Regulation of synaptic responses to high-frequency stimulation and LTP by neurotrophins in the hippocampus

• Published in: Nature (London) 1996-06, Vol.381 (6584), p.706-709
• Main Authors: Figurov, Alexander, Pozzo-Miller, Lucas D., Olafsson, Petur, Wang, Ti, Lu, Bai
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Brain; Brain-Derived Neurotrophic Factor; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Evoked Potentials; Fundamental and applied biological sciences. Psychology; Hippocampus - physiology; Humanities and Social Sciences; Humans; Immunoglobulin G - immunology; In Vitro Techniques; letter; Long-Term Potentiation - physiology; Male; Molecular biology; multidisciplinary; Nerve Growth Factors - antagonists & inhibitors; Nerve Growth Factors - physiology; Nerve Tissue Proteins - antagonists & inhibitors; Nerve Tissue Proteins - physiology; Neurons; Plasticity; Rats; Rats, Sprague-Dawley; Receptor, Ciliary Neurotrophic Factor; Receptors, Nerve Growth Factor - physiology; Recombinant Proteins - pharmacology; Science; Science (multidisciplinary); Synapses - physiology; Vertebrates: nervous system and sense organs
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/381706a0

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 1–3 . In developing hippocampus, the expression of brain-derived neurotrophic factor (BDNF) and its receptor TrkB 4–7 increases in parallel with the ability to undergo long-term potentiation (LTP) 8–10 . 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 11 , 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.