The entorhinal cortex (EC) is an area of the brain's
allocortex
The allocortex or heterogenetic cortex, and neocortex are the two types of cerebral cortex in the brain. The allocortex is the much smaller area of cortex taking up just 10 %, the neocortex takes up the remaining 90 %. It is characterized by havi ...
, located in the
medial temporal lobe
The temporal lobe is one of the four major lobes of the cerebral cortex in the brain of mammals. The temporal lobe is located beneath the lateral fissure on both cerebral hemispheres of the mammalian brain.
The temporal lobe is involved in pro ...
, whose functions include being a widespread network hub for
memory
Memory is the faculty of the mind by which data or information is encoded, stored, and retrieved when needed. It is the retention of information over time for the purpose of influencing future action. If past events could not be remembered ...
, navigation, and the perception of time.
[Integrating time from experience in the lateral entorhinal cortex Albert Tsao, Jørgen Sugar, Li Lu, Cheng Wang, James J. Knierim, May-Britt Moser & Edvard I. Moser Naturevolume 561, pages57–62 (2018)] The EC is the main interface between the
hippocampus
The hippocampus (via Latin from Greek , ' seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, ...
and
neocortex. The
EC-hippocampus system plays an important role in declarative (autobiographical/episodic/semantic) memories and in particular
spatial memories including
memory formation
Memory is the faculty of the mind by which data or information is encoded, stored, and retrieved when needed. It is the retention of information over time for the purpose of influencing future action. If past events could not be remembered, ...
,
memory consolidation
Memory consolidation is a category of processes that stabilize a memory trace after its initial acquisition. A memory trace is a change in the nervous system caused by memorizing something. Consolidation is distinguished into two specific processe ...
, and memory optimization in
sleep
Sleep is a sedentary state of mind and body. It is characterized by altered consciousness, relatively inhibited sensory activity, reduced muscle activity and reduced interactions with surroundings. It is distinguished from wakefulness by a de ...
. The EC is also responsible for the pre-processing (familiarity) of the input signals in the reflex
nictitating membrane response of classical trace conditioning; the association of impulses from the
eye and the
ear
An ear is the organ that enables hearing and, in mammals, body balance using the vestibular system. In mammals, the ear is usually described as having three parts—the outer ear, the middle ear and the inner ear. The outer ear consists of ...
occurs in the entorhinal cortex.
Structure
In rodents, the EC is located at the
caudal end of the
temporal lobe
The temporal lobe is one of the four major lobes of the cerebral cortex in the brain of mammals. The temporal lobe is located beneath the lateral fissure on both cerebral hemispheres of the mammalian brain.
The temporal lobe is involved in pro ...
. In primates it is located at the
rostral end of the temporal lobe and stretches dorsolaterally. It is usually divided into
medial and
lateral
Lateral is a geometric term of location which may refer to:
Healthcare
*Lateral (anatomy), an anatomical direction
* Lateral cricoarytenoid muscle
* Lateral release (surgery), a surgical procedure on the side of a kneecap
Phonetics
*Lateral co ...
regions with three bands with distinct properties and connectivity running perpendicular across the whole area. A distinguishing characteristic of the EC is the lack of cell bodies where layer IV should be; this layer is called the ''Lamina dissecans''.
Connections
![Apoe-cortical-thickness-entorhinal](https://upload.wikimedia.org/wikipedia/commons/b/b7/Apoe-cortical-thickness-entorhinal.jpg)
The superficial layers – layers II and III – of EC project to the
dentate gyrus
The dentate gyrus (DG) is part of the hippocampal formation in the temporal lobe of the brain, which also includes the hippocampus and the subiculum. The dentate gyrus is part of the hippocampal trisynaptic circuit and is thought to contribute t ...
and
hippocampus
The hippocampus (via Latin from Greek , ' seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, ...
: Layer II projects primarily to
dentate gyrus
The dentate gyrus (DG) is part of the hippocampal formation in the temporal lobe of the brain, which also includes the hippocampus and the subiculum. The dentate gyrus is part of the hippocampal trisynaptic circuit and is thought to contribute t ...
and hippocampal region CA3; layer III projects primarily to hippocampal region CA1 and the
subiculum
The subiculum (Latin for "support") is the most inferior component of the hippocampal formation. It lies between the entorhinal cortex and the CA1 subfield of the hippocampus proper.
