A subset of primary sensory neuronsproduces BDNF, which is implicated in control of nociceptiveneurotransmission. We previously localized full-lengthtrkB receptors on their terminals within lamina II. To functionallystudy these receptors, we here employed patchclamprecordings, calcium imaging and immunocytochemistryon slices from 8–12 days post-natal rats. In this preparation,BDNF (100–500 ng/mL) enhances the release of sensoryneurotransmitters (glutamate, substance P, CGRP) in laminaII by acting on trkB receptors expressed by primaryafferent fibers of the peptidergic nociceptive type (PNPAFs).Effect was blocked by trk antagonist K252a or antitrkBantibody clone 47.Apre-synaptic mechanism was demonstratedafter (i) patch-clamp recordings where the neurotrophininduced a significant increase in frequency, but notamplitude, of AMPA-mediated mEPSCs, (ii) real time calciumimaging, where sustained application of BDNF evokedan intense response in up to 57% lamina II neurons with asignificant frequency rise. Antagonists of ionotropic glutamatereceptors and NK1 receptors completely inhibited thecalcium response to BDNF. Reduction of CGRP (a specificmarker of PN-PAFs) and substance P content in dorsal hornfollowing BDNF preincubation, and analysis of the calciumresponse after depletion with capsaicin, confirmed that theneurotrophin presynaptically enhanced neurotransmitterrelease from PN-PAFs. This is the first demonstration thattrkB receptors expressed by PN-PAF terminals in lamina IIare functional during postnatal development. Implicationsof this finding are discussed considering that BDNF can bereleased by these same terminals and microglia, a fraction ofwhich (as shown here) contains BDNF also in unactivatedstate

Pre-synaptic functional trkB receptors mediate the release of excitatory neurotransmitters from primary afferent terminals in lamina II (substantia gelatinosa) of post-natal rat spinal cord / A., Merighi; Bardoni, Rita; C., Salio; L., Lossi; F., Ferrini; Prandini, Massimiliano; M., Zonta; S., Gustincich; G., Carmignoto. - In: DEVELOPMENTAL NEUROBIOLOGY. - ISSN 1932-8451. - STAMPA. - 68:(2008), pp. 457-475.

Pre-synaptic functional trkB receptors mediate the release of excitatory neurotransmitters from primary afferent terminals in lamina II (substantia gelatinosa) of post-natal rat spinal cord

BARDONI, Rita;PRANDINI, Massimiliano;
2008-01-01

Abstract

A subset of primary sensory neuronsproduces BDNF, which is implicated in control of nociceptiveneurotransmission. We previously localized full-lengthtrkB receptors on their terminals within lamina II. To functionallystudy these receptors, we here employed patchclamprecordings, calcium imaging and immunocytochemistryon slices from 8–12 days post-natal rats. In this preparation,BDNF (100–500 ng/mL) enhances the release of sensoryneurotransmitters (glutamate, substance P, CGRP) in laminaII by acting on trkB receptors expressed by primaryafferent fibers of the peptidergic nociceptive type (PNPAFs).Effect was blocked by trk antagonist K252a or antitrkBantibody clone 47.Apre-synaptic mechanism was demonstratedafter (i) patch-clamp recordings where the neurotrophininduced a significant increase in frequency, but notamplitude, of AMPA-mediated mEPSCs, (ii) real time calciumimaging, where sustained application of BDNF evokedan intense response in up to 57% lamina II neurons with asignificant frequency rise. Antagonists of ionotropic glutamatereceptors and NK1 receptors completely inhibited thecalcium response to BDNF. Reduction of CGRP (a specificmarker of PN-PAFs) and substance P content in dorsal hornfollowing BDNF preincubation, and analysis of the calciumresponse after depletion with capsaicin, confirmed that theneurotrophin presynaptically enhanced neurotransmitterrelease from PN-PAFs. This is the first demonstration thattrkB receptors expressed by PN-PAF terminals in lamina IIare functional during postnatal development. Implicationsof this finding are discussed considering that BDNF can bereleased by these same terminals and microglia, a fraction ofwhich (as shown here) contains BDNF also in unactivatedstate
68
457
475
Pre-synaptic functional trkB receptors mediate the release of excitatory neurotransmitters from primary afferent terminals in lamina II (substantia gelatinosa) of post-natal rat spinal cord / A., Merighi; Bardoni, Rita; C., Salio; L., Lossi; F., Ferrini; Prandini, Massimiliano; M., Zonta; S., Gustincich; G., Carmignoto. - In: DEVELOPMENTAL NEUROBIOLOGY. - ISSN 1932-8451. - STAMPA. - 68:(2008), pp. 457-475.
A., Merighi; Bardoni, Rita; C., Salio; L., Lossi; F., Ferrini; Prandini, Massimiliano; M., Zonta; S., Gustincich; G., Carmignoto
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/612909
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