Dentate gyrus

Brain: 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 left.)
Latin	gyrus dentatus
Gray's	subject #189 827
Part of	Temporal lobe
Artery	Posterior cerebral Anterior choroidal
NeuroNames	hier-161
MeSH	Dentate+Gyrus
NeuroLex ID	birnlex_1178

The dentate gyrus is part of the hippocampal formation. It is thought to contribute to new memories as well as other functional roles.^[1][2] It is notable as being one of a select few brain structures currently known to have high rates of neurogenesis in adult rats,^[3] (other sites include the olfactory bulb and cerebellum).^[4][5]

Structure

Main article: Hippocampal subfields

The dentate gyrus consists of three layers of neurons: molecular, granular, and polymorphic. The middle layer is most prominent and contains granule cells that project to the CA3 subfield of the hippocampus.^[6] These granule cells project mostly to interneurons, but also to pyramidal cells and are the principal excitatory neurons of the dentate gyrus. The major input to the dentate gyrus (the so-called perforant pathway) is from layer 2 of the entorhinal cortex, and the dentate gyrus receives no direct inputs from other cortical structures. The perforant pathway is divided into the medial perforant path and the lateral perforant path, 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 the distal dendrites of these same cells.

Development

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.^[7] 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.^[8][9] The germinal sources of granule cells and their migration pathways ^[10][11] 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.^[12] 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,^[13][14] which add to the total population. Thus, granule cells in the dentate gyrus are possibly the only known population of neurons in the brain that are constantly increasing their numbers. In 2010, it was shown that the balance between neural stem cells (NSCs) and neural progenitor cells (NPCs) is maintained by an interaction between the epidermal growth factor receptor signaling pathway and Notch signaling pathway.^[15]

Function

Phenotypes of proliferating cells in the dentate gyrus. A fragment of an illustration from Faiz et al., 2005.^[16]

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

Memory

The dentate gyrus is one of the few regions of the adult brain where neurogenesis (i.e., the birth of new neurons) takes place. Neurogenesis is thought to play a role in the formation of new memories. New memories could preferentially utilize newly-formed dentate gyrus cell, providing a potential mechanism for distinguishing multiple instances of similar events or multiple visits to the same location.^{[citation needed]} A Study at the Human Nutrition Research Center on Aging showed that feeding blueberry extract to older rats for a short time frame increases neurogenesis in the dentate gyrus. This increased neurogenesis is associated with improved spatial memory, as seen through performance in a maze.^{[citation needed][17]}

Stress and Depression

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.^[18] On the contrary, however, 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.^[19] Both endogenous and exogenous glucocorticoids are known to cause psychosis and depression,^[20] implying that neurogenesis in the dentate gyrus may play an important role in modulating symptoms of stress and depression.

Other

Some evidence suggests that neurogenesis in the dentate gyrus increases in response to aerobic exercise.^[21]

Blood Sugar

Studies by researchers at Columbia University Medical Center indicate that poor glucose control can lead to deleterious effects on the dentate gyrus.^[22]

