Figure 4.

Mouse model of depressionChAT-p11 cKO shows differential projections to NAc ChIs. (A) Representative images of projection neurons labeled with RV-GFP in MO-VO region of the prefrontal cortex, DR, and vHIP in ChAT-CRE and ChAT-p11 cKO mice lines. The injections were designed to infect a small number of cells to allow optimal quantification of projecting neurons. (B) Quantification of GFP+ cells in MO-VO, DR, AMY, and vHIP regions showed significantly different number of cells only in vHIP region between ChAT-CRE control (333.0, n = 5) and ChAT-p11 cKO (152.0, n = 5) PVal = 0.0317; Mann–Whitney t test. (C) Low-magnification image of ventral hippocampus showing CaMK2a-ChR2 (H134R)—eYFP infection CA1 and subiculum pyramidal neurons. (D) Differential interference contrast image showing the area from NAc where we recorded from ChI and MSN neurons. (E) Representative traces of tonic firing of ChI neurons from control (CTR) and p11 KO mice and histograms quantifying the firing frequency of recorded neurons from each genotype, * PVal = 0.0499, Kolmogorov–Smirnov test (n = 10 neurons/4 mice for CTR and 8/3 for p11 KO). (F) Pie chart showings the percentage of CTR and p11KO ChI neurons that responded to ChR2 stimulation of vHIP terminals in NAc and representative paired-pulse (100 ms interstimulus) traces in response to ChR2 field light stimulation. (G and H) Histograms showing the amplitude of the first response (gE) and the paired-pulse ratio at 100 ms interstimulus (H) in response to ChR2 field light stimulation of NAc in CTR and p11KO ChI neurons. (I) Pie chart showings the percentage of CTR and p11KO MSN neurons that responded to ChR2 stimulation of vHIP terminals in NAc and representative paired-pulse (100 ms interstimulus) traces in response to ChR2 field light stimulation. (J and K) Histograms showing the amplitude of the first response (J) and the paired-pulse ratio at 100 ms interstimulus (K) in response to ChR2 field light stimulation of NAc in CTR and p11KO MSN neurons.

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