scholarly journals Downstream projection of Barrington's nucleus to the spinal cord in mice

Author(s):  
Masahiro Kawatani ◽  
William deGroat ◽  
Keiichi Itoi ◽  
Katsuya Uchida ◽  
Kenji Sakimura ◽  
...  

Barrington's nucleus (Bar) which controls micturition behavior through downstream projections to the spinal cord contains two types of projection neurons BarCRH and BarESR1 that have different functions and target different spinal circuitry. Both types of neurons project to the L6-S1 spinal intermediolateral (IML) nucleus while BarESR1 neurons also project to the dorsal commissural nucleus (DCN). To obtain more information about the spinal circuits targeted by Bar, we used patch-clamp recording in spinal slices from adult mice in combination with optogenetic stimulation of Bar terminals. Recording of opto-evoked excitatory post synaptic currents (oEPSCs) in DiI-labeled lumbosacral preganglionic neurons (LS-PGN) revealed that both Bar neuronal populations make strong glutamatergic monosynaptic connections with LS-PGN, while BarESR1 neurons also elicited smaller amplitude glutamatergic polysynaptic oEPSCs or polysynaptic inhibitory post synaptic currents (oIPSCs) in some LS-PGN. Optical stimulation of BarCRH and BarESR1 terminals also elicited monosynaptic oEPSCs and polysynaptic oIPSCs in sacral DCN neurons, some of which must include interneurons projecting either to the IML or ventral horn. Application of capsaicin increased opto-evoked firing during repetitive stimulation of Bar terminals through the modulation of spontaneous post synaptic currents in LS-PGN. In conclusion, our experiments have provided insights into the synaptic mechanisms underlying the integration of inputs from Bar to autonomic circuitry in the lumbosacral spinal cord that may control micturition.

2018 ◽  
Vol 314 (3) ◽  
pp. G341-G348 ◽  
Author(s):  
Hiroyuki Nakamori ◽  
Kiyotada Naitou ◽  
Yuuki Horii ◽  
Hiroki Shimaoka ◽  
Kazuhiro Horii ◽  
...  

Colorectal motility is regulated by two defecation centers located in the brain and spinal cord. In previous studies, we have shown that administration of serotonin (5-HT) in the lumbosacral spinal cord causes enhancement of colorectal motility. Because spinal 5-HT is derived from neurons of the medullary raphe nuclei, including the raphe magnus, raphe obscurus, and raphe pallidus, we examined whether stimulation of the medullary raphe nuclei enhances colorectal motility via the lumbosacral defecation center. Colorectal pressure was recorded with a balloon in vivo in anesthetized rats. Electrical stimulation of the medullary raphe nuclei failed to enhance colorectal motility. Because GABAergic neurons can be simultaneously activated by the raphe stimulation and released GABA masks accelerating actions of the raphe nuclei on the lumbosacral defecation center, a GABAA receptor antagonist was preinjected intrathecally to manifest excitatory responses. When spinal GABAA receptors were blocked by the antagonist, electrical stimulation of the medullary raphe nuclei increased colorectal contractions. This effect of the raphe nuclei was inhibited by intrathecal injection of 5-hydroxytryptamine type 2 (5-HT2) and type 3 (5-HT3) receptor antagonists. In addition, injection of a selective 5-HT reuptake inhibitor in the lumbosacral spinal cord augmented the raphe stimulation-induced enhancement of colorectal motility. Transection of the pelvic nerves, but not transection of the colonic nerves, prevented the effect of the raphe nuclei on colorectal motility. These results demonstrate that activation of the medullary raphe nuclei causes augmented contractions of the colorectum via 5-HT2 and 5-HT3 receptors in the lumbosacral defecation center. NEW & NOTEWORTHY We have shown that electrical stimulation of the medullary raphe nuclei causes augmented contractions of the colorectum via pelvic nerves in rats. The effect of the medullary raphe nuclei on colorectal motility is exerted through activation of 5-hydroxytryptamine type 2 and type 3 receptors in the lumbosacral defecation center. The descending serotoninergic raphespinal tract represents new potential therapeutic targets against colorectal dysmotility such as irritable bowel syndrome.


1987 ◽  
Vol 84 (15) ◽  
pp. 5492-5495 ◽  
Author(s):  
M. Kadekaro ◽  
W. H. Vance ◽  
M. L. Terrell ◽  
H. Gary ◽  
H. M. Eisenberg ◽  
...  

