Time from context transition controls SignalNE when mice are moved to novel arenas. A) Histological confirmation of GRABNE expression (GFP) and fiber placement over dorsal CA1. B) Schematic of experimental timeline. C) Example session showing increases in SignalNE around each context and homecage (HC) transition. D) Mean SignalNE measured across all transitions (black) and cross-validated prediction from the saturated model (red) or a reduced model lacking terms related to time from transfer (blue). E) Change in CVMSE due to removal of various potential behavioral variables. Only removal of the terms related to time from transition significantly decreased model performance (t(7) = 3.30, p = 0.01).

Time from context transition controls SignalNE when mice are moved to a linear track. A) Example session showing SignalNE (black) aligned with acceleration (red) and reward delivery (·). Vertical gray lines show that local peaks in SignalNE do not align to bouts of acceleration nor reward timing. Shaded area shows last 60s before removing from track during which SignalNE was not modeled. B) Mean SignalNE measured across all linear track transitions (black) and cross-validated prediction from the saturated model (red). C) Change in CVMSE due to removal of various potential behavioral variables. Only removal of the terms related to time from transition significantly decreased model performance (t(7) = 7.20,p = 0.0008).

Time from object introduction controls SignalNE A) Photographs of five novel objects presented to the mouse. B) Example session showing SignalNE (black) aligned object introduction (dashed line) and object sampling (·). C) Mean SignalNE measured across all object presentations (black) and cross-validated prediction from the saturated model (red). C) Change in CVMSE due to removal of various potential behavioral variables. Only removal of the terms related to time from object introduction significantly decreased model performance (t(5) = 3.54, p =0.017).

Novel objects do not affect NE dynamics after transfer to a familiar linear track. A) Mean SignalNE across experimental sessions when the track was baited with a novel object (black); control sessions were run without new objects (red). B) Estimated τ describing SignalNE decay after moving to the linear track did not change in the presence of a novel object (t(4) = 1.47, p = 0.22). C) Change in CVMSE due to removal of various potential behavioral variables. Only removal of the terms related to time from linear track transfer significantly decreased model performance (t(5) = 3.22, p = 0.03).

Experience accelerates SignalNE decay after context transition. A) Mean SignalNE plotted as a function of time from context transition (dashed line) and color coded by number of days of experience. Black trace shows SignalNE recordedafter transitioning back to the home cage (HC). B) Estimated SignalNE derived from the saturated model. C) Parameter estimates for the magnitude (β) and decay rate (τ) of SignalNE after context transition color-coded by days of experience. D) Decay rate (τ) after transfer to the arena hastens over days of exposure (mixed-effect linear model; t(73) = 2.31, p = 0.02) and is most rapid during transfer to the HC (Day N vs HC, all p ≤0.01).

SignalNE is depressed relative to baseline after periods of sustained elevation. A) Mean SignalNE recorded after moving mice back to the home cage from the arena (red) or the linear track (black). B) Same data as Figure 5C with the addition of parameter estimates for the behavior of SignalNE after transition to home cage from the linear track. C) The decrease in SignalNE was significantly larger after transitioning mice to the home cage from the linear track as compared to from the novel arenas (t(5) = 3.74, p = 0.005)

CA1 spatial code takes minutes to stabilize after context transition in novel and familiar spaces. A) Example UMAP embedding of population firing rate vectors (100-ms), color-coded by where the mouse was physically located on a linear track when the data was recorded. B) Same embedding color coded by time from context transfer. C) Representational similarity (Pearson R) of the observed population firing rate vector at each moment in a novel environment relative to the mean of the next 3 most similar vectors recorded in the same location. D) Same as Panel C recorded in a familiar environment. E) In a novel environment, the patterns recorded in the first minute were less correlated than those observed 10 minutes into the session (t(7) = 8.05, p = 0.00009) F) Same as Panel E recorded in a familiar environment (t(7) = 8.20, p = 0.00008). G) Initial representations were more correlated to their nearest neighbors in a familiar environment as compared to those recorded in a novel environment (t(7) = 7.58, p = 0.0001).

