BDNF attenuates hippocampal LTD via activation of phospholipase C: implications for a vertical shift in the frequency-response curve of synaptic plasticity.
Recent evidence shows that neurotrophins are not only involved in neuronal survival and differentiation during development but also in modulating synaptic strength in the mature brain. To understand how neurotrophins alter this synaptic modification, we have investigated the effect of brain-derived neurotrophic factor (BDNF) on long-term depression (LTD) at Schaffer collateral-CA1 synapses in rat hippocampal slices. The slices treated with BDNF for 5 min showed significantly less LTD in response to a 1-Hz tetanus compared with controls but displayed normal LTD when the afferents were tetanized at 10 Hz. Because BDNF enhanced long-term potentiation (LTP) induced by a 30-Hz tetanus, the synaptic modification threshold (theta(m)) as defined in the 'BCM' theory of Bienenstock Cooper & Monroe [Bienenstock et al. (1982), J. Neurosci., 2, 32-48] was not shifted. BNDF is likely to alter the capability of the plastic changes in synaptic efficacy, i.e. to produce an upward shift in the BCM curve. The suppressive effect of BDNF on LTD was prevented by either the tyrosine kinase (Trk) receptor inhibitor K252a or the phospholipase C inhibitor U73122. Thus, TrkB activation may attenuate LTD through phospholipase C signalling pathway.
Ikegaya
Yuji
Y
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. ikegaya@tk.airnet.ne.jp
Ishizaka
Yoko
Y
Matsuki
Norio
N
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D004558:Electric Stimulation; D006624:Hippocampus / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology; D017774:Long-Term Potentiation; D009473:Neuronal Plasticity; D051381:Rats; D017208:Rats, Wistar; D020813:Receptor, trkB / Q000378:metabolism; D009435:Synaptic Transmission; D010738:Type C Phospholipases / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D020813:Receptor, trkB; D010738:Type C Phospholipases