References

1. ^ Helen Scharfman, ed (2007). The Dentate Gyrus: A comprehensive guide to structure, function, and clinical imiplications. 163. 1–840. 
2. ^ Saab BJ, Georgiou J, Nath A, Lee FJ, Wang M, Michalon A, Liu F, Mansuy IM, Roder JC. (2009). "NCS-1 in the dentate gyrus promotes exploration, synaptic plasticity, and rapid acquisition of spatial memory.". Neuron 63 (5): 643–56. doi:10.1016/j.neuron.2009.08.014. PMID 19755107. 
3. ^ Cameron HA, McKay RD (2001). "Adult neurogenesis produces a large pool of new granule cells in the dentate gyrus". J Comp Neurol 435 (4): 406–17. doi:10.1002/cne.1040. PMID 11406822. 
4. ^ Graziadei PP, Monti Graziadei GA (1985). "Neurogenesis and plasticity of the olfactory sensory neurons". PLoS ONE 457: 127–42. doi:10.1111/j.1749-6632.1985.tb20802.x. PMID 3913359. 
5. ^ Ponti G, Peretto B, Bonfanti L (2008). Reh, Thomas A.. ed. "Genesis of neuronal and glial progenitors in the cerebellar cortex of peripuberal and adult rabbits". PLoS ONE 3 (6): e2366. doi:10.1371/journal.pone.0002366. PMC 2396292. PMID 18523645. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2396292. 
6. ^ Nolte, John (2002). The Human Brain: An Introduction to Its Functional Neuroanatomy (fifth ed.). pp. 570–573. 
7. ^ Bayer, S.; Altman, J. (1974). "Hippocampal development in the rat: cytogenesis and morphogenesis examined with autoradiography and low-level X-irradiation". The Journal of Comparative Neurology 158 (1): 55–79. doi:10.1002/cne.901580105. PMID 4430737.  edit
8. ^ Bayer SA Altman J (2008). The Human Brain During The Early First Trimester. 5 Atlas of Human Central Nervous System Development. 
9. ^ Eriksson PS, Perfilieva E, Björk-Eriksson T, et al. (November 1998). "Neurogenesis in the adult human hippocampus". Nat Med. 4 (11): 1313–7. doi:10.1038/3305. PMID 9809557. 
10. ^ Altman, J.; Bayer, S. (1990). "Migration and distribution of two populations of hippocampal granule cell precursors during the perinatal and postnatal periods". The Journal of Comparative Neurology 301 (3): 365–381. doi:10.1002/cne.903010304. PMID 2262596.  edit
11. ^ Altman, J.; Bayer, S. (1990). "Mosaic organization of the hippocampal neuroepithelium and the multiple germinal sources of dentate granule cells". The Journal of Comparative Neurology 301 (3): 325–342. doi:10.1002/cne.903010302. PMID 2262594.  edit
12. ^ Angevine Jr, J. (1965). "Time of neuron origin in the hippocampal region. An autoradiographic study in the mouse". Experimental neurology. Supplement: Suppl Supp2:1–Supp2. PMID 5838955.  edit
13. ^ Bayer, S. A.; Yackel, J. W.; Puri, P. S. (1982). "Neurons in the rat dentate gyrus granular layer substantially increase during juvenile and adult life". Science 216 (4548): 890–892. Bibcode 1982Sci...216..890B. doi:10.1126/science.7079742. PMID 7079742.  edit
14. ^ Bayer, S. A. (1982). "Changes in the total number of dentate granule cells in juvenile and adult rats: a correlated volumetric and 3H-thymidine autoradiographic study". Experimental brain research. Experimentelle Hirnforschung. Experimentation cerebrale 46 (3): 315–323. PMID 7095040.  edit
15. ^ Aguirre A, Rubio ME, Gallo V (September 1998). "Notch and EGFR pathway interaction regulates neural stem cell number and self-renewal". Nat.. 467 (7313): 323–7. doi:10.1038/nature09347. PMC 2941915. PMID 20844536. http://www.nature.com/nature/journal/v467/n7313/full/nature09347.html. 
16. ^ Faiz M, Acarin L, Castellano B, Gonzalez B (2005). "Proliferation dynamics of germinative zone cells in the intact and excitotoxically lesioned postnatal rat brain". BMC Neurosci 6 (1): 26. doi:10.1186/1471-2202-6-26. PMC 1087489. PMID 15826306. http://www.biomedcentral.com/1471-2202/6/26. 
17. ^ Bliss, Rosalie Marion. “Food and the Aging Mind”. First in a Series: Nutrition and Brain Function. http://www.ars.usda.gov/is/ar/archive/aug07/aging0807.htm. (27 February 2010)
18. ^ Malberg JE, Eisch AJ, Nestler EJ, Duman RS (2000). "Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus". J. Neurosci 20 (24): 9104–9110. PMID 11124987. 
19. ^ Gould E, Tanapat P, McEwen BS, Flugge G, Fuchs E (1998). "Proliferation of granule cell precursors in the dentate gyrus of adult monkeys is diminished by stress". PNAS 95 (6): 3168–3171. doi:10.1073/pnas.95.6.3168. PMC 19713. PMID 9501234. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=19713. 
20. ^ Jacobs B, Praag H, Gage F (2000). "Adult brain neurogenesis and psychiatry: a novel theory of depression". Mol. Psychiatry 5 (3): 262–9. doi:10.1038/sj.mp.4000712. PMID 10889528. 
21. ^ Kempermann G, Kuhn HG, Gage FH, (1997). "More hippocampal neurons in adult mice living in an enriched environment". Nature 386 (6624): 493–495. doi:10.1038/386493a0. PMID 9087407. 
22. ^ "Blood Sugar Control Linked to Memory Decline, Study Says". Nytimes.com. 1 January 2009. http://www.nytimes.com/2009/01/01/health/31memory.html?_r=1&em=&pagewanted=print. Retrieved 2011-03-13. 

External links

• Slide at psycheducation.org
• BrainMaps at UCDavis Dentate gyrus

• "Dentate Gyrus NMDA Receptors Mediate Rapid Pattern Separation in the Hippocampal Network". Science 7 June 2007 DOI: 10.1126/science.1140263 - The source of déjà vu
• NIF Search - Dentate Gyrus via the Neuroscience Information Framework
• See Altman and Bayer's work on dentate gyrus development and adult neurogenesis