Moments immediately after transition are not preferentially replayed. A) Percentage of ripples recorded before (black) and after (red) experiencing a novel environment that showed significant reactivation of each moment after transition. Dashed line shows false positive (FP) rate. B) Moments recorded 10-11 minutes after novel context transition were more likely to be reactivated than those recorded 0-1 minutes after transition (t(7) = 2.46, p = 0.04). C) Same as Panel C showing reactivation rates as a function of time after transition to a familiar environment. D) There is no difference in reactivation rate for early vs late moment in a familiar environment (t(7) = 0.40, p = 0.70).

Validation of GRABNE sensor and behavioral correlates of SignalNE.A) SignalNE increases after injection of desipramine. B) The normal increase in SignalNE after context transition is eliminated after injection with yohimbine. C) Fluctuations in behavior as a function of time after context transition. D) Time series correlations (Pearson R) in independent behavioral variables used to predict SignalNE. E) SignalNE plotted as a function of different behavioral variables. F) SignalNE plotted as a function of mouse position in each of the novel arenas. G) SignalNE plotted for each mouse as a function of time around rearing (data for one subject was not available).

No change in SignalNE due to acceleration nor reward delivery on a linear track. A) Mean SignalNE plotted as a function of acceleration conditioned on time after transition. B) No change in SignalNE after reward delivery (dashed line).

SignalNE is related to object introduction, not sampling. A) Observed mean SignalNE around each object’s introduction. B) Estimated fits derived from the saturated model. C) Mean ± SEM point estimates for the increase (β) and decay (τ) in SignalNE around introduction of each object. D) Mean observed SignalNE around each object sample.

Change in behavior across days. Change in A) acceleration, B) velocity, C) propensity to rear, and D) distance to the edge across day 1 (D1) and day 2 (2) in the novel arena.

Time from context transfer explains SignalNE in the home cage. A) Change in CVMSE due to removal of various potential behavioral variables. Only removal of the terms related to time from home cage track transfer from the arena significantly decreased model performance, (t(7) = 2.62, p = 0.03) B) Same as Panel A with transitions to the home cage from the linear track (t(5) = 4.44, p = 0.007)

CA1 activity decorrelates faster in the first minute after transfer to a novel, but not familiar, environment. A) Population vector correction plotted as a function of lag (note log scale) during Minute 1 (black) or Minute 10 (blue) after transfer to a novel environment. Bar = p<0.01. B) The decay rate of the autocorrelation was significantly steeper in the first minute of exposure (t(7) = 3.07, p =0.018). C) Same as Panel A with data recorded in a familiar environment. D) No difference in ACG decay rates during the minute 1 vs minute 10 of exposure to a familiar environment (t(7) = 0.50, p =0.63).

Variations in velocity and acceleration do not explain time-dependent changes in nearest-neighbor (NN) representational similarity. A) Deviations in z-scored firing rates from the mean place field activity in a novel environment. Top, firing rates within a place field increased over time. Bottom, out-of-field firing decreased over time. B) Same as Panel A with data recorded in familiar environments. C) At each moment after transitioning to a novel environment, we identified another 100-ms time bin with the most similar neural representational and calculated the absolute difference in velocity (|Δvel|NN) and acceleration (|Δacc|NN) recorded at these times. As compared to Figure 7C, neither |Δvel|NN nor |Δacc|NN co-varies with time as did the measure of representational uniqueness. D) Same as Panel C recorded after a transition to a familiar environment. E) Only removing time from transition decreased ability to predict NN representational similarity, t(7) = 3.52, p = 0.01. F) Same as panel E, recorded in a familiar environment, t(7) = 3.12, p = 0.017. G) In a novel environment, the patterns recorded in the first minute were less correlated to others captured in the same recording session than those observed 10 minutes into the recording (t(7) = 5.23, p = 0.001). H) Same as Panel G recorded in a familiar environment (t(7) = 5.60, p = 0.0008).