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The action of BDNF on GABA_A currents changes from potentiating to suppressing during maturation of rat hippocampal CA1 pyramidal neurons

Yoshito Mizoguchi, Hitoshi Ishibashi and Junichi Nabekura

During the development of the hippocampus, the action of GABA shifts from depolarizing to hyperpolarizing, and brain-derived neurotrophic factor (BDNF) has important roles in GABAergic transmission. We demonstrate that BDNF (20 ng ml^-1) rapidly and reversibly potentiates postsynaptic GABA_A receptor-mediated currents (by 80.5 ± 14.3 %, n = 10) in hippocampal CA1 pyramidal neurons isolated from postnatal day (P)6 rats, using nystatin-perforated patch-clamp recordings. This potentiation is caused by an elevation of intracellular Ca²⁺ that occurs in response to the activation of Trk B receptor tyrosine kinase and phospholipase C-. The modulation of the GABA_A responses by BDNF in hippocampal CA1 pyramidal neurons isolated from P10 rats was more diverse (from potentiating to inhibitory), and at P14, BDNF induced a long-lasting inhibition. In addition, Ca²⁺/calmodulin-dependent protein kinase 2 plays important roles in the potentiating, but not in the inhibitory effect, of BDNF on the GABA_A responses. These results suggest that changes in the intracellular signalling pathway could contribute to the developmental shift of the actions of BDNF on inhibitory systems.

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