Finally, Virginia @vmsruetten.bsky.social is now on the job market, ready to expand WHOLISTIC into a larger research program. Any institute will be lucky to hire her.

Thanks to all authors, including Wei Zheng and Guoqiang Yu, Amy Hu, and the Janelia @hhmijanelia.bsky.social and 4DCP communities, Maneesh Sahani, and others.

and with Igor Siwanowicz are working towards whole-body atlases.

Together with Paul Tillberg, we advanced Whole Body Expansion Microscopy to access the subcellular scales of the organism and match cellular dynamics to their molecular substrate,

Combining WHOLISTIC with optogenetics, correlative brain–body dynamics can be tested causally, yielding a topological mapping between brain and body.

and coupled activation of motor circuits and muscle groups, as well as responses in other tissues, including the skin.

visualizes gut peristalsis together with enteric nervous system activity,

skin epithelium (video 100x sped up),

WHOLISTIC reveals many phenomena, including traveling waves along the kidney,

Using pan-cellular calcium sensors, WHOLISTIC simultaneously records activity across all organs of the larval zebrafish - brain, liver, muscle, pancreas, kidney, skin, and more.

Preprint -
Excited to present WHOLISTIC, which extends the concept of whole-brain functional imaging to the entire body. Pioneering work by incredibly talented Virginia Ruetten @vmsruetten.bsky.social, this platform reveals whole-organism cellular dynamics in vivo.
www.biorxiv.org/content/10.1...

We also applied the framework as a screen for a number of other psychoactive compounds. We hope that this will eventually impact our understanding of ketamine’s antidepressant effects in humans

It looks like the brief hyperexcitation of the NE-astroglial system by ketamine changes their cellular properties long-term, affecting behavior and making the animals more resilient to behavioral failures. The next step will be to find out what exactly changes in these cells.

In mouse, Eric Hsu and Dwight Bergles found that astrocytes are also activated during a learned-helplessness type assay, and that ketamine activates mouse astrocytes through NE. The dynamics are similar between mouse and fish.

The surprising thing we found was that, after ketamine caused NE-astroglial hyperactivation, the NE-astroglial system was less sensitive to behavioral failures for at least a day, which explains why fish persevered more. Essentially, behavioral failures are less saliently detected by the brain.

Background from past work: We knew that during normal giving-up behavior, NE activates astrocytes as fish struggle to regain control. After about 20 seconds of this failure integration, astrocytes then activate neurons that shut off swim attempts. Ketamine's effects looked a bit similar. Old movie:

Imaging neurons and astroglia during ketamine exposure showed strong activation of noradrenergic (NE) neurons in the hindbrain. Astrocytes were activated through NE receptors, and for about 20 minutes, were in a hyper-excited state:

Here we found that, also similar to ketamine’s effects on learned helplessness in rodents, a transient dose of ketamine had long-term consequences on this fish behavior, even after the drug was removed: fish gave up less, and persevered more