1999 ◽  
pp. 49
Author(s):  
Duk-Yoon Kim ◽  
Alyssa A. Hawranko ◽  
Matthew O. Fraser ◽  
Mitsuharu Yoshiyama ◽  
Michael B. Chancellor ◽  
...  

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Amirali Toossi ◽  
Dirk G. Everaert ◽  
Steve I. Perlmutter ◽  
Vivian K. Mushahwar

Abstract Implantable spinal-cord-neuroprostheses aiming to restore standing and walking after paralysis have been extensively studied in animal models (mainly cats) and have shown promising outcomes. This study aimed to take a critical step along the clinical translation path of these neuroprostheses, and investigated the organization of the neural networks targeted by these implants in a non-human primate. This was accomplished by advancing a microelectrode into various locations of the lumbar enlargement of the spinal cord, targeting the ventral horn of the gray matter. Microstimulation in these locations produced a variety of functional movements in the hindlimb. The resulting functional map of the spinal cord in monkeys was found to have a similar overall organization along the length of the spinal cord to that in cats. This suggests that the human spinal cord may also be organized similarly. The obtained spinal cord maps in monkeys provide important knowledge that will guide the very first testing of these implants in humans.


2019 ◽  
Vol 317 (4) ◽  
pp. G545-G555 ◽  
Author(s):  
Hiroyuki Nakamori ◽  
Kiyotada Naitou ◽  
Yuuki Horii ◽  
Hiroki Shimaoka ◽  
Kazuhiro Horii ◽  
...  

We previously demonstrated that administration of norepinephrine, dopamine, and serotonin into the lumbosacral defecation center caused propulsive contractions of the colorectum. It is known that the monoamines in the spinal cord are released mainly from descending neurons in the brainstem. In fact, stimulation of the medullary raphe nuclei, the origin of descending serotonergic neurons, enhances colorectal motility via the lumbosacral defecation center. Therefore, the purpose of this study was to examine the roles of the noradrenergic nucleus locus coeruleus (LC) and dopaminergic nucleus A11 region in the defecation reflex. Colorectal motility was measured with a balloon in anesthetized rats. Electrical stimulation of the LC and A11 region increased colorectal pressure only when a GABAA receptor antagonist was injected into the lumbosacral spinal cord. The effects of the LC stimulation and A11 region stimulation on colorectal motility were inhibited by antagonists of α1-adrenoceptors and D2-like dopamine receptors injected into the lumbosacral spinal cord, respectively. Spinal injection of a norepinephrine-dopamine reuptake inhibitor augmented the colokinetic effect of LC stimulation. The effect of stimulation of each nucleus was abolished by surgical severing of the parasympathetic pelvic nerves. Our findings demonstrate that activation of descending noradrenergic neurons from the LC and descending dopaminergic neurons from the A11 region causes enhancement of colorectal motility via the lumbosacral defecation center. The present study provides a novel concept that the brainstem monoaminergic nuclei play a role as supraspinal defecation centers. NEW & NOTEWORTHY The present study demonstrates that electrical and chemical stimulations of the locus coeruleus or A11 region augment contractions of the colorectum. The effects of locus coeruleus and A11 stimulations on colorectal motility are due to activation of α1-adrenoceptors and D2-like dopamine receptors in the lumbosacral defecation center, respectively. The present study provides a novel concept that the brainstem monoaminergic nuclei play a role as supraspinal defecation centers.


2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Ran Won ◽  
Bae Hwan Lee

We have previously reported the crossed-withdrawal reflex in which the rats with nerve injury developed behavioral pain responses of the injured paw to stimuli applied to the contralateral uninjured paw. This reflex indicates that contralateral plastic changes may occur in the spinal cord after unilateral nerve injury. The present study was performed to elucidate the mechanisms and morphological correlates underlying the crossed-withdrawal reflex by using quantitative14C-2-deoxyglucose (2-DG) autoradiography which can examine metabolic activities and spatial patterns simultaneously. Under pentobarbital anesthesia, rats were subjected to unilateral nerve injury. Mechanical allodynia was tested for two weeks after nerve injury. After nerve injury, neuropathic pain behaviors developed progressively. The crossed-withdrawal reflex was observed at two weeks postoperatively. Contralateral enhancement of 2-DG uptake in the ventral horn of the spinal cord to electrical stimulation of the uninjured paw was observed. These results suggest that the facilitation of information processing from the uninjured side to the injured side may contribute to the crossed-withdrawal reflex by plastic changes in the spinal cord of nerve-injured rats.


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