Cortical representations recreate features of the outside world in a language that is suitable for brain computation. Such representations exist at different levels of complexity, ranging from the relatively simple transformations of the spatial organization of peripheral sensory receptors found in primary sensory cortices to representations with no discernible relationship to properties of any sensory receptor population at higher hierarchical levels of the cortex. Grid cells in the medial entorhinal cortex (MEC) are examples of a high-level cortical representation.
Pattern formation and transformation processes in the well-studied primary visual cortex may provide clues as to how neural circuit computation occurs in the entorhinal cortex.
Grid cells are spatially modulated cells with periodic hexagonally spaced firing fields. They have been identified in and around the MEC in several mammalian species. Grid cells provide a window into neural circuit computation in higher-level association cortices, as they are many synapses away from both sensory receptors and motor output.
Grid cells provide the entorhinal–hippocampal spatial map with a metric. The regular structure of the grid pattern is likely to depend on path integration.
Grid cells simultaneously exhibit topographic and non-topographic organization. Firing location is non-topographic, whereas the grid scale changes in discrete but overlapping steps along the dorsoventral MEC axis. The entangled organization of grid modules differs from the continuous arrangement of many variables represented in sensory cortices.
Many properties of grid cells point to a continuous attractor network mechanism for the formation of hexagonal firing patterns. The exact implementation of such a mechanism remains elusive. Although continuous attractor networks rely on preferential and asymmetrical connections between grid cells with similar but not identical grid phases, such connections have yet to be demonstrated experimentally.
Grid cells provide a major spatial input to hippocampal place cells but border cells may also contribute. The mechanism for the transformation of the apparently universal entorhinal representation of space to environmentally- specific hippocampal spatial representations may involve local circuit mechanisms as well as plasticity. Teasing apart the relative contributions and dynamics of entorhinal inputs to hippocampal place cells remains one of the most intriguing challenges in the field.
One of the grand challenges in neuroscience is to comprehend neural computation in the association cortices, the parts of the cortex that have shown the largest expansion and differentiation during mammalian evolution and that are thought to contribute profoundly to the emergence of advanced cognition in humans. In this Review, we use grid cells in the medial entorhinal cortex as a gateway to understand network computation at a stage of cortical processing in which firing patterns are shaped not primarily by incoming sensory signals but to a large extent by the intrinsic properties of the local circuit.
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The authors are grateful to T. Mrsic-Flogel for comments on the manuscript. The authors thank the European Research Council ('CIRCUIT' Advanced Investigator Grant, grant agreement 232608; 'ENSEMBLE' Advanced Investigator Grant, grant agreement 268598), the European Commission's FP7 FET Proactive programme on Neuro-Bio-Inspired Systems (grant agreement 600725), an FP7 Marie Curie Training Network Grant (NETADIS; grant agreement 290038), the Louis-Jeantet Prize for Medicine, the Kavli Foundation and the Centre of Excellence scheme and the FRIPRO and NEVRONOR programmes of the Research Council of Norway for support. The authors thank T. Stensola for the design of figure 1 parts b and d. The authors are also grateful to F. Pinheiro for suggesting the Borges quote.
The authors declare no competing financial interests.
- Entorhinal cortex
An interface between the three-layered hippocampal cortex and six-layered neocortex. It provides the main cortical input to the dentate gyrus.
- Place cell
A type of hippocampal neuron that typically has a single environmentally specific spatial receptive field. There is no discernible relationship between firing patterns in different environments.
- Grid cells
Parahippocampal neurons that have regularly repeating hexagonally spaced receptive fields. Co-activity patterns remain largely the same across different environments.
- Theta rhythm
Oscillatory activity in the range of 6–10 Hz in the local field potential of the hippocampus. It is produced by large and widespread ensembles of hippocampal neurons that oscillate in synchrony.
- Salt-and-pepper-like organization
Cortical architecture in which single cells are tuned for the orientation of a stimulus but show no particular order in their arrangement. This arrangement is seen in the rodent visual cortex.
- Head direction cells
Neurons found throughout parahippocampal areas and in other brain regions (for example, the anterior thalamus) for which the primary feature of the receptive field is the direction in which the animals head is pointing.
- Attractor network
A network with one or more stable firing-rate pattern that is stored in the structure of the synaptic connectivity.
- Continuous attractor
An attractor network in which the collection of attracting points form not a discrete set but a continuum (a ring or a sheet).
- Mexican hat connectivity
The connectivity of networks in which neurons are arranged on a ring or sheet such that the excitatory connections of each neuron decrease progressively with distance, whereas inhibitory connections increase in strength.
- Stellate cells
Morphologically defined as cells with a round soma and dendrites radiating from it in all directions. In the medial entorhinal cortex, stellate cells are the main origin of the projection to the dentate gyrus and CA3.
- Recurrent networks
Neural networks in which each neuronal element provides an input onto many of the other neurons in the network.
Adaptation refers to the decrease in firing frequency that neurons exhibit following a period of repeated discharge.
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Moser, E., Roudi, Y., Witter, M. et al. Grid cells and cortical representation. Nat Rev Neurosci 15, 466–481 (2014). https://doi.org/10.1038/nrn3766
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