Space and time: Pathways to understanding high-level brain functions Edvard Moser (NTNU, Kavli Institute for Systems Neuroscience, Trondheim, Norway) PL12
In mammals, location in the environment is mapped by specialized position-coding cell types in entorhinal cortex and hippocampus. These cells include entorhinal grid cells, which are active only when animals are at locations that tile the environment in a periodic hexagonal pattern. Their hexagonal pattern of firing is maintained across environments and between awake and sleep states, suggesting that grid cells collectively form a low-dimensional network representation governed by the intrinsic dynamics of local neural networks more than by sensory inputs. The nature of the representation thus provides important clues about underlying mechanisms of the grid pattern. I will proceed to ask how entorhinal networks, consisting of grid cells and other spatial cell types, are organized in time. To determine how activity is self-organized in the entorhinal network, we have tested mice in a spontaneous locomotion task under sensory-deprived conditions, when activity is determined primarily by the intrinsic structure of the network. Using 2-photon calcium imaging, we monitored the activity of several hundreds of entorhinal layer-2 neurons. We find a striking presence of stereotyped sequence elements in the network activity. These may be recruited during encoding of space, and more widely experience, in the entorhinal-hippocampal network. Deficiencies in these mechanisms may be at the core of neurological diseases characterized by early entorhinal cell death, spatial disorientation and memory dysfunction, such as Alzheimer's disease. Due to the experimental accessibility of grid cells and their entorhinal partner cells, exploring the mechanisms of space and time in the entorhinal cortex has served, and continues to serve, as a gateway to understanding high-level cognitive brain functions.