Impaired GABAergic inhibition in the visual cortex of brain-derived neurotrophic factor heterozygous knockout mice

Brain derived neurotrophic factor (BDNF) promotes the formation, maturation and stabilization of inhibitory synapses in the central nervous system. In addition, BDNF has been suggested to regulate the critical period for ocular dominance plasticity in the visual system. Here we further evaluated the role of BDNF in the visual cortex by studying the GABAergic synaptic transmission under conditions of chronically reduced levels of BDNF. Whole-cell patch-clamp recordings were performed from pyramidal neurons located in layers II/III of visual cortical slices in heterozygous BDNF knockout mice (BDNF (+/-)) and their wild-type littermates at the age of 21-25 days. The BDNF (+/-) mice showed a decreased frequency and amplitude of miniature inhibitory postsynaptic currents (mIPSCs) as well as a reduced amplitude and prolonged decay time constant of evoked IPSCs. Further analyses indicated an impaired presynaptic GABAergic function in BDNF (+/-) mice, as shown by the decreased release probability, steady-state release and synchronous release of GABA. However, the number of functional release sites remained unchanged. In line with these observations, an impaired glutamate-driven GABA release was observed in BDNF (+/-) mice. Furthermore, the overall balance in the strength of cortical excitation to inhibition shifted towards a decreased inhibition. Finally, the reversal potential for chloride-mediated evoked IPSCs was not affected. These findings suggested that chronically reduced levels of BDNF strongly impair the GABAergic inhibitory function in visual cortex by altering postsynaptic properties and by reducing presynaptic GABA release as well as the overall strength of inhibition onto pyramidal neurons within the cortical network. These impairments of inhibitory function are compatible with a rather immature status of the GABAergic system in BDNF (+/-) mice, which supports the hypothesis that the level of expression for BDNF critically affects maturation and function of the GABAergic inhibition.