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The Journal of Comparative Neurology Jun 2017We recently demonstrated a bilateral projection to the supraoculomotor area from the central mesencephalic reticular formation (cMRF), a region implicated in horizontal...
We recently demonstrated a bilateral projection to the supraoculomotor area from the central mesencephalic reticular formation (cMRF), a region implicated in horizontal gaze changes. C-group motoneurons, which supply multiply innervated fibers in the medial rectus muscle, are located within the primate supraoculomotor area, but their inputs and function are poorly understood. Here, we tested whether C-group motoneurons in Macaca fascicularis monkeys receive a direct cMRF input by injecting this portion of the reticular formation with anterograde tracers in combination with injection of retrograde tracer into the medial rectus muscle. The results indicate that the cMRF provides a dense, bilateral projection to the region of the medial rectus C-group motoneurons. Numerous close associations between labeled terminals and each multiply innervated fiber motoneuron were present. Within the oculomotor nucleus, a much sparser ipsilateral projection onto some of the A- and B- group medial rectus motoneurons that supply singly innervated fibers was observed. Ultrastructural analysis demonstrated a direct synaptic linkage between anterogradely labeled reticular terminals and retrogradely labeled medial rectus motoneurons in all three groups. These findings reinforce the notion that the cMRF is a critical hub for oculomotility by proving that it contains premotor neurons supplying horizontal extraocular muscle motoneurons. The differences between the cMRF input patterns for C-group versus A- and B-group motoneurons suggest the C-group motoneurons serve a different oculomotor role than the others. The similar patterns of cMRF input to C-group motoneurons and preganglionic Edinger-Westphal motoneurons suggest that medial rectus C-group motoneurons may play a role in accommodation-related vergence.
Topics: Animals; Female; Image Processing, Computer-Assisted; Macaca fascicularis; Male; Microscopy, Electron, Transmission; Midbrain Reticular Formation; Motor Neurons; Neural Pathways; Oculomotor Muscles
PubMed: 28177529
DOI: 10.1002/cne.24187 -
Acta Neuropathologica Mar 2017Detection of α-synuclein lesions in peripheral tissues is a feature of human synucleinopathies of likely pathogenetic relevance and bearing important clinical...
Detection of α-synuclein lesions in peripheral tissues is a feature of human synucleinopathies of likely pathogenetic relevance and bearing important clinical implications. Experiments were carried out to elucidate the relationship between α-synuclein accumulation in the brain and in peripheral organs, and to identify potential pathways involved in long-distance protein transfer. Results of this in vivo study revealed a route-specific transmission of α-synuclein from the rat brain to the stomach. Following targeted midbrain overexpression of human α-synuclein, the exogenous protein was capable of reaching the gastric wall where it was accumulated into preganglionic vagal terminals. This brain-to-stomach connection likely involved intra- and inter-neuronal transfer of non-fibrillar α-synuclein that first reached the medulla oblongata, then gained access into cholinergic neurons of the dorsal motor nucleus of the vagus nerve and finally traveled via efferent fibers of these neurons contained within the vagus nerve. Data also showed a particular propensity of vagal motor neurons and efferents to accrue α-synuclein and deliver it to peripheral tissues; indeed, following its midbrain overexpression, human α-synuclein was detected within gastric nerve endings of visceromotor but not viscerosensory vagal projections. Thus, the dorsal motor nucleus of the vagus nerve represents a key relay center for central-to-peripheral α-synuclein transmission, and efferent vagal fibers may act as unique conduits for protein transfer. The presence of α-synuclein in peripheral tissues could reflect, at least in some synucleinopathy patients, an ongoing pathological process that originates within the brain and, from there, reaches distant organs innervated by motor vagal projections.
Topics: Animals; Autonomic Fibers, Preganglionic; Brain; Choline O-Acetyltransferase; Female; Gastric Mucosa; Green Fluorescent Proteins; Humans; Neurons; Nodose Ganglion; RNA, Messenger; Rats; Rats, Sprague-Dawley; Time Factors; Transduction, Genetic; Vagus Nerve; alpha-Synuclein
PubMed: 28012041
DOI: 10.1007/s00401-016-1661-y -
Movement Disorders : Official Journal... Mar 2017The objective of this study was to characterize the degree, pattern, lesion site, and temporal evolution of sudomotor dysfunction in multiple system atrophy (MSA) and to...
BACKGROUND
The objective of this study was to characterize the degree, pattern, lesion site, and temporal evolution of sudomotor dysfunction in multiple system atrophy (MSA) and to evaluate differences by parkinsonian (MSA-parkinsonism) and cerebellar (MSA-cerebellar) subtypes.
