The Experts below are selected from a list of 201 Experts worldwide ranked by ideXlab platform
Malinda E C Fitzgerald - One of the best experts on this subject based on the ideXlab platform.
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role of the Superior Salivatory Nucleus in parasympathetic control of choroidal blood flow and in maintenance of retinal health
Experimental Eye Research, 2021Co-Authors: Malinda E C Fitzgerald, Nobel Del Mar, Hongbing Wang, Corey Haughey, Marcia G Honig, Anton ReinerAbstract:Abstract The vasodilatory pterygopalatine ganglion (PPG) innervation of the choroid is under the control of preganglionic input from the Superior Salivatory Nucleus (SSN), the parasympathetic portion of the facial motor Nucleus. We sought to confirm that choroidal SSN drives a choroid-wide vasodilation and determine if such control is important for retinal health. To the former end, we found, using transscleral laser Doppler flowmetry, that electrical activation of choroidal SSN significantly increased choroidal blood flow (ChBF), at a variety of choroidal sites that included more posterior as well as more anterior ones. We further found that the increases in ChBF were significantly reduced by inhibition of neuronal nitric oxide synthase (nNOS), thus implicating nitrergic PPG terminals in the SSN-elicited ChBF increases. To evaluate the role of parasympathetic control of ChBF in maintaining retinal health, some rats received unilateral lesions of SSN, and were evaluated functionally and histologically. In eyes ipsilateral to choroidal SSN destruction, we found that the flash-evoked scotopic electroretinogram a-wave and b-wave peak amplitudes were both significantly reduced by 10 weeks post lesion. Choroidal baroregulation was evaluated in some of these rats, and found to be impaired in the low systemic arterial blood pressure (ABP) range where vasodilation normally serves to maintain stable ChBF. In retina ipsilateral to SSN destruction, the abundance of Muller cell processes immunolabeled for glial fibrillary acidic protein (GFAP) and GFAP message were significantly upregulated. Our studies indicate that the SSN-PPG circuit mediates parasympathetic vasodilation of choroid, which appears to contribute to ChBF baroregulation during low ABP. Our results further indicate that impairment in this adaptive mechanism results in retinal dysfunction and pathology within months of the ChBF disturbance, indicating its importance for retinal health.
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disinhibition of neurons of the Nucleus of solitary tract that project to the Superior Salivatory Nucleus causes choroidal vasodilation implications for mechanisms underlying choroidal baroregulation
Neuroscience Letters, 2016Co-Authors: Malinda E C Fitzgerald, Nobel Del Mar, Anton ReinerAbstract:Preganglionic neurons in the Superior Salivatory Nucleus (SSN) that mediate parasympathetic vasodilation of choroidal blood vessels receive a major excitatory input from the baroresponsive part of the Nucleus of the solitary tract (NTS). This input appears likely to mediate choroidal vasodilation during systemic hypotension, which prevents decreases in choroidal blood flow (ChBF) due to reduced perfusion pressure. It is uncertain, however, how low blood pressure signals to NTS from the aortic depressor nerve (ADN), which fires at a low rate during systemic hypotension, could yield increased firing in the NTS output to SSN. The simplest hypothesis is that SSN-projecting NTS neurons are under the inhibitory control of ADN-receptive GABAergic NTS neurons. As part of evaluating this hypothesis, we assessed if SSN-projecting NTS neurons, in fact, receive prominent inhibitory input and if blocking GABAergic modulation of them increases ChBF. We found that SSN-projecting NTS neuronal perikarya identified by retrograde labeling are densely coated with GABAergic terminals, but lightly coated with excitatory terminals. We also found that, infusion of the GABA-A receptor antagonist GABAzine into NTS increased ChBF. Our results are consistent with the possibility that low blood pressure signals from the ADN produce vasodilation in choroid by causing diminished activity in ADN-receptive NTS neurons that tonically suppress SSN-projecting NTS neurons.
