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Presynaptic functional trkB receptors mediate the release of excitatory neurotransmitters from primary afferent terminals in lamina II (substantia gelatinosa) of postnatal rat spinal cord
Author(s) -
Merighi Adalberto,
Bardoni Rita,
Salio Chiara,
Lossi Laura,
Ferrini Francesco,
Prandini Massimiliano,
Zonta Micaela,
Gustincich Stefano,
Carmignoto Giorgio
Publication year - 2008
Publication title -
developmental neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.716
H-Index - 129
eISSN - 1932-846X
pISSN - 1932-8451
DOI - 10.1002/dneu.20605
Subject(s) - neuroscience , tropomyosin receptor kinase b , biology , glutamate receptor , medicine , endocrinology , receptor , neurotrophic factors , biochemistry
A subset of primary sensory neurons produces BDNF, which is implicated in control of nociceptive neurotransmission. We previously localized full‐length trkB receptors on their terminals within lamina II. To functionally study these receptors, we here employed patch‐clamp recordings, calcium imaging and immunocytochemistry on slices from 8–12 days post‐natal rats. In this preparation, BDNF (100–500 ng/mL) enhances the release of sensory neurotransmitters (glutamate, substance P, CGRP) in lamina II by acting on trkB receptors expressed by primary afferent fibers of the peptidergic nociceptive type (PN‐PAFs). Effect was blocked by trk antagonist K252a or anti‐trkB antibody clone 47. A pre‐synaptic mechanism was demonstrated after (i) patch‐clamp recordings where the neurotrophin induced a significant increase in frequency, but not amplitude, of AMPA‐mediated mEPSCs, (ii) real time calcium imaging, where sustained application of BDNF evoked an intense response in up to 57% lamina II neurons with a significant frequency rise. Antagonists of ionotropic glutamate receptors and NK 1 receptors completely inhibited the calcium response to BDNF. Reduction of CGRP (a specific marker of PN‐PAFs) and substance P content in dorsal horn following BDNF preincubation, and analysis of the calcium response after depletion with capsaicin, confirmed that the neurotrophin presynaptically enhanced neurotransmitter release from PN‐PAFs. This is the first demonstration that trkB receptors expressed by PN‐PAF terminals in lamina II are functional during postnatal development. Implications of this finding are discussed considering that BDNF can be released by these same terminals and microglia, a fraction of which (as shown here) contains BDNF also in unactivated state. © 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2008.