Differential axonal trafficking of Neuropeptide Y-, LAMP1-, and RAB7-tagged organelles in vivo

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Different organelles traveling through neurons exhibit distinct properties in vitro, but this has not been investigated in the intact mammalian brain. We established simultaneous dual color two-photon microscopy to visualize the trafficking of Neuropeptide Y (NPY)-, LAMP1-, and RAB7-tagged organelles in thalamocortical axons imaged in mouse cortex in vivo. This revealed that LAMP1- and RAB7-tagged organelles move significantly faster than NPY-tagged organelles in both anterograde and retrograde direction. NPY traveled more selectively in anterograde direction than LAMP1 and RAB7. By using a synapse marker and a calcium sensor, we further investigated the transport dynamics of NPY-tagged organelles. We found that these organelles slow down and pause at synapses. In contrast to previous in vitro studies, a significant increase of transport speed was observed after spontaneous activity and elevated calcium levels in vivo as well as electrically stimulated activity in acute brain slices. Together, we show a remarkable diversity in speeds and properties of three axonal organelle marker in vivo that differ from properties previously observed in vitro.

Original languageEnglish
Article numbere81721
Pages (from-to)1-22
Number of pages22
JournaleLife
Volume11
DOIs
Publication statusPublished - 2 Dec 2022

Bibliographical note

Publisher Copyright:
© 2022, Nassal et al.

Funding

We thank Joke Wortel and Robbert Zalm for the extensive help with animal experiments and produc-tion of viral particles. We thank Aygul Subkhangulova for testing the signal-dead NPY reporter and Jessie Brunner for advice on statistical analyses. This work was supported by a European Research Council (ERC) Advanced grant (322966) of the European Union (to MV). COSYN (Comorbidity and Synapse Biology in Clinically Overlapping Psychiatric Disorders); the NWO Gravitation program BRAINSCAPE: A Roadmap from Neurogenetic to Neurobiology (NWO: 024.004.012, to MV) and the Netherlands Scientific Organisation and De Hersenstichting (013-17-002), under the frame of the Neuron Cofund ERA-Net SNAREopathy (to RFT). We thank Joke Wortel and Robbert Zalm for the extensive help with animal experiments and production of viral particles. We thank Aygul Subkhangulova for testing the signal-dead NPY reporter and Jessie Brunner for advice on statistical analyses. This work was supported by a European Research Council (ERC) Advanced grant (322966) of the European Union (to MV). COSYN (Comorbidity and Synapse Biology in Clinically Overlapping Psychiatric Disorders); the NWO Gravitation program BRAINSCAPE: A Roadmap from Neurogenetic to Neurobiology (NWO: 024.004.012, to MV) and the Netherlands Scientific Organisation and De Hersenstichting (013-17-002), under the frame of the Neuron Cofund ERA-Net SNAREopathy (to RFT).

FundersFunder number
Netherlands Scientific Organisation and De Hersenstichting013-17-002
European Commission
European Research Council322966
Nederlandse Organisatie voor Wetenschappelijk Onderzoek024.004.012

    Keywords

    • cell biology
    • dense core vesicles
    • in vivo imaging
    • mouse
    • neuropeptides
    • organelle trafficking

    Fingerprint

    Dive into the research topics of 'Differential axonal trafficking of Neuropeptide Y-, LAMP1-, and RAB7-tagged organelles in vivo'. Together they form a unique fingerprint.

    Cite this