METHODS
All cases of MSA evaluated at Mayo Clinic Rochester between 2005 and 2010 with postganglionic sudomotor testing and thermoregulatory sweat test were reviewed. Pattern and lesion site (preganglionic, postganglionic, or mixed) were determined based on thermoregulatory sweat test and postganglionic sudomotor testing.
RESULTS
The majority of the 232 patients were MSA-parkinsonism (145, 63%). Initial postganglionic sudomotor testing was abnormal in 59%, whereas thermoregulatory sweat test was abnormal in 95% of all patients. MSA-parkinsonism patients were more likely to have an abnormal thermoregulatory sweat test compared with MSA-cerebellar (98% versus 90%, P = 0.006) and had a higher mean percentage of anhidrosis (57%) compared with MSA-cerebellar (48%; P = 0.033). Common anhidrosis patterns were regional (38%) and global (35%). The site of the lesion was preganglionic in 47% and mixed (preganglionic and postganglionic) in 41%. The increase in anhidrosis per year was 6.2% based on 70 repeat thermoregulatory sweat tests performed on 29 patients. The frequency of postganglionic sudomotor abnormalities increased over time.
CONCLUSIONS
Our findings suggest: (1) sudomotor dysfunction is almost invariably present in MSA and even more common and severe in MSA-parkinsonism than MSA-cerebellar; (2) a preganglionic pattern of sweat loss is common in MSA; however, pre- and postganglionic abnormalities may coexist; and (3) the increasing frequency of postganglionic sudomotor dysfunction over time suggests involvement of postganglionic fibers or sweat glands later in the disease course. © 2016 International Parkinson and Movement Disorder Society.
Topics: Aged; Autonomic Nervous System Diseases; Cerebellar Diseases; Female; Humans; Hypohidrosis; Male; Middle Aged; Multiple System Atrophy; Parkinsonian Disorders
PubMed: 27859565
DOI: 10.1002/mds.26864 -
The Journal of Physiology Nov 2016Heart Failure (HF) is accompanied by reduced ventricular function, activation of compensatory neurohormonal mechanisms and marked autonomic dysfunction characterized by...
KEY POINTS
Heart Failure (HF) is accompanied by reduced ventricular function, activation of compensatory neurohormonal mechanisms and marked autonomic dysfunction characterized by exaggerated sympathoexcitation and reduced parasympathetic activity. With 6 weeks of exercise training, HF-related loss of choline acetyltransferase (ChAT)-positive vagal preganglionic neurones is avoided, restoring the parasympathetic tonus to the heart, and the immunoreactivity of dopamine β-hydroxylase-positive premotor neurones that drive sympathetic outflow to the heart is reduced. Training-induced correction of autonomic dysfunction occurs even with the persistence of abnormal ventricular function. Strong positive correlation between improved parasympathetic tonus to the heart and increased ChAT immunoreactivity in vagal preganglionic neurones after training indicates this is a crucial mechanism to restore autonomic function in heart failure.
ABSTRACT
Exercise training is an efficient tool to attenuate sympathoexcitation, a hallmark of heart failure (HF). Although sympathetic modulation in HF is widely studied, information regarding parasympathetic control is lacking. We examined the combined effects of sympathetic and vagal tonus to the heart in sedentary (Sed) and exercise trained (ET) HF rats and the contribution of respective premotor and preganglionic neurones. Wistar rats submitted to coronary artery ligation or sham surgery were assigned to training or sedentary protocols for 6 weeks. After haemodynamic, autonomic tonus (atropine and atenolol i.v.) and ventricular function determinations, brains were collected for immunoreactivity assays (choline acetyltransferase, ChATir; dopamine β-hydroxylase, DBHir) and neuronal counting in the dorsal motor nucleus of vagus (DMV), nucleus ambiguus (NA) and rostroventrolateral medulla (RVLM). HF-Sed vs. SHAM-Sed exhibited decreased exercise capacity, reduced ejection fraction, increased left ventricle end diastolic pressure, smaller positive and negative dP/dt, decreased intrinsic heart rate (IHR), lower parasympathetic and higher sympathetic tonus, reduced preganglionic vagal neurones and ChATir in the DMV/NA, and increased RVLM DBHir. Training increased treadmill performance, normalized autonomic tonus and IHR, restored the number of DMV and NA neurones and corrected ChATir without affecting ventricular function. There were strong positive correlations between parasympathetic tonus and ChATir in NA and DMV. RVLM DBHir was also normalized by training, but there was no change in neurone number and no correlation with sympathetic tonus. Training-induced preservation of preganglionic vagal neurones is crucial to normalize parasympathetic activity and restore autonomic balance to the heart even in the persistence of cardiac dysfunction.