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Stimulation of Baroresponsive Parts of the Nucleus of the Solitary Tract Produces Nitric Oxide-mediated Choroidal Vasodilation in Rat Eye
Frontiers Media S.A., 2016Co-Authors: Malinda E C Fitzgerald, Nobel Del Mar, Anton ReinerAbstract:Preganglionic parasympathetic neurons of the ventromedial part of the Superior Salivatory Nucleus (SSN) mediate vasodilation of orbital and choroidal blood vessels, via their projection to the nitrergic pterygopalatine ganglion (PPG) neurons that innervate these vessels. We recently showed that the baroresponsive part of the Nucleus of the solitary tract (NTS) innervates choroidal control parasympathetic preganglionic neurons of SSN in rats. As this projection provides a means by which blood pressure signals may modulate ChBF, we investigated if activation of baroresponsive NTS evokes ChBF increases in rat eye, using Laser Doppler flowmetry to measure ChBF transclerally. We found that electrical activation of ipsilateral baroresponsive NTS and its efferent fiber pathway to choroidal SSN increased mean ChBF by about 40-80% above baseline, depending on current level. The ChBF responses obtained with stimulation of baroresponsive NTS were driven by increases in both choroidal blood volume (i.e. vasodilation) and choroidal blood velocity (presumed orbital vessel dilation). Stimulation of baroresponsive NTS, by contrast, yielded no significant mean increases in systemic arterial blood pressure. We further found that the increases in ChBF with NTS stimulation were significantly reduced by administration of the neuronal nitric oxide synthase inhibitor Nω-propyl-l-arginine (NPA), thus implicating nitrergic PPG terminals in the NTS-elicited ChBF increases. Our results show that NTS neurons projecting to choroidal SSN do mediate increase in ChBF, and thus suggest a role of baroresponsive NTS in the blood pressure-dependent regulation of ChBF
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The identification and neurochemical characterization of central neurons that target parasympathetic preganglionic neurons involved in the regulation of choroidal blood flow in the rat eye using pseudorabies virus, immunolabeling and conventional pathway tracing methods
Frontiers Media S.A., 2015Co-Authors: Chunyan Eli, Mark S. Ledoux, Malinda E C Fitzgerald, Nobel Edel Mar, Sherry Ecuthbertson, Suzhen Egong, James Patrick RyanAbstract:The choroidal blood vessels of the eye provide the main vascular support to the outer retina. These blood vessels are under parasympathetic vasodilatory control via input from the pterygopalatine ganglion (PPG), which in turn receives its preganglionic input from the Superior Salivatory Nucleus (SSN) of the hindbrain. The present study characterized the central neurons projecting to the SSN neurons innervating choroidal PPG neurons, using pathway tracing and immunolabeling. In the initial set of studies, minute injections of the Bartha strain of the retrograde transneuronal tracer pseudorabies virus (PRV) were made into choroid in rats in which the Superior cervical ganglia had been excised (to prevent labeling of sympathetic circuitry). Diverse neuronal populations beyond the choroidal part of ipsilateral SSN showed transneuronal labeling, which notably included the parvocellular part of the paraventricular Nucleus of the hypothalamus (PVN), the periaqueductal gray, the raphe magnus (RaM), the B3 region of the pons, A5, the Nucleus of the solitary tract (NTS), the rostral ventrolateral medulla (RVLM), and the intermediate reticular Nucleus of the medulla. The PRV+ neurons were located in the parts of these cell groups that are responsive to systemic blood pressure signals and involved in systemic blood pressure regulation by the sympathetic nervous system. In a second set of studies using PRV labeling, conventional pathway tracing, and immunolabeling, we found that PVN neurons projecting to SSN tended to be oxytocinergic and glutamatergic, RaM neurons projecting to SSN were serotonergic, and NTS neurons projecting to SSN were glutamatergic. Our results suggest that blood pressure and volume signals that drive sympathetic constriction of the systemic vasculature may also drive parasympathetic vasodilation of the choroidal vasculature, and may thereby contribute to choroidal baroregulation during low blood pressure
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projections from the hypothalamic paraventricular Nucleus and the Nucleus of the solitary tract to prechoroidal neurons in the Superior Salivatory Nucleus pathways controlling rodent choroidal blood flow
Brain Research, 2010Co-Authors: Mark S. Ledoux, Malinda E C Fitzgerald, Nobel Del Mar, Suzhen Gong, Patrick T Ryan, Anton ReinerAbstract:Using intrachoroidal injection of the transneuronal retrograde tracer pseudorabies virus (PRV) in rats, we previously localized preganglionic neurons in the Superior Salivatory Nucleus (SSN) that regulate choroidal blood flow (ChBF) via projections to the pterygopalatine ganglion (PPG). In the present study, we used higher-order transneuronal retrograde labeling following intrachoroidal PRV injection to identify central neuronal cell groups involved in parasympathetic regulation of ChBF via input to the SSN. These prominently included the hypothalamic paraventricular Nucleus (PVN) and the Nucleus of the solitary tract (NTS), both of which are responsive to systemic BP and are involved in systemic sympathetic vasoconstriction. Conventional pathway tracing methods were then used to determine if the PVN and/or NTS project directly to the choroidal subdivision of the SSN. Following retrograde tracer injection into SSN (biotinylated dextran amine 3K or Fluorogold), labeled perikarya were found in PVN and NTS. Injection of the anterograde tracer, biotinylated dextran amine 10K (BDA10K), into PVN or NTS resulted in densely packed BDA10K+terminals in prechoroidal SSN (as defined by its enrichment in nitric oxide synthase-containing perikarya). Double-label studies showed these inputs ended directly on prechoroidal nitric oxide synthase-containing neurons of SSN. Our study thus establishes that PVN and NTS project directly to the part of SSN involved in parasympathetic vasodilatory control of the choroid via the PPG. These results suggest that control of ChBF may be linked to systemic blood pressure and central control of the systemic vasculature.
Ryuji Matsuo - One of the best experts on this subject based on the ideXlab platform.
