Editing Gap junction (section)

====Neurons====
A gap junction located between neurons is often referred to as an [[electrical synapse]]. The electrical synapse was discovered using electrical measurements before the gap junction structure was described. In mammals, electrical synapses are present throughout the central nervous system and have been studied specifically in the [[neocortex]], [[hippocampus]], [[vestibular nucleus]], [[thalamic reticular nucleus]], [[locus coeruleus]], [[inferior olivary nucleus]], mesencephalic nucleus of the [[trigeminal nerve]], [[ventral tegmental area]], [[olfactory bulb]], [[retina]] and [[spinal cord]] of [[vertebrate]]s.<ref>{{cite journal | last1 = Connors | last2 = Long | year = 2004 | title = Electrical synapses in the mammalian brain | url = https://zenodo.org/record/894386| journal = Annu Rev Neurosci | volume = 27 | pages = 393–418 | doi=10.1146/annurev.neuro.26.041002.131128 | pmid=15217338}}<!--https://zenodo.org/record/894386--></ref>  In invertibrates, gap gunctions are known to be expressed widely in the brain of the fruit fly, ''Drosophila''.<ref name="Ammer">{{cite journal 
  |title=Anatomical distribution and functional roles of electrical synapses in Drosophila
  |last1=Ammer |first1=Georg |last2=Vieira |first2=Renee M |last3=Fendl |first3=Sandra |last4=Borst |first4=Alexander
  |journal=Current Biology
  |volume=32
  |issue=9
  |year=2022
  |pages=2022–2036.e4 |publisher=Elsevier|doi=10.1016/j.cub.2022.03.040 |pmid=35385694 |bibcode=2022CBio...32E2022A }}</ref>

There has been some observation of coupling in the [[locus coeruleus]] between weak neurons and [[glial cell]]s and in the [[cerebellum]] between [[Purkinje neuron]]s and [[Bergmann glial cell]]s. It appears that [[astrocyte]]s are coupled by gap junctions, both to other astrocytes and to [[oligodendrocyte]]s.<ref>{{cite journal|last=Orthmann-Murphy|first=Jennifer L.|author2=Abrams, Charles K. |author3=Scherer, Steven S. |title=Gap Junctions Couple Astrocytes and Oligodendrocytes|journal=Journal of Molecular Neuroscience|date=May 2008|volume=35|issue=1|pages=101–116|doi=10.1007/s12031-007-9027-5|pmid=18236012 |pmc=2650399}}</ref> Moreover, mutations in the gap junction genes Cx43 and Cx56.6 cause white matter degeneration similar to that observed in [[Pelizaeus–Merzbacher disease]] and [[multiple sclerosis]].

Connexin proteins expressed in neuronal gap junctions include m[[GJD2|CX36]], mCX57, and m[[GJC1|CX45]], with mRNAs for at least five other connexins (m[[GJB2|Cx26]], m[[GJC3|Cx30.2]], m[[GJB1|Cx32]], m[[GJA1|Cx43]], m[[GJC2|Cx47]]) detected but without immunocytochemical evidence for the corresponding protein within ultrastructurally-defined gap junctions. Those mRNAs appear to be downregulated or destroyed by micro interfering RNAs ([[miRNA]]s) that are cell-type and cell-lineage specific.

Within the brain of the fruit fly ''Drosophila'', gap junctions are known to be critical for a variety of functions.<ref>{{cite journal 
  |title=Heterotypic gap junctions between two neurons in the Drosophila brain are critical for memory
  |last1= Wu |first1= Chia-Lin |last2= Shih |first2= Meng-Fu Maxwell |last3= Lai |first3= Jason Sih-Yu
  |last4= Yang |first4= Hsun-Ti |last5= Turner |first5= Glenn C |last6= Chen |first6= Linyi
  |last7= Chiang |first7= Ann-Shyn
  |journal=Current Biology
  |volume=21
  |issue=10
  |pages=848–854
  |year=2011
  |publisher=Elsevier  |doi= 10.1016/j.cub.2011.02.041 |pmid= 21530256 |bibcode= 2011CBio...21..848W }}</ref>
<ref name="Ammer"/>
<ref>{{cite journal 
  |title=Gap junction networks in mushroom bodies participate in visual learning and memory in Drosophila
  |last1=Liu |first1=Qingqing |last2=Yang |first2=Xing |last3=Tian |first3=Jingsong  |last4=Gao |first4=Zhongbao
  |last5=Wang |first5=Meng |last6=Li |first6=Yan |last7=Guo |first7=Aike
  |journal=eLife
  |volume=5
  |pages=e13238
  |year=2016
  |url=https://elifesciences.org/articles/13238.pdf
  |publisher=eLife Sciences Publications, Ltd |doi=10.7554/eLife.13238 |doi-access=free |pmid=27218450 |pmc=4909397 }}</ref>

