Synaptic Inputs to the Mouse Dorsal Vagal Complex and Its Resident Preproglucagon Neurons.
The Journal of neuroscience : the official journal of the Society for Neuroscience
Society for Neuroscience
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Holt, M. K., Pomeranz, L. E., Beier, K. T., Reimann, F., Gribble, F., & Rinaman, L. (2019). Synaptic Inputs to the Mouse Dorsal Vagal Complex and Its Resident Preproglucagon Neurons.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 39 (49), 9767-9781. https://doi.org/10.1523/jneurosci.2145-19.2019
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 (GLP-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. Mono- 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 mono- 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.
Solitary Nucleus, Hypothalamus, Thalamus, Posterior Horn Cells, Neural Pathways, Neurons, Axons, Neurons, Afferent, Vagus Nerve, Synapses, Animals, Mice, Inbred C57BL, Mice, Restraint, Physical, Stress, Psychological, Reflex, Monosynaptic, Female, Male, Proglucagon
National Institutes of Health Wellcome
WELLCOME TRUST (106262/Z/14/Z & 106263/Z/14/Z)
External DOI: https://doi.org/10.1523/jneurosci.2145-19.2019
This record's URL: https://www.repository.cam.ac.uk/handle/1810/297874
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