El Duvelle NeuroFeb 19, 2025

#NeuroESC #JournalClub
Reading Mental exploration of future choices during immobility theta oscillations

If you've read it, will you let me know what you think?

The authors look at #ThetaSequences in a working memory task in a radial arm maze. They find theta during immobility (makes sense, e.g. we saw that in our two-goals task). They also find that theta sequences might preferentially represent the next goal (also makes sense, e.g. Hippocampal theta sequences reflect current goals)!

I have only done a quick reading so far, but am confused by a few points:

Let me know what you think!

#LeutgebLab #NeuroRat #Neuroscience #SpatialCognition

Mental exploration of future choices during immobility theta oscillations

Mental exploration enables flexible evaluation of potential future choices, guiding decision-making without requiring direct real-world iterations. Although the hippocampus is known to be active while imagining the future, the precise mechanisms that support mental exploration of future choices remain unclear. In the hippocampus, the theta rhythm (4-12 Hz) is prevalent during movement and supports memory coding during real-world exploration by organizing neuronal activity patterns into short virtual path segments (theta sequences) around the ratā€™s location. We observed these theta-related neural activity patterns during movement in a hippocampus-dependent working memory task and also, unexpectedly, theta oscillations and theta-related neural activity during immobility. Compared to standard theta sequences during movement, theta sequences during immobility differed in that they occurred at a shifted theta phase and preferentially represented remote locations, in particular the next choice in the working memory task. Coding for future locations was also observed during awake sharp wave ripple, but these short-lasting events occurred rarely and were biased toward frequently visited locations. Therefore, our findings suggest that recurring bouts of theta oscillations during immobility, which are also observed in primates and humans, support the cognitive demands of mental exploration in the hippocampal network and facilitate ongoing predictions of future choices. ### Competing Interest Statement The authors have declared no competing interest.

bioRxiv
Show threadRedish LabDec 17, 2024

@elduvelle_neuro

2/2

Importantly, not preplay, which occurs before any experience, but shortcuts, which occur after experience and allow the animal to learn the connectivity of the map.

One of the useful things lost in the publication is that Gupta et al 2010 (http://www.cell.com/neuron/abstract/S0896-6273(10)00060-7) and Gupta et al 2012 (http://www.nature.com/neuro/journal/vaop/ncurrent/abs/nn.3138.html) are the same data. 2010 is #SharpWaveRipples and 2012 is #ThetaSequences. What's cool is that the theta segments the task, while SWRs link those segments together.

El Duvelle NeuroDec 17, 2024

A short commentary by the great Anna Gillespie on awake replay:

Ruminating on replay during the awake state

#GillespieLab (https://www.gillespie-lab.com/)

Interesting bits:

"replay during sleep is generally thought to occur in the forward direction"

I believe this is true too, but has anyone actually analyzed it? It could be done on several existing datasets...

"The idea that awake replay might serve a planning role was broadly adopted by the field, even though direct experimental evidence [...] has been slow to emerge"

YES because replay is not related to immediate planning, however nice it would be if it was

"We, as a field, also need to be more precise with our terminology. For instance, what exactly should we consider evidence of ā€˜planningā€™ or ā€˜deliberationā€™ in an animal model? "

YES

Related: history of the 'genesis' of #ThetaSequences narrated in this retrospective by @adredish: Mental Time Travel: A Retrospective
(original post:
https://neuromatch.social/@adredish/113662497894186335) #RedishLab

I'd actually argue that replay, and not theta sequences, might be closer to mental time-travel... but we probably don't know enough about either to be sure yet!

#Neuroscience #HippocampalReplay #Hippocampus

Ruminating on replay during the awake state - Nature Reviews Neuroscience

In this Journal Club, Anna Gillespie discusses how the discovery of hippocampal replay during the awake state reshaped our understanding of its role in memory function.

Nature
Eleonora RussoOct 23, 2024

šŸ“¢ New work on the Integration of rate and phase codes by hippocampal cell assemblies to support the encoding of spatiotemporal context
https://www.nature.com/articles/s41467-024-52988-x

It was a pleasure to work with Nadine Becker, Aleks P. F. Domanski, Timothy Howe, Kipp Freud, @DurstewitzLab, and Matt Jones.
@SantAnnaPisa @BristolNeurosci @zi_mannheim @BernsteinNetwork
#Neuroscience #Hippocampus #ThetaSequences #PlaceCells

Integration of rate and phase codes by hippocampal cell-assemblies supports flexible encoding of spatiotemporal context - Nature Communications

Russo et al. show that context-specific place cell assemblies support hippocampal integration of past experiences into future plans during goal-directed behavior and propose a biophysical mechanism behind the formation of goal dependent theta sequences.

Nature
El Duvelle NeuroOct 11, 2024

#JournalClub on Closed-loop modulation of remote hippocampal representations with neurofeedback, from #FrankLab: little summary + comments.

  • The goal is to see if rats can deliberately reactivate internal representations, without external cues.
  • The authors design a closed-loop system that does clusterless real-time decoding of position and rewards the rats when they reactivate a specific maze arm end.
  • The rats go through a gradual training process: first getting reward on the actual maze (a T-maze), then getting reward in the home box when they orient towards the target arm of the maze [head-direction task], then getting reward in the home box when they reactivate the representation of the target maze end [neurofeedback task].
  • The rat's performance is not too bad given the difficulty of the task, kudos to Rat2 who seemed to really know what he was doing.
  • interestingly, the reactivations do not happen during #SharpWaveRipples, and not really during theta either, just during an uncharacterised LFP state.
  • Little caveat 1: as far as I can see, the head-direction of the rats is not shown in any plot and it is not possible to say if the rats might still be doing the head-direction task during the neurofeedback task. That being said, the rats clearly reactivate the target arm more in the neurofeedback than head-direction task, which is quite convincing.

