Calcium-dependent and synapsin-dependent pathways for the presynaptic actions of BDNF

We used cultured hippocampal neurons to determine the signaling pathways mediating brain-derived neurotrophic factor (BDNF) regulation of spontaneous glutamate and GABA release. BDNF treatment elevated calcium concentration in presynaptic terminals; this calcium signal reached a peak within 1 min an...

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Main Authors: Cheng, Qing, Song, Sang-Ho, Augustine, George James
Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
Format: Article
Language:English
Published: 2018
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Online Access:https://hdl.handle.net/10356/88507
http://hdl.handle.net/10220/45823
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spelling sg-ntu-dr.10356-885072020-11-01T05:25:29Z Calcium-dependent and synapsin-dependent pathways for the presynaptic actions of BDNF Cheng, Qing Song, Sang-Ho Augustine, George James Lee Kong Chian School of Medicine (LKCMedicine) Neurotrophins Synapsins DRNTU::Science::Medicine We used cultured hippocampal neurons to determine the signaling pathways mediating brain-derived neurotrophic factor (BDNF) regulation of spontaneous glutamate and GABA release. BDNF treatment elevated calcium concentration in presynaptic terminals; this calcium signal reached a peak within 1 min and declined in the sustained presence of BDNF. This BDNF-induced transient rise in presynaptic calcium was reduced by SKF96365, indicating that BDNF causes presynaptic calcium influx via TRPC channels. BDNF treatment increased the frequency of miniature excitatory postsynaptic currents (mEPSCs). This response consisted of two components: a transient component that peaked within 1 min of initiating BDNF application and a second component that was sustained, at a lower mEPSC frequency, for the duration of BDNF application. The initial transient component was greatly reduced by removing external calcium or by treatment with SKF96365, as well as by Pyr3, a selective blocker of TRPC3 channels. In contrast, the sustained component was unaffected in these conditions but was eliminated by U0126, an inhibitor of the MAP kinase (MAPK) pathway, as well as by genetic deletion of synapsins in neurons from a synapsin triple knock-out (TKO) mouse. Thus, two pathways mediate the ability of BDNF to enhance spontaneous glutamate release: the transient component arises from calcium influx through TRPC3 channels, while the sustained component is mediated by MAPK phosphorylation of synapsins. We also examined the ability of these two BDNF-dependent pathways to regulate spontaneous release of the inhibitory neurotransmitter, GABA. BDNF had no effect on the frequency of spontaneous miniature inhibitory postsynaptic currents (mIPSCs) in neurons from wild-type (WT) mice, but surprisingly did increase mIPSC frequency in synapsin TKO mice. This covert BDNF response was blocked by removal of external calcium or by treatment with SKF96365 or Pyr3, indicating that it results from calcium influx mediated by TRPC3 channels. Thus, the BDNF-activated calcium signaling pathway can also enhance spontaneous GABA release, though this effect is suppressed by synapsins under normal physiological conditions. MOE (Min. of Education, S’pore) Published version 2018-09-05T03:52:27Z 2019-12-06T17:04:46Z 2018-09-05T03:52:27Z 2019-12-06T17:04:46Z 2017 Journal Article Cheng, Q., Song, S.-H., & Augustine, G. J. (2017). Calcium-dependent and synapsin-dependent pathways for the presynaptic actions of BDNF. Frontiers in Cellular Neuroscience, 11, 75-. doi:10.3389/fncel.2017.00075 https://hdl.handle.net/10356/88507 http://hdl.handle.net/10220/45823 10.3389/fncel.2017.00075 en Frontiers in Cellular Neuroscience © 2017 Cheng, Song and Augustine. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution and reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. 12 p. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Neurotrophins
Synapsins
DRNTU::Science::Medicine
spellingShingle Neurotrophins
Synapsins
DRNTU::Science::Medicine
Cheng, Qing
Song, Sang-Ho
Augustine, George James
Calcium-dependent and synapsin-dependent pathways for the presynaptic actions of BDNF
description We used cultured hippocampal neurons to determine the signaling pathways mediating brain-derived neurotrophic factor (BDNF) regulation of spontaneous glutamate and GABA release. BDNF treatment elevated calcium concentration in presynaptic terminals; this calcium signal reached a peak within 1 min and declined in the sustained presence of BDNF. This BDNF-induced transient rise in presynaptic calcium was reduced by SKF96365, indicating that BDNF causes presynaptic calcium influx via TRPC channels. BDNF treatment increased the frequency of miniature excitatory postsynaptic currents (mEPSCs). This response consisted of two components: a transient component that peaked within 1 min of initiating BDNF application and a second component that was sustained, at a lower mEPSC frequency, for the duration of BDNF application. The initial transient component was greatly reduced by removing external calcium or by treatment with SKF96365, as well as by Pyr3, a selective blocker of TRPC3 channels. In contrast, the sustained component was unaffected in these conditions but was eliminated by U0126, an inhibitor of the MAP kinase (MAPK) pathway, as well as by genetic deletion of synapsins in neurons from a synapsin triple knock-out (TKO) mouse. Thus, two pathways mediate the ability of BDNF to enhance spontaneous glutamate release: the transient component arises from calcium influx through TRPC3 channels, while the sustained component is mediated by MAPK phosphorylation of synapsins. We also examined the ability of these two BDNF-dependent pathways to regulate spontaneous release of the inhibitory neurotransmitter, GABA. BDNF had no effect on the frequency of spontaneous miniature inhibitory postsynaptic currents (mIPSCs) in neurons from wild-type (WT) mice, but surprisingly did increase mIPSC frequency in synapsin TKO mice. This covert BDNF response was blocked by removal of external calcium or by treatment with SKF96365 or Pyr3, indicating that it results from calcium influx mediated by TRPC3 channels. Thus, the BDNF-activated calcium signaling pathway can also enhance spontaneous GABA release, though this effect is suppressed by synapsins under normal physiological conditions.
author2 Lee Kong Chian School of Medicine (LKCMedicine)
author_facet Lee Kong Chian School of Medicine (LKCMedicine)
Cheng, Qing
Song, Sang-Ho
Augustine, George James
format Article
author Cheng, Qing
Song, Sang-Ho
Augustine, George James
author_sort Cheng, Qing
title Calcium-dependent and synapsin-dependent pathways for the presynaptic actions of BDNF
title_short Calcium-dependent and synapsin-dependent pathways for the presynaptic actions of BDNF
title_full Calcium-dependent and synapsin-dependent pathways for the presynaptic actions of BDNF
title_fullStr Calcium-dependent and synapsin-dependent pathways for the presynaptic actions of BDNF
title_full_unstemmed Calcium-dependent and synapsin-dependent pathways for the presynaptic actions of BDNF
title_sort calcium-dependent and synapsin-dependent pathways for the presynaptic actions of bdnf
publishDate 2018
url https://hdl.handle.net/10356/88507
http://hdl.handle.net/10220/45823
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