articles/s41586-024

Visual system: Garner et al. 2024 (Wernet, Kim) nature.com/articles/s41586-024 and Matsliah et al. (Murthy, Seung) nature.com/articles/s41586-024

Seung also put out a solo paper on predicting visual function from the connectome: nature.com/articles/s41586-024

Control of halting in walking: Sapkal et al. 2024 (Bidaye) nature.com/articles/s41586-024

FAFB imaged by @davi 's group back in 2018: cell.com/cell/fulltext/S0092-8

For #SciArtSeptember: 50 EPG neurons from the #Drosophila, segmented from electron microscopy images, rendered in #Blender3d driven by neuVid. This ring of neurons forms part of the fly’s internal compass. As the fly changes its heading, neuronal activity moves around the ring, as shown by the false color gradient. Imaging and reconstruction by #HHMIJanelia and Google Research (www.janelia.org/project-team/flyem/hemibrain); function described by Hulse et al (doi.org/10.7554/eLife.66039).

Today the peer-reviewed version of our preprint is out:

"The #connectome of an insect brain"
science.org/doi/10.1126/scienc

Congrats to co-first authors Michael Winding and Benjamin Pedigo, and to all our lab members and collaborators who made this work possible over the years. A journey that started over 10 years ago–and yet this is but a new beginning. So much more to come.

See my #tootprint on the preprint from back in the Autumn: mathstodon.xyz/@albertcardona/

The data is available both as supplements and directly via #CATMAID thanks to hosting by the #VirtualFlyBrain:
l1em.catmaid.virtualflybrain.o)

(The "Winding, Pedigo et al. 2023" annotation listing all included neurons will appear very soon in an upcoming update.)

Intro: I'm a #Biology professor researching the #Neurogenetics of #learning and #memory in #Drosophila. I study how operant or motor memories are formed and how other forms of learning regulate these processes. As spontaneous behavior is required for operant learning, I also study how #spontaneity arises in nervous systems.

Our lab practices #openscience

Disclaimer: Since I got tenure in 2012, my non-tenured co-authors decide where our manuscripts are submitted.

Continued thread

Then we studied recurrent circuits in the #Drosophila larval brain.

By starting bi-directional multi-hop signal cascades at any one cluster, we found that the cluster containing the dopaminergic neurons (DANs) of the centre for associative learning and memory, the insect mushroom body (MB), present the most cascades where the beginning and the end of the cascade is itself!

In other words DANs, which mediate learning, are the most recurrent neurons in the brain.

#neuroscience #connectomics 6/

Continued thread

Next, we explored the #Drosophila larval #connectome with multi-hop signal cascades (left) that extended across synapses up to a depth of 5. We sorted neurons into labelled lines and multisensory (right).

Neurons were considered to receive sensory input when visited in most cascade iterations.

The majority of brain neurons integrate from all sensory types, but a few neurons integrated from only one sensory modality (labelled line) or from a combination.

#neuroscience #connectomics

5/

Continued thread

Having split the #Drosophila larval brain #connectome into 4 types of edges, hierarchical spectral clustering defined about 90 groups of neurons.

Remarkably, clusters defined by connectivity alone were internally consistent for other features, such as neuron morphology or function.

Clusters were sorted from sensory neurons (SNs) to descending neurons (DNs) using the Walk-Sort algorithm. To the right, example clusters with intracluster morphological similarity score using NBLAST.

4/

Continued thread

Our analysis of the #Drosophila larval brain starts by recognizing that neurons are polarized: 95.5% of all brain neurons present clearly segregated axons and dendrites.

In the #connectome, we found 66% axo-dendritic synapses, 26% axo-axonic, 6% dendro-dendritic and 2% dendro-axonic.

This matters because inputs onto dendrites contribute to the integration function of a neuron; inputs onto an axon modulate its output. Analysing them separately makes sense.

#neuroscience #connectomics 3/

3,013 neurons, half a million synapses: the complete #connectome of the whole #Drosophila larval brain!

Winding, Pedigo et al. 2022. "The connectome of an insect brain" biorxiv.org/content/10.1101/20

We’ve mapped and analysed its circuit architecture, from sensory neurons to brain output neurons, as reconstructed from volume electron microscopy, and here is what we found. 1/