Editing Adult neurogenesis (section)

==Model organisms of neurogenesis==
{{Main |Model organism}}

===Planarian===
[[Planarian]] are one of the earliest [[model organism]]s used to study [[Regeneration (biology)|regeneration]] with [[Peter Simon Pallas|Pallas]] as the forefather of planarian studies. Planarian are a classical invertebrate model that in recent decades have been used to examine neurogenesis. The central nervous system of a planarian is simple, though fully formed with two lobes located in the head and two [[ventral nerve cord]]s. This model reproduces asexually producing a complete and fully functioning nervous system after division allowing for consistent examination of neurogenesis.

===Axolotl===
The [[axolotl]] is less commonly used than other vertebrates, but is still a classical model for examining regeneration and neurogenesis. Though the axolotl has made its place in biomedical research in terms of limb regeneration,<ref>{{cite journal|last=Carlson|first=B. M.|date=December 1975|title=The effects of rotation and positional change of stump tissues upon morphogenesis of the regenerating axolotl limb|journal=Developmental Biology|volume=47|issue=2|pages=269–291|issn=0012-1606|pmid=1204936|doi=10.1016/0012-1606(75)90282-1|hdl=1874/15361|hdl-access=free}}</ref><ref>{{cite journal|last1=Kragl|first1=Martin|last2=Knapp|first2=Dunja|last3=Nacu|first3=Eugen|last4=Khattak|first4=Shahryar|last5=Maden|first5=Malcolm|last6=Epperlein|first6=Hans Henning|last7=Tanaka|first7=Elly M.|date=2009-07-02|title=Cells keep a memory of their tissue origin during axolotl limb regeneration|journal=Nature|volume=460|issue=7251|pages=60–65|doi=10.1038/nature08152|issn=1476-4687|pmid=19571878|bibcode=2009Natur.460...60K|s2cid=4316677}}</ref> the model organism has displayed a robust ability to generate new neurons following damage.<ref>{{cite journal|last1=Maden|first1=Malcolm|last2=Manwell|first2=Laurie A.|last3=Ormerod|first3=Brandi K.|date=2013-01-17|title=Proliferation zones in the axolotl brain and regeneration of the telencephalon|journal=Neural Development|volume=8|pages=1|doi=10.1186/1749-8104-8-1|issn=1749-8104|pmc=3554517|pmid=23327114 |doi-access=free }}</ref><ref>{{cite journal|last1=Clarke|first1=J. D.|last2=Alexander|first2=R.|last3=Holder|first3=N.|date=1988-06-17|title=Regeneration of descending axons in the spinal cord of the axolotl|journal=Neuroscience Letters|volume=89|issue=1|pages=1–6|issn=0304-3940|pmid=3399135|doi=10.1016/0304-3940(88)90471-5|s2cid=23650500}}</ref> Axolotls have contributed as a bridge organism between invertebrates and mammals, as the species has the regenerative capacity to undergo complete neurogenesis forming a wide range of neuronal populations not limited to a small niche,<ref>{{cite journal|last1=Amamoto|first1=Ryoji|last2=Huerta|first2=Violeta Gisselle Lopez|last3=Takahashi|first3=Emi|last4=Dai|first4=Guangping|last5=Grant|first5=Aaron K|last6=Fu|first6=Zhanyan|last7=Arlotta|first7=Paola|title=Adult axolotls can regenerate original neuronal diversity in response to brain injury|journal=eLife|volume=5|doi=10.7554/eLife.13998|issn=2050-084X|pmc=4861602|pmid=27156560|year=2016 |doi-access=free }}</ref> yet the complexity and architecture is complex and analogous in many ways to human neural development.