  • Little caveat 2: the performance is always shown in terms of total rewards collected, and not reward rate. So in different sessions rats might reach the maximum reward but take twice the time. Showing reward rate would be more informative.

  • conclusion: this is pretty cool, but we would really need to know about the head-direction.

  • question for the audience: what do you think the rats "think about" during those reactivation moments??

#Neuroscience #HippocampalReplay (not really) #ThetaSequences (not really) #PlaceCells #NeuroRat #Hippocampus

El Duvelle NeuroMay 27, 2024

@Andrewpapale I thought that too but I think #ThetaSequences tend to be much shorter, and are generally (always) relatively local no? While the example on the left here definitely looks like a replay sequence..

In any case, itā€™s certainly something to rule out and Iā€™m sure the reviewers will ask them to exclude high theta power periodsā€¦

Show threadEl Duvelle NeuroFeb 25, 2024

@thetransmitter
Oh yes - like this (#Hippocampal #ThetaSequences):
https://m.youtube.com/watch?v=IU8wKl5PcLU

Or this (#HippocampalReplay):
https://m.youtube.com/watch?v=q0kD2RSejRo

(source: #vanDerMeerLab)

Sonification of hippocampal ensemble activity during experience

YouTube
Show threadRedish LabNov 21, 2023

@elduvelle_neuro @BenoitGirard @Raphael_Brito

A few notes.

1. Remember that even the #SharpWaveSequences that Pfeiffer and Foster 2013 [https://pubmed.ncbi.nlm.nih.gov/23594744/] saw going ahead of the animal is a very very small proportion. (Home was twice as likely as the other 35 options. So it's 2/37 vs 1/37 or an increase of 2.7%. ) Still real. But small. Also, lots of people have seen #SWRSequences go to places rats are not going to go. (Such as Gupta et al 2010 [https://pubmed.ncbi.nlm.nih.gov/20223204/], where it was more likely to go to the other side if the animal was NOT going there next - perhaps "keeping the map flat"?)

2. We know that in Wikenheiser and Redish 2016 (https://pubmed.ncbi.nlm.nih.gov/25559082/), #ThetaSequences on the first part of the journey go longer when the rat is going to run longer (where start of journey is same, but distance from rat to goal varies), but on the last part of the journey, the sequences are the same length (when start of journey is different, but distance from rat to goal is the same).

3. We also know that both time of second half of theta and sequences go longer the more time it will take to reach the goal. (Schmidt and Redish 2019 [https://pubmed.ncbi.nlm.nih.gov/30892976/]).

4. That all being said, @elduvelle_neuro is correct that on two-alternative-forced-choice tasks (2AFC) #ThetaSequences while deliberating do not reflect the final choice made in any way we've been able to detect, and that when they do (such as in Johnson and Redish 2007 [https://pubmed.ncbi.nlm.nih.gov/17989284/] or Kay...Frank 2020 [https://pubmed.ncbi.nlm.nih.gov/32004462/]) the rat does not seem to be deliberating anymore.

My suspicion is that this may be because of the 2AFC structure of the task, where knowing you don't want to go one way is just as informative as saying you want to go the other way. We are now starting to try to develop tasks with multiple paths to goals (so not 2AFC). @elduvelle_neuro 's cool star-shaped task is a good one for this. As are a bunch of the cool new hex tasks from the Loren Frank lab that were presented at #SFN2023 this year.

Hippocampal place-cell sequences depict future paths to remembered goals - PubMed

Effective navigation requires planning extended routes to remembered goal locations. Hippocampal place cells have been proposed to have a role in navigational planning, but direct evidence has been lacking. Here we show that before goal-directed navigation in an open arena, the rat hippocampus gener ā€¦

PubMed
Show threadEl Duvelle NeuroNov 21, 2023

@BenoitGirard @Raphael_Brito Nicely said! #ThetaSequences are where Iā€™ll look next actually :) However, Iā€™m not fully sure theyā€™ll be predicting the behaviour, and @adredish would probably tell you that they donā€™t, earlier in training (even if the rat ends up deciding where to go), and when they do later in training the rat is already automatizedā€¦ see also work from the #JadhavLab.

On the other hand (and do correct me if Iā€™m missing something) Iā€™m not sure that anyone has looked at theta sequences in a place / allocentric task, so maybe weā€™ll see the hippocampus doing something different in that case!

Show threadEl Duvelle NeuroNov 5, 2023

@edeno cool thanks! Putting some screenshots for illustration.. it definitely seems like a lot of events happen at the choice point, but strangely, most if not all of the replay examples shown in the paper are from the reward locations.

Also, as you say, it is not clear that those events were during SWRs and not theta - the theta/delta ratio around ā€œreplaysā€ does seem quite similar to the rest of behaviour... it would have been nice if they had made this figure separately for reward vs choice point events. Actually they even say that their choice point events could be similar to @adredish ā€˜s #VTE activity, which is definitely #ThetaSequences. šŸ¤”

(For reference, here is the paper:
Awake replay of remote experiences in the hippocampus)

Awake replay of remote experiences in the hippocampus - Nature Neuroscience

Hippocampal replay is thought to be essential for the consolidation of event memories. Sleep replay involves the reactivation of stored representations in the absence of specific sensory inputs, whereas awake replay is thought to reflect input from the current environment. Here the authors find that the hippocampus consistently replays past experiences during brief pauses in waking behavior, suggesting a role for waking replay in memory consolidation and retrieval.

Nature