Activity-dependent release of endogenous BDNF from mossy fibers evokes a TRPC3 current and Ca2+ elevations in CA3 pyramidal neurons

Yong Li, Gaston Calfa, Takafumi Inoue, Michelle D. Amaral, Lucas Pozzo-Miller

    Research output: Contribution to journalArticle

    39 Citations (Scopus)

    Abstract

    Multiple studies have demonstrated that brain-derived neurotrophic factor (BDNF) is a potent modulator of neuronal structure and function in the hippocampus. However, the majority of studies to date have relied on the application of recombinant BDNF. We herein report that endogenous BDNF, released via theta burst stimulation of mossy fibers (MF), elicits a slowly developing cationic current and intracellular Ca2+ elevations in CA3 pyramidal neurons with the same pharmacological profile of the transient receptor potential canonical 3 (TRPC3)-mediated IBDNF activated in CA1 neurons by brief localized applications of recombinant BDNF. Indeed, sensitivity to both the extracellular BDNF scavenger tropomyosin-related kinase B (TrkB)-IgG and small hairpin interference RNA-mediated TRPC3 channel knockdown confirms the identity of this conductance as such, henceforth-denoted MF-IBDNF. Consistent with such activity-dependent release of BDNF, these MF-I BDNF responses were insensitive to manipulations of extracellular Zn2+ concentration. Brief theta burst stimulation of MFs induced a long-lasting depression in the amplitude of excitatory postsynaptic currents (EPSCs) mediated by both AMPA and N-methyl-D-aspartate (NMDA) receptors without changes in the NMDA receptor/AMPA receptor ratio, suggesting a reduction in neurotransmitter release. This depression of NMDAR-mediated EPSCs required activitydependent release of endogenous BDNF from MFs and activation of Trk receptors, as it was sensitive to the extracellular BDNF scavenger TrkB-IgG and the tyrosine kinase inhibitor k-252b. These results uncovered the most immediate response to endogenously released - native - BDNF in hippocampal neurons and lend further credence to the relevance of BDNF signaling for synaptic function in the hippocampus.

    Original languageEnglish
    Pages (from-to)2846-2856
    Number of pages11
    JournalJournal of Neurophysiology
    Volume103
    Issue number5
    DOIs
    Publication statusPublished - 2010 May

    Fingerprint

    Pyramidal Cells
    Brain-Derived Neurotrophic Factor
    Excitatory Postsynaptic Potentials
    N-Methyl-D-Aspartate Receptors
    Hippocampus
    Immunoglobulin G
    Neurons
    alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
    AMPA Receptors
    Protein-Tyrosine Kinases
    Small Interfering RNA
    Neurotransmitter Agents
    Pharmacology

    ASJC Scopus subject areas

    • Physiology
    • Neuroscience(all)

    Cite this

    Activity-dependent release of endogenous BDNF from mossy fibers evokes a TRPC3 current and Ca2+ elevations in CA3 pyramidal neurons. / Li, Yong; Calfa, Gaston; Inoue, Takafumi; Amaral, Michelle D.; Pozzo-Miller, Lucas.

    In: Journal of Neurophysiology, Vol. 103, No. 5, 05.2010, p. 2846-2856.

    Research output: Contribution to journalArticle

    Li, Yong ; Calfa, Gaston ; Inoue, Takafumi ; Amaral, Michelle D. ; Pozzo-Miller, Lucas. / Activity-dependent release of endogenous BDNF from mossy fibers evokes a TRPC3 current and Ca2+ elevations in CA3 pyramidal neurons. In: Journal of Neurophysiology. 2010 ; Vol. 103, No. 5. pp. 2846-2856.
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