Box 2: Anatomy of hippocampal formation and parahippocampal region
One of the principal features of the cortex is its layered organization. The cortex has essentially two forms, the neocortex (also called the isocortex), which is generally thought to comprise five or six layers, and the allocortex, which is characterized by three layers. In between these two types, several transition areas have been recognized, where the number of layers increases from three to six. The entorhinal cortex together with the presubiculum (PrS) and parasubiculum (PaS) are parts of this transition domain.
Part a of the figure shows the right hemisphere of a rat brain, with a focus on the hippocampal formation and the parahippocampal region. The left part is a horizontal section through the hemisphere; the right part shows a mid-sagittal view of the hemisphere, based on the rat Waxholm space200. The dorsoventral position of the section is indicated by the dashed line through the hemisphere. Together, the images illustrate the positions of key hippocampal and parahippocampal areas: the dentate gyrus (DG), CA1–CA3, the subiculum, the medial entorhinal cortex (MEC), the lateral entorhinal cortex (LEC), the PrS and the PaS. The borders and the extent of individual subregions are colour-coded.
In the current standard connectivity model of the hippocampal formation and parahippocampal region (see the figure, part b), the MEC provides input to the hippocampal formation, with layer II projecting to the DG, CA3 and CA2, and layer III projecting to CA1 and the subiculum. CA1 and the subiculum provide output to entorhinal cortex layer V. All entorhinal layers seem to be reciprocally connected (indicated by the double-headed arrows). This connectional route, in green, is paralleled by a similarly organized route starting and ending in the LEC, indicated in grey. The two pathways converge onto single neurons in the DG, CA3 and CA2 but target different neurons in CA1 and the subiculum. Projections from and to the MEC link to neurons in CA1 close to CA2 (proximal) and neurons in the subiculum close to the PrS (distal), and the opposite pattern holds for projections from and to the LEC. Inputs selective for the MEC originate from the PrS and the PaS.
A, anterior; D, dorsal; P, posterior; V, ventral.
Kavli Institute for Systems Neuroscience and Centre for Neural Computation, Norwegian University of Science and Technology, 7491 Trondheim, Norway.
- Edvard I. Moser,
- Yasser Roudi,
- Menno P. Witter,
- Clifford Kentros,
- Tobias Bonhoeffer &
- May-Britt Moser
Institute of Neuroscience, University of Oregon, Eugene, Oregon 97403-1254, USA.
- Clifford Kentros
Max Planck Institute of Neurobiology, Am Klopferspitz 18, 82152 Planegg-Martinsried, Germany.
- Tobias Bonhoeffer
Competing interests statement
The authors declare no competing interests.
Edvard I. Moser
Edvard I. Moser received his Ph.D. on the mechanisms of memory formation in the hippocampus in 1995 at the University of Oslo, Norway, under the supervision of Per Andersen. After short postdoctoral training with Richard Morris and John O'Keefe, he started his own laboratory, jointly with May-Britt Moser, at the Norwegian University of Science and Technology, Trondheim, in 1996. In 2002, he became the Founding Director of the Centre for the Biology of Memory and in 2007 the Founding Director of the Kavli Institute for Systems Neuroscience. He is interested in how spatial location and spatial memory are computed in the brain. His work, conducted mostly with May-Britt Moser, includes the discovery of grid cells in the entorhinal cortex. Subsequent to this discovery, the Mosers have identified additional space-representing cell types in the entorhinal cortex, and they are beginning to unravel how the neural microcircuit is organized. For more information, see the Kavli Institute for Systems Neuroscience Centre for Neural Computation website.
Yasser Roudi studied at Sharif University of Technology in Tehran, Iran, and SISSA (The International School for Advanced Studies) in Trieste, Italy, where he obtained his Ph.D. in 2005 with Alessandro Treves, working on statistical mechanics of neural networks. After postdoctoral training with Peter Latham at the Gatsby Computational Neuroscience Unit of University College London, UK, he accepted a fellowship at NORDITA, the Nordic Institute for Theoretical Physics, in Stockholm, Sweden, in 2008. During this period, together with John Hertz, he mainly worked on problems at the interface of statistical mechanics and inference. In 2010, he moved to the Kavli Institute for Systems Neuroscience at the Norwegian University of Science and Technology, Trondheim, where he established a new research group. His research has two main branches: the use of methods from statistical mechanics for modelling and inference in high-throughput biological data, and the development of network models to explain the properties of grid cells and other functional cell types. For more information, see the Kavli Institute for Systems Neuroscience Centre for Neural Computation website.
