Preproglucagon neurons project widely to autonomic control areas in the mouse brain

Feb 19, 2011Neuroscience

Preproglucagon neurons send signals widely to mouse brain areas controlling automatic body functions

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Abstract

PPG neurons primarily innervate brain regions involved in autonomic control.

PPG neurons produce GLP-1 in the central nervous system and are associated with regulating food intake and blood glucose levels.
In transgenic mice, PPG neurons showed intense yellow fluorescent protein (YFP) immunoreactivity, allowing clear differentiation of axons from dendrites.
The majority of YFP-immunoreactive cell bodies were localized in the caudal nucleus tractus solitarius (NTS), with additional presence in nearby nuclei.
A dense network of dendrites from PPG neurons was observed in the caudal NTS, extending into the area postrema.
Widespread immunoreactive axons were found throughout the NTS, dorsal vagal nucleus, and reticular nucleus, indicating extensive connectivity.
Moderate innervation was noted in various other brain regions, suggesting potential pathways for PPG-mediated modulation of autonomic functions.

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Glucagon-like peptide 1 (GLP-1) and its analogue exendin-4 inhibit food intake, reduce blood glucose levels and increase blood pressure and heart rate by acting on GLP-1 receptors in many brain regions. Within the CNS, GLP-1 is produced only by preproglucagon (PPG) neurons. We suggest that PPG neurons mediate the central effects of GLP-1 by modulating sympathetic and vagal outflow. We therefore analysed the projections of PPG neurons to brain sites involved in autonomic control. In transgenic mice expressing yellow fluorescent protein (YFP) under the control of the PPG promoter, we assessed YFP-immunoreactive innervation using an anti-GFP antiserum and avidin-biotin-peroxidase. PPG neurons were intensely YFP-immunoreactive and axons could be easily discriminated from dendrites. YFP-immunoreactive cell bodies occurred primarily within the caudal nucleus tractus solitarius (NTS) with additional somata ventral to the hypoglossal nucleus, in raphé obscurus and in the intermediate reticular nucleus. The caudal NTS contained a dense network of dendrites, some of which extended into the area postrema. Immunoreactive axons were widespread throughout NTS, dorsal vagal nucleus and reticular nucleus with few in the hypoglossal nucleus and pyramids. The dorsomedial and paraventricular hypothalamic nuclei, ventrolateral periaqueductal grey and thalamic paraventricular nucleus exhibited heavy innervation. The area postrema, rostral ventrolateral medulla, pontine central grey, locus coeruleus/Barrington's nucleus, arcuate nucleus and the vascular organ of the lamina terminalis were moderately innervated. Only a few axons occurred in the amygdala and subfornical organ. Our results demonstrate that PPG neurons innervate primarily brain regions involved in autonomic control. Thus, central PPG neurons are ideally situated to modulate sympathetic and parasympathetic outflow through input at a variety of central sites. Our data also highlight that immunohistochemistry improves detection of neurons expressing YFP. Hence, animals in which specific populations of neurons have been genetically-modified to express fluorescent proteins are likely to prove ideal for anatomical studies.

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Preproglucagon neurons project widely to autonomic control areas in the mouse brain

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