'''Astrocytes'''

An important feature of astrocytes is their high expression levels of the gap junction proteins [[connexin 30]] (Cx30) and [[connexin 43]] (Cx43). These proteins play crucial roles in regulating brain homeostasis through potassium buffering, intercellular communication, and nutrient transport. <ref>{{Cite journal |last1=Pannasch |first1=Ulrike |last2=Vargová |first2=Lydia |last3=Reingruber |first3=Jürgen |last4=Ezan |first4=Pascal |last5=Holcman |first5=David |last6=Giaume |first6=Christian |last7=Syková |first7=Eva |last8=Rouach |first8=Nathalie |date=2011-05-17 |title=Astroglial networks scale synaptic activity and plasticity |journal=Proceedings of the National Academy of Sciences |language=en |volume=108 |issue=20 |pages=8467–8472 |doi=10.1073/pnas.1016650108 |doi-access=free |issn=0027-8424 |pmc=3100942 |pmid=21536893|bibcode=2011PNAS..108.8467P }}</ref> Connexins typically form gap junction channels that allow direct intercellular communication between astrocytes. However, they can also form hemichannels that facilitate the exchange of ions and molecules with the extracellular space.

Studies have highlighted channel-independent functions of connexins, involving intracellular signaling, protein interactions, and cell adhesion. <ref>{{Cite journal |last1=Ghézali |first1=Grégory |last2=Dallérac |first2=Glenn |last3=Rouach |first3=Nathalie |date=2016 |title=Perisynaptic astroglial processes: dynamic processors of neuronal information |url=http://link.springer.com/10.1007/s00429-015-1070-3 |journal=Brain Structure and Function |language=en |volume=221 |issue=5 |pages=2427–2442 |doi=10.1007/s00429-015-1070-3 |pmid=26026482 |issn=1863-2653}}</ref> Specifically, Cx30 has been shown to regulate the insertion of astroglial processes into synaptic clefts, which controls the efficacy of glutamate clearance. This, in turn, affects the synaptic strength and long-term plasticity of excitatory terminals, indicating a significant role in modulating synaptic transmission. Levels of Cx30 regulate synaptic glutamate concentration, hippocampal excitatory synaptic strength, plasticity, and memory. Astroglial networks have a physiologically optimized size to appropriately regulate neuronal functions.<ref>{{Cite journal |last1=Hardy |first1=Eléonore |last2=Moulard |first2=Julien |last3=Walter |first3=Augustin |last4=Ezan |first4=Pascal |last5=Bemelmans |first5=Alexis-Pierre |last6=Mouthon |first6=Franck |last7=Charvériat |first7=Mathieu |last8=Rouach |first8=Nathalie |last9=Rancillac |first9=Armelle |date=2023-04-11 |editor-last=Eroglu |editor-first=Cagla |title=Upregulation of astroglial connexin 30 impairs hippocampal synaptic activity and recognition memory |journal=PLOS Biology |language=en |volume=21 |issue=4 |pages=e3002075 |doi=10.1371/journal.pbio.3002075 |doi-access=free |issn=1545-7885 |pmc=10089355 |pmid=37040348 |quote=Cx30 upregulation increases the connectivity of astroglial networks, it decreases spontaneous and evoked synaptic transmission. This effect results from a reduced neuronal excitability and translates into an alteration in the induction of synaptic plasticity and an in vivo impairment in learning processes. Altogether, these results suggest that astroglial networks have a physiologically optimized size to appropriately regulate neuronal functions.}}</ref>

Cx30 is not limited to regulating excitatory synaptic transmission but also plays a crucial role in inhibitory synaptic regulation and broader neuronal network activities.<ref>{{Cite journal |last1=Hardy |first1=Eléonore |last2=Cohen-Salmon |first2=Martine |last3=Rouach |first3=Nathalie |last4=Rancillac |first4=Armelle |date=September 2021 |title=Astroglial Cx30 differentially impacts synaptic activity from hippocampal principal cells and interneurons |url=https://onlinelibrary.wiley.com/doi/10.1002/glia.24017 |journal=Glia |language=en |volume=69 |issue=9 |pages=2178–2198 |doi=10.1002/glia.24017 |pmid=33973274 |issn=0894-1491 |quote=Cx30 differentially alters the electrophysiological and morphological properties of hippocampal cell populations. They modulates both excitatory and inhibitory inputs. Astrocytes, via Cx30, are thus active modulators of both excitatory and inhibitory synapses in the hippocampus.}}</ref> This highlights the importance of connexins in maintaining the intricate balance required for proper brain function.