Editing GABA (section)

=== Brain development ===
GABA is an inhibitory transmitter in the mature brain; its actions were thought to be primarily excitatory in the developing brain.<ref name="pmid18500393"/><ref name="pmid17928584">{{cite journal |vauthors= Ben-Ari Y, Gaiarsa JL, Tyzio R, Khazipov R |title= GABA: a pioneer transmitter that excites immature neurons and generates primitive oscillations |journal= Physiol. Rev. |volume= 87 |issue= 4 |pages= 1215–1284 |date= October 2007 |pmid= 17928584 |doi= 10.1152/physrev.00017.2006}}</ref> The gradient of chloride was reported to be reversed in immature neurons, with its reversal potential higher than the resting membrane potential of the cell; activation of a GABA-A receptor thus leads to efflux of Cl<sup>−</sup> ions from the cell (that is, a depolarizing current). The differential gradient of chloride in immature neurons was shown to be primarily due to the higher concentration of NKCC1 co-transporters relative to KCC2 co-transporters in immature cells. GABAergic interneurons mature faster in the hippocampus and the GABA machinery appears earlier than glutamatergic transmission. Thus, GABA is considered the major excitatory neurotransmitter in many regions of the brain before the [[neural development|maturation]] of [[glutamate]]rgic synapses.<ref>{{Cite book|last1=Schousboe|first1=Arne|url=https://books.google.com/books?id=rrKVDQAAQBAJ&pg=PA311|title=The Glutamate/GABA-Glutamine Cycle: Amino Acid Neurotransmitter Homeostasis|last2=Sonnewald|first2=Ursula|date=2016-11-25|publisher=Springer|isbn=978-3-319-45096-4|language=en}}</ref>

In the developmental stages preceding the formation of synaptic contacts, GABA is synthesized by neurons and acts both as an [[autocrine]] (acting on the same cell) and [[paracrine]] (acting on nearby cells) signalling mediator.<ref name="isbn0-87893-697-1">{{cite book |veditors=Purves D, Fitzpatrick D, Hall WC, Augustine GJ, Lamantia AS |title= Neuroscience |edition= 4th |publisher= Sinauer |location= Sunderland, Mass |year= 2007 |pages= [https://archive.org/details/neuroscienceissu00purv/page/n160 135], box 6D |isbn= 978-0-87893-697-7 |url=https://archive.org/details/neuroscienceissu00purv|url-access=limited }}</ref><ref name="pmid16512345">{{cite book |vauthors= Jelitai M, Madarasz E |title= GABA in Autism and Related Disorders |chapter= The role of GABA in the early neuronal development  |volume= 71 |pages= 27–62 |year= 2005 |pmid= 16512345 |doi= 10.1016/S0074-7742(05)71002-3 |chapter-url=https://books.google.com/books?id=IUb5ewXY09YC&pg=PA27 |isbn= 9780123668721 |series= International Review of Neurobiology}}</ref> The [[ganglionic eminence]]s also contribute greatly to building up the GABAergic cortical cell population.<ref name="pmid11715055">{{cite journal |vauthors= Marín O, Rubenstein JL |title= A long, remarkable journey: tangential migration in the telencephalon |journal= Nat. Rev. Neurosci. |volume= 2 |issue= 11 |pages= 780–90 |date= November 2001 |pmid= 11715055 |doi= 10.1038/35097509|s2cid= 5604192 }}</ref>