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effects of cevimeline on excitability of parasympathetic preganglionic neurons in the Superior Salivatory Nucleus of rats
Autonomic Neuroscience: Basic and Clinical, 2017Co-Authors: Yoshihiro Mitoh, Hirotaka Ueda, Masako Fujita, Motoi Kobashi, Hiroyuki Ichikawa, Ryuji MatsuoAbstract:The Superior Salivatory Nucleus (SSN) contains parasympathetic preganglionic neurons innervating the submandibular and sublingual salivary glands. Cevimeline, a muscarinic acetylcholine receptor (mAChR) agonist, is a sialogogue that possibly stimulates SSN neurons in addition to the salivary glands themselves because it can cross the blood-brain barrier (BBB). In the present study, we examined immunoreactivities for mAChR subtypes in SSN neurons retrogradely labeled with a fluorescent tracer in neonatal rats. Additionally, we examined the effects of cevimeline in labeled SSN neurons of brainstem slices using a whole-cell patch-clamp technique. Mainly M1 and M3 receptors were detected by immunohistochemical staining, with low-level detection of M4 and M5 receptors and absence of M2 receptors. Most (110 of 129) SSN neurons exhibited excitatory responses to application of cevimeline. In responding neurons, voltage-clamp recordings showed that 84% (101/120) of the neurons exhibited inward currents. In the neurons displaying inward currents, the effects of the mAChR antagonists were examined. A mixture of M1 and M3 receptor antagonists most effectively reduced the peak amplitude of inward currents, suggesting that the excitatory effects of cevimeline on SSN neurons were mainly mediated by M1 and M3 receptors. Current-clamp recordings showed that application of cevimeline induced membrane depolarization (9/9 neurons). These results suggest that most SSN neurons are excited by cevimeline via M1 and M3 muscarinic receptors.
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muscarinic receptor immunoreactivity in the Superior Salivatory Nucleus neurons innervating the salivary glands of the rat
Neuroscience Letters, 2011Co-Authors: Hirotaka Ueda, Yoshihiro Mitoh, Masako Fujita, Motoi Kobashi, Takashi Yamashiro, Tomosada Sugimoto, Hiroyuki Ichikawa, Ryuji MatsuoAbstract:The Superior Salivatory Nucleus (SSN) contains preganglionic parasympathetic neurons to the submandibular and sublingual salivary glands. Cevimeline, a muscarinic acetylcholine receptor agonist, stimulates the salivary glands and is presently used as sialogogue in the treatment of dry mouth. Since cevimeline passes through the blood-brain barrier, it is also able to act on muscarinic acetylcholine receptors in the central nervous system. Our preliminary experiment using the whole-cell patch-clamp technique has shown that cevimeline excites SSN neurons in rat brain slices, suggesting that SSN neurons have muscarinic acetylcholine receptors; however, it is unclear which subtypes of muscarinic acetylcholine receptors exist in SSN neurons. In the present study, we investigated immunohistochemically muscarinic acetylcholine receptor subtypes, M1 receptor (M1R), M2R, M3R, M4R, and M5R in SSN neurons. SSN neurons innervating the salivary glands, retrogradely labeled with a fluorescent tracer from the chorda-lingual nerve, mostly expressed M3R immunoreactivity (-ir) (92.3%) but not M1R-ir. About half of such SSN neurons also showed M2R- (40.1%), M4R- (54.0%) and M5R-ir (46.0%); therefore, it is probable that SSN neurons co-express M3R-ir with at least two of the other muscarinic receptor subtypes. This is the first report to show that SSN neurons contain muscarinic acetylcholine receptors.
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development of inhibitory synaptic transmission to the Superior Salivatory Nucleus in rats
Brain Research, 2008Co-Authors: Yoshihiro Mitoh, Masako Fujita, Motoi Kobashi, Makoto Funahashi, Akihito Fujii, Ryuji MatsuoAbstract:The primary parasympathetic center of the submandibular and sublingual salivary glands is the Superior Salivatory (SS) Nucleus, neurons of which receive excitatory (glutamatergic) and inhibitory (GABAergic and glycinergic) synaptic transmissions in rats. In the present study, to examine postnatal neural development, we focused on inhibitory transmission to the SS neurons in neonatal rats from postnatal day 2 (P2) to P14. Conventional and gramicidin-perforated whole-cell patch-clamp techniques were applied to the neurons in brainstem slices. The decay time constants of GABAergic and glycinergic postsynaptic currents (PSCs) consisted of fast (tau(fast)) and slow (tau(slow)) components. Both tau(fast) and tau(slow) of PSC components tended to become faster with development. The equilibrium potential of Cl(-) (E(Cl-)) was estimated from the reversal potentials of total PSCs (GABAergic plus glycinergic). The E(Cl-) in the P8-P14 group was significantly more negative than E(Cl-) in the P2-P7 group. Exogenous GABA application at the resting potentials produced depolarization in 83% of SS neurons at P2-P7 and accompanied the action potential in some neurons. In contrast, at P8-P14, GABA evoked hyperpolarization in 78% of SS neurons; therefore, SS neurons did not acquire mature inhibitory systems until P14. The development of SS neurons is discussed as compared with the development of peripheral salivary gland tissue and brainstem neurons that participate in oral motor and sensory functions.
