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Research ArticleResearch Article: New Research, Cognition and Behavior

Forebrain Glucocorticoid Receptor Overexpression Alters Behavioral Encoding of Hippocampal CA1 Pyramidal Cells in Mice

Swapnil Gavade, Qiang Wei, Colin Johnston, Savannah Kounelis-Wuillaume, Klaudia Laborc, Salisha Baranwal, Huda Akil and Joanna L. Spencer-Segal
eNeuro 23 November 2022, 9 (6) ENEURO.0126-22.2022; https://doi.org/10.1523/ENEURO.0126-22.2022
Swapnil Gavade
1Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI
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Qiang Wei
1Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI
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Colin Johnston
1Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI
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Savannah Kounelis-Wuillaume
1Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI
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Klaudia Laborc
1Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI
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Salisha Baranwal
1Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI
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Huda Akil
1Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI
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Joanna L. Spencer-Segal
1Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI
2Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI
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  • Figure 1.
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    Figure 1.

    A, Schematic showing AAV5-CamKlla-Gcamp6f injection, lens implantation, and calcium imaging in open field arena steps for the experiment. B, Histology demonstrating GCamp6f expression in dorsal CA1 pyramidal cells. White arrows delineate the lower lens border. C, Representative frame from calcium imaging recording after applying spatial filtering. D, Behavior of each mouse in the experiment including total time spent in the center, velocity during the entire trial, and velocity (cm/s) in the periphery and center. E, Increased immunolabeling for GR in the CA1, dentate gyrus, and cortex of representative male WT and GRov mice.

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    Figure 2.

    A, Example traces from five cells in one mouse during open field exploration. Yellow areas show when the mouse was in the center of the open field. B, Example distributions of the ratio of calcium event rate in high/low mobility behavior bins for each neuron in original and shuffled data. Vertical dotted lines show thresholds for 1% (green line) and 99% (red line) of the distribution based on the shuffled data within genotype. C, D, Example traces of one center cell and one high mobility cell. Red line shows animal velocity (cm/s), while the highlighted yellow region shows when the animal was in the center. Blue line shows the calcium amplitude.

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    Figure 3.

    Bar graphs show the fraction of CA1 pyramidal cells out of total registered CA1 pyramidal cells (N = 1359) sensitive to center location (A, C) and mobility (B, D) based on calcium amplitude measure (A, B) or event rate measure (C, D).

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    Figure 4.

    Graph shows the percentage of mobility-sensitive and location-sensitive neurons based on calcium amplitude (A, B) and event rate (C, D). A, C, Total number of mobility-sensitive cells (“total mobility cells”) based on each measure, and then these populations are broken down into high and low mobility cells. B, D, Total number of center-sensitive cells (“total location cells”), and then these populations are broken down into center and periphery cells. *p < 0.05 compared with WT. Extended Data Figure 4-1 shows that the statistical results were similar when compared using χ2 or Fisher’s exact test.

  • Figure 5.
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    Figure 5.

    Venn diagrams show the percentage of all behavior-sensitive neurons sensitive to each behavior, with the overlap representing cells with sensitivity for both mobility and center location. + represents high mobility cells, – represents low mobility cells; CS = center cells, PS = periphery cells. Extended Data Figure 5-1 shows the overall fraction of mobility-sensitive cells calculated using only data when mice were in the periphery.

  • Figure 6.
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    Figure 6.

    Venn diagrams for each genotype show the percentage of all behavior-sensitive neurons sensitive to each behavior, with the overlap representing cells with sensitivity for both mobility and center location, separately for neurons of each genotype. + represents high mobility cells, – represents low mobility cells; CS = center cells, PS = periphery cells.

  • Figure 7.
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    Figure 7.

    Fraction of uniquely low mobility (–), high mobility (+), center and periphery cells in WT and GRov as a percentage of the total cells. These cells showed sensitivity to either center location or mobility without overlap. *p < 0.01.

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    Figure 8.

    Distribution of the change in average calcium activity in the precenter bin (1 second before mouse entered into center location) from average calcium activity in the rest of the periphery bin for all center cells in the total population (A) and separately for WT (B) and GRov (C). Density on the y-axis indicates the number of cells with the given change in calcium amplitude. Most cells had a negative change in calcium amplitude, suggesting an anticipatory increase in activity just before the mouse entered the center. D, E, Two different neural activity patterns of center selective cells with anticipatory neural activity (D) and without anticipatory neural activity (E) when the mouse spent at least 5 s in the center.

Extended Data

  • Figures
  • Extended Data Figure 4-1

    p-values from χ2 and Fisher’s exact statistical tests to compare percentage of mobility-sensitive and location-sensitive cells between genotypes. A, Statistical tests for calcium amplitude measure. B, Statistical test for event rate measure. Download Figure 4-1, EPS file.

  • Extended Data Figure 5-1

    Figure shows overall fraction of mobility-sensitive cells out of all cells only when mice were in the periphery. A, B, Fraction of mobility selective cells based on calcium amplitude and event rate, respectively. C, Fraction of mobility-sensitive cells in WT and GRov based on calcium amplitude. Download Figure 5-1, EPS file.

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Forebrain Glucocorticoid Receptor Overexpression Alters Behavioral Encoding of Hippocampal CA1 Pyramidal Cells in Mice
Swapnil Gavade, Qiang Wei, Colin Johnston, Savannah Kounelis-Wuillaume, Klaudia Laborc, Salisha Baranwal, Huda Akil, Joanna L. Spencer-Segal
eNeuro 23 November 2022, 9 (6) ENEURO.0126-22.2022; DOI: 10.1523/ENEURO.0126-22.2022

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Forebrain Glucocorticoid Receptor Overexpression Alters Behavioral Encoding of Hippocampal CA1 Pyramidal Cells in Mice
Swapnil Gavade, Qiang Wei, Colin Johnston, Savannah Kounelis-Wuillaume, Klaudia Laborc, Salisha Baranwal, Huda Akil, Joanna L. Spencer-Segal
eNeuro 23 November 2022, 9 (6) ENEURO.0126-22.2022; DOI: 10.1523/ENEURO.0126-22.2022
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Keywords

  • CA1
  • glucocorticoid
  • hippocampus
  • miniScope
  • open field

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