Hippocampal functional organization: A microstructure of the place cell network encoding space

•The functional neuronal organization of hippocampus is thought to be non-topographic.•Using Zif268, we observed a cluster-type organization in dorsal CA1 and CA3 fields.•Recordings within the Zif268 clusters confirmed these to be place cells.•Blockade of glutamatergic NMDAR resulted in a disruption of the Zif268 clusters.•We propose a cluster-type hippocampal organization to encode all types of memories. A clue to hippocampal function has been the discovery of place cells, leading to the ‘spatial map’ theory. Although the firing attributes of place cells are well documented, little is known about the organization of the spatial map. Unit recording studies, thus far, have reported a low coherence between neighboring cells and geometric space, leading to the prevalent view that the spatial map is not topographically organized. However, the number of simultaneously recorded units is severely limited, rendering construction of the spatial map nearly impossible. To visualize the functional organization of place cells, we used the activity-dependent immediate-early gene Zif268 in combination with behavioral, pharmacological and electrophysiological methods, in mice and rats exploring an environment. Here, we show that in animals confined to a small part of a maze, principal cells in the CA1/CA3 subfields of the dorsal hippocampus immunoreactive (IR) for Zif268 adhere to a ‘cluster-type’ organization. Unit recordings confirmed that the Zif268 IR clusters correspond to active place cells, while blockade of NMDAR (which alters place fields) disrupted the Zif268 IR clusters. Contrary to the prevalent view that the spatial map consists of a non-topographic neural network, our results provide evidence for a ‘cluster-type’ functional organization of hippocampal neurons encoding for space.