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excitatory and inhibitory postsynaptic currents of the Superior Salivatory Nucleus innervating the salivary glands and tongue in the rat
Brain Research, 2004Co-Authors: Yoshihiro Mitoh, Motoi Kobashi, Makoto Funahashi, Ryuji MatsuoAbstract:Abstract The excitatory and inhibitory synaptic inputs to parasympathetic preganglionic neurons in the Superior Salivatory (SS) Nucleus were investigated in brain slices of neonatal (4–8 days old) rat using the whole-cell patch-clamp technique. The SS neurons innervating the submandibular and sublingual salivary glands and innervating the lingual artery in the anterior region of the tongue were identified by retrograde transport of a fluorescent tracer. Whole-cell currents were evoked by electrical stimulation of tissue surrounding the cell. These evoked postsynaptic currents were completely abolished by antagonists for N-methyl- d -aspartate (NMDA) glutamate, non-NMDA glutamate, γ-aminobutyric acid type A (GABAA), and glycine receptors, suggesting that SS neurons receive glutamatergic excitatory, and GABAergic and glycinergic inhibitory synaptic inputs. In SS neurons for the salivary glands, the ratio of the NMDA component to the total excitatory postsynaptic current (EPSC) was larger than that of the non-NMDA component. This profile was reversed in the SS neurons for the tongue. In SS neurons for the salivary glands, the ratio of the GABAA component to the total IPSC was larger than the ratio of the glycine component to total inhibitory postsynaptic current (IPSC). The decay time constants of the GABAA component were slower than those for glycine. These characteristics of the excitatory and inhibitory inputs may be involved in determining the firing properties of the SS neurons innervating the salivary glands and the tongue.
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two types of parasympathetic preganglionic neurones in the Superior Salivatory Nucleus characterized electrophysiologically in slice preparations of neonatal rats
The Journal of Physiology, 1998Co-Authors: Ryuji Matsuo, Youngnam KangAbstract:Parasympathetic preganglionic neurones of the Superior Salivatory Nucleus are diffusely distributed in the lateral reticular formation of the medulla oblongata (e.g. Contreras et al. 1980; Mitchell & Templeton, 1981). Many of the Superior Salivatory neurones send their fibres (the preganglionic parasympathetic fibres) to the submandibular ganglia and to the intra-lingual ganglia in the anterior part of the tongue, via the intermediate, chorda tympani and chorda-lingual nerves (Chibuzo et al. 1980; Yu & Srinivasan, 1980). As with other parasympathetic preganglionic neurones, the Superior Salivatory neurones are considered to be cholinergic (Large & Sim, 1986; Yawo, 1989). Biophysical studies have revealed that cholinergic neurones, such as preganglionic sympathetic neurones (Yoshimura et al. 1987) and pedunculopontine tegmental or mesopontine neurones (Kamondi et al. 1992), often express the transient outward current (A-current), which is reflected in a late spiking pattern or a large spike after-hyperpolarization (Manis, 1990; Kang & Kitai, 1990). However, little is known about the electrophysiological properties of preganglionic parasympathetic neurones, including the Superior Salivatory neurones. The firing patterns of the Superior Salivatory neurones during reflex activation have been indirectly examined by recording impulses from the preganglionic fibres supplying the salivary glands of anaesthetized rodents. Most of the fibres showed tonic firing at a low rate (5–18 impulses s−1, mean value over 5–15 s), while some fibres showed periodical grouped discharges or phasic tonic discharges (Kawamura & Yamamoto, 1978; Matsuo & Kusano, 1984; Matsuo & Yamamoto, 1989). These findings suggest that the Superior Salivatory neurones may have biophysical membrane properties that limit firing frequencies to relatively low values, and that the neurones may be separated into different subtypes based on their firing pattern. To test this hypothesis and to investigate the membrane properties, we made whole-cell recordings on retrogradely identified Superior Salivatory neurones maintained in brainstem slice preparations obtained from neonatal rats aged 6–15 days. We investigated mainly voltage-activated potassium currents, which are important for limiting the firing frequency and for determining the firing pattern and action potential waveform (for review see Rudy, 1988). The neurones were found to display two distinct types of A-currents, depending on their peripheral targets (i.e. the salivary glands and the anterior part of the tongue). Since the rat submandibular gland as well as the submandibular ganglia undergo progressive development to attain mature functions during the early postnatal period (e.g. Jacoby & Leeson, 1959; Schneyer & Schneyer, 1961; Lichtman, 1977; Bylund et al. 1982), the Superior Salivatory neurones of neonatal rats are also likely to be under development. However, a clear developmental trend of maturation was seen in the activation and inactivation kinetics of the A-currents expressed in the neurones obtained from rats aged 1 and 2 weeks.
Anton Reiner - One of the best experts on this subject based on the ideXlab platform.
