Figure 2. The entorhinal-hippocampal circuit, MEC grid cells, and LEC object + reward cells.

A, Diagram of the major connections of the mouse entorhinal-hippocampal circuit. The hippocampus receives information from the neocortex and sends information to it through the entorhinal cortex (EC). The medial entorhinal cortex (MEC) and the lateral entorhinal cortex (LEC) project to CA1 through the perforant and temporoammonic paths. In the perforant path, axons of layer 2 (L2) reelin-expressing (RE+) stellate cells (MEC) and fan cells (LEC) converge on the same population of cells in the dentate gyrus (DG) and CA3, but project to distal and proximal dendrites, respectively. This mixed information in DG and CA3 is conveyed to CA1 via mossy fibers and Schaffer collaterals. By contrast, EC layer 3 (L3) pyramidal cells and calbindin-expressing (CB+) MEC layer 2 (L2) pyramidal cells form the temporoammonic pathway. Pyramidal cells in MEC largely project to proximal CA1 (prox), whereas layer III cells in LEC project to distal CA1 (dist). Output from CA1 is conveyed directly to the EC layer 5 (L5) cells, or via the subiculum. CB+ L2 pyramidal cells in the LEC, as well as L5a cells in the MEC and LEC form output axonal projection to various cortical areas, whereas L5b neurons form recurrent projections in the EC.

B, In vivo electrophysiological recording of MEC grid cells in rodents. MEC Layer 2 single neurons were recorded using an implanted recording device having multiple tetrodes targeting the MEC. Spike activity was recorded for ~20 minutes while animals ran throughout an open field behavioral enclosure. Firing rate map was generated by calculating spike counts divided by time visited by the animal in each small spatial bin. Grid cells show equilateral triangular grid patterns with different spacings (grid cells #1, #2 and #3).. Modified from [18, 30, 31].

C, In vivo electrophysiological recording of LEC object + reward cells. For selectively recording LEC L2 RE+ fan cells, a cell-type-specific optogenetic-assisted electrophysiological recording technique was used [106]. Mice were trained in an odor object-reward associative memory task. When an odor (for example, banana odor) was paired with sucrose water reward, LEC L2 RE+ fan cells started to show enhanced firing, as depicted schematically in the single-neuron recording trace (top panel). By contrast (lower panel), this neuron came to exhibit decreased firing to an odor (for example, pine odor) paired with bitter quinine water. When fan cell activity was optogenetically inhibited, mice were no longer able to learn the associative memory task, indicating that LEC odor + reward cells support object memory. Modified from [49].