(((Dr Hannah Wirtshafter))) 🔬

New preprint out 🎉

What happens to the hippocampal “place code” when an animal is actively engaged in a task?

The answer surprised us (and might surprise you too!).

Let's dive in ⬇️

Link:
"Hippocampal trace coding dominates and disrupts place coding"
https://www.biorxiv.org/content/10.64898/2026.02.17.706430v1

Hippocampal trace coding dominates and disrupts place coding

The hippocampus is widely viewed as a spatial mapping system because many CA1 neurons show location-specific activity during exploration. However, the hippocampus is also required for non-spatial learning, including trace eye-blink conditioning. Because most prior reports of non-spatial signals were obtained in immobile animals, it has been proposed that the hippocampus encodes space during locomotion and non-spatial variables during immobility. To test this directly, we used calcium imaging to record thousands of CA1 neurons while rats performed trace eye-blink conditioning during free exploration of an open field. Across more than 6,000 neurons from five rats, mean firing rates during trace-conditioning periods were ∼1.5-fold higher than during non-trial periods, and this difference persisted after controlling for locomotor speed. At the single-cell level, task-related modulation was widespread and strongly biased toward increased firing. Task-enhanced neurons outnumbered spatially selective neurons by more than threefold, indicating that trace coding predominated over place coding. Although trace-conditioning events occurred at random spatial locations and during continuous locomotion, trace-related activity remained robust at both single-cell and population levels. In contrast, spatial coding was reduced during trace periods, with lower spatial information and decreased similarity between task and non-task rate maps. These findings show that during active behavior, trace coding dominates and disrupts place coding, challenging the view that the hippocampus functions primarily as a stable spatial map. ### Competing Interest Statement The authors have declared no competing interest. National Institute of Mental Health, https://ror.org/04xeg9z08, K99 MH135062 National Institute of Neurological Disorders and Stroke, https://ror.org/01s5ya894, R01 NS113804/NS/NINDS National Institute on Aging, T32-AG020506/AG/NIA, R37-AG008796/AG/NIA

bioRxiv
Feb 20 at 6:56pmWeb
Show thread(((Dr Hannah Wirtshafter))) 🔬Feb 20

This builds directly on our (heavily) revised manifold paper:

Conserved hippocampal population geometry supports task generalization
https://www.biorxiv.org/content/10.1101/2024.10.24.620127v6

Together, they argue that task engagement can shift the dominant population structure in CA1 -- even during navigation.

Conserved hippocampal population geometry supports task generalization

How learning generalizes across contexts is a fundamental question in neuroscience, as successful behavior often requires transferring acquired knowledge to new environments. Conditioning tasks provide a clear example of such generalization, with learned responses rapidly expressed across distinct spatial contexts. A central challenge in understanding the neural basis of this ability is determining how the hippocampus represents task-related information across environments, given that its spatial representations remap with context. Here, we used calcium imaging to record hippocampal population activity as rats performed a conditioning task across multiple spatial contexts. To characterize task-related population structure, we applied dimensionality reduction and alignment methods to construct low-dimensional manifolds of hippocampal activity. We found that task-related population activity occupied a stable geometric structure across contexts, despite pronounced remapping of spatial representations. Strikingly, this task-related geometry was conserved not only across contexts within individual animals but also across animals, revealing a shared organization of task representations in the hippocampus. These findings provide a population-level account of how task-related information is preserved across changing spatial environments and suggest that hippocampal task representations follow shared population-level geometric organization across individuals. ### Competing Interest Statement The authors have declared no competing interest. National Institute of Mental Health, K99 MH135062 National Institute on Aging, R37 AG008796/AG/NIA National Institute of Neurological Disorders and Stroke, R01 NS113804/NS/NINDS

bioRxiv
Show thread(((Dr Hannah Wirtshafter))) 🔬Feb 20

When non-spatial responses show up, they’re often interpreted as place field gating or arousal.

But most of that work was done in immobile or restrained animals.
But our rats were freely moving the whole time, and the task was administered at random times and locations

Show thread(((Dr Hannah Wirtshafter))) 🔬Feb 20

During task performance we saw two big things happen:

3× more neurons increased event rate to the task than were spatially tuned
Spatial reliability dropped significantly

The task didn’t just get pasted on top of the spatial map.
It shifted the dominant population structure.

