Download Effects of reduced levels of Brain-derived neurotrophic factor (BDNF

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Transcript
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Abstract
Brain derived neurotrophic factor (BDNF) plays an important role in activity
dependent processes of the central nervous system like in synaptic transmission and
plasticity. The effect of BDNF on synaptic transmission seems to be region specific
and also differs according to pre- and post-synaptic cell types. In this study we further
characterized the influence of chronically reduced levels of BDNF on synaptic
transmission in the mammalian visual cortex. We used 21-25 days old mice, which
partially lack the BDNF coding gene (BDNF +/-), while matched wild type
littermates (wt) served as controls. By using whole-cell patch clamp recordings we
studied possible presynaptic and postsynaptic alterations for both, the excitatory and
inhibitory transmission. Our data revealed that the excitatory synaptic transmission
was impaired in the visual cortex of BDNF (+/-) mice. The effect was mainly due to a
decreased release of presynaptic glutamate. In contrast, the functional properties of
AMPAR and NMDAR mediated currents were not different indicating a preservation
of the postsynaptic properties of the glutamatergic neurotransmission. For the
inhibitory system, the release probability and frequency of mIPSCs were decreased in
BDNF (+/-) mice, whereas the number of release sites was not different. Also the
amplitude of evoked and spontaneous inhibitory currents was reduced, and the decay
constants were prolonged in BDNF (+/-) mice. In this case alterations were more
profound and suggested both pre- and post-synaptic roles of BDNF. These findings
suggest that chronically reduced BDNF depressed both the excitatory and inhibitory
synaptic transmission in the visual cortex, but via different cellular mechanisms, and
the effect appears more prominent on the inhibitory system.