Inhaler recording setup.

<p>Inhaler recording setup.</p

Average accuracy (%) of inhalation flow profile parameter estimation across all flow rates at different SNR levels.

<p>Average accuracy (%) of inhalation flow profile parameter estimation across all flow rates at different SNR levels.</p

Boxplots representing the median, interquartile range and 1.5×interquartile range of regression coefficients.

<p>(A) <i>a</i> and (B) <i>b</i> regression coefficients where *p<0.05 and **p<0.01 corrected for multiple comparisons using Bonferroni correction.</p

Participant information and baseline lung function (mean ± standard deviation).

<p>Participant information and baseline lung function (mean ± standard deviation).</p

Average audio-based flow estimation errors.

<p>(A) <i>Average</i>_<i>error</i>, (B) <i>PIFR</i>_<i>error</i>, (C) <i>IC</i>_<i>error</i> and (D) <i>Tr</i>_<i>error</i> (%) (± standard error). Results are divided into models calibrated using high, medium and low flow inhalation recordings and tested on high, medium and low flow ranges.</p

Navigation preference correlates with the place field assembly distribution.

<p>(A) Spatial distribution of the spikes (colored dots) from the reward loop cells (represented by different colors) recorded from 3 preference group animals and (B) from 3 nonpreference group animals. The straight red line denotes the weighted spatial population vector (SPV) between the southwest (SW) corner at 0° and the northeast (NE) corner at 90°. (C) Spatial distribution from all cells recorded from the same animals from the preference and (D) nonpreference groups, respectively. (E) Weighted SPV (left) for the preference group (<i>n</i> = 10 rats) and the nonpreference group (<i>n</i> = 10 rats), 2-tailed independent <i>t</i> test, <i>t</i>(18) = −6.116, ***<i>p</i> < 0.001; and averaged SPV (right), 2-tailed independent <i>t</i> test, <i>t</i>(18) = −7.283, ***<i>p</i> < 0.001, for reward loop cells. Error bars, mean ± SEM. (F) Weighted SPV (left), 2-tailed independent <i>t</i> test; <i>t</i>(18) = −5.048, ***<i>p</i> < 0.001; and averaged SPV (right), 2-tailed independent <i>t</i> test, <i>t</i>(18) = −5.208, **<i>p</i> = 0.006, for all cells. Error bars, mean ± SEM. (G) Comparison of the weighted SPV (left), <i>n</i> = 10, paired <i>t</i> test; <i>t</i>(9) = 5.043, ***<i>p</i> < 0.001; and averaged SPV (right), <i>n</i> = 10, paired <i>t</i> test; <i>t</i>(9) = 4.331, **<i>p</i> = 0.002 between the reward loop cells and all cells for the preference group. (H) Comparison of the weighted SPV (left), <i>n</i> = 10, paired <i>t</i> test; <i>t</i>(9) = −1.823, <i>p</i> = 0.102; and averaged SPV (right), <i>n</i> = 10, paired <i>t</i> test; <i>t</i>(9) = −1.740, <i>p</i> = 0.116 between the reward loop cells and all cells for the nonpreference group. (I) Correlation between the SW/NE passes ratio and the weighted SPV of the reward loop cells (left), <i>n</i> = 20 rats, Pearson’s <i>r</i> = −0.92, <i>p</i> < 0.001; and all cells (right), <i>n</i> = 20, Pearson’s <i>r</i> = −0.90, <i>p</i> < 0.001. (J) Correlation between the SW/NE passes ratio and the averaged SPV of the reward loop cells (left), <i>n</i> = 20, Pearson’s <i>r</i> = −0.91, <i>p</i> < 0.001; and all cells (right), <i>n</i> = 20, Pearson’s <i>r</i> = −0.75, <i>p</i> < 0.001. <i>Files dataset is available at Figshare public repository in Tsanov 2016 data / Continuous T-maze folder</i> <a href="https://figshare.com/s/b86a9a111353ba04bd32" target="_blank"><i>https</i>:<i>//figshare</i>.<i>com/s/b86a9a111353ba04bd32</i></a> <i>and Tsanov 2017 data / Continuous T-maze CA1 folder</i> <a href="https://figshare.com/s/5c5ba9b2811f3d7b7696" target="_blank"><i>https</i>:<i>//figshare</i>.<i>com/s/5c5ba9b2811f3d7b7696</i></a>.</p

Dopamine signal directs the shift of place field center of mass (COM).