=== Zebrafish ===
[[Zebrafish]] have long been a classical [[Human development (biology)|developmental]] model due to their transparency during [[organogenesis]] and have been utilized heavily in early development neurogenesis.<ref>{{cite journal|last=Zupanc|first=G. K. H.|date=2006-06-01|title=Neurogenesis and neuronal regeneration in the adult fish brain|journal=Journal of Comparative Physiology A|language=en|volume=192|issue=6|pages=649–670|doi=10.1007/s00359-006-0104-y|pmid=16463148|s2cid=24063389|issn=0340-7594}}</ref><ref>{{cite journal|last1=Schmidt|first1=Rebecca|last2=Strähle|first2=Uwe|last3=Scholpp|first3=Steffen|date=2013-02-21|title=Neurogenesis in zebrafish — from embryo to adult|journal=Neural Development|volume=8|pages=3|doi=10.1186/1749-8104-8-3|issn=1749-8104|pmc=3598338|pmid=23433260 |doi-access=free }}</ref> The zebrafish displays a strong neurogenerative capacity capable of regenerating a variety of tissues and complete neuronal diversity (with the exception of [[astrocyte]]s, as they have yet to be identified within the zebrafish brain) with continued neurogenesis through the life span. In recent decades the model has solidified its role in adult regeneration and neurogenesis following damage.<ref>{{cite journal|last1=Hentig|first1=James T.|last2=Byrd-Jacobs|first2=Christine A.|date=2016-08-31|title=Exposure to Zinc Sulfate Results in Differential Effects on Olfactory Sensory Neuron Subtypes in Adult Zebrafish|journal=International Journal of Molecular Sciences|volume=17|issue=9|pages=1445|doi=10.3390/ijms17091445|issn=1422-0067|pmc=5037724|pmid=27589738|doi-access=free}}</ref><ref>{{cite journal|last1=Gorsuch|first1=Ryne A.|last2=Hyde|first2=David R.|date=June 2014|title=Regulation of Müller glial dependent neuronal regeneration in the damaged adult zebrafish retina|journal=Experimental Eye Research|volume=123|pages=131–140|doi=10.1016/j.exer.2013.07.012|issn=1096-0007|pmc=3877724|pmid=23880528}}</ref><ref>{{cite journal |last1=Trimpe |first1=D. M. |last2=Byrd-Jacobs |first2=C. A. |date=2016 |title=Patterns of olfactory bulb neurogenesis in the adult zebrafish are altered following reversible deafferentation |url=|journal=Neuroscience |volume=331 |pages=134–147 | pmid=27343831 | doi=10.1016/j.neuroscience.2016.06.026|pmc=6496944 }}</ref><ref>{{cite journal|last1=Kroehne|first1=Volker|last2=Freudenreich|first2=Dorian|last3=Hans|first3=Stefan|last4=Kaslin|first4=Jan|last5=Brand|first5=Michael|date=November 2011|title=Regeneration of the adult zebrafish brain from neurogenic radial glia-type progenitors|journal=Development|volume=138|issue=22|pages=4831–41|doi=10.1242/dev.072587|issn=1477-9129|pmid=22007133|doi-access=free}}</ref> The zebrafish, like the axolotl, has played a key role as a bridge organism between invertebrates and mammals. The zebrafish is a rapidly developing organism that is relatively inexpensive to maintain, while providing the field ease of genetic manipulation and a complex nervous system.

=== Chick ===
Though avians have been used primarily to study early embryonic development, in recent decades the developing [[Chicken|chick]] has played a critical role in the examination of neurogenesis and regeneration as the young chick is capable of neuronal-turnover at a young age, but loses the neurogenerative capacity into adulthood.<ref>{{cite journal|last=Fischer|first=Andy J.|date=March 2005|title=Neural regeneration in the chick retina|journal=Progress in Retinal and Eye Research|volume=24|issue=2|pages=161–182|doi=10.1016/j.preteyeres.2004.07.003|issn=1350-9462|pmid=15610972|s2cid=43652371}}</ref> The loss of neuroregenerative ability over maturation has allowed investigators to further examine genetic regulators of neurogenesis.

