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

Nov 1, 2019The Journal of neuroscience : the official journal of the Society for Neuroscience

Brain signals connecting to the mouse dorsal vagal complex and its hormone-producing neurons

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Abstract

neurons in the caudal nucleus of the solitary tract receive significant monosynaptic and polysynaptic input from multiple brain regions.

Monosynaptic inputs to PPG neurons originate from the lateral and paraventricular nuclei of the hypothalamus, parasubthalamic nucleus, central amygdala, and Barrington's nucleus.
Direct input also comes from vagal sensory neurons in the nodose ganglia and spinal sensory neurons from the dorsal horn.
Polysynaptic inputs to PPG neurons include connections from the hippocampal formation, paraventricular thalamus, and prefrontal cortex.
Activation marker cFOS is expressed in cNTS-projecting neurons within PVN, LH, and Bar after restraint stress, suggesting these neurons may contribute to stress responses.
PPG neurons are positioned to integrate signals related to homeostatic and psychogenic stress.

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Stress responses are coordinated by widespread neural circuits. Homeostatic and psychogenic stressors activate preproglucagon () 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.Recent research has indicated a crucial role for glucagon-like peptide-1-producing preproglucagon (PPG) neurons in regulating both appetite and behavioral and autonomic responses to acute stress. Intriguingly, the central glucagon-like peptide-1 system defined in rodents is conserved in humans, highlighting the translational importance of understanding its anatomical organization. Findings reported here indicate that PPG neurons receive significant monosynaptic and polysynaptic input from brain regions implicated in autonomic and behavioral responses to stress, as well as direct input from vagal and spinal sensory neurons. Improved understanding of the neural pathways underlying the recruitment of PPG neurons may facilitate the development of novel therapies for the treatment of stress-related disorders. SIGNIFICANCE STATEMENT

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Monosynaptic Inputs Identified

Key brain regions providing direct synaptic input to neurons.

Total Mice Used

Total number of male and female transgenic mice bred for the study.

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

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