Induction of long-term potentiation and depression is reflected by corresponding changes in secretion of endogenous brain-derived neurotrophic factor

doi:10.1073/pnas.0406960101

Induction of long-term potentiation and depression is reflected by corresponding changes in secretion of endogenous brain-derived neurotrophic factor

^*Department of Human and General Physiology, University of Bologna, Via San Donato 19/2, I-40126 Bologna, Italy; ^†Interdepartment Centre “Luigi Galvani,” University of Bologna, Via San Giacomo 12, I-40126 Bologna, Italy; ^§Department of Pharmacology, University of Bologna, Via Irnerio 48, I-40126 Bologna, Italy; ^¶Institute of Organ Transplant and Immunocytology, Bologna Unit, Consiglio Nazionaledelle Ricerche, Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, I-40138 Bologna, Italy; and ^∥Max Planck Institute of Neurobiology, Am Klopferspitz 18, D-82152 Martinsried, Germany

Contributed by Hans Thoenen, September 21, 2004

Abstract

Neurotrophins play an important role in modulating activity-dependent neuronal plasticity. In particular, threshold levels of brain-derived neurotrophic factor (BDNF) are required to induce long-term potentiation (LTP) in acute hippocampal slices. Conversely, the administration of exogenous BDNF prevents the induction of long-term depression (LTD) in the visual cortex. A long-standing missing link in the analysis of this modulatory role of BDNF was the determination of the time-course of endogenous BDNF secretion in the same organotypic preparation in which LTP and LTD are elicited. Here, we fulfilled this requirement in slices of perirhinal cortex. Classical theta-burst stimulation patterns evoking LTP lasting >180 min elicited a large increase in BDNF secretion that persisted 5-12 min beyond the stimulation period. Weaker theta-burst stimulation patterns leading only to the initial phase of LTP (≈35 min) were accompanied by a smaller increase in BDNF secretion lasting <1 min. Sequestration of BDNF by TrkB-IgG receptor bodies prevented LTP. Low-frequency stimulations leading to LTD were accompanied by reductions in BDNF secretion that never lasted beyond the duration of the stimulation.

Footnotes

↵ ** To whom correspondence should be addressed. E-mail: marco{at}biocfarm.unibo.it.
↵ ‡ G.A., E.A., and S.C. contributed equally to this work.
Abbreviations: BDNF, brain-derived neurotrophic factor; FP, field potential; LFS, low-frequency stimulation; LTD, long-term depression; LTP, long-term potentiation; NeuN, neuronal nuclear antigen; PRh, perirhinal; TBS, theta-burst stimulation; TTX, tetrodotoxin.