Show thread(((Dr Hannah Wirtshafter))) 🔬Feb 20

And no, this wasn’t speed.
And yes, animals were running during the trace window.
And no, task activity wasn’t confined to place fields.
And no, task activity wasn’t restricted to ripple/sitting states.

The signal survived all of that.

Show thread(((Dr Hannah Wirtshafter))) 🔬Feb 20

At the population level, task–task similarity > everything else.

Task periods put CA1 into a distinct state.

And this wasn't a small modulation, it was a large-scale reweighting of the code.

Show thread(((Dr Hannah Wirtshafter))) 🔬Feb 20

That raised a deeper question:

If CA1 reorganizes during task engagement,
what shape does that reorganization take?

That’s what our revised manifold paper addresses:

Conserved hippocampal population geometry supports task generalization
https://www.biorxiv.org/content/10.1101/2024.10.24.620127v6

Conserved hippocampal population geometry supports task generalization

How learning generalizes across contexts is a fundamental question in neuroscience, as successful behavior often requires transferring acquired knowledge to new environments. Conditioning tasks provide a clear example of such generalization, with learned responses rapidly expressed across distinct spatial contexts. A central challenge in understanding the neural basis of this ability is determining how the hippocampus represents task-related information across environments, given that its spatial representations remap with context. Here, we used calcium imaging to record hippocampal population activity as rats performed a conditioning task across multiple spatial contexts. To characterize task-related population structure, we applied dimensionality reduction and alignment methods to construct low-dimensional manifolds of hippocampal activity. We found that task-related population activity occupied a stable geometric structure across contexts, despite pronounced remapping of spatial representations. Strikingly, this task-related geometry was conserved not only across contexts within individual animals but also across animals, revealing a shared organization of task representations in the hippocampus. These findings provide a population-level account of how task-related information is preserved across changing spatial environments and suggest that hippocampal task representations follow shared population-level geometric organization across individuals. ### Competing Interest Statement The authors have declared no competing interest. National Institute of Mental Health, K99 MH135062 National Institute on Aging, R37 AG008796/AG/NIA National Institute of Neurological Disorders and Stroke, R01 NS113804/NS/NINDS

bioRxiv
Show thread(((Dr Hannah Wirtshafter))) 🔬Feb 20

In this revised preprint, we show that during trace learning:

- Population activity forms structured trajectories in low-dimensional space
- These trajectories reflect task structure over time
- And they align across days & animals

Show thread(((Dr Hannah Wirtshafter))) 🔬Feb 20

Together, the two papers argue:

CA1 is not simply a spatial map with task signals layered on top.

When a task demands it, temporally structured task coding can dominate -- EVEN during navigation.

In other words, space stops being the hippocampus's organizing principle.

Show thread(((Dr Hannah Wirtshafter))) 🔬Feb 20
The new paper shows that CA1 reorganizes to task demands.
The population geometry paper shows what the organization can do.
Show thread(((Dr Hannah Wirtshafter))) 🔬Feb 20

Thank you thank you thank you to all my coauthors, any and all people who gave feedback, and the NIH FOR SUPPORTING THIS RESEARCH!!

Would love any questions/complaints/feedback :)

Show threadMoritz NegwerFeb 20

@aheadofthenerve Super nice, thanks for this excellent preprint and explainer thread!
If you don't mind me asking, how do you think this switch in population code is triggered? Is it just a change in excitatory input patterns to CA1 that overrides an otherwise active place cell network? Or also a change in neuromodulatory input (e.g. dopaminergic burst or so)?

If ok I'd also add some hashtags for greater reach:
#neuroscience #newpreprint #tootsuite #hippocampus #placecells #invivo

Show threadEl Duvelle NeuroFeb 20

@moritz_negwer

Congratulations @aheadofthenerve!! Looking forward to reading it (but for now I'll rely on your great thread :) )

I would guess that this makes sense with the view that HPC is a multisensory integrator, the shock is just another type of sensory input just like distal cues, self-motion cues etc.? It is a little weird that the hippocampus cares about it if it's happening at random though.. Or is it paired with a predictive cue? I will re-read the thread.

By the way: what is the task?