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role of the Superior Salivatory Nucleus in parasympathetic control of choroidal blood flow and in maintenance of retinal health
Experimental Eye Research, 2021Co-Authors: Malinda E C Fitzgerald, Nobel Del Mar, Hongbing Wang, Corey Haughey, Marcia G Honig, Anton ReinerAbstract:Abstract The vasodilatory pterygopalatine ganglion (PPG) innervation of the choroid is under the control of preganglionic input from the Superior Salivatory Nucleus (SSN), the parasympathetic portion of the facial motor Nucleus. We sought to confirm that choroidal SSN drives a choroid-wide vasodilation and determine if such control is important for retinal health. To the former end, we found, using transscleral laser Doppler flowmetry, that electrical activation of choroidal SSN significantly increased choroidal blood flow (ChBF), at a variety of choroidal sites that included more posterior as well as more anterior ones. We further found that the increases in ChBF were significantly reduced by inhibition of neuronal nitric oxide synthase (nNOS), thus implicating nitrergic PPG terminals in the SSN-elicited ChBF increases. To evaluate the role of parasympathetic control of ChBF in maintaining retinal health, some rats received unilateral lesions of SSN, and were evaluated functionally and histologically. In eyes ipsilateral to choroidal SSN destruction, we found that the flash-evoked scotopic electroretinogram a-wave and b-wave peak amplitudes were both significantly reduced by 10 weeks post lesion. Choroidal baroregulation was evaluated in some of these rats, and found to be impaired in the low systemic arterial blood pressure (ABP) range where vasodilation normally serves to maintain stable ChBF. In retina ipsilateral to SSN destruction, the abundance of Muller cell processes immunolabeled for glial fibrillary acidic protein (GFAP) and GFAP message were significantly upregulated. Our studies indicate that the SSN-PPG circuit mediates parasympathetic vasodilation of choroid, which appears to contribute to ChBF baroregulation during low ABP. Our results further indicate that impairment in this adaptive mechanism results in retinal dysfunction and pathology within months of the ChBF disturbance, indicating its importance for retinal health.
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disinhibition of neurons of the Nucleus of solitary tract that project to the Superior Salivatory Nucleus causes choroidal vasodilation implications for mechanisms underlying choroidal baroregulation
Neuroscience Letters, 2016Co-Authors: Malinda E C Fitzgerald, Nobel Del Mar, Anton ReinerAbstract:Preganglionic neurons in the Superior Salivatory Nucleus (SSN) that mediate parasympathetic vasodilation of choroidal blood vessels receive a major excitatory input from the baroresponsive part of the Nucleus of the solitary tract (NTS). This input appears likely to mediate choroidal vasodilation during systemic hypotension, which prevents decreases in choroidal blood flow (ChBF) due to reduced perfusion pressure. It is uncertain, however, how low blood pressure signals to NTS from the aortic depressor nerve (ADN), which fires at a low rate during systemic hypotension, could yield increased firing in the NTS output to SSN. The simplest hypothesis is that SSN-projecting NTS neurons are under the inhibitory control of ADN-receptive GABAergic NTS neurons. As part of evaluating this hypothesis, we assessed if SSN-projecting NTS neurons, in fact, receive prominent inhibitory input and if blocking GABAergic modulation of them increases ChBF. We found that SSN-projecting NTS neuronal perikarya identified by retrograde labeling are densely coated with GABAergic terminals, but lightly coated with excitatory terminals. We also found that, infusion of the GABA-A receptor antagonist GABAzine into NTS increased ChBF. Our results are consistent with the possibility that low blood pressure signals from the ADN produce vasodilation in choroid by causing diminished activity in ADN-receptive NTS neurons that tonically suppress SSN-projecting NTS neurons.
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Stimulation of Baroresponsive Parts of the Nucleus of the Solitary Tract Produces Nitric Oxide-mediated Choroidal Vasodilation in Rat Eye
Frontiers Media S.A., 2016Co-Authors: Malinda E C Fitzgerald, Nobel Del Mar, Anton ReinerAbstract:Preganglionic parasympathetic neurons of the ventromedial part of the Superior Salivatory Nucleus (SSN) mediate vasodilation of orbital and choroidal blood vessels, via their projection to the nitrergic pterygopalatine ganglion (PPG) neurons that innervate these vessels. We recently showed that the baroresponsive part of the Nucleus of the solitary tract (NTS) innervates choroidal control parasympathetic preganglionic neurons of SSN in rats. As this projection provides a means by which blood pressure signals may modulate ChBF, we investigated if activation of baroresponsive NTS evokes ChBF increases in rat eye, using Laser Doppler flowmetry to measure ChBF transclerally. We found that electrical activation of ipsilateral baroresponsive NTS and its efferent fiber pathway to choroidal SSN increased mean ChBF by about 40-80% above baseline, depending on current level. The ChBF responses obtained with stimulation of baroresponsive NTS were driven by increases in both choroidal blood volume (i.e. vasodilation) and choroidal blood velocity (presumed orbital vessel dilation). Stimulation of baroresponsive NTS, by contrast, yielded no significant mean increases in systemic arterial blood pressure. We further found that the increases in ChBF with NTS stimulation were significantly reduced by administration of the neuronal nitric oxide synthase inhibitor Nω-propyl-l-arginine (NPA), thus implicating nitrergic PPG terminals in the NTS-elicited ChBF increases. Our results show that NTS neurons projecting to choroidal SSN do mediate increase in ChBF, and thus suggest a role of baroresponsive NTS in the blood pressure-dependent regulation of ChBF
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projections from the hypothalamic paraventricular Nucleus and the Nucleus of the solitary tract to prechoroidal neurons in the Superior Salivatory Nucleus pathways controlling rodent choroidal blood flow
Brain Research, 2010Co-Authors: Mark S. Ledoux, Malinda E C Fitzgerald, Nobel Del Mar, Suzhen Gong, Patrick T Ryan, Anton ReinerAbstract:Using intrachoroidal injection of the transneuronal retrograde tracer pseudorabies virus (PRV) in rats, we previously localized preganglionic neurons in the Superior Salivatory Nucleus (SSN) that regulate choroidal blood flow (ChBF) via projections to the pterygopalatine ganglion (PPG). In the present study, we used higher-order transneuronal retrograde labeling following intrachoroidal PRV injection to identify central neuronal cell groups involved in parasympathetic regulation of ChBF via input to the SSN. These prominently included the hypothalamic paraventricular Nucleus (PVN) and the Nucleus of the solitary tract (NTS), both of which are responsive to systemic BP and are involved in systemic sympathetic vasoconstriction. Conventional pathway tracing methods were then used to determine if the PVN and/or NTS project directly to the choroidal subdivision of the SSN. Following retrograde tracer injection into SSN (biotinylated dextran amine 3K or Fluorogold), labeled perikarya were found in PVN and NTS. Injection of the anterograde tracer, biotinylated dextran amine 10K (BDA10K), into PVN or NTS resulted in densely packed BDA10K+terminals in prechoroidal SSN (as defined by its enrichment in nitric oxide synthase-containing perikarya). Double-label studies showed these inputs ended directly on prechoroidal nitric oxide synthase-containing neurons of SSN. Our study thus establishes that PVN and NTS project directly to the part of SSN involved in parasympathetic vasodilatory control of the choroid via the PPG. These results suggest that control of ChBF may be linked to systemic blood pressure and central control of the systemic vasculature.
