Regulation of synaptic responses to high-frequency stimulation and LTP by neurotrophins in the hippocampus.
Neurotrophins promote neuronal survival and differentiation, but the fact that their expression is modified by neuronal activity, suggests a role in regulating synapse development and plasticity. In developing hippocampus, the expression of brain derived neurotrophic factor (BDNF) and its receptor TrkB increases in parallel with the ability to undergo long-term potentiation (LTP). Here we report a mechanism by which BDNF modulates hippocampal LTP. Exogenous BDNF promoted the induction of LTP by tetanic stimulation in young (postnatal day 12-13) hippocampal slices, which in the absence of BDNF show only short-term potentiation (STP). This effect was due to an enhanced ability of hippocampal synapses to respond to tetanic stimulation, rather than to a direct modulation of the LTP-triggering mechanism. A TrkB-IgG fusion protein, which scavenges endogenous BDNF, reduced the synaptic responses to tetanus as well as the magnitude of LTP in adult hippocampus. Our results suggest that BDNF may regulate LTP in developing and adult hippocampus by enhancing synaptic responses to tetanic stimulation.
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Roche Institue of Molecular Biology, Nutley, New Jersey 07110, USA.
Pozzo-Miller
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LD
Olafsson
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Wang
T
T
Lu
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B
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor; D005071:Evoked Potentials; D006624:Hippocampus / Q000502:physiology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D009414:Nerve Growth Factors / Q000037:antagonists & inhibitors / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D013569:Synapses / Q000502:physiology*
D019208:Brain-Derived Neurotrophic Factor; D007074:Immunoglobulin G; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor; D011994:Recombinant Proteins