The Phillip A. Sharp Lecture in Neural Circuits is an annual lecture in honor of Phillip Sharp, who served as founding director of McGovern Institute from 2000-2004. 

Talk Title: Neural computation of space: From single cells to neural populations

Abstract: A key element of the mammalian position-coding circuit is the network of grid cells in medial entorhinal cortex – cells that are active when animals are at specific locations that tile environments in a periodic hexagonal pattern. I will discuss how recent technological developments allow principles underlying the collective dynamics of grid cells to be extracted in behaving rodents. First, I will show how the joint activity of grid cells operates on a low-dimensional manifold with the topology of a torus, irrespective of the animal´s behavior, across wake and sleep states. In developing rat pups, this toroidal topology of the spatial map appears abruptly in conjunction with internal cortical dynamics at postnatal day 10, before eyes and ear canals open and before upright walking, pointing to a preconfigured internal network origin of the dynamics. Second, I will show that the periodic locations represented by grid cells are not punctual but move along highly stereotypic spatial trajectories within individual 125-ms theta cycles, trajectories that linearly and unconditionally sweep outwards from the animal’s location into the ambient environment, alternating between left and right of the animal, independently of whether or not the animal ever visits places on those trajectories. The sweep-like dynamics of grid cells is controlled by an upstream population of internal direction cells in the parasubiculum, in which decoded direction alternates in synchrony with sweeps in grid cells. I will show that on top of the stereotyped default pattern of sweeps and direction signals, the signals are modulated in a behavior-dependent manner, with direction, frequency and width of the sweeps and direction signals directed in an attention-like manner to regions of interest.  Third, I will show that sweeps and internal direction signals are controlled further upstream by a population of conjunctive head direction × internal direction cells that align internal direction with head direction. These cells uniquely exhibit hemispheric lateralization: left hemisphere cells fire exclusively on rightward sweeps, while right hemisphere cells fire exclusively on leftward sweeps. We are testing whether these lateralized cell populations, by reciprocally inhibiting each other, are part of a cortical central pattern generator-like circuit [MM1] [RS2] that alternately biases rightward and leftward theta sweeps much like locomotion-controlling circuits in the spinal cord. Finally, I will show how, through modular organization, the low-dimensional grid map in the medial entorhinal cortex is transformed downstream, in the hippocampus, into a rich repertoire of independent place cell maps suitable for memory storage.

Bio: Edvard Moser is a Professor of Neuroscience and Scientific Director of the Kavli Institute for Systems Neuroscience (KISN) at the Norwegian University of Science and Technology (NTNU). He is interested in neural network coding in the cortex, with particular emphasis on space, time and memory. His work, conducted in collaboration with May-Britt Moser since they started the NTNU lab in 1996, includes the Nobel-awarded discovery of grid cells. Moser’s current focus is on unravelling how neural microcircuits for space and time are organized at the neural network level, among large numbers of diverse neurons with known functional identity, a computational neuroscience endeavour significantly boosted by the technological development of Neuropixels probes and 2-photon miniscopes for freely-moving rodents - technologies that the Mosers have participated in developing.  

Edvard Moser received his PhD training at the University of Oslo under Per Andersen and postdoctoral training under Richard Morris at the University of Edinburgh and John O’Keefe at the University College of London. In 1996 the Mosers accepted faculty positions in psychology at NTNU. They founded the Centre for the Biology of Memory in 2002, the Kavli Institute in 2007, the Centre for Neural Computation in 2013, and the Centre for Algorithms in the Cortex in 2023, with funding from the Norwegian Research Council’s Centre of Excellence scheme. The Mosers have received numerous scientific awards, including the 2014 Nobel Prize in Medicine or Physiology.