The subicular complex comprises a set of related structures ...
. These layers receive input from other cortical areas, especially associational,
perirhinal, and
parahippocampal cortices, as well as
prefrontal cortex
In mammalian brain anatomy, the prefrontal cortex (PFC) covers the front part of the frontal lobe of the cerebral cortex. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, BA13, BA14, BA24, BA25, BA32, BA44, BA45, BA46 ...
. EC as a whole, therefore, receives highly processed input from every sensory modality, as well as input relating to ongoing cognitive processes, though it should be stressed that, within EC, this information remains at least partially segregated.
The deep layers, especially layer V, receive one of the three main outputs of the
hippocampus
The hippocampus (via Latin from Greek , ' seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, ...
and, in turn, reciprocate connections from other cortical areas that project to superficial EC.
The rodent entorhinal cortex shows a modular organization, with different properties and connections in different areas.
Brodmann's areas
*
Brodmann area 28
Brodmann area 28 is a subdivision of the cerebral cortex defined on the basis of cytoarchitecture. It is located on the medial aspect of the temporal lobe and is part of the entorhinal cortex (Brodmann-1909).
Human
In humans, Brodmann area 28, ...
is known as the "area entorhinalis"
*
Brodmann area 34
Brodmann area 34 is a part of the brain.
It has been described as part of the entorhinal area and the superior temporal gyrus.
The entorhinal area is the main interface between the hippocampus and neocortex and involved in memory, navigation an ...
is known as the "area entorhinalis dorsalis"
Function
Neuron information processing
In 2005, it was discovered that entorhinal cortex contains a
neural map of the spatial environment in rats.
In 2014, John O'Keefe, May-Britt Moser and Edvard Moser received the
Nobel Prize in Physiology or Medicine
The Nobel Prize in Physiology or Medicine is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, accord ...
, partly because of this discovery.
In rodents, neurons in the lateral entorhinal cortex exhibit little spatial selectivity, whereas neurons of the medial entorhinal cortex (MEC), exhibit multiple "place fields" that are arranged in a hexagonal pattern, and are, therefore, called "
grid cells
A grid cell is a type of neuron within the entorhinal cortex that fires at regular intervals as an animal navigates an open area, allowing it to understand its position in space by storing and integrating information about location, distance, and ...
". These fields and spacing between fields increase from the dorso-lateral MEA to the ventro-medial MEA.
The same group of researchers has found speed cells in the medial entorhinal cortex of rats. The speed of movement is translated from proprioceptive information and is represented as firing rates in these cells. The cells are known to fire in correlation to future speed of the rodent.
Recently, a general theory has been proposed to elucidate the function of the reelin positive cells in the layer II of the entorhinal cortex. According to this concept, these cells would be generally organized into 1-dimensional ring attractors, and in the ''medial'' (in humans: ''posteromedial'') portion, would function as
grid cells
A grid cell is a type of neuron within the entorhinal cortex that fires at regular intervals as an animal navigates an open area, allowing it to understand its position in space by storing and integrating information about location, distance, and ...
(anatomically: stellate cells) while in ''lateral'' (in humans: ''anterolateral'') portion, where they appear as fan cells, would enable the encoding of new episodic memories. This concept is underscored by the fact that fan cells of the entorhinal cortex are indispensable for the formation of episodic-like memories in rodents.
Single-unit recording
In neuroscience, single-unit recordings provide a method of measuring the electro-physiological responses of a single neuron using a microelectrode system. When a neuron generates an action potential, the signal propagates down the neuron as a cu ...
of neurons in humans playing
video game
Video games, also known as computer games, are electronic games that involves interaction with a user interface or input device such as a joystick, controller, keyboard, or motion sensing device to generate visual feedback. This fee ...
s find path cells in the EC, the activity of which indicates whether a person is taking a clockwise or counterclockwise path. Such EC "direction" path cells show this directional activity irrespective of the location of where a person experiences themselves, which contrasts them to place cells in the hippocampus, which are activated by specific locations.