Mark S. Ledoux - One of the best experts on this subject based on the ideXlab platform.
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The identification and neurochemical characterization of central neurons that target parasympathetic preganglionic neurons involved in the regulation of choroidal blood flow in the rat eye using pseudorabies virus, immunolabeling and conventional pathway tracing methods
Frontiers Media S.A., 2015Co-Authors: Chunyan Eli, Mark S. Ledoux, Malinda E C Fitzgerald, Nobel Edel Mar, Sherry Ecuthbertson, Suzhen Egong, James Patrick RyanAbstract:The choroidal blood vessels of the eye provide the main vascular support to the outer retina. These blood vessels are under parasympathetic vasodilatory control via input from the pterygopalatine ganglion (PPG), which in turn receives its preganglionic input from the Superior Salivatory Nucleus (SSN) of the hindbrain. The present study characterized the central neurons projecting to the SSN neurons innervating choroidal PPG neurons, using pathway tracing and immunolabeling. In the initial set of studies, minute injections of the Bartha strain of the retrograde transneuronal tracer pseudorabies virus (PRV) were made into choroid in rats in which the Superior cervical ganglia had been excised (to prevent labeling of sympathetic circuitry). Diverse neuronal populations beyond the choroidal part of ipsilateral SSN showed transneuronal labeling, which notably included the parvocellular part of the paraventricular Nucleus of the hypothalamus (PVN), the periaqueductal gray, the raphe magnus (RaM), the B3 region of the pons, A5, the Nucleus of the solitary tract (NTS), the rostral ventrolateral medulla (RVLM), and the intermediate reticular Nucleus of the medulla. The PRV+ neurons were located in the parts of these cell groups that are responsive to systemic blood pressure signals and involved in systemic blood pressure regulation by the sympathetic nervous system. In a second set of studies using PRV labeling, conventional pathway tracing, and immunolabeling, we found that PVN neurons projecting to SSN tended to be oxytocinergic and glutamatergic, RaM neurons projecting to SSN were serotonergic, and NTS neurons projecting to SSN were glutamatergic. Our results suggest that blood pressure and volume signals that drive sympathetic constriction of the systemic vasculature may also drive parasympathetic vasodilation of the choroidal vasculature, and may thereby contribute to choroidal baroregulation during low blood pressure
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Parasympathetic Innervation of the Meibomian Glands in Rats
2013Co-Authors: Mark S. Ledoux, Bryan R Murphy, Melissa L Greene, Qihong Zhou, Patrick RyanAbstract:PURPOSE. To determine the location of parasympathetic neurons that innervate the meibomian glands in rats. METHODS. The B subunit of cholera toxin (CTB), fast blue, and a retrograde transneuronal tracer, the Bartha strain of pseudorabies virus (PRV-Ba), were injected into the upper eyelids of adult Sprague-Dawley rats after sectioning the ipsilateral branches of the facial nerve and resecting the Superior cervical ganglia. Brains and orbital tissues were processed for the immunohistochemical detection of PRV-Ba and CTB. In selected cases, series of brain sections were double labeled for PRV-Ba and tyrosine hydroxylase to determine the relationship between the A5 noradrenergic cell group and Superior Salivatory Nucleus, or for PRV-Ba and choline acetyltransferase to establish the neurochemical phenotype of parasympathetic preganglionic neurons
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projections from the hypothalamic paraventricular Nucleus and the Nucleus of the solitary tract to prechoroidal neurons in the Superior Salivatory Nucleus pathways controlling rodent choroidal blood flow
Brain Research, 2010Co-Authors: Mark S. Ledoux, Malinda E C Fitzgerald, Nobel Del Mar, Suzhen Gong, Patrick T Ryan, Anton ReinerAbstract:Using intrachoroidal injection of the transneuronal retrograde tracer pseudorabies virus (PRV) in rats, we previously localized preganglionic neurons in the Superior Salivatory Nucleus (SSN) that regulate choroidal blood flow (ChBF) via projections to the pterygopalatine ganglion (PPG). In the present study, we used higher-order transneuronal retrograde labeling following intrachoroidal PRV injection to identify central neuronal cell groups involved in parasympathetic regulation of ChBF via input to the SSN. These prominently included the hypothalamic paraventricular Nucleus (PVN) and the Nucleus of the solitary tract (NTS), both of which are responsive to systemic BP and are involved in systemic sympathetic vasoconstriction. Conventional pathway tracing methods were then used to determine if the PVN and/or NTS project directly to the choroidal subdivision of the SSN. Following retrograde tracer injection into SSN (biotinylated dextran amine 3K or Fluorogold), labeled perikarya were found in PVN and NTS. Injection of the anterograde tracer, biotinylated dextran amine 10K (BDA10K), into PVN or NTS resulted in densely packed BDA10K+terminals in prechoroidal SSN (as defined by its enrichment in nitric oxide synthase-containing perikarya). Double-label studies showed these inputs ended directly on prechoroidal nitric oxide synthase-containing neurons of SSN. Our study thus establishes that PVN and NTS project directly to the part of SSN involved in parasympathetic vasodilatory control of the choroid via the PPG. These results suggest that control of ChBF may be linked to systemic blood pressure and central control of the systemic vasculature.
