Final Report Summary - CIRCUIT (Neural circuits for space representation in the mammalian cortex)
The project has used a combination of state-of-the-art technologies for investigating brain circuits at the intersection between anatomy, physiology, and molecular biology. In the first part of the project, we determined the intrinsic connectivity of the stellate-cell network in the MEC. This network was found to differ from other cortical circuits in that connections are almost exclusively inhibitory, via local interneurons. This network organization was found in a computational model to be sufficient to generate hexagonal firing in a network with attractor properties.
A second part of the project showed that the progressive expansion of grid scale along the dorsoventral axis of the entorhinal cortex is not continuous but rather organized into discrete levels of grid spacing. Individual modules of grid cells were differently affected by geometric features of the environment. The discrete topography of the grid-map, and the apparent autonomy of the modules, differ from the graded topography of maps for continuous variables in several sensory systems, raising the possibility that the modularity of the grid-map is a product of local self-organizing network dynamics. The findings have important implications for understanding the overall network organization of grid cells and point to an attractor mechanism for grid formation.
A third finding deals with the cellular basis of the topographic expansion of grid scale between the dorsal (upper) and ventral (lower) ends of the long axis of the entorhinal cortex. We found that the scale of grid cells, i.e. the distance between the firing locations, is critically dependent on a certain ion channel. We show that the HCN1 subunit of the mammalian h channel is necessary for normal scaling. The findings identify h currents as essential for the mechanism by which movement signals are transformed into spatially periodic signals. The study is probably the first to relate grid activity to a specific molecule in the nervous system.
Finally, a viral vector-based approach has been developed to express light-sensitive ion channels specifically in cells that project between the entorhinal cortex and the hippocampus. These cells can be identified by applying light within the brain, above the entorhinal cortex. The project shows that multiple functional cell types in the MEC – grid cells, border cells, and head direction cells – connect directly with the place-cell circuit in the hippocampus. The findings have major implications for the mechanisms for place-cell formation in the hippocampus.
The major aims of the project have been reached, although a few additional papers are still in the pipeline.