GABA regulates the proliferation of neural [[progenitor cell]]s,<ref name="pmid8845153">{{cite journal |vauthors= LoTurco JJ, Owens DF, Heath MJ, Davis MB, Kriegstein AR |title= GABA and glutamate depolarize cortical progenitor cells and inhibit DNA synthesis |journal= Neuron |volume= 15 |issue= 6 |pages= 1287–1298 |date= December 1995 |pmid= 8845153 |doi= 10.1016/0896-6273(95)90008-X|s2cid= 1366263 |doi-access= free }}</ref><ref name="pmid10908617">{{cite journal |vauthors= Haydar TF, Wang F, Schwartz ML, Rakic P |title= Differential modulation of proliferation in the neocortical ventricular and subventricular zones |journal= J. Neurosci. |volume= 20 |issue= 15 |pages= 5764–74 |date= August 2000 |pmid= 10908617 |pmc= 3823557 |doi= 10.1523/JNEUROSCI.20-15-05764.2000}}</ref> the migration<ref name="pmid9698329">{{cite journal |vauthors= Behar TN, Schaffner AE, Scott CA, O'Connell C, Barker JL |title= Differential response of cortical plate and ventricular zone cells to GABA as a migration stimulus |journal= J. Neurosci. |volume= 18 |issue= 16 |pages= 6378–87 |date= August 1998 |pmid= 9698329 |pmc= 6793175 |doi= 10.1523/JNEUROSCI.18-16-06378.1998}}</ref> and [[cellular differentiation|differentiation]]<ref name="pmid11371348">{{cite journal |vauthors= Ganguly K, Schinder AF, Wong ST, Poo M |title= GABA itself promotes the developmental switch of neuronal GABAergic responses from excitation to inhibition |journal= Cell |volume= 105 |issue= 4 |pages= 521–32 |date= May 2001 |pmid= 11371348 |doi= 10.1016/S0092-8674(01)00341-5|s2cid= 8615968 |doi-access= free }}</ref><ref name="pmid8390627">{{cite journal |vauthors= Barbin G, Pollard H, Gaïarsa JL, Ben-Ari Y |title= Involvement of GABAA receptors in the outgrowth of cultured hippocampal neurons |journal= Neurosci. Lett. |volume= 152 |issue= 1–2 |pages= 150–154 |date= April 1993 |pmid= 8390627 |doi= 10.1016/0304-3940(93)90505-F|s2cid= 30672030 }}</ref> the elongation of [[neurite]]s<ref name="pmid11264309">{{cite journal |vauthors= Maric D, Liu QY, Maric I, Chaudry S, Chang YH, Smith SV, Sieghart W, Fritschy JM, Barker JL |title= GABA expression dominates neuronal lineage progression in the embryonic rat neocortex and facilitates neurite outgrowth via GABA(A) autoreceptor/Cl<sup>−</sup> channels |journal= J. Neurosci. |volume= 21 |issue= 7 |pages= 2343–60 |date= April 2001 |pmid= 11264309 |pmc= 6762405 |doi= 10.1523/JNEUROSCI.21-07-02343.2001}}</ref> and the formation of synapses.<ref name="pmid12209121">{{cite journal |vauthors= Ben-Ari Y |title= Excitatory actions of gaba during development: the nature of the nurture |journal= Nat. Rev. Neurosci. |volume= 3 |issue= 9 |pages= 728–739 |date= September 2002 |pmid= 12209121 |doi= 10.1038/nrn920|s2cid= 8116740 |url=http://www.hal.inserm.fr/inserm-00484852 |url-access= subscription }}</ref>

GABA also regulates the growth of [[embryonic stem cell|embryonic]] and [[neural stem cell]]s. GABA can influence the development of neural progenitor cells via [[brain-derived neurotrophic factor]] (BDNF) expression.<ref name="pmid12163549">{{cite journal |vauthors= Obrietan K, Gao XB, Van Den Pol AN |title= Excitatory actions of GABA increase BDNF expression via a MAPK-CREB-dependent mechanism—a positive feedback circuit in developing neurons |journal= J. Neurophysiol. |volume= 88 |issue= 2 |pages= 1005–15 |date= August 2002 |pmid= 12163549 |doi= 10.1152/jn.2002.88.2.1005}}</ref> GABA activates the [[GABAA receptor|GABA<sub>A</sub> receptor]], causing cell cycle arrest in the S-phase, limiting growth.<ref name="pmid18852839">{{cite journal |vauthors= Wang DD, Kriegstein AR, Ben-Ari Y |title= GABA regulates stem cell proliferation before nervous system formation |journal= Epilepsy Curr |volume= 8 |issue= 5 |pages= 137–9 |year= 2008 |pmid= 18852839 |pmc= 2566617 |doi= 10.1111/j.1535-7511.2008.00270.x}}</ref>