mteb/BrightProPsychologyRetrieval huggingface dataset:
**a** ) Schematic of the experiment. Nine mice were habituated to the
apparatus and running on the ball for several days. On the day of the
experiment, some mice were exposed to a virtual environment and spatial
navigation task, while others remained in the dark as on previous days.
Approximately 3.5 h after the start of behavior, brains were harvested,
followed by staining for Fos expression. **b** ) Representative histology
images for Fos staining and corresponding atlas plate (reproduced, with
permission, from Franklin and Paxinos   79
.") ). Red
boxes indicate approximate locations of enlarged image regions on the right.
RSP, retrospenial; SSP, somatosensory; DG, dentate gyrus. **c** ) Number of
Fos-positive cells in 200 x 200 µm regions-of-interest (Methods). Error bars
indicate mean ± s.e.m. n = 4 control mice and 4 exposed mice (2 with slices
containing SSP). p = 0.046 (DG), p = 0.010 (CA1), p = 0.062 (RSP), p = 0.82
(SSP); two-sided _t_ -test.
2. Ee-Lynn Yap
###   Source Data Extended Data Fig. 8
###  Position decoder
See also Figure S5.
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Beyond the relationships to place coding, our work investigates the activity
patterns that drive Fos expression in the hippocampus during behaviour and
examines a causal role for Fos in regulating the overall activity levels of
neurons   10 .") ,  17 .") ,  53 .") . During spatial navigation, Fos is induced
most strongly in cells with higher total calcium influx and long-duration
calcium transients, and removal of Fos results in longer calcium transients.
While these results may be due to differences in the underlying spiking
activity, future work will be needed to characterize how the number, rate and
pattern of spikes differ between these groups. It is possible that Fos
operates in a negative-feedback loop to regulate a cell’s overall activity
levels, whereby higher activity drives Fos induction and Fos then acts to
restrict the type of activity that led to its induction.
In addition, the place fields of Fos-KO cells were significantly less stable
than those of their wild-type neighbours (Fig.  5i
 ). The lower stability in Fos-KO cells
was specific to the unrewarded parts of the track (Fig.  5i
 ), in line with the finding that the
biggest difference in stability between Fos-high and Fos-low cells was at
locations away from the reward site. Together, the results for Fos-high and
Fos-KO cells show that Fos expression is associated with stable maps that are
mostly spatially unbiased and span the entire track. By contrast, cells with
low Fos induction or disrupted Fos function have stable place fields only near
the reward site and thus do not form stable maps of the entire track.
Therefore, these results define a strong relationship between Fos expression
and the neural ensembles that make up stable and spatially uniform maps. While
we did not test the necessity or sufficiency of these neurons in spatial
memory, the organization of these ensembles as sequences of place cells that
are stable across days matches the expected form of a neural population
underlying an engram for spatial memories.
The effects in Fos-KO cells were notably consistent across sessions, although
the magnitude of the differences between Fos-KO and wild-type cells was
relatively small and probably a substantial underestimate of the role of Fos
in place cell coding. It would have been ideal to compare Fos-KO and wild-type
cells using just the Fos-induced (that is, Fos-high) population. However,
because of the already complicated loss-of-function mouse genetics, we were
unable to additionally incorporate the _Fos_ -transgenic reporter into these
neurons to allow us to identify cells within the wild-type population with
high Fos induction as in the experiments from Figs.  1
 and  2
 . As a result, given that Fos induction
tends to be relatively sparse, most of the wild-type cells probably would not
have induced Fos in the first place. Thus, we could not directly compare the
two relevant populations, namely wild-type cells with high Fos induction and
Fos-KO cells that would normally have induced a high level of Fos. Together,
these factors are expected to result in a substantial undermeasurement of the
effect of Fos expression in place cell coding. It is therefore remarkable that
we were able to observe consistent effects from loss of Fos from session to
session, implying a robust role for Fos in hippocampal place codes.