Topics: Animals; Autonomic Fibers, Preganglionic; Blood Pressure; Heart; Heart Failure; Heart Rate; Male; Neurons; Physical Conditioning, Animal; Rats; Rats, Wistar; Vagus Nerve
PubMed: 27444212
DOI: 10.1113/JP272730 -
Frontiers in Neuroanatomy 2016Preganglionic parasympathetic neurons of the ventromedial part of the superior salivatory nucleus (SSN) mediate vasodilation of orbital and choroidal blood vessels, via...
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 (BP) signals may modulate choroidal blood flow (ChBF), we investigated if activation of baroresponsive NTS evokes ChBF increases in rat eye, using Laser Doppler Flowmetry (LDF) 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 (ChBVol; i.e., vasodilation) and choroidal blood velocity (ChBVel; possibly due to orbital vessel dilation). Stimulation of baroresponsive NTS, by contrast, yielded no significant mean increases in systemic arterial blood pressure (ABP). We further found that the increases in ChBF with NTS stimulation were significantly reduced by administration of the neuronal nitric oxide (NO) synthase inhibitor N-propyl-l-arginine (NPA), thus implicating nitrergic PPG terminals in the NTS-elicited ChBF increases. Our results show that the NTS neurons projecting to choroidal SSN do mediate increase in ChBF, and thus suggest a role of baroresponsive NTS in the BP-dependent regulation of ChBF.
PubMed: 27774055
DOI: 10.3389/fnana.2016.00094 -
Nature Communications Sep 2015The sympathetic nervous system is essential for maintaining mammalian homeostasis. How this intricately connected network, composed of preganglionic neurons that reside...
The sympathetic nervous system is essential for maintaining mammalian homeostasis. How this intricately connected network, composed of preganglionic neurons that reside in the spinal cord and post-ganglionic neurons that comprise a chain of vertebral sympathetic ganglia, arises developmentally is incompletely understood. This problem is especially complex given the vertebral chain of sympathetic ganglia derive secondarily from the dorsal migration of 'primary' sympathetic ganglia that are initially located several hundred microns ventrally from their future pre-synaptic partners. Here we report that the dorsal migration of discrete ganglia is not a simple migration of individual cells but a much more carefully choreographed process that is mediated by extensive interactions of pre-and post-ganglionic neurons. Dorsal migration does not occur in the absence of contact with preganglionic axons, and this is mediated by BDNF/TrkB signalling. Thus BDNF released by preganglionic axons acts chemotactically on TrkB-positive sympathetic neurons, to pattern the developing peripheral nervous system.
Topics: Animals; Autonomic Fibers, Preganglionic; Axons; Brain-Derived Neurotrophic Factor; Cell Movement; Chemotaxis; Chick Embryo; Ganglia, Sympathetic; Gene Expression Regulation, Developmental; Immunohistochemistry; In Situ Hybridization; In Vitro Techniques; Microscopy, Confocal; Receptor, trkB; Signal Transduction; Spinal Cord; Sympathetic Nervous System; Time-Lapse Imaging
PubMed: 26404565
DOI: 10.1038/ncomms9281 -
The Journal of Comparative Neurology Aug 2015Mammalian extraocular muscles contain singly innervated twitch muscle fibers (SIF) and multiply innervated nontwitch muscle fibers (MIF). In monkey, MIF motoneurons lie...
Mammalian extraocular muscles contain singly innervated twitch muscle fibers (SIF) and multiply innervated nontwitch muscle fibers (MIF). In monkey, MIF motoneurons lie around the periphery of oculomotor nuclei and have premotor inputs different from those of the motoneurons inside the nuclei. The most prominent MIF motoneuron group is the C group, which innervates the medial rectus (MR) and inferior rectus (IR) muscle. To explore the organization of both cell groups within the C group, we performed small injections of choleratoxin subunit B into the myotendinous junction of MR or IR in monkeys. In three animals the IR and MR myotendinous junction of one eye was injected simultaneously with different tracers (choleratoxin subunit B and wheat germ agglutinin). This revealed that both muscles were supplied by two different, nonoverlapping populations in the C group. The IR neurons lie adjacent to the dorsomedial border of the oculomotor nucleus, whereas MR neurons are located farther medially. A striking feature was the differing pattern of dendrite distribution of both cell groups. Whereas the dendrites of IR neurons spread into the supraoculomotor area bilaterally, those of the MR neurons were restricted to the ipsilateral side and sent a focused bundle dorsally to the preganglionic neurons of the Edinger-Westphal nucleus, which are involved in the "near response." In conclusion, MR and IR are innervated by independent neuron populations from the C group. Their dendritic branching pattern within the supraoculomotor area indicates a participation in the near response providing vergence but also reflects their differing functional roles.