=== Rodents ===
{{Further|Animal testing on rodents}}
[[Rodent]]s, mice and rats, have been the most prominent model organism since the discovery of modern neurons by [[Santiago Ramón y Cajal|Santiago Ramon y Cajal]]. Rodents have a very similar architecture and a complex nervous system with very little regenerative capacity similar to that found in humans. For that reason, rodents have been heavily used in [[Pre-clinical development|pre-clinical testing]]. Rodents display a wide range of neural circuits responsible for complex behaviors making them ideal for studies of dendritic pruning and axonal shearing.<ref>{{cite journal|last1=Jones|first1=Theresa A.|last2=Schallert|first2=Timothy|date=1992-05-22|title=Overgrowth and pruning of dendrites in adult rats recovering from neocortical damage|journal=Brain Research|volume=581|issue=1|pages=156–160|doi=10.1016/0006-8993(92)90356-E|pmid=1498666|s2cid=34248397}}</ref> While the organism makes for a strong human analog, the model has its limitations not found in the previous models: higher cost of maintenance, lower breeding numbers, and the limited neurogenerative abilities.

To some extent, adult neurogenesis in rodents may be induced by selective disruption of [[Notch signalling]] in [[astrocytes]]:<ref>{{cite journal |last1=Magnusson |first1=Jens |title=A latent neurogenic program in astrocytes regulated by Notch signaling in the mouse |journal=Science |date=2014-10-10 |volume=346 |issue=6206 |pages=237–241 |doi=10.1126/science.346.6206.237 |pmid=25301628 |bibcode=2014Sci...346..237M |s2cid=14534396 |url=https://www.science.org/doi/abs/10.1126/science.346.6206.237|url-access=subscription }}</ref> this produces novel neurons which functionally integrate into the [[striatal]] circuit.<ref>{{cite journal |last1=Dorst |first1=Matthijs |title=Astrocyte-derived neurons provide excitatory input to the adult striatal circuitry |journal=Proceedings of the National Academy of Sciences |date=2021-08-17 |volume=118 |issue=33 |doi=10.1073/pnas.2104119118 |pmc=8379996  |pmid=34389674 |bibcode=2021PNAS..11804119D |doi-access=free }}</ref>

Adult neurogenesis in the subventricular zone and dentate gyrus of rodents generates [[oxidative stress]] and production of [[reactive oxygen species]] that can damage both [[DNA]] and [[lipid]]s.<ref name="Walton2012">{{cite journal |vauthors=Walton NM, Shin R, Tajinda K, Heusner CL, Kogan JH, Miyake S, Chen Q, Tamura K, Matsumoto M |title=Adult neurogenesis transiently generates oxidative stress |journal=PLOS ONE |volume=7 |issue=4 |pages=e35264 |date=2012 |pmid=22558133 |pmc=3340368 |doi=10.1371/journal.pone.0035264 |doi-access=free|bibcode=2012PLoSO...735264W }}</ref> The oxidative stress caused by postnatal neurogenesis may significantly contribute to the reduced [[learning]] and [[memory]] that occurs with increasing age.<ref name = Walton2012/>