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###   Reporting Summary
To examine the stability of place fields across days, we tracked the same
cells across multiple sessions, with sessions typically occurring on
consecutive days (Fig.  5a,b  ). The
place fields in Fos-high cells tended to be stable and present at similar
locations on subsequent sessions, whereas the place fields in Fos-low cells
tended to disappear or shift in their location across sessions (Fig.  5b,c
 ). To quantify this observation, we
computed spatial stability maps based on the across-day similarity of place
fields (Fig.  5d  ). Fos-high neurons
exhibited higher stability in their place code (Fig.  5e
 ). Fos-high cells had similar stability
across all locations on the track, whereas Fos-low cells were most stable near
the reward zone (Fig.  5e  ). As a
result, the largest difference in stability between Fos-high and Fos-low cells
was in the unrewarded part of the track (Fig.  5f–h
 ). This result is consistent with our
earlier finding that Fos-high neurons more uniformly tile the track than Fos-
low cells, which are enriched at the reward site (Fig.  2e
 ).
Acute slice preparation was carried out as previously described   24
.") . Mice aged 4–5 weeks were anaesthetized by
ketamine/xylazine injection and transcardially perfused with ice-cold
oxygenated (95% O  2  /5% CO  2  ) choline-based artificial cerebrospinal
fluid (choline-ACSF) consisting of (in mM) 110 choline chloride, 25 NaHCO  3
, 1.25 NaH  2  PO  4  , 2.5 KCl, 7 MgCl  2  , 25 glucose, 0.5 CaCl  2  , 11.6
sodium  l  -ascorbate and 3.1 sodium pyruvate. Transverse 300-μm hippocampal
slices were prepared from both hemispheres using a vibratome (Leica, VT1000).
The dorsal hippocampal slices were collected in a holding chamber containing
oxygenated ACSF consisting of (in mM) 127 NaCl, 25 NaHCO  3  , 1.25 NaH  2  PO
4  , 2.5 KCl, 1 MgCl  2  , 10 glucose and 2 CaCl  2  . The slices were then
incubated at 32 °C for 20 min followed by 30 min at room temperature before
recordings. Recordings were carried out at room temperature. For all
solutions, pH was set to 7.2 and osmolarity was set to 280–290 mOsm.
where _a_ group  is the activity of all cells in the group being used for
decoding, _C_ is the normalization constant, _τ_ is the temporal bin size of
one frame (one-thirtieth of a second), _N_ is the total number of cells and
for each cell _f_ _i_ (pos) is the spatially binned activity template and _a_
_i_ is the activity on the frame. The bin with the maximum posterior
probability was selected as the decoded position on that frame. To compare
decoder performance across cell groups, equally sized groups were used for
decoding. For Fos-GFP imaging experiments, a decoder was trained and tested on
each induction decile group independently. Fos-low and Fos-high decoding
performance was the average performance of deciles 1–2 and 9–10, respectively.
To compare Cre  \+  and wild-type groups, the number of cells used for
decoding was selected on the basis of the size of the smaller cell group, with
a minimum of 10 cells up to a maximum of 100 cells used for decoding. Each
group was then randomly downsampled to this number of cells, and the decoder
was trained and tested using these equally sized populations. The
downsampling, training and testing procedure was repeated 100 times, and
decoder performance was averaged for each group across these repetitions.
Sessions were only included if they contained at least ten cells in the
smaller cell group. The code for the naive Bayes’ decoder was modified from
code available on the Buzsaki laboratory’s GIT repository ( 
https://github.com/buzsakilab/buzcode 
).