EC neurons process general information such as directional activity in the environment, which contrasts to that of the hippocampal neurons, which usually encode information about specific places. This suggests that EC encodes general properties about current contexts that are then used by hippocampus to create unique representations from combinations of these properties.
Research generally highlights a useful distinction in which the medial entorhinal cortex (MEC) mainly supports processing of space, whereas the lateral entorhinal cortex (LEC) mainly supports the processing of time.
The MEC exhibits a strong ~8 Hz
rhythmic neural activity known as
theta
Theta (, ; uppercase: Θ or ; lowercase: θ or ; grc, ''thē̂ta'' ; Modern: ''thī́ta'' ) is the eighth letter of the Greek alphabet, derived from the Phoenician letter Teth . In the system of Greek numerals, it has a value of 9.
Gr ...
. Alterations in the neural activity across the brain region results in an observed "
traveling wave
In physics, mathematics, and related fields, a wave is a propagating dynamic disturbance (change from equilibrium) of one or more quantities. Waves can be periodic, in which case those quantities oscillate repeatedly about an equilibrium (re ...
" phenomena across the MEC long-axis, similar to that of the
hippocampus
The hippocampus (via Latin from Greek , ' seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, ...
, due to asymmetric theta oscillations.
[ ] The underlying cause of these phase shifts and their waveform changes are unknown.
Individual variation in the volume of EC is linked to taste perception. People with a larger EC in the left hemisphere found quinine, the source of bitterness in
tonic water
Tonic water (or Indian tonic water) is a carbonated soft drink in which quinine is dissolved. Originally used as a prophylactic against malaria, tonic water usually has a significantly lower quinine content and is consumed for its distinctive ...
, less bitter.
Clinical significance
Alzheimer's disease
The entorhinal cortex is the first area of the brain to be affected in
Alzheimer's disease; a recent
functional magnetic resonance imaging study has localised the area to the lateral entorhinal cortex. Lopez ''et al.'' have shown, in a multimodal study, that there are differences in the volume of the left entorhinal cortex between progressing (to Alzheimer's disease) and stable mild cognitive impairment patients. These authors also found that the volume of the left entorhinal cortex inversely correlates with the level of alpha band phase synchronization between the right anterior cingulate and temporo-occipital regions.
In 2012, neuroscientists at
UCLA
The University of California, Los Angeles (UCLA) is a public land-grant research university in Los Angeles, California. UCLA's academic roots were established in 1881 as a teachers college then known as the southern branch of the California ...
conducted an experiment using a virtual taxi video game connected to seven epilepsy patients with electrodes already implanted in their brains, allowing the researchers to monitor neuronal activity whenever memories were being formed. As the researchers stimulated the nerve fibers of each of the patients' entorhinal cortex as they were learning, they were then able to better navigate themselves through various routes and recognize landmarks more quickly. This signified an improvement in the patients' spatial memory.
Effect of aerobic exercise
A study finds that regardless of gender, young adults who have greater aerobic fitness also have greater volume of their entorhinal cortex. It suggests that aerobic exercise may have a positive effect on the medial temporal lobe memory system (which includes the entorhinal cortex) in healthy young adults. This also suggests that exercise training, when designed to increase aerobic fitness, might have a positive effect on the brain in healthy young adults
Additional Images
File:Entorhinal - DK ATLAS.png, Entorhinal cortex, shown in the right cerebral hemisphere.
References
External links
*
NIF Search - Entorhinal Cortexvia the
Neuroscience Information Framework
The Neuroscience Information Framework is a repository of global neuroscience web resources, including experimental, clinical, and translational neuroscience databases, knowledge bases, atlases, and genetic/genomic resources and provides many auth ...
* For delineating the Entorhinal cortex, see Desikan RS, Ségonne F, Fischl B, Quinn BT, Dickerson BC, Blacker D, Buckner RL, Dale AM, Maguire RP, Hyman BT, Albert MS, Killiany RJ. An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. Neuroimage. 2006 Jul 1;31(3):968-80.
{{DEFAULTSORT:Entorhinal Cortex
Limbic system
Cerebral cortex