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

In the mature healthy mammalian neuronal networks, γ-aminobutyric acid (GABA) mediates synaptic inhibition by acting on GABA_A and GABA_B receptors (GABA_AR, GABA_BR). 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_AR produces paradoxical depolarizing action that favors neuronal network excitation. The depolarizing action of GABA_AR is a consequence of deregulated chloride ion homeostasis. In addition to depolarizing action of GABA_AR, the GABA_BR 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^NTR). In this review article, we discuss recent finding illuminating how mBDNF-TrkB and proBDNF-p75^NTR signaling pathways regulate GABA related neurotransmission under physiological conditions and during epilepsy.