\(2018\).") (version 3.3.2). No statistical method was used to predetermine sample size. Sample sizes in terms of mice, sessions and neurons are similar to those in other contemporary studies in the field   16 .") . For in vivo imaging experiments, comparisons were made between simultaneously recorded neurons within mice that were subjected to the same experimental conditions; randomization across subjects and blinding to experimental conditions were not necessary and did not take place during calcium imaging experiments or analysis. During manual classification of Cre  \+  cells, the experimenter did not have access to information about the activity or functional properties of the cells. For manual cell counting of labelling with anti-Fos antibody, the experimenter was blinded to mouse identity and experimental group during both brain region ROI selection and cell counting (see ‘Histology’). For hypothesis testing, we used permutation shuffle tests, two-sided paired-sample _t_ tests and two-sided two-sample _t_ tests, showing both individual data points and difference histograms when possible. In Fig.  1i  , representative images are shown from one session of the 27 sessions in 6 mice that were analysed in Fig.  1j–n  . In Fig.  3b  , representative images (cropped from the full field of view for the purposes of visualization) are shown from one mouse of the 6 mice analysed in Fig.  3  . In Fig.  5a  , two representative fields of view are shown from one mouse of the 6 mice analysed in Fig.  5  .
For each mouse, a reference session was chosen for alignment (approximately
halfway between the first and last days of imaging, to maximize similarity to
other imaging sessions). All sessions were registered with the reference
session using non-rigid alignment on the mean jRGECO1a images (NoRMCorre)  
65 .") . Source masks were transformed using this alignment to place all
source masks for a mouse into a common reference space. CellReg   69
.") (a distance model) was used on these aligned images to
match cell IDs across different sessions.
###  Classification of Fos-KO cells
The characteristics of Fos-expressing cells we describe here point to a link
between the cognitive map theory of hippocampal function   1
.") ,  2 .") —a
framework for describing how spaces are encoded by the activity of neurons—and
contextual memory encoding, which the hippocampal engram has been most shown
to support  7  ,  8  ,  9 .") . Fos expression, which is often used to define hippocampal
engrams, seems to be specifically related to the encoding of place, rather
than the encoding of features of the animal’s behaviour or valence (in this
case, reward). In addition, the correlated activity among Fos-high neurons is
suggestive of an ensemble of functionally interconnected cells, a feature of
engrams that has been proposed   4 .") to support recall of
an entire environment or experience from the synchronous activation of just a
few neurons. Finally, the stable and spatially uniform maps formed by Fos-
expressing neurons could act as a contextual reference for memory formation
and recall. Because the same cells induce Fos on repeated days, these cells
are involved in multiple experiences that take place in the same context   18
.") ,  41 .") . Such a map that is invariant
to specific experiences and stable over time could act as a general spatial
reference participating in multiple episodic memory engrams that share a
common environmental context.
Despite roles for engram neurons and place cells in hippocampal memories,
remarkably little is known about the relationship between these cells, in part
because of the difficulty in relating Fos expression to preceding neural
activity patterns during behaviour   5 .") ,  11 .") ,
17  ,  18  ,  19  ,  20  ,  21 .") and
because hippocampal Fos-expressing neurons have not been extensively
characterized in typical spatial learning paradigms used to study place cells.
We therefore sought to clarify the neural activity patterns that drive Fos
expression in the hippocampus of mice performing a spatial memory task.
###   Extended Data Fig. 9 Spike-evoked calcium influx and
electrophysiological properties of Fos-KO and wildtype neurons.
Data are available from the corresponding authors on request.  Source data
 are provided with this paper.
###   Source Data Extended Data Fig. 1
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3. Michael E. Greenberg
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We therefore tested whether Fos expression has a causal role in regulating
hippocampal place codes. Previously, we have shown that, of the seven
partially redundant members of the Fos family of transcription factors, Fos,
FosB and JunB are substantially more inducible in the hippocampus, and removal
of these three members effectively disrupts the function of the Fos
transcription factor complex   24 .") . We therefore used a
triple-conditional knockout mouse line to ablate Fos, FosB and JunB and
limited this knockout to only a small fraction of imaged neurons.
