Inhibition of GABAA synaptic responses by brain-derived neurotrophic factor (BDNF) in rat hippocampus.
Brain-derived neurotrophic factor (BDNF) is one of neurotrophins involved in the development and maintenance of both the peripheral nervous system and CNS. Although the expression of BDNF and its receptor TrkB still occurs in the adult stage, their physiological role in the mature CNS is not fully understood. In the present study we examined in detail the possibility that BDNF modulates synaptic neurotransmissions by using patch-clamp technique in rat hippocampal CA1 region. BDNF (20-100 ng/ml) did not show any appreciable effect on evoked EPSCs, but it markedly reduced both evoked and spontaneous IPSCs within 5 min, and the reduction persisted while BDNF was present. BDNF also attenuated GABAA receptor-mediated response to applied GABA. However, BDNF failed to attenuate IPSCs when the postsynaptic pyramidal neuron was loaded intracellularly with 200 nM K252a, an alkaloid that inhibits the kinase activity of Trk receptor family, through the patch pipette. Intracellular application of 200 nM K252b, a weaker inhibitor of Trk-type kinase, did not affect the inhibition. The attenuating effect also was prevented by postsynaptic injection of U73122 (5 microM), a broad-spectrum PLC inhibitor, and by strong chelation of intracellular Ca2+ with 10 mM BAPTA. These data suggest that BDNF modulates GABAA synaptic responses by postsynaptic activation of Trk-type receptor and subsequent Ca2+ mobilization in the CNS.
Tanaka
T
T
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113, Japan.
Saito
H
H
Matsuki
N
N
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*
D019208:Brain-Derived Neurotrophic Factor; D011963:Receptors, GABA-A