<p>(A) Atlas schematic shows E123T/T159C virus injection in the ventral tegmental area (VTA) of TH::Cre rats with optic fiber and tetrodes implanted in the hippocampal CA1. (B) Baseline recording of a sample place cell. Top left panel represents the animal trajectory with spikes (red dots), top middle panel shows the coordinates of the subsequent laser application (blue dashed lines), and top right panel shows color-coded Bhattacharyya distance metric (bhatt) overlap between the distribution of spikes and the applied light pulses from the subsequent photostimulation session (lower bhatt values mean higher overlap of both distributions). Bottom image shows 3D color-coded firing rate map. Blue line superimposed on the 3D firing map indicates where the laser light was applied. The x-coordinate is indicated with a blue arrow. Note that the overlapping of the 3D place field and the blue line and arrow is least evident during the first baseline recording. (C) First photostimulation session of the same place cell (channelrhodopsin 2 [ChR2]). Top middle panel shows the location of the applied laser light pulses (red dots). (D) Second baseline (baseline 2) and (E) second photostimulation (ChR2 2). (F) 2D color-coded rate maps for the same recordings (B-E). Comparison of the COM (marked with black circle) between the baseline (top), first photostimulation, second baseline, and second photostimulation (bottom). ΔCOM is measured by the change of COM location at the x-y coordinate system. COM and ΔCOM values (cm) are shown for each session on the right. Blue dashed lines indicate the laser application. Note the increasing proximity between the COM and the vertical dashed line. (G) ΔCOM for control (yellow fluorescent protein [YFP], <i>n</i> = 16 cells) and ChR2 (<i>n</i> = 18 cells) groups between the baseline and the first photostimulation, 2-tailed independent <i>t</i> test, <i>t</i>(32) = 2.101, *<i>p</i> = 0.030; second baseline (base 2), <i>t</i>(32) = 3.042, **<i>p</i> = 0.009; second photostimulation, <i>t</i>(32) = 4.184, ***<i>p</i> < 0.001. Error bars, mean ± SEM; **<i>p</i> < 0.01. (H) 3D color-coded raw map (above) and smoothed rate map (below) of the overlap between the delivered light pulses and the place field from the second baseline recording. High overlap is represented by red colors while low overlap is in blue. (I) Ratio of bhatt values of the baseline relative to the first photostimulation session; second baseline, 2-tailed independent <i>t</i> test, <i>t</i>(32) = 2.803, **<i>p</i> = 0.009; second photostimulation session, <i>t</i>(32) = 2.863, **<i>p</i> = 0.007 for YFP (<i>n</i> = 16) and ChR2 (<i>n</i> = 18) groups. Error bars, mean ± SEM. <i>Files dataset is available at Figshare public repository in Tsanov 2016 data addition folder</i> <a href="https://figshare.com/s/b2c6e7a8a0417820720c" target="_blank"><i>https</i>:<i>//figshare</i>.<i>com/s/b2c6e7a8a0417820720c</i></a>.</p

Differential navigation in continuous T-maze.

<p>(A) Behavioral setup of the training sessions for the continuous T-maze. The animals were placed on the starting choice point (marked with a white arrow) and allowed to freely navigate for 12 minutes. Two pellets were continuously positioned at the end of the southwest (SW) corner (reward zone, marked with filled black circle), while no pellets were positioned in the northeast (NE) corner. The acquisition of the task was based on the spatial guiding of both maze geometry (proximal cues) and geometric paper signs on the curtains surrounding the arena (distal cues). The identification of the distal cues was designed in a manner in which approximately half of the animals would rely on them for spatial navigation. During the training sessions, the animals were placed on the starting choice point (marked with a white arrow) and allowed to explore the maze. Direct passes between the SW and NE zones were not rewarded with pellets. The opposite section of the maze was visible for the rats but not accessible. The animals (<i>n</i> = 20 rats) underwent 9 training sessions over 3 days. (B) During the probe session (on day 4), the animals were exposed to a reversed configuration of the maze, in which access to the training T-maze was disconnected. The animals were placed on the starting choice point of the opposite T-maze (marked with a white arrow), while access to the training T-maze was disconnected. In this way, the rats were exposed to the same proximal but opposite distal cues. Two pellets were constantly positioned in both SW and NE corners. We evaluated the direction of the passes from the starting choice point (marked with a white arrow) and the central choice point. (C) Comparison of the ratio of SW to NE passes. Error bars, mean ± SEM, <i>n</i> = 10 rats (preference group), <i>n</i> = 10 rats (nonpreference group), 2-tailed independent <i>t</i> test, <i>t</i>(18) = 6.955, ***<i>p</i> < 0.001. Both groups (the preference and nonpreference groups) had the same training. The chance level of preferential versus nonpreferential navigation was based on the number of passes from the choice points towards each of the corners given the total number of passes; binomial probability values of <i>p</i> < 0.05 indicated preferential navigation. (D) Learning curve of the animals’ navigation during the training sessions. All animals underwent 9 training sessions over 3 days. White bars show the number of passes towards the rewarded SW corner for the first 120 seconds of each recording session, while the grey bars show the number of passes towards the NE corner (with no reward) for the first 120 seconds. Two-way ANOVA, between groups, F_(1,19) = 59.812, <i>p</i> < 0.001, <i>n</i> = 20. (E) Representation of the passes from the preference group rat towards the SW corner (in red) and towards NE corner (in blue) from the central choice point (above) and from the starting choice point (below). (F) Representation of the passes from the nonpreference group rat towards the SW corner (in red) and towards NE corner (in blue) from the central choice point (above) and from the starting choice point (below). The grey lines indicate passes from the corners towards the choice points or direct passes between the reward points. <i>Files dataset is available at Figshare public repository in Tsanov 2016 data / Continuous T-maze folder</i> <a href="https://figshare.com/s/b86a9a111353ba04bd32" target="_blank"><i>https</i>:<i>//figshare</i>.<i>com/s/b86a9a111353ba04bd32</i></a> <i>and Tsanov 2017 data / Continuous T-maze CA1 folder</i> <a href="https://figshare.com/s/5c5ba9b2811f3d7b7696" target="_blank"><i>https</i>:<i>//figshare</i>.<i>com/s/5c5ba9b2811f3d7b7696</i></a>.</p