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Retrograde signaling
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===Types of retrograde neurotransmitters=== The most prevalent endogenous retrograde neurotransmitters are [[nitric oxide]]<ref name="O'Dell 1991" /><ref name="Malen 1997" /> and various [[cannabinoid|endocannabinoid]]s, which are lipophilic ligands.<ref name=":0" /><ref>{{Cite book|last1=Vaughan|first1=C. W.|last2=Christie|first2=M. J.|date=2005|title=Retrograde signalling by endocannabinoids|series=Handbook of Experimental Pharmacology|volume=168|issue=168|pages=367–383|doi=10.1007/3-540-26573-2_12|issn=0171-2004|pmid=16596781|isbn=3-540-22565-X}}</ref> The retrograde neurotransmitter, nitric oxide (NO) is a soluble gas that can readily diffuse through various cell membranes.<ref>{{Cite journal|last1=Arancio|first1=Ottavio|last2=Kiebler|first2=Michael|last3=Lee|first3=C. Justin|last4=Lev-Ram|first4=Varda|last5=Tsien|first5=Roger Y.|last6=Kandel|first6=Eric R.|last7=Hawkins|first7=Robert D.|date=1996-12-13|title=Nitric Oxide Acts Directly in the Presynaptic Neuron to Produce Long-Term Potentiationin Cultured Hippocampal Neurons|journal=Cell|language=English|volume=87|issue=6|pages=1025–1035|doi=10.1016/S0092-8674(00)81797-3|pmid=8978607|s2cid=10550701|issn=0092-8674|doi-access=free}}</ref> Nitric oxide synthase is the enzyme responsible for the synthesis of NO in various presynaptic cells.<ref>{{Cite journal|last1=Overeem|first1=Kathie A.|last2=Ota|first2=Kristie T.|last3=Monsey|first3=Melissa S.|last4=Ploski|first4=Jonathan E.|last5=Schafe|first5=Glenn E.|date=2010-02-05|title=A Role for Nitric Oxide-Driven Retrograde Signaling in the Consolidation of a Fear Memory|journal=Frontiers in Behavioral Neuroscience|volume=4|page=2|doi=10.3389/neuro.08.002.2010|issn=1662-5153|pmc=2820379|pmid=20161806|doi-access=free}}</ref> Specifically, NO is known to play a critical role in LTP, which plays an important role in memory storage within the hippocampus.<ref>{{Cite web|title=Long-Term Potentiation - an overview {{!}} ScienceDirect Topics|url=https://www.sciencedirect.com/topics/neuroscience/long-term-potentiation|access-date=2021-05-05|website=www.sciencedirect.com}}</ref> Additionally, literature suggests that NO can act as intracellular messengers in the brain and can also have an effect on the presynaptic glutamatergic and GABAergic synapses.<ref>{{Cite journal|last1=Hardingham|first1=Neil|last2=Dachtler|first2=James|last3=Fox|first3=Kevin|date=2013|title=The role of nitric oxide in pre-synaptic plasticity and homeostasis|journal=Frontiers in Cellular Neuroscience|language=English|volume=7|page=190|doi=10.3389/fncel.2013.00190|pmid=24198758|pmc=3813972|issn=1662-5102|doi-access=free}}</ref> Utilizing retrograde signaling, endocannabinoids, a type of retrograde neurotransmitter, are activated when they bind to G-protein coupled receptors on the presynaptic terminals of neurons.<ref name=":1">{{Cite journal|date=2002-06-01|title=Retrograde signaling by endocannabinoids|url=https://www.sciencedirect.com/science/article/abs/pii/S0959438802003288|journal=Current Opinion in Neurobiology|language=en|volume=12|issue=3|pages=324–330|doi=10.1016/S0959-4388(02)00328-8|issn=0959-4388|last1=Kreitzer|first1=A.|last2=Regehr|first2=W. G.|pmid=12049940|s2cid=5846728|url-access=subscription}}</ref> The activation of endocannabinoids results in the release of particular neurotransmitters at the excitatory and inhibitory synapses of a neuron, ultimately impacting various forms of plasticity.<ref>{{Cite journal|date=2012-10-04|title=Endocannabinoid Signaling and Synaptic Function|journal=Neuron|language=en|volume=76|issue=1|pages=70–81|doi=10.1016/j.neuron.2012.09.020|issn=0896-6273|doi-access=free|last1=Castillo|first1=Pablo E.|last2=Younts|first2=Thomas J.|last3=Chávez|first3=Andrés E.|last4=Hashimotodani|first4=Yuki|pmid=23040807|pmc=3517813}}</ref><ref name=":0" /><ref name=":1" />
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