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Free keywords:
BDNF
neurotrophins
LTP
synaptic plasticity
gene-targeting
Shc
TrkB
receptor
nerve growth-factor
activated protein-kinase
neurotrophic factor
synaptic transmission
signal-transduction
neurons
brain
bdnf
responses
mice
Neurosciences & Neurology
Pharmacology & Pharmacy
Abstract:
Recent evidence shows that neurotrophins are not only involved in neuronal survival and differentiation but also in modulating synaptic strength in the developing and adult nervous system. To understand how neurotrophins induce changes in synaptic strength, we have investigated signaling pathways downstream of the TrkB receptor, which binds brain-derived neurotrophic factor (BDNF) or NT-4/5. To test whether the She-site activated signaling pathway, which has been shown to be important for neuronal survival in vivo, also plays a role in processes like long-term potentiation (LTP), we have generated a mouse strain carrying a mutation in the She-binding site of the TrkB receptor. In hippocampal slices from these mice we investigated whether basal synaptic transmission, early-LTP (E-LTP) or late-LTP (L-LTP) were affected by this mutation. We found that homo- and heterozygous mutant mice show no difference in the induction-rate or magnitude of E-LTP and L-LTP induced by theta-burst or tetanus stimulation, suggesting that the She-binding site in the TrkB receptor and its downstream activated signaling cascade is not involved in hippocampal synaptic plasticity. (C) 2000 Elsevier Science Ltd. All rights reserved.
