| Budget Amount *help |
¥14,600,000 (Direct Cost: ¥14,600,000)
Fiscal Year 2006: ¥5,900,000 (Direct Cost: ¥5,900,000)
Fiscal Year 2005: ¥8,700,000 (Direct Cost: ¥8,700,000)
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| Research Abstract |
I investigated the role of BDNF in the production of long-term potentiation (LTP) at inhibitory synapses of layer 5 pyramidal neurons in developing (postnatal 20-30 days) rat visual cortex. In visual cortical slices, postsynaptic currents were recorded from layer 5 pyramidal neurons in response to electrical stimulation of presynaptic fibers under pharmacological blockade of excitatory synaptic transmission using whole-cell voltage-clamp method. To induce LTP, high-frequency (50 Hz, 1 Hz) stimulation (HFS) was applied 10 times at intervals of 10 s. Investigation using 200 nM of K252a, which inhibits Trk tyrosine kinases selectively at that dose, demonstrated that LTP induction required the activation of presynaptic Trk receptors. Bath application of TrkB-IgG, selectively binding to TrkB, and anti-BDNF antibody, inhibiting BDNF function, both prevented the induction of LTP, indicating that the activation of TrkB with BDNF is necessary to induce LTP. Although LTP was not produced in the cells to which Ca^<2+> chelator BAPTA (30 mM) was loaded from patch pipettes, LTP occurred even in this condition when BDNF was applied during HFS. In addition, LTP induction was prevented by pharmacological blockade of MAP kinase, which is one of the downstream signaling molecules of TrkB. It is known that BDNF is synthesized and released from pyramidal neurons but not inhibitory neurons in neocortex. Thus, these results suggest that HFS produces postsynaptic Ca^<2+> increase and subsequent BDNF release from the postsynaptic cells and the released BDNF activates presynaptic TrKB followed by the activation of MAP kinases, leading to potentiation of inhibitory synaptic transmission at the presynaptic site.
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