=== Octopus ===

A [[cephalopod]] also known as the [[common octopus]], this organism has an intricate nervous system that demonstrates the brain's capacity to produce new cells. In this case and in other taxa when compared,  these organisms adapt to unpredictable environments by using newly formed brain cells.<ref>{{cite journal |vauthors=Di Cosmo A, Bertapelle C, Porcellini A, Polese G |title=Magnitude Assessment of Adult Neurogenesis in the ''Octopus vulgaris'' Brain Using a Flow Cytometry-Based Technique |journal=Front Physiol |volume=9 |pages=1050 |date=2018 |pmid=30116204 |pmc=6082961 |doi=10.3389/fphys.2018.01050 |doi-access=free}}</ref> This is over a short life-span (female about one year) where wild common octopuses focus most of their energy on mating and offspring care.<ref>{{cite book |last1=Di Cosmo |first1=A. |last2=Polese |first2=G. |chapter=Cephalopods meet neuroecology: the role of chemoreception in ''Octopus vulgaris'' reproductive behaviour |editor-first=A. |editor-last=Di Cosmo |editor2-first=W. |editor2-last=Winlow |title=Neuroecology and Neuroethology in Molluscs: The Interface Between Behaviour and Environment |publisher=NOVA Science |date=2014 |isbn=978-1-62948-983-4 |oclc=870272738 |pages=117–132 }}
</ref><ref name="pmid25449183">{{cite journal | vauthors = Polese G, Bertapelle C, Di Cosmo A | title = Role of olfaction in Octopus vulgaris reproduction | journal = Gen. Comp. Endocrinol. | volume = 210 | pages = 55–62 | date = January 2015 | pmid = 25449183 | doi = 10.1016/j.ygcen.2014.10.006 }}</ref> Findings suggest that the octopus vulgaris like other short-lived species have a complex hippocampal proliferation,<ref name="pmid18957357">{{cite journal | vauthors = Amrein I, Lipp HP | title = Adult hippocampal neurogenesis of mammals: evolution and life history | journal = Biol. Lett. | volume = 5 | issue = 1 | pages = 141–4 | date = February 2009 | pmid = 18957357 | pmc = 2657751 | doi = 10.1098/rsbl.2008.0511 }}</ref><ref name="pmid21929629">{{cite journal | vauthors = Amrein I, Isler K, Lipp HP | title = Comparing adult hippocampal neurogenesis in mammalian species and orders: influence of chronological age and life history stage | journal = Eur. J. Neurosci. | volume = 34 | issue = 6 | pages = 978–87 | date = September 2011 | pmid = 21929629 | doi = 10.1111/j.1460-9568.2011.07804.x | s2cid = 36231667 | url = https://www.zora.uzh.ch/id/eprint/54811/1/ComparingAdultHippocampalNeurogenesisInMammalianSpeciesAndOrders.pdf }}</ref> needed for spatial/navigation, and short and long-term memory.<ref>[[Hippocampus]]</ref>{{Circular reference|date=May 2020}}

=== Chickadees ===
{{Further information|Adult neurogenesis in songbirds}}
[[Black-capped chickadees]] are a well-known [[model species]] in the field of neuroscience for their neural mechanisms in [[Bird vocalization|song vocalization]], [[Synaptic plasticity|plasticity]], and memory. Black-capped chickadees are different from other species in the larger group of songbirds because they are characterized by food-caching behaviors. Due to this behavior, chickadees can be described through their remarkable [[spatial memory]]. Seasonal changes in hippocampal densities have been described since 1994<ref name=":1">{{cite journal|last1=Barnea|first1=A.|last2=Nottebohm|first2=F.|date=1994-11-08|title=Seasonal recruitment of hippocampal neurons in adult free-ranging black-capped chickadees.|journal=Proceedings of the National Academy of Sciences|volume=91|issue=23|pages=11217–21|doi=10.1073/pnas.91.23.11217|pmid=7972037|pmc=45198|bibcode=1994PNAS...9111217B|issn=0027-8424|doi-access=free}}</ref> where neuronal survival peaks during the fall (October),<ref name=":1" /> measured by [[thymidine]] (see tracking neurogenesis below) labeled cells, weeks after injection.<ref name=":1" /> When compared to non-food caching birds such as the house sparrow, chickadees had significantly more hippocampal neuron recruitment from fall to spring.<ref name=":2">{{cite journal|last1=Hoshooley|first1=Jennifer S.|last2=Sherry|first2=David F.|date=March 2007|title=Greater hippocampal neuronal recruitment in food-storing than in non-food-storing birds|journal=Developmental Neurobiology|volume=67|issue=4|pages=406–414|doi=10.1002/dneu.20316|pmid=17443797|s2cid=15930160|issn=1932-8451|doi-access=free}}</ref> The changes in hippocampal density is directly associated with increased hoarding behavior,<ref name=":2" /> especially during the winter when better spatial memory maximizes their survival.

