Dentate gyrus

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Dentate gyrus
Diagram of hippocampal regions. DG: Dentate gyrus.
Coronal section of brain immediately in front of pons. (Label for "Gyrus dentatus" is at bottom center.)
Part of Temporal lobe
Artery Posterior cerebral
Anterior choroidal
Latin gyrus dentatus
MeSH D018891
NeuroNames 179
NeuroLex ID birnlex_1178
TA A14.1.09.237
FMA 61922
Anatomical terms of neuroanatomy

The dentate gyrus is part of a brain region known as the hippocampus (part of the hippocampal formation). The dentate gyrus is thought to contribute to the formation of new episodic memories,[1][2] the spontaneous exploration of novel environments,[2] and other functions.[3] It is notable as being one of a select few brain structures currently known to have significant rates of adult neurogenesis in many species of mammals, from rodents to primates[4] (other sites include the subventricular zone of the striatum[5] and cerebellum[6]). However, whether neurogenesis exists in the adult human dentate gyrus is currently a matter of debate.[7][8]


The dentate gyrus (DG) consists of three distinct layers: molecular, granular, and polymorphic, and participates in the 'hippocampal circuit' or trisynaptic loop.[9] The neurons of the granule cell layer are called granule cells and project axons called mossy fibers to synapse on the dendrites of CA3 pyramidal neurons. Granule cells of the DG receive excitatory input from the entorhinal cortex by way of the perforant pathway.[10] This input is primarily made up of signals from layer II of the entorhinal cortex, and the dentate gyrus receives no direct inputs from other cortical structures.[11] The perforant pathway is divided into the medial and lateral perforant paths, generated, respectively, at the medial and lateral portions of the entorhinal cortex. The medial perforant path synapses onto the proximal dendritic area of the granule cells, whereas the lateral perforant path does so onto their distal dendrites. Most lateral views of the dentate gyrus may appear to suggest a structure consisting of just one entity, but medial movement may provide evidence of the ventral and dorsal parts of the dentate gyrus.[12]


The granule cells in the dentate gyrus are distinguished by their late time of formation during brain development. In rats, approximately 85% of the granule cells are generated after birth.[13] In humans, it is estimated that granule cells begin to be generated during gestation weeks 10.5 to 11, and continue being generated during the second and third trimesters, after birth and all the way into adulthood.[14][15] The germinal sources of granule cells and their migration pathways [16][17] have been studied during rat brain development. The oldest granule cells are generated in a specific region of the hippocampal neuroepithelium and migrate into the primordial dentate gyrus around embryonic days (E) 17/18, and then settle as the outermost cells in the forming granular layer. Next, dentate precursor cells move out of this same area of the hippocampal neuroepithelium and, retaining their mitotic capacity, invade the hilus (core) of the forming dentate gyrus. This dispersed germinal matrix is the source of granule cells from that point on. The newly generated granule cells accumulate under the older cells that began to settle in the granular layer. As more granule cells are produced, the layer thickens and the cells are stacked up according to age - the oldest being the most superficial and the youngest being deeper.[18] The granule cell precursors remain in a subgranular zone that becomes progressively thinner as the dentate gyrus grows, but these precursor cells are retained in adult rats. These sparsely scattered cells constantly generate granule cell neurons,[19][20] which add to the total population. There are a variety of other differences in the rat, monkey and human dentate gyrus. The granule cells only have apical dendrites in the rat. But in the monkey and human, many granule cells also have basal dendrites.[21]


Phenotypes of proliferating cells in the dentate gyrus. A fragment of an illustration from Faiz et al., 2005.[22]

The dentate gyrus is thought to contribute to the formation of memories, and to play a role in depression.


The role of the hippocampus in learning and memory has been studied for many decades since early lesion studies. One of the most prominent early cases of anterograde amnesia (inability to form new memories) linking the hippocampus to memory formation was the case of Henry Molaison (anonymously known as Patient H.M. until his death in 2008).[23] His epilepsy was treated with surgical removal of his hippocampi (left and right hemispheres each have their own hippocampus) as well as some surrounding tissue. This targeted brain tissue removal left Mr. Molaison with an inability to form new memories, and the hippocampus has been thought critical to memory formation since that time.[23] It remains unclear how the hippocampus enables new memory formation, but one process, called long term potentiation (LTP), occurs in this brain region.[23] LTP involves long-lasting strengthening of synaptic connections after repeated stimulation.[10] While the dentate gyrus shows LTP, it is also one of the few regions of the adult mammalian brain where neurogenesis (i.e., the birth of new neurons) takes place. Some studies hypothesize that new memories could preferentially use newly formed dentate gyrus cells, providing a potential mechanism for distinguishing multiple instances of similar events or multiple visits to the same location.[24] This increased neurogenesis is associated with improved spatial memory in rodents, as seen through performance in a maze.[25]

Stress and depression[edit]

The dentate gyrus may also have a functional role in stress and depression. For instance, neurogenesis has been found to increase in response to chronic treatment with antidepressants.[26] The physiological effects of stress, often characterized by release of glucocorticoids such as cortisol, as well as activation of the sympathetic division of the autonomic nervous system, have been shown to inhibit the process of neurogenesis in primates.[27] Both endogenous and exogenous glucocorticoids are known to cause psychosis and depression,[28] implying that neurogenesis in the dentate gyrus may play an important role in modulating symptoms of stress and depression.[29]


Some evidence suggests neurogenesis in the dentate gyrus increases in response to aerobic exercise.[30] Several experiments have shown neurogenesis (the development of nerve tissues) often increases in the dentate gyrus of adult rodents when they are exposed to an enriched environment.[31][32] The dentate gyrus is also known to serve as a pre-processing unit. When information enters, it is known to separate very similar information into distinct and unique details. This prepares the relevant data for storage in the hippocampal CA3 section.[33]

Spatial behavior[edit]

Studies have shown that after destroying about 90% of their dentate gyrus (dg) cells, rats had extreme difficulty in maneuvering through a maze they had been through, prior to the lesion being made. When being tested a number of times to see whether they could learn a maze, the results showed that the rats did not improve at all, indicating that their working memories were severely impaired. Rats had trouble with place strategies because they could not consolidate learned information about a maze into their working memory, and, thus, could not remember it when maneuvering through the same maze in a later trial. Every time a rat entered the maze, the rat behaved as if it was seeing the maze for the first time.[34]

Blood sugar[edit]

Studies by researchers at Columbia University Medical Center indicate poor glucose control can lead to deleterious effects on the dentate gyrus.[35]


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