Abstract:
:Peptidergic dorsal root ganglion (DRG) neurons transmit sensory and nociceptive information from the periphery to the central nervous system. Their synaptic activity is profoundly affected by neuromodulatory peptides stored and released from large dense-core vesicles (LDCVs). However, the mechanism of peptide secretion from DRG neurons is poorly understood. Using total internal reflection fluorescence microscopy (TIRFM), we visualized individual LDCVs loaded with fluorescent neuropeptide Y (NPY) and analyzed their stimulation-dependent release. We tested several protocols and found an overall low stimulation-secretion coupling that increased after raising intracellular Ca2+ concentration by applying a weak pre-stimulus. Interestingly, the stimulation protocol also influenced the mechanism of LDCV fusion. Depolarization of DRG neurons with a solution containing 60mM KCl triggered full fusion, kiss-and-run, and kiss-and-stay exocytosis with equal frequency. In contrast, field electrode stimulation primarily induced full fusion exocytosis. Finally, our results indicate that NPY can promote LDCV secretion. These results shed new light on the mechanism of NPY action during modulation of DRG neuron activity, an important pathway in the treatment of chronic pain.
journal_name
Neurosciencejournal_title
Neuroscienceauthors
Bost A,Shaib AH,Schwarz Y,Niemeyer BA,Becherer Udoi
10.1016/j.neuroscience.2017.01.006subject
Has Abstractpub_date
2017-03-27 00:00:00pages
1-13eissn
0306-4522issn
1873-7544pii
S0306-4522(17)30012-Xjournal_volume
346pub_type
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