Changes in neuropeptide large dense core vesicle trafficking dynamics contribute to adaptive responses to a systemic homeostatic challenge

Matthew K Kirchner; Ferdinand Althammer; Kevin J Donaldson; Daniel N Cox; Javier E Stern

doi:10.1016/j.isci.2023.108243

Changes in neuropeptide large dense core vesicle trafficking dynamics contribute to adaptive responses to a systemic homeostatic challenge

iScience. 2023 Oct 18;26(11):108243. doi: 10.1016/j.isci.2023.108243. eCollection 2023 Nov 17.

Authors

Matthew K Kirchner^{1

2}, Ferdinand Althammer^{1

3}, Kevin J Donaldson^{2

4}, Daniel N Cox^{2

4}, Javier E Stern^{1

2}

Affiliations

¹ Center for Neuroinflammation and Cardiometabolic Diseases, Georgia State University, Atlanta, GA 30303, USA.
² Neuroscience Institute, Georgia State University, Atlanta, GA 30303, USA.
³ Institute of Human Genetics, Heidelberg University Hospital, 69120 Heidelberg, Germany.
⁴ Center for Neuromics, Georgia State University, Atlanta, GA 30303, USA.

Abstract

Neuropeptides are packed into large dense core vesicles (LDCVs) that are transported from the soma out into their processes. Limited information exists regarding mechanisms regulating LDCV trafficking, particularly during challenges to bodily homeostasis. Addressing this gap, we used 2-photon imaging in an ex vivo preparation to study LDCVs trafficking dynamics in vasopressin (VP) neurons, which traffic and release neuropeptide from their dendrites and axons. We report a dynamic bidirectional trafficking of VP-LDCVs with important differences in speed and directionality between axons and dendrites. Acute, short-lasting stimuli known to alter VP firing activity and axonal/dendritic release caused modest changes in VP-LDCVs trafficking dynamics. Conversely, chronic/sustained systemic osmotic challenges upregulated VP-LDCVs trafficking dynamic, with a larger effect in dendrites. These results support differential regulation of dendritic and axonal LDCV trafficking, and that changes in trafficking dynamics constitute a novel mechanism by which peptidergic neurons can efficiently adapt to conditions of increased hormonal demand.

Keywords: Biochemistry; Biological sciences; Cell biology; Cellular neuroscience; Functional aspects of cell biology; Molecular neuroscience; Natural sciences; Neuroscience.

Abstract

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