Excitatory and inhibitory neurotransmitter release at synapses in the visual cortex of heterozygous knock-out mice for brain-derived neurotrophic factor

Brain derived neurotrophic factor (BDNF) is a member of the nerve growth factor family (NGF), and involved in axonal and dendritic growth as well as synapse formation. BDNF is also reported to contribute to fast synaptic transmission and plasticity. The effect of BDNF on synaptic transmission seems to be region specific. In this study we further characterize the influence of BDNF on synaptic transmission in the mammalian visual cortex. We used 21-27 days old mice, which partially lack the BDNF coding gene (Heterozygous mice, HT, n=19). Age matched wild type littermates served as controls (n=20). Spontaneous postsynaptic currents were recorded from layer II/III pyramidal neurons of the visual cortex by using the whole-cell patch clamp method. We analyzed miniature postsynaptic excitatory currents (mEPSCs) and miniature inhibitory postsynaptic currents (mIPSPs). Furthermore, the paired pulse modulation (PPM) ratio was calculated after electrical stimulation of afferent fibers in cortical layer IV. The frequency of both, mEPSCs and mIPSCs were found to be significantly reduced (p=0.019; p=0.0001, respectively) in the visual cortex of HT mice (n=9) when compared to results from wild type controls (n=9). The amplitude of mIPSCs was significantly decreased in HT (p=0.007, n=8) compared to recordings in slices from wild type mice (n=17). However, the amplitude of mEPSCs did not differ between HT and wild type animals. The paired pulse interaction ratio was significantly higher at inter stimulus intervals of 35 ms and 50 ms in HT animals compared to wild type controls (p=0.03 and p=0.04, respectively). These findings indicate that reduced level of BDNF effects both, excitatory and inhibitory neurotransmission in the neocortex. Furthermore, the reduced mEPSC frequency and increased PPF ratio in HT animals suggest a decreased presynaptic glutamate release. This study was supported by the IGSN and DFG (SBF 509, C4)