Mature dentate granule cells show different intrinsic properties depending on the behavioral context of their activation

Abstract

1The dentate gyrus (DG) plays a crucial role in learning, memory and spatial navigation. Only a 2 small fraction of mature dentate granule cells (mDGCs) is active during behavior, while the 3 large majority remains silent. To date, the properties of this active subset of neurons remain 4 61 5 throughout the experiment (see Materials and Methods), received a water reward at the end of 62 the track after successfully traversing the full track length. After receiving a reward at the first 63 reward zone, the mice then turned around for running in the opposite direction to receive the 64 next reward at the end of the track. In the first sessions (up to 8), the mice moved slowly and 65 erratically along the track as they learned the task. By 8-10 sessions, the mice moved 66 consistently back and forth along the track, and they received rewards at increasing rates over 67 time (1.14 ± 0.05 reward/min, n = 8 mice), they ran reliably back and forth along the track, and 68 they slowed down before reaching the track end consistent with learning of the task (Figure 69 1C). 70To analyse the fraction of DGCs activated in the different behavioral contexts (see above), we 71 used a strain of transgenic mice in which the synthesis of fosGFP fusion protein is controlled 72 by the promoter of the activity-dependent immediate early gene (IEG) c-fos (see Materials and 73 Methods). These mice enabled an ex vivo characterization of activated cells with a recent history 74 of elevated activity in vivo (Barth et al., 2004; Yassin et al., 2010) . In VR training conditions, 75 examination of cells expressing fosGFP was performed ex vivo in hippocampal slices obtained 76 shortly after the last training session (about 18-20 sessions, see Materials and Methods).77Quantification of cells expressing fosGFP was performed in the dorsal hippocampus, which is 78 known to play a crucial role in spatial memory (Moser et al., 1993). When mice were 79 maintained in their home cage, a discreet fraction of DGCs (Prox1-positive, Figure 2C) was 80 activated, since they expressed fosGFP (fosGFP + cells) (1.06 ± 0.1% of DGCs, n = 25 slices, n 81 = 6 mice) (see Figure 1D,E, Materials and Methods) . In line with previous observations (Liu 82 et al., 2012; Kirschen et al., 2017; Shevtsova et al., 2017; Stefanelli et al., 2016), we observed 83 a significant higher fraction of fosGFP + cells in the dorsal hippocampus in mice trained in VR 84(1.92 ± 0.16% of DGCs, n = 19 slices, n = 5 mice, p< 0.0001) ( Figure 1D, E). 85 6 We then explored the distribution of fosGFP + cells across the DG in dorsal hippocampus in the 86 different experimental conditions. To address this question, we plotted the localization of 87 fosGFP + cells in DG and investigated their lateral and radial distributions. DG cell layer extends 88 laterally from the upper (suprapyramidal) blade to the lower (infrapyramidal) blade and from 89 the outer layer (near the molecular layer) to the inner layer (near the hilus) in a radial direction 90 (Altman and Bayer , 1990). In order to reliably...

Dentate Granule Cells Recruited in the Home Environment Display Distinctive Properties

“…S. Corby-Pellegrino for heading the animal house facility. Part of this manuscript has been released as a pre-print at Peret et al ( 2019 ).…”