AUTHOR=Porcher Christophe , Medina Igor , Gaiarsa Jean-Luc 

TITLE=Mechanism of BDNF Modulation in GABAergic Synaptic Transmission in Healthy and Disease Brains

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=12

YEAR=2018

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2018.00273

DOI=10.3389/fncel.2018.00273

ISSN=1662-5102

ABSTRACT=<p>In the mature healthy mammalian neuronal networks, γ-aminobutyric acid (GABA) mediates synaptic inhibition by acting on GABA<sub>A</sub> and GABA<sub>B</sub> receptors (GABA<sub>A</sub>R, GABA<sub>B</sub>R). In immature networks and during numerous pathological conditions the strength of GABAergic synaptic inhibition is much less pronounced. In these neurons the activation of GABA<sub>A</sub>R produces paradoxical depolarizing action that favors neuronal network excitation. The depolarizing action of GABA<sub>A</sub>R is a consequence of deregulated chloride ion homeostasis. In addition to depolarizing action of GABA<sub>A</sub>R, the GABA<sub>B</sub>R mediated inhibition is also less efficient. One of the key molecules regulating the GABAergic synaptic transmission is the brain derived neurotrophic factor (BDNF). BDNF and its precursor proBDNF, can be released in an activity-dependent manner. Mature BDNF operates via its cognate receptors tropomyosin related kinase B (TrkB) whereas proBDNF binds the p75 neurotrophin receptor (p75<sup>NTR</sup>). In this review article, we discuss recent finding illuminating how mBDNF-TrkB and proBDNF-p75<sup>NTR</sup> signaling pathways regulate GABA related neurotransmission under physiological conditions and during epilepsy.</p>