Whole-Brain Neural Connectivity to Lateral Pontine Tegmentum GABAergic Neurons in Mice.

Ze-Ka Chen,Miao He,Hui Dong,Xiang-Shan Yuan,Yong-Fang Wu,Gui-Hai Chen,Zhi-Li Huang,Wei-Min Qu

doi:10.3389/fnins.2019.00375

Abstract

The GABAergic neurons in the lateral pontine tegmentum (LPT) play key roles in the regulation of sleep and locomotion. The dysfunction of the LPT is related to neurological disorders such as rapid eye movement sleep behavior disorder and ocular flutter. However, the whole-brain neural connectivity to LPT GABAergic neurons remains poorly understood. Using virus-based, cell-type-specific, retrograde and anterograde tracing systems, we mapped the monosynaptic inputs and axonal projections of LPT GABAergic neurons in mice. We found that LPT GABAergic neurons received inputs mainly from the superior colliculus, substantia nigra pars reticulata, dorsal raphe nucleus (DR), lateral hypothalamic area (LHA), parasubthalamic nucleus, and periaqueductal gray (PAG), as well as the limbic system (e.g., central nucleus of the amygdala). Further immunofluorescence assays revealed that the inputs to LPT GABAergic neurons were colocalized with several markers associated with important neural functions, especially the sleep-wake cycle. Moreover, numerous LPT GABAergic neuronal varicosities were observed in the medial and midline part of the thalamus, the LHA, PAG, DR, and parabrachial nuclei. Interestingly, LPT GABAergic neurons formed reciprocal connections with areas related to sleep-wake and motor control, including the LHA, PAG, DR, parabrachial nuclei, and superior colliculus, only the LPT-DR connections were in an equally bidirectional manner. These results provide a structural framework to understand the underlying neural mechanisms of rapid eye movement sleep behavior disorder and disorders of saccades.

Highlights

The pontine tegmentum, a brainstem structure, are all the regions from the basilar pons to the fourth ventricle
The lateral pontine tegmentum (LPT) is identified as the site between the ventral lateral periaqueductal gray and the pedunculopontine tegmental nucleus (PPT) on the LPT GABAergic Neuronal Connectivity ventro-dorsal localization, and is a trip lying the region medial to the PPT on the rostro-caudal extent in rodents (Franklin and Paxinos, 2001; Lu et al, 2006; Sherman et al, 2015)
GAD2-IRES-Cre mice were injected in the LPT with associated virus (AAV) helper viruses fused to green fluorescent protein (GFP)

Summary

Introduction

The pontine tegmentum, a brainstem structure, are all the regions from the basilar pons to the fourth ventricle. It plays important roles in perception, movement, vigilance, respiration, and the sleep-wake regulation (Plazzi et al, 1996; Alheid et al, 2004; Tziridis et al, 2012). Ocular flutter was found to be related to the right upper pontine tegmentum damage, which contained LPT neurons (Tsutsumi et al, 2009). C-fos, a marker of activated neurons, was strongly expressed in the LPT after REM sleep deprivation and colocalized with glutamate decarboxylase, a key enzyme for the production of GABA, suggesting that LPT GABAergic neurons are involved in REM sleep regulation (Lu et al, 2006; Sapin et al, 2009)

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Results

Conclusion