Final take-home: experience reorganizes population activity in visual cortex to reflect how visual information unfolds over time.
Beautiful work led by Lily Kramer.
doi.org/10.64898/202... /end

On a personal note, Lily joined our lab as a tech right after college & lucky for me joined us in Chicago for her PhD. Watching her raw curiosity, talent, & drive evolve into an exceptional scientist who will use her education to make this world better has been a joy.

I will always be a fan. 10/

Together, these findings show that experience reorganizes the geometry of visual population activity to reflect temporal structure. Big novelty responses transform into organized representations that reflect how visual stimuli fit in context. 9/

During active practice of self-selected routines that encompass a sequence of decisions, experience also increased the extent to which task-relevant variables are represented orthogonally.

Population activity more clearly distinguished features relevant for guiding behavior. 8/

Experience passively viewing image sequences made temporal position more linearly decodable from V4 population activity.

Temporal structure becomes more explicitly represented with experience. 7/

Across all three experiments, experience constrained population responses toward a typical activity pattern. But that constraint didn’t reduce information content. It reorganized it.
6/

Many studies show that repeated experience reduces firing rates in visual cortex. That signal is useful for detecting novelty, but it does not capture how populations represent temporal relationships.

We asked how experience with temporal structure changes the geometry of population activity. 5/

Lily recorded neuronal populations in area V4 across contexts that varied in temporal structure and behavioral relevance:

• repeated presentation of single images

• passive exposure to structured image sequences

• repeated execution of self-directed action sequences for reward
4/

Visual experience can make different things familiar: an image (view from your window), a sequence of images (scenes along a daily route), or a sequence of visually guided actions (walking the same way to work each day).

Lily asked how these shape population representations. 3/

ALT:

Something special about Lily as a scientist is that she wants both general principles about how things fit together and a deep understanding of each piece.

So of course she designed, ran, and analyzed THREE experiments comparing how different forms of experience shape population responses. 2/

More new results, this time from the amazing Lily Kramer! 🎉
“Sequential experience reshapes population representations in visual cortex” doi.org/10.64898/202...
Visual experience unfolds in time. We asked how temporal structure reshapes population activity in visual cortex.
🧪🧵1/

Thank you, Jay! That means a lot to me.

Thank you, Jenni!

Thanks so much, Nicole!

Thanks, Yasmine!

Also, I am sorry for all of the black rectangles in this post. I tried to do alt text and failed. I would like to think that my science is better than my social media prowess.

Thanks for reading this far. We would be very grateful for your thoughts and feedback! www.biorxiv.org/content/10.6... /end

a magnifying glass shows the word thank you in black ALT: a magnifying glass shows the word thank you in black

This work is so multifaceted. The diverse expertise of our coauthors and contributors was absolutely essential. Drew, Ram, Gio, Devon, Danielle, Sean, Kayla, Carissa, Scott, Jeff, thank you. 17/

This would not have been possible without John Morrison at the CNPRC. Our foundation is his transformative animal models, especially by @daniellebeckman.bsky.social and ongoing work by www.linkedin.com/in/devon-gri... And he provided space & scientific home for Doug. Amazing. 16/

a dog is sitting on a couch with the words thank you thank you thank you ALT: a dog is sitting on a couch with the words thank you thank you thank you

Doug began working with us 5 months after I started the lab (and 3 days before the birth of my first child – not an easy start!). The impact he’s had on me and on the past, present, and future of our lab cannot be overstated. Gratitude is too small a word. 15/

This was a massive collaborative effort led by @douglasruff.bsky.social. He set up a satellite lab, designed & juggled a hugely complex experimental paradigm, did these experiments day in and day out for 2 years, & sorted through an enormous pile of data to find the diamonds. 14/

This project was a real change for our lab. It grew out of curiosity-driven work on how neuronal population activity relates to behavior.

It is a reminder, at least for me, that work like that can lead to something that matters for human lives, even if the path is not obvious at the start. 13/

Approaches that connect levels of analysis in this way are not always easy to execute.

But they can change what we are able to see, measure, and potentially treat. 12/

If I'm being honest, this attempt to tightly integrate fundamental and translational neuroscience went even better than I hoped.

Studying neuronal population activity did not just explain behavior. It revealed a coherent description of early disease that we believe can impact people’s lives. 11/

So early Alzheimer’s is characterized by a breakdown in coordinated neuronal activity, expressed behaviorally as disorganization rather than failure. We think coordination is a scale invariant property that can link molecules, cells, circuits, populations, networks, behavior, and beyond. 10/

We also asked whether this state is modifiable. We previously showed that methylphenidate (Ritalin) reshapes population coordination, so as proof of principle, we tried it.

It caused a transient improvement in behavioral organization! 9/

Neuronal population activity changed with the same time course. We found progressive reductions in coordinated activity within and between visual and parietal cortices. Single-neuron tuning remained stable.

So the early change isn't cell death or information loss, but a loss of coordination. 8/

Visual exploration was more erratic and less principled, reward-based foraging was more random, there were more early eye movements, and behavior became harder to predict from the structure of the task and stimuli.

This is not failure. It is disorganization. 7/

A key behavioral result:
task performance remained largely intact,
but behavior became less organized. 6/

To do this, we longitudinally tracked visually guided behavior, multi-area neuronal population activity, and fluid and histological biomarkers in a model of early-stage disease. 5/