iiinova — where your digital self keeps evolving

Reposted by Paul Kristian LaFosse

Miguel Nunez @nunezkant.bsky.social · 26/05/2026

1/ 🚨🚨Preprint alert! "Perfect" isn't always smart 🧠. Anyone can tell apart two stimuli (including our mice). But how do we extract rules that apply to new stimuli? 🧵 biorxiv.org/content/10.6... @marius10p.bsky.social @computingnature.bsky.social #neuroAI #neuroscience #AI

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Paul Kristian LaFosse @lafosse.bsky.social · 15/05/2026

Huge thanks to all involved, including @ Janelia (jET/Vivarium/MolGen/Viral Tools), MBF, and our collaborators for the amazing viruses/mice! @sverregr.bsky.social, @klensj.bsky.social, @mariannefyhn.bsky.social, Tony Drinnenberg, Charu Ramakrishnan, @deisseroth.bsky.social, and those at Allen /end

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Paul Kristian LaFosse @lafosse.bsky.social · 15/05/2026

While there are tradeoffs to using raster photostim (e.g. no simultaneous activation like holo photostim), we hope this tool helps to simplify and increase access for others wanting to do all-optical experiments, especially at a large-scale/across different brain regions! 7/n

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Paul Kristian LaFosse @lafosse.bsky.social · 15/05/2026

To enable large-scale expts in vivo, we relied on SOTA viral/transgenic strategies from our collaborators to express GCaMP and super-sensitive ChRmine opsin across the cortex. This allowed us to photostim ~1,000+ neurons across a 3.5 mm FOV using a two-photon mesoscope! 6/n

top left: example 3.5 mm two-photon FOV with photostimulation-evoked responses in targeted neurons; top right: average response timecourses for targeted neurons showing activation at the time of stimulation, and response decaying afterwards; bottom: histograms of responses in targeted neurons, shuffled responses of targeted neurons, and non-targeted neurons, showing strong and specific activation across 5 mice.

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Paul Kristian LaFosse @lafosse.bsky.social · 15/05/2026

Similarly, raster photostimulation could be used at a much smaller scale to target individual dendrites or groups of dendrites of a single neuron. 5/n

2p image of a single example neuron with suite2p-segemented dendrites and soma; segments are combined to create a photostimulation mask covering the dendrites and soma; evoked fluorescence on a fluorescein slide showing accurate targeting of the dendrites and soma

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Paul Kristian LaFosse @lafosse.bsky.social · 15/05/2026

With raster photostim, we can perform photostim experiments at a large scale, for example by targeting thousands of neurons in a single pattern and updating those patterns on a frame-by-frame basis. 4/n

large-scale suite2p recording example with 32,000 neurons detected; 4 pattern of 10,000 neurons are defined; patterns stimulated on successive imaging frames show cell-specific evoked fluorescence on a fluorescein slide

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Paul Kristian LaFosse @lafosse.bsky.social · 15/05/2026

Our solution: instead of a complex/separate optical path, we route our ⚡ ️laser through the same resonant-scanning path as the imaging laser and simply turn it on/off over neurons/areas of interest. This allows for pixel-resolution accuracy, and ability to ⚡ ️anywhere in the FOV you can image. 3/n

photostimulation mask over 5mm FOV of text excerpt, with photostimulation-evoked fluorescence showing precise stimulation below

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Paul Kristian LaFosse @lafosse.bsky.social · 15/05/2026

We were driven by a desire to easily ⚡️ large groups of neurons to study computations requiring coordinated activity across the 🧠 Tools exist to photostim select patterns of neurons, e.g. holographic stim, but these can be a bit restrictive; both in # of neurons, but also in setup/maintenance. 2/n

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Paul Kristian LaFosse @lafosse.bsky.social · 15/05/2026

🚨 Ever wanted a simple way to control the activity of thousands of neurons? We introduce an all-optical raster photostimulation method to do just that! w/ @computingnature.bsky.social @marius10p.bsky.social #FluorescenceFriday #neuroskyence www.biorxiv.org/content/10.6... 1/n

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Reposted by Paul Kristian LaFosse

Mark Histed @markhisted.org · 14/03/2026

My travel to Cosyne was barred by the Trump admin, so I'm here on my personal dime. I care about the COSYNE community, I committed to co-chairing. And I always learn here. But the worst part about this travel ban is my lab colleagues— students and fellows—couldn't come. /1

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Reposted by Paul Kristian LaFosse

Mark Histed @markhisted.org · 11/03/2026

Headed to @cosynemeeting.bsky.social ! We have a poster, and I'm speaking at a workshop on mech interp and the brain. Poster (Fri): "Patterned input creates new functional subnetworks in the cortex, gated by acetylcholine." From Haleigh Mulholland and @lafosse.bsky.social. Hope to see ppl there!

Friday, March 13th
[2-098] Patterned input creates new functional subnetworks in the cortex, gated by acetylcholine
Posters

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Reposted by Paul Kristian LaFosse

Carsen Stringer @computingnature.bsky.social · 12/02/2026

🔬🧠 Releasing the 1.0 version of #Suite2p and THE PAPER w/ @marius10p.bsky.social! Now with GPU acceleration. Want to use Suite2p but don’t have 100,000 neuron recordings? We show you how to get those with a standard 2p microscope #neuroscience #imaging #neuroAI www.biorxiv.org/content/10.6...