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parasympathetic innervation of the meibomian glands in rats
Investigative Ophthalmology & Visual Science, 2001Co-Authors: Mark S. Ledoux, Bryan R Murphy, Melissa L Greene, Qihong Zhou, Patrick RyanAbstract:PURPOSE. To determine the location of parasympathetic neurons that innervate the meibomian glands in rats. METHODS. The B subunit of cholera toxin (CTB), fast blue, and a retrograde transneuronal tracer, the Bartha strain of pseudorabies virus (PRV-Ba), were injected into the upper eyelids of adult Sprague-Dawley rats after sectioning the ipsilateral branches of the facial nerve and resecting the Superior cervical ganglia. Brains and orbital tissues were processed for the immunohistochemical detection of PRV-Ba and CTB. In selected cases, series of brain sections were double labeled for PRV-Ba and tyrosine hydroxylase to determine the relationship between the A5 noradrenergic cell group and Superior Salivatory Nucleus, or for PRV-Ba and choline acetyltransferase to establish the neurochemical phenotype of parasympathetic preganglionic neurons. RESULTS. Labeled ganglionic cells were diffusely distributed within the ipsilateral pterygopalatine ganglion (PPG) and along the more proximal portions of the greater petrosal nerve (GPN). Labeled preganglionic neurons were cholinergic and were located immediately dorsolateral to the rostral-most portion of the facial Nucleus and caudal Superior olive, where they intermingled with A5 noradrenergic cells. CONCLUSIONS. The meibomian glands and other structures within the lid margin are subject to parasympathetic regulation by ganglion cells diffusely distributed within the PPG and along more proximal portions of the GPN. Cholinergic parasympathetic preganglionic neurons that project to meibomian gland-innervating ganglion cells are located immediately lateral, dorsal, and rostral to the facial motor Nucleus in the region commonly referred to as the Superior Salivatory Nucleus.
Yoshihiro Mitoh - One of the best experts on this subject based on the ideXlab platform.
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effects of cevimeline on excitability of parasympathetic preganglionic neurons in the Superior Salivatory Nucleus of rats
Autonomic Neuroscience: Basic and Clinical, 2017Co-Authors: Yoshihiro Mitoh, Hirotaka Ueda, Masako Fujita, Motoi Kobashi, Hiroyuki Ichikawa, Ryuji MatsuoAbstract:The Superior Salivatory Nucleus (SSN) contains parasympathetic preganglionic neurons innervating the submandibular and sublingual salivary glands. Cevimeline, a muscarinic acetylcholine receptor (mAChR) agonist, is a sialogogue that possibly stimulates SSN neurons in addition to the salivary glands themselves because it can cross the blood-brain barrier (BBB). In the present study, we examined immunoreactivities for mAChR subtypes in SSN neurons retrogradely labeled with a fluorescent tracer in neonatal rats. Additionally, we examined the effects of cevimeline in labeled SSN neurons of brainstem slices using a whole-cell patch-clamp technique. Mainly M1 and M3 receptors were detected by immunohistochemical staining, with low-level detection of M4 and M5 receptors and absence of M2 receptors. Most (110 of 129) SSN neurons exhibited excitatory responses to application of cevimeline. In responding neurons, voltage-clamp recordings showed that 84% (101/120) of the neurons exhibited inward currents. In the neurons displaying inward currents, the effects of the mAChR antagonists were examined. A mixture of M1 and M3 receptor antagonists most effectively reduced the peak amplitude of inward currents, suggesting that the excitatory effects of cevimeline on SSN neurons were mainly mediated by M1 and M3 receptors. Current-clamp recordings showed that application of cevimeline induced membrane depolarization (9/9 neurons). These results suggest that most SSN neurons are excited by cevimeline via M1 and M3 muscarinic receptors.