Topics: Animals; Cholera Toxin; Dendrites; Immunohistochemistry; Macaca mulatta; Motor Neurons; Neuroanatomical Tract-Tracing Techniques; Neuronal Tract-Tracers; Oculomotor Muscles; Oculomotor Nuclear Complex; Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate
PubMed: 25684641
DOI: 10.1002/cne.23760 -
Actas Dermo-sifiliograficas Sep 2015
Review
Topics: Acyclovir; Aged; Antiviral Agents; Arm; Autonomic Fibers, Preganglionic; Eyelids; Female; Ganglia, Sympathetic; Herpes Zoster; Herpesvirus 3, Human; Horner Syndrome; Humans; Neck; Spinal Cord; Thorax; Valacyclovir; Valine
PubMed: 25661418
DOI: 10.1016/j.ad.2014.12.013 -
Spinally projecting preproglucagon axons preferentially innervate sympathetic preganglionic neurons.Neuroscience Jan 2015Glucagon-like peptide-1 (GLP-1) affects central autonomic neurons, including those controlling the cardiovascular system, thermogenesis, and energy balance....
Glucagon-like peptide-1 (GLP-1) affects central autonomic neurons, including those controlling the cardiovascular system, thermogenesis, and energy balance. Preproglucagon (PPG) neurons, located mainly in the nucleus tractus solitarius (NTS) and medullary reticular formation, produce GLP-1. In transgenic mice expressing glucagon promoter-driven yellow fluorescent protein (YFP), these brainstem PPG neurons project to many central autonomic regions where GLP-1 receptors are expressed. The spinal cord also contains GLP-1 receptor mRNA but the distribution of spinal PPG axons is unknown. Here, we used two-color immunoperoxidase labeling to examine PPG innervation of spinal segments T1-S4 in YFP-PPG mice. Immunoreactivity for YFP identified spinal PPG axons and perikarya. We classified spinal neurons receiving PPG input by immunoreactivity for choline acetyltransferase (ChAT), nitric oxide synthase (NOS) and/or Fluorogold (FG) retrogradely transported from the peritoneal cavity. FG microinjected at T9 defined cell bodies that supplied spinal PPG innervation. The deep dorsal horn of lower lumbar cord contained YFP-immunoreactive neurons. Non-varicose, YFP-immunoreactive axons were prominent in the lateral funiculus, ventral white commissure and around the ventral median fissure. In T1-L2, varicose, YFP-containing axons closely apposed many ChAT-immunoreactive sympathetic preganglionic neurons (SPN) in the intermediolateral cell column (IML) and dorsal lamina X. In the sacral parasympathetic nucleus, about 10% of ChAT-immunoreactive preganglionic neurons received YFP appositions, as did occasional ChAT-positive motor neurons throughout the rostrocaudal extent of the ventral horn. YFP appositions also occurred on NOS-immunoreactive spinal interneurons and on spinal YFP-immunoreactive neurons. Injecting FG at T9 retrogradely labeled many YFP-PPG cell bodies in the medulla but none of the spinal YFP-immunoreactive neurons. These results show that brainstem PPG neurons innervate spinal autonomic and somatic motor neurons. The distributions of spinal PPG axons and spinal GLP-1 receptors correlate well. SPN receive the densest PPG innervation. Brainstem PPG neurons could directly modulate sympathetic outflow through their spinal inputs to SPN or interneurons.
Topics: Adrenergic Fibers; Animals; Axons; Bacterial Proteins; Choline O-Acetyltransferase; Female; Glucagon-Like Peptide-1 Receptor; Immunoenzyme Techniques; Interneurons; Luminescent Proteins; Male; Medulla Oblongata; Mice, Transgenic; Motor Neurons; Neuroanatomical Tract-Tracing Techniques; Nitric Oxide Synthase; Peritoneal Cavity; Posterior Horn Cells; Proglucagon; Sacrum; Stilbamidines; Thoracic Vertebrae
PubMed: 25450967
DOI: 10.1016/j.neuroscience.2014.10.043 -
The Journal of Neuroscience : the... Nov 2014Brainstem catecholaminergic neurons play key roles