Over the 2 decades since the initial discovery,<ref name=":1" /> the specific role of chickadee hippocampus in memory has gained wide attention. In an experimental setting, hippocampal lesions affect memory for locations,<ref>{{cite journal|last1=Hampton|first1=Robert R.|last2=Shettleworth|first2=Sara J.|date=1996|title=Hippocampal lesions impair memory for location but not color in passerine birds.|url=|journal=Behavioral Neuroscience|volume=110|issue=4|pages=831–5|doi=10.1037/0735-7044.110.4.831|pmid=8864273|issn=1939-0084}}</ref> validating previous notions for this specific role. Further, experimentally inhibiting neuronal proliferation decreases scores on spatial memory tasks,<ref>{{cite journal|last1=Hall|first1=Zachary J.|last2=Delaney|first2=Shauna|last3=Sherry|first3=David F.|date=2014-04-28|title=Inhibition of cell proliferation in black-capped chickadees suggests a role for neurogenesis in spatial learning|url=|journal=Developmental Neurobiology|volume=74|issue=10|pages=1002–10|doi=10.1002/dneu.22180|pmid=24723376|s2cid=17537082|issn=1932-8451}}</ref> supporting that new neurons hold the same role as pre-existing ones. The specific function of the hippocampus, coupled with seasonal changes in their volume, point towards their temporary advantages for spatial memory consolidation. Taken all together, adult neurogenesis in the hippocampus of black-capped chickadees suggest a selective mechanisms for neuronal survival in direct correlation with seasonal food caching behavior.

Developmentally, [[progenitor cell]]s called [[Radial glial cell|radial glial]] cells are thought to mitigate newly born neurons to their destinations.<ref>{{cite journal|last=Doetsch|first=Fiona|date=2003-10-28|title=The glial identity of neural stem cells|url=|journal=Nature Neuroscience|volume=6|issue=11|pages=1127–34|doi=10.1038/nn1144|pmid=14583753|s2cid=16088822|issn=1097-6256}}</ref> Radial glial cells extend processes from their soma in the avian ventricular zone to the parenchyma of the adult forebrain.<ref name=":3">{{cite journal|last1=Sherry|first1=David F.|last2=Hoshooley|first2=Jennifer S.|date=2010-03-27|title=Seasonal hippocampal plasticity in food-storing birds|url= |journal=Philosophical Transactions of the Royal Society B: Biological Sciences|volume=365|issue=1542|pages=933–943|doi=10.1098/rstb.2009.0220|pmid=20156817|issn=0962-8436|pmc=2830249}}</ref> These new neurons have been observed as early as 3 days after thymidine administration in the HVC<ref>{{cite journal|last1=Kirn|first1=John R.|last2=Fishman|first2=Yon|last3=Sasportas|first3=Kari|last4=Alvarez-Buylla|first4=Arturo|last5=Nottebohm|first5=Fernando|date=1999-08-30|title=Fate of new neurons in adult canary high vocal center during the first 30 days after their formation|journal=The Journal of Comparative Neurology|volume=411|issue=3|pages=487–494|doi=10.1002/(sici)1096-9861(19990830)411:3<487::aid-cne10>3.0.co;2-m|pmid=10413781|s2cid=24242592 |issn=0021-9967}}</ref> and as early as 7 days before reaching the hippocampus.<ref name=":2" /> Avian migration of new neurons are analogous to mammalian species,<ref name=":3" /> providing a future direction in exploring neurogenesis in mammalian species and beyond. However, captivity has been shown to reduce hippocampal volumes when compared to wild counterparts.<ref name=":4">{{cite journal|last1=Tarr|first1=Bernard A.|last2=Rabinowitz|first2=Jeremy S.|last3=Imtiaz|first3=Mubdiul Ali|last4=DeVoogd|first4=Timothy J.|date=December 2009|title=Captivity reduces hippocampal volume but not survival of new cells in a food-storing bird|url= |journal=Developmental Neurobiology|volume=69|issue=14|pages=972–981|doi=10.1002/dneu.20736|pmid=19813245|issn=1932-8451|pmc=4597778}}</ref> Reduced neurogenesis in captive birds may be caused by stress, lack of exercise, diminished social interaction, and limited caching opportunities.<ref name=":4" />