Specifically, we injected a low titre of adeno-associated virus (AAV) encoding
Cre recombinase fused to GFP into CA1 of _Fos_ _fl_ / _fl_ ; _Fosb_ _fl_ /
_fl_ ; _Junb_ _fl_ / _fl_ mice (Fig.  3a,b
 ). We identified knockout cells
(hereafter referred to as Fos-KO cells) on the basis of appreciable Cre
expression measured by GFP fluorescence. We have previously shown   24
.") that expression of Cre, but not a catalytically inactive
control, leads to excision of all three genes, permitting identification of
effects specific to the disruption of Fos function. Approximately 20% of cells
were Fos-KO cells (mean, 22.5%; range, 11.2–31.5%). We chose to disrupt the
function of Fos in only a subset of cells because it is advantageous to
compare Fos-KO cells to neighbouring wild-type cells side by side in the same
session, thus controlling for any variability across sessions and mice.
Moreover, this approach allows for identification of the cell-autonomous
effects of Fos and eliminates confounds of network-level effects that may
arise from global disruption of Fos.
###   Extended Data Fig. 5 Spike-evoked calcium influx and
electrophysiological properties of Fos-expressing neurons.
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To quantify the degree to which mice remembered and licked selectively near
the reward zone, we compared licking in an area 10 cm immediately before the
start of the reward zone (where mice exhibited anticipatory licking) to an
equally sized area on the opposite side of the track (100 cm removed, not
associated with reward). Licking selectivity was defined as the difference in
the number of licks within each of these zones divided by their sum: (licks
pre-reward  – licks  unrewarded  )/(licks  pre-reward  \+ licks  unrewarded
). Licking selectivity ranges from −1 to 1, with 1 indicating licking only in
the pre-reward zone and 0 indicating chance levels. All analysis was performed
on stable performance sessions, defined as the first session in which mice
reached a licking selectivity of 0.6 and any sessions thereafter. Learning
sessions (Fig.  1c  ) were defined as the
first three sessions in the environment, regardless of performance (not
exclusive with stable performance sessions).
https://doi.org/10.1101/2021.10.21.465345
###  Two-photon imaging
Further information on research design is available in the  Nature Research
Reporting Summary  linked to this
article.
In addition, using the entire population of neurons, we clustered cells on the
basis of their correlations with other cells, as calculated above (Fig.  4c
 ). Each cluster was a group of cells that
had highly correlated activity with one another, regardless of their place
field locations. Fos-high neurons were more likely to reside in the same
cluster than Fos-low neurons, further indicating that Fos-high cells are a
population with substantially higher activity correlations with one another
(Fig.  4f  ). Together, these results
demonstrate that Fos-high cells form ensembles with highly correlated
activity.
The authors declare no competing interests.
###  Subjects
To examine the neural activity patterns that are potentially responsible for
induction of Fos, we expressed the red-shifted calcium indicator jRGECO1a in
Fos-GFP reporter mice. Using two-photon imaging, we monitored neural activity
as calcium transients (Extended Data Fig.  4
 ) in hundreds of CA1 neurons with
cellular resolution as mice performed the behavioural task for approximately
30–60 min and quantified GFP expression from the Fos-GFP reporter for each
session as described above (Fig.  1f–i 
). When we refer to neural activity, we are quantifying significant ∆ _F_ /
_F_ calcium activity, not spiking or inferred spiking activity (Extended Data
Fig.  4  and  Methods
 ). Within each session, we compared
simultaneously imaged neurons from the same field of view that had differing
levels of Fos induction, with a focus on the cells with the 20% highest (Fos-
high) and 20% lowest (Fos-low) fold induction. This side-by-side comparison of
Fos-high and Fos-low cells from the same session allowed us to eliminate
variability in behavioural performance and calcium indicator expression that
occurs when comparisons are performed across animals and sessions.
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###  Place cell definition
###  Surgery: cannula implantation
##  Peer review
62. Ulivi, A. F. et al. Longitudinal two-photon imaging of dorsal hippocampal CA1 in live mice. _J. Vis. Exp._  https://doi.org/10.3791/59598  (2019).