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muscarinic receptor immunoreactivity in the Superior Salivatory Nucleus neurons innervating the salivary glands of the rat
Neuroscience Letters, 2011Co-Authors: Hirotaka Ueda, Yoshihiro Mitoh, Masako Fujita, Motoi Kobashi, Takashi Yamashiro, Tomosada Sugimoto, Hiroyuki Ichikawa, Ryuji MatsuoAbstract:The Superior Salivatory Nucleus (SSN) contains preganglionic parasympathetic neurons to the submandibular and sublingual salivary glands. Cevimeline, a muscarinic acetylcholine receptor agonist, stimulates the salivary glands and is presently used as sialogogue in the treatment of dry mouth. Since cevimeline passes through the blood-brain barrier, it is also able to act on muscarinic acetylcholine receptors in the central nervous system. Our preliminary experiment using the whole-cell patch-clamp technique has shown that cevimeline excites SSN neurons in rat brain slices, suggesting that SSN neurons have muscarinic acetylcholine receptors; however, it is unclear which subtypes of muscarinic acetylcholine receptors exist in SSN neurons. In the present study, we investigated immunohistochemically muscarinic acetylcholine receptor subtypes, M1 receptor (M1R), M2R, M3R, M4R, and M5R in SSN neurons. SSN neurons innervating the salivary glands, retrogradely labeled with a fluorescent tracer from the chorda-lingual nerve, mostly expressed M3R immunoreactivity (-ir) (92.3%) but not M1R-ir. About half of such SSN neurons also showed M2R- (40.1%), M4R- (54.0%) and M5R-ir (46.0%); therefore, it is probable that SSN neurons co-express M3R-ir with at least two of the other muscarinic receptor subtypes. This is the first report to show that SSN neurons contain muscarinic acetylcholine receptors.
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development of inhibitory synaptic transmission to the Superior Salivatory Nucleus in rats
Brain Research, 2008Co-Authors: Yoshihiro Mitoh, Masako Fujita, Motoi Kobashi, Makoto Funahashi, Akihito Fujii, Ryuji MatsuoAbstract:The primary parasympathetic center of the submandibular and sublingual salivary glands is the Superior Salivatory (SS) Nucleus, neurons of which receive excitatory (glutamatergic) and inhibitory (GABAergic and glycinergic) synaptic transmissions in rats. In the present study, to examine postnatal neural development, we focused on inhibitory transmission to the SS neurons in neonatal rats from postnatal day 2 (P2) to P14. Conventional and gramicidin-perforated whole-cell patch-clamp techniques were applied to the neurons in brainstem slices. The decay time constants of GABAergic and glycinergic postsynaptic currents (PSCs) consisted of fast (tau(fast)) and slow (tau(slow)) components. Both tau(fast) and tau(slow) of PSC components tended to become faster with development. The equilibrium potential of Cl(-) (E(Cl-)) was estimated from the reversal potentials of total PSCs (GABAergic plus glycinergic). The E(Cl-) in the P8-P14 group was significantly more negative than E(Cl-) in the P2-P7 group. Exogenous GABA application at the resting potentials produced depolarization in 83% of SS neurons at P2-P7 and accompanied the action potential in some neurons. In contrast, at P8-P14, GABA evoked hyperpolarization in 78% of SS neurons; therefore, SS neurons did not acquire mature inhibitory systems until P14. The development of SS neurons is discussed as compared with the development of peripheral salivary gland tissue and brainstem neurons that participate in oral motor and sensory functions.
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excitatory and inhibitory postsynaptic currents of the Superior Salivatory Nucleus innervating the salivary glands and tongue in the rat
Brain Research, 2004Co-Authors: Yoshihiro Mitoh, Motoi Kobashi, Makoto Funahashi, Ryuji MatsuoAbstract:Abstract The excitatory and inhibitory synaptic inputs to parasympathetic preganglionic neurons in the Superior Salivatory (SS) Nucleus were investigated in brain slices of neonatal (4–8 days old) rat using the whole-cell patch-clamp technique. The SS neurons innervating the submandibular and sublingual salivary glands and innervating the lingual artery in the anterior region of the tongue were identified by retrograde transport of a fluorescent tracer. Whole-cell currents were evoked by electrical stimulation of tissue surrounding the cell. These evoked postsynaptic currents were completely abolished by antagonists for N-methyl- d -aspartate (NMDA) glutamate, non-NMDA glutamate, γ-aminobutyric acid type A (GABAA), and glycine receptors, suggesting that SS neurons receive glutamatergic excitatory, and GABAergic and glycinergic inhibitory synaptic inputs. In SS neurons for the salivary glands, the ratio of the NMDA component to the total excitatory postsynaptic current (EPSC) was larger than that of the non-NMDA component. This profile was reversed in the SS neurons for the tongue. In SS neurons for the salivary glands, the ratio of the GABAA component to the total IPSC was larger than the ratio of the glycine component to total inhibitory postsynaptic current (IPSC). The decay time constants of the GABAA component were slower than those for glycine. These characteristics of the excitatory and inhibitory inputs may be involved in determining the firing properties of the SS neurons innervating the salivary glands and the tongue.