Menno P. Witter
Menno P. Witter received his Ph.D. from the VU University in Amsterdam, the Netherlands, where he subsequently started his independent research, continuing to work on the anatomical organization of the hippocampal region. He trained with David Amaral at the Salk Institute for Biological Studies, San Diego, California, USA, and Gary Van Hoesen at the University of Iowa, Iowa City, USA. In his early work, he postulated the existence of functional differentiations within both the hippocampus and the entorhinal cortex. He joined May-Britt Moser and Edvard I. Moser as a visiting professor at the Kavli Institute for Systems Neuroscience at the Norwegian University of Science and Technology, Trondheim, in 2007, concluding a productive collaborative period that led to the discovery of grid cells. Recent research has resulted in the discovery of the inhibitory network between putative grid cells. His current research focuses on the functional architecture of the lateral and medial entorhinal cortex. He is currently Chair of the Norwegian Research School in Neuroscience. For more information, see the Kavli Institute for Systems Neuroscience Centre for Neural Computation website.
Clifford Kentros obtained his Ph.D. on potassium channels with Bernardo Rudy at New York University, USA. During his postdoctoral work with Robert Muller at the State University of New York Health Science Center, Brooklyn, USA, and Eric Kandel at Columbia University, New York, USA, he investigated the relationship between place cells and memory. His subsequent research has taken advantage of his dual molecular and neurophysiological background. He has combined the anatomical specificity of molecular genetics with in vivo electrophysiological recordings and anatomical analysis, first at the University of Oregon, Eugene, USA, and now at the Kavli Institute of Systems Neuroscience at the Norwegian University of Science and Technology, Trondheim. The laboratory uses mice that are capable of driving the expression of transgenes in particular subsets of neurons in brain areas involved in learning and memory to determine their precise connectivity and to modulate their neural activity while recording from other cell types. In this way, the laboratory investigates the anatomical and functional circuitry underlying learning and memory. For more information, see the Kavli Institute for Systems Neuroscience Centre for Neural Computation website.
Tobias Bonhoeffer received his Ph.D. in neuroscience for research that he did at the Max Planck Institute (MPI) for Biological Cybernetics in Tübingen, Germany. After 2 years of postdoctoral training with Amiram Grinvald and Torsten Wiesel at the Rockefeller University in New York, USA, he returned to Germany and worked in the laboratory of Wolf Singer at the MPI for Brain Research in Frankfurt, Germany. In 1993, he started his own laboratory at the MPI of Neurobiology in Munich, Germany. Five years later, he became Director at that institute and subsequently was made professor of the Ludwig Maximilians University in Munich. Throughout his career, Tobias Bonhoeffer has been interested in how information is represented and stored in the brain and how this representation is affected by experience in the sensory environment. Among other things, he is well known for his discovery of the pinwheel arrangement of orientation domains in the primary visual cortex of higher mammals and the demonstration that functional synaptic plasticity entails structural changes at the level of dendritic spines. Since 2014, he is a visiting professor at the Norwegian University of Science and Technology, Trondheim. Tobias Bonhoeffer's homepage.
May-Britt Moser received her Ph.D. on the structural basis of hippocampal memory in 1995 at the University of Oslo, Norway, under the supervision of Per Andersen. After short postdoctoral training with Richard Morris and John O'Keefe, she started her own laboratory, jointly with Edvard I. Moser, at the Norwegian University of Science and Technology, Trondheim in 1996. She has been the Vice Director of the Centre for the Biology of Memory (2002–2012) and the Kavli Institute for Systems Neuroscience (since 2007) and in 2013 became the Founding Director of the Centre for Neural Computation. Her research, conducted with Edvard I. Moser as a long-term collaborator, includes the discovery of grid cells as well as other functional cell types of the spatial representation system in the entorhinal cortex. Her current research includes studies of how grid cells develop and their relationship with memory. For more information, see the Kavli Institute for Systems Neuroscience Centre for Neural Computation website.
- 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.