4. Christopher D. Harvey
Table 1
Statistics for Figure 1
Motion correction of jRGECO1a calcium imaging movies was performed offline
using a custom MATLAB pipeline (available at 
https://github.com/HarveyLab/Acquisition2P_class
 ) as previously described
 63 .") ,  64 .") . Motion correction accounted for non-rigid deformations taking
place on subframe, full-frame and minute-long timescales. GFP stacks were
registered in MATLAB using non-rigid registration (NoRMCorre)   65
.") for frames
within each plane, followed by an fast Fourier transform (FFT)-based rigid
registration across planes. Stacks were aligned to the imaging plane using the
red channel, and GFP planes out of plane with the imaging target plane were
discarded from further analysis.
###   Extended Data Fig. 7 Calcium activity and place coding properties of
Fos-high and Fos-low cells during virtual navigation in the absence of a task.
###   Source Data Extended Data Fig. 10
Article  Open access  13 March 2024
36. Evans, S. W. et al. A positively tuned voltage indicator reveals electrical correlates of calcium activity in the brain. Preprint at _bioRxiv_  https://doi.org/10.1101/2021.10.21.465345  (2021).
###   Neural and behavioural state switching during hippocampal dentate
spikes
(R) Closed-Door bridge indices in all sessions.
###  Place field stability analyses
###  Fos induction measurements
* ###   Large-scale recording of neuronal activity in freely-moving mice at cellular resolution
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###   Source Data Fig. 1
##  Stable place maps in Fos-high ensembles
###  Quick links
Next, we asked whether there are differences in the place coding properties of
Fos-high and Fos-low neurons. As expected, during the task, many of the cells
in CA1 had activity that was significantly modulated across the track and
formed place fields (Fig.  2a,b  ).
Although place cells could be found in both the Fos-high and Fos-low
populations, Fos-high cells were more likely to be place cells than Fos-low
cells (Fig.  2d  ). Fos-high cells also
had higher spatial information than Fos-low cells, measured as the normalized
mutual information between a cell’s activity and the mouse’s location, which
is independent of our place field definition (Fig.  2c,d
 ). Fos-high place fields tended to be
wider than Fos-low place fields (Extended Data Fig.  6a,b
 ). Notably, Fos-high and Fos-low place
cells exhibited distinct distributions of their place fields across the track,
with Fos-low place fields enriched near the reward zone and Fos-high place
fields mostly uniformly distributed across the track and even showing a slight
bias away from the reward zone (Fig.  2e,f
 ). Fos-high cells also had more reliable
calcium transients from trial to trial, measured as the correlation in
activity for pairs of trials during a session (Fig.  2g
 ). Moreover, Fos-high cells had activity
within their place field on a larger fraction of trials than Fos-low cells
(Fig.  2h  ).
Given the strong correlation between Fos expression and spatial coding, we
wondered whether Fos expression may causally shape CA1 activity and place
codes. The place cell activity we measured on each day arose before Fos
induction on that day, suggesting that the more reliable and spatially
informative activity seen in Fos-high place cells may drive induction of Fos
expression. However, we noticed that from session to session a similar set of
cells had high Fos induction   39 .") (Extended
Data Fig.  6i–k  ), raising the
possibility that Fos induction from the previous day could contribute to the
reliability and accuracy of spatial coding in place cells on the subsequent
session.
###   Source Data Extended Data Fig. 2
_Nature_  ** volume  609 ** ,  pages  327–334 (  2022  )  Cite this
article
* ###   Putting memories in their place
78. Yatsenko, D., Walker, E. Y. & Tolias, A. S. DataJoint: a simpler relational data model. Preprint at _arXiv_  https://doi.org/10.48550/arXiv.1807.11104  (2018).
###   Extended Data Fig. 1 Muscimol-based inactivation of CA1.
Article  Open access  20 March 2024
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(C) Proportion of fields within 25 cm of a door.
###   Extended Data Fig. 6 Place field size of Fos-high and Fos-low cells,
position decoding and spatial information in activity-matched Fos-high and
Fos-low populations, and consistency of Fos induction across stable
performance sessions.