Suppressive effect of the swallowing reflex by stimulation of the pedunculopontine tegmental nucleus
Introduction
Several previous studies indicated that the swallowing is programmed by the swallowing central pattern generator (CPG). The swallowing CPG is classified into two regions. One is the nucleus of the solitary tract (NTS) and the adjacent reticular formation. The another is the lateral reticular formation above the nucleus ambiguus. The former and the latter are called as a dorsal swallowing group (DSG) and a ventral swallowing group (VSG), respectively. The DSG initiates swallowing and programs the swallowing event. The VSG receives input from the DSG, and sends motor outputs to the motoneurons related to the swallowing (Jean, 1984a, 1984b, 2001).
The pedunculopontine tegmental nucleus (PTg) is located in the mesopontine tegmentum. Morphological and electrophysiological studies have demonstrated that the PTg receives projections from the ipsilateral side of the substantia nigra pars reticulata and from the internal globus pallidus, which are the output nuclei in the basal ganglia (Nakamura et al., 1989; Spann and Grofova, 1991; Semba and Fibiger, 1992; Lavoie and Parent, 1994; Takakusaki et al., 1997; Saitoh et al., 2003). The PTg projects to the to the pars compacta of the substantia nigra (SNC) (Jackson and Crossman, 1983; Beninato and Spencer, 1987) and to the lateral reticular formation above the nucleus ambiguous (Rye et al., 1988; Yasui et al., 1990). Electrical stimulation of the PTg induces the release of dopamine in the striatum via the SNC (Forster and Blaha, 2003; Miller and Blaha, 2004).
Dysphagia is a symptom of Parkinson’s disease (Suttrup and Warnecke, 2016; Simons, 2017) and Huntington's disease (de Tommaso et al., 2015; Aldaz et al., 2019; Manor et al., 2019). Parkinson’s disease is due to degeneration of dopaminergic neurons in the SNC (Kalia and Lang, 2015). Neuronal loss in the PTg is observed in Parkinson’s disease (Hirsch et al., 1987; Zweig et al., 1989; Rinne et al., 2008; Kay et al., 2015; Pienaar et al., 2015). Deep brain stimulation of the PTg has been used in attempts to improve movement disorder in patients with Parkinson’s disease (French and Muthusamy, 2018; Thevathasan et al., 2018; Nowacki et al., 2019). Huntington's disease is an inherited neurodegenerative disease of the striatum (Nopoulos, 2016). The PTg is related to the control of body posture (Mori et al., 2016; Takakusaki et al., 2016). It has been demonstrated that postural techniques for dysphagia are effective clinically (Umeda et al., 2011; Solazzo et al., 2012; Park et al., 2013). If so, dysphagia is influenced by the PTg.
Based on above studies, it is assumed that the PTg is involved in the control of swallowing. The aim of this study is investigating whether the swallowing reflex is modulated by electrical or chemical stimulation of the PTg.
Section snippets
Materials and methods
Fifteen male Sprague-Dawley rats (326−370 g) were used. This study was approved by the Laboratory Animal Committee of The Nippon Dental University School of Life Dentistry at Niigata and by the Niigata University Intramural Animal Care and Use Committee (approval number 186) and was performed in accordance with the National Institute of Health Guide for the Care and Use of Laboratory Animals. The rats were anesthetized with urethane (1.3 g/kg, i.p.). A cannula was inserted into the left femoral
Results
The threshold for evoking the swallowing reflex by stimulating the SLN was 12−130 μA (56.5 ± 39.3 μA, mean ± SD, n = 22). In some cases, the threshold of the SLN for evoking the swallowing reflex increased after the head of rats was fixed using a stereotaxic apparatus. When the number of swallows in the post-control was less than during electrical stimulation of the PTg, or when the number of swallows did not return at 30 min after injection of glutamate to the condition prior to injection,
Discussion
The swallowing reflex showed the suppressive effect by electrical stimulation of the PTg in this study. Glutamate injection into the PTg also reduces the number of swallows, extension of onset latency of the first swallow and shortening of the duration of Myl EMG bursts. These results suggest that suppression of the swallowing reflex by electrical stimulation of the PTg is caused by excitation of the cell bodies in the PTg, rather than excitation of fibers passing through the PTg (Goodchild et
Declaration of Competing Interest
None.
Acknowledgment
This work was supported by Research Promotion Grant (NDUF-19-10) from The Nippon Dental University.
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