Figure 1

Optogenetic excitation of GCs and MCs. (a) 3D representation of the mouse brain (Allen Mouse Brain Institute; www.alleninstitute.org) showing recording electrode configuration in the dorsal dentate gyrus of DRD2-Cre and POMC-Cre mice injected with AAV/hSyn-FLEX-Chronos-GFP. (b) Left, scheme showing the location of the hilus and granule cell layer on a coronal section of the hippocampus. Right, layout of recording sites and optic fiber for a shank of the silicon probe and profile of a local field potential dentate spike 2 (LFP DS2). (c) Low-magnification images, confocal images of GFP-virus expression (green) and DAPI staining (blue), together with immune-staining (red) for calretinin (left) and GluR2/3 (middle) in DRD2-Cre and for calbindin (right) in POMC-Cre mice. The rectangles indicate the regions selected for the high-magnification images shown below. High-magnification images, DAPI, GFP and calretinin (or GluR2/3 or calbindin) signals shown separately and merged. (d) Examples of the cell response (raster and peri-stimulus histogram (PSTH)) to light stimuli (473 nm wavelength, ~50 µW amplitude, 100-ms-duration single sine waves), for a light-excited cell (upper) and an unaffected cell (lower) in DRD2-Cre (left) and POMC-Cre (right) mice. (e) Color-coded representations of cell PSTH (left) and spike autocorrelograms (ACGs) (right) for DRD2-Cre (upper) and POMC-Cre (lower) mice. Cells are represented in the rows of the matrices and ordered according to the magnitude of light responses. Red box indicates the light-excited cells, i.e., cells with light response Z-score > 5 (DRD2, n = 49 cells; POMC, n = 25 cells). (f) Average cell ACG for DRD2 (red) and POMC (blue) light-excited cells (line, average; shadow, s.e.m). Note the wider profile of the average ACG for DRD2 light-excited cells. (g) Upper, ACG of a DRD2 light-excited cell and illustration of the measure ACG refractory gap (defined as the duration for the ACG to reach 75% of peak value). Lower, distribution of ACG refractory gap values for DRD2 (red) and POMC (blue) light-excited cells (mean ± s.e.m; DRD2, 15.5 ± 1.2 ms; POMC, 9.8 ± 1.7 ms; p = 0.0055, unpaired t-test). (h) Example of spike waveform and illustration of how spike duration and asymmetry are measured (left) and distribution of spike duration (middle, DRD2, 0.7 ± 0.01 ms; POMC, 0.6 ± 0.03 ms; p = 0.0050, unpaired t-test) and spike asymmetry (right, DRD2, −0.05 ± 0.01; POMC, −0.1 ± 0.02; p = 0.045, unpaired t-test) values for DRD2 (red) and POMC (blue) light-excited cells. (i) Distribution of cell-preferred gamma phases for DRD2 (red) and POMC (blue) light-excited cells.