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Reposted by Paul Kristian LaFosse

Mark Histed @markhisted.org · 12/01/2026

Addgene gave our lab at #NIH the Blue Flame Award for making a plasmid requested at least 100 times by other scientists. It's a bicistronic stable opsin-GCaMP8s pair for pattern stim. Congrats to @lafosse.bsky.social, Z Zhou, and B Akitake who led this work. 🥳🥳 Addgene

Blue Flame Award
The blue flame is a symbol used on our website to designate plasmids that have been requested more than 100 times.

The Blue Flame Award, first distributed in 2016, serves to congratulate researchers who have at least one plasmid deposited at Addgene that has been distributed more than 100 times.

The list below denotes the depositing labs who have the most highly requested plasmids. Currently, there are more than 950 depositors worldwide who have one or more blue flame plasmids. Interested in depositing with Addgene? Learn more about our Plasmid Deposit Process.

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Reposted by Paul Kristian LaFosse

Mark Histed @markhisted.org · 19/11/2025

Our lab had a poster at the #SFN2025 meeting in San Diego, but the #NIH people were not able to attend. I wanted to call in Haleigh Mulholland, postdoctoral fellow (2nd pic). Haleigh was a major driver behind this project, and I encourage anyone with questions to reach out to her. /1

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Session PSTR025 - Visual System: Plasticity and Repair
PSTR025.14 / K8 - Pattern-specific plasticity in visual cortex is gated by acetylcholine
Add to Itinerary
November 15, 2025, 1:00 PM - 5:00 PM SDCC Halls B-H
Presenter at Poster
Sat., Nov. 15, 2025 2 - 3:00 p.m.
Session Type
Poster
Grant Support
NIH BRAIN Initiative Grant U19NS107464
Grant Support
NIMH Intramural Research Program ZIAMH0020967
Citation
*P. K. LAFOSSE1, H. N. MULHOLLAND2, Z. ZHOU2, M. H. HISTED2;
1Janelia / HHMI, Ashburn, VA; 2Natl. Inst. of Mental Hlth., NIH / NIMH, Bethesda, MD. Pattern-specific plasticity in visual cortex is gated by acetylcholine. Program No. PSTR025.14. 2025 Neuroscience Meeting Planner. San Diego, CA. : Society for Neuroscience, 2025. Online.
Authors
*P. K. LAFOSSE1, H. N. MULHOLLAND2, Z. ZHOU2, M. H. HISTED2;
1Janelia / HHMI, Ashburn, VA; 2Natl. Inst. of Mental Hlth., NIH / NIMH, Bethesda, MD
Disclosures
P.K. LaFosse: None. H.N. Mulholland: None. Z. Zhou: None. M.H. Histed: None.
Abstract
To navigate the world, animals must readily adapt to new sensory information. In the cortex, this information is represented as dynamic patterns of activity across networks of neurons, which are refined with learning. The classic Hebbian theory of learning posits that coactivated neurons become functionally coupled via synaptic strengthening, possibly enabling network computations useful for behavior such as pattern amplification. However, recent work shows that photostimulation of neurons alone without behavioral engagement is not sufficient to induce plasticity (Akitake, Douglas et al., 2023), suggesting plasticity may require both neuronal coactivation and neuromodulatory signals. Acetylcholine (ACh), involved in arousal and attention and broadly released throughout the cortex, plays an important role in learning and may gate this form of behavior-dependent plasticity in neural circuits (Gold, 2003; Kang et al., 2014). To test this, we aimed to …

Haleigh Mulholland, was not able to attend

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Reposted by Paul Kristian LaFosse

Mark Histed @markhisted.org · 07/11/2025

Sigh. NIH normally sends several hundred scientists to the SFN annual meeting to learn, exchange info, come up with new ideas, and advance science. (The exchange of ideas is the very core of the scientific enterprise.) This year, no one from NIH will attend due to the gov't implosion.

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Reposted by Paul Kristian LaFosse

Mark Histed @markhisted.org · 25/09/2025

The brain is incredibly densely connected. Human cerebral cortex may have as many as *one trillion* connections. Most of those cortical connections are recurrent, inside each area. What do they do? New paper from me in Annual Reviews: 🧪 🧠📈 1/ www.annualreviews.org/content/jour...

annualreviews.org

Active Filtering: A Predictive Function of Recurrent Circuits of Sensory Cortex | Annual Reviews

Our brains encode many features of the sensory world into memories: We can sing along with songs we have heard before, interpret spoken and written language composed of words we have learned, and reco...

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Reposted by Paul Kristian LaFosse

Mark Histed @markhisted.org · 12/03/2025

Thank you very much @hhmijanelia.bsky.social and @hhmi.org for inviting me to give a seminar! That talk was supposed to be today, Tues Mar 11th. I would have talked about @lafosse.bsky.social's work on neural activation functions (con't below)... But I had to cancel due to the NIH travel ban. 🧪 1/

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