BDNF occludes GABA_B receptor‐mediated inhibition of GABA release in rat hippocampal CA1 pyramidal neurons

Abstract

During the development of the rat hippocampus, both gamma-aminobutyric acid (GABA)(B) autoreceptors and brain-derived neurotrophic factor (BDNF) play important roles in the formation of GABAergic synapses as well as in the GABA(A) receptor-mediated transmissions. While a number of studies have reported rapid effects of BDNF on GABA(A) receptor-mediated responses, the interactions between GABA(B) autoreceptors and BDNF are less clear. Using conventional whole-cell patch-clamp recordings, we demonstrated here that BDNF significantly occludes baclofen-induced suppression of GABA(A) receptor-mediated transmissions in each of the preparations including hippocampal slices prepared from P14 rats, hippocampal CA1 pyramidal neurons isolated from P14 and P21 rats, and cultured hippocampal pyramidal neurons. This effect of BDNF was rapid and reversible, and was mediated via the activation of presynaptic TrkB receptor tyrosine kinases, and subsequent activation of phospholipase C and protein kinase C. On the contrary, in hippocampal CA1 pyramidal neurons isolated from P7 rats, BDNF failed to occlude the GABA(B) receptor-mediated inhibition of GABA release. Thus, the ability of BDNF to occlude the GABA(B) receptor-mediated inhibition of GABA release develops between P7 and P14. This demonstrates a novel aspect of the effects of BDNF on inhibitory transmissions in rat hippocampus, which may have some functional roles in the induction of developmental plasticity and/or pathophysiology of epilepsy.

GET73 increases rat extracellular hippocampal CA1 GABA levels through a possible involvement of local mGlu5 receptor

“…Thus, GET73 affects both hippocampal glutamate and GABA levels without interfering with local aminoacid neurotransmitter reuptake mechanisms. Furthermore, neither selective intrahippocampal CA1 GABA A nor GABA B receptor blockade—with bicuculline and CGP35348, respectively—alters the GET73 (10 mg/kg)‐induced increase in local GABA release—ruling out the possibility a local GET73‐induced GABA A and/or GABA B receptor‐mediate increase in GABA levels (Cobb et al, ; Davies et al, ; Mizoguchi et al, ). The present findings, at least in part, support recent in vitro rat binding studies reporting that GET73 fails to display affinity for a series of alternative receptor targets, including the dopamine (D 1 , D 2 , D 3 ), serotonin (5‐HT 1 , 5‐HT 2 , 5‐HT 3 ), GABA A , GABA B , or ionotropic glutamate (NMDA, AMPA, or kainate) receptor (Loche et al, ).…”

Endogenous cannabinoids mediate the effect of BDNF at CA1 inhibitory synapses in the hippocampus

“…In rat hippocampal cultures, BDNF caused a rapid reduction in the postsynaptic GABA receptor number that was responsible for a decrease in mIPSC amplitude (Brunig, Penschuck, Berninger, Benson, & Fritschy, 2001). A study by Mizoguchi et al (2006) suggested that the effect of BDNF on GABA release was dependent on age. BDNF suppressed mIPSC frequency and amplitude in hippocampal preparations of age P14 and P21 rats but not in P7 rats.…”