Editing Brain-derived neurotrophic factor (section)

=== GABAergic signaling ===

One mechanism through which BDNF appears to maintain elevated levels of neuronal excitation is through preventing [[GABA]]ergic signaling activities.<ref name="Henneberger_2002">{{cite journal | vauthors = Henneberger C, Jüttner R, Rothe T, Grantyn R | title = Postsynaptic action of BDNF on GABAergic synaptic transmission in the superficial layers of the mouse superior colliculus | journal = Journal of Neurophysiology | volume = 88 | issue = 2 | pages = 595–603 | date = August 2002 | pmid = 12163512 | doi =  10.1152/jn.2002.88.2.595| s2cid = 9287511 }}</ref>  While glutamate is the brain's major excitatory neurotransmitter and phosphorylation normally activates receptors, [[GABA]] is the brain's primary inhibitory neurotransmitter and phosphorylation of [[GABAA receptor|GABA<sub>A</sub> receptor]]s tend to reduce their activity.{{Clarify|date=March 2019}} Blockading BDNF signaling with a tyrosine kinase inhibitor or a PKC inhibitor in wild type mice produced significant reductions in spontaneous [[action potential]] frequencies that were mediated by an increase in the amplitude of GABAergic [[Inhibitory postsynaptic potential|inhibitory postsynaptic currents]] (IPSC).<ref name="Henneberger_2002"/>  Similar effects could be obtained in BDNF knockout mice, but these effects were reversed by local application of BDNF.<ref name="Henneberger_2002"/> 
This suggests BDNF increases excitatory synaptic signaling partly through the post-synaptic suppression of GABAergic signaling by activating PKC through its association with TrkB.<ref name="Henneberger_2002"/>  Once activated, PKC can reduce the amplitude of IPSCs through to GABAA receptor phosphorylation and inhibition.<ref name="Henneberger_2002"/>  In support of this putative mechanism, activation of PKCε leads to phosphorylation of N-ethylmaleimide-sensitive factor (NSF) at serine 460 and threonine 461, increasing its ATPase activity which downregulates GABAA receptor surface expression and subsequently attenuates inhibitory currents.<ref name="pmid20962217">{{cite journal | vauthors = Chou WH, Wang D, McMahon T, Qi ZH, Song M, Zhang C, Shokat KM, Messing RO | title = GABAA receptor trafficking is regulated by protein kinase C(epsilon) and the N-ethylmaleimide-sensitive factor | journal = The Journal of Neuroscience | volume = 30 | issue = 42 | pages = 13955–65 | date = October 2010 | pmid = 20962217 | pmc = 2994917 | doi = 10.1523/JNEUROSCI.0270-10.2010 }}</ref>