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Synaptic Inputs to the Mouse Dorsal Vagal Complex and Its Resident Preproglucagon Neurons

Holt, MK; Pomeranz, LE; Beier, KT; Reimann, F; Gribble, FM; Rinaman, L; (2019) Synaptic Inputs to the Mouse Dorsal Vagal Complex and Its Resident Preproglucagon Neurons. Journal of Neuroscience , 39 (49) pp. 9767-9781. 10.1523/JNEUROSCI.2145-19.2019. Green open access

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Abstract

Stress responses are coordinated by widespread neural circuits. Homeostatic and psychogenic stressors activate preproglucagon (PPG) neurons in the caudal nucleus of the solitary tract (cNTS) that produce glucagon-like peptide-1; published work in rodents indicates that these neurons play a crucial role in stress responses. While the axonal targets of PPG neurons are well established, their afferent inputs are unknown. Here we use retrograde tracing with cholera toxin subunit b to show that the cNTS in male and female mice receives axonal inputs similar to those reported in rats. Monosynaptic and polysynaptic inputs specific to cNTS PPG neurons were revealed using Cre-conditional pseudorabies and rabies viruses. The most prominent sources of PPG monosynaptic input include the lateral (LH) and paraventricular (PVN) nuclei of the hypothalamus, parasubthalamic nucleus, lateral division of the central amygdala, and Barrington's nucleus (Bar). Additionally, PPG neurons receive monosynaptic vagal sensory input from the nodose ganglia and spinal sensory input from the dorsal horn. Sources of polysynaptic input to cNTS PPG neurons include the hippocampal formation, paraventricular thalamus, and prefrontal cortex. Finally, cNTS-projecting neurons within PVN, LH, and Bar express the activation marker cFOS in mice after restraint stress, identifying them as potential sources of neurogenic stress-induced recruitment of PPG neurons. In summary, cNTS PPG neurons in mice receive widespread monosynaptic and polysynaptic input from brain regions implicated in coordinating behavioral and physiological stress responses, as well as from vagal and spinal sensory neurons. Thus, PPG neurons are optimally positioned to integrate signals of homeostatic and psychogenic stress.

Type: Article
Title: Synaptic Inputs to the Mouse Dorsal Vagal Complex and Its Resident Preproglucagon Neurons
Open access status: An open access version is available from UCL Discovery
DOI: 10.1523/JNEUROSCI.2145-19.2019
Publisher version: https://doi.org/10.1523/JNEUROSCI.2145-19.2019
Language: English
Additional information: This is an open-access article distributed under the terms of the Creative Commons Attribution License Creative Commons Attribution 4.0 International, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. https://creativecommons.org/licenses/by/4.0/
Keywords: GLP1; nodose ganglion; pseudorabies; rabies; stress; viral tracing
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
URI: https://discovery.ucl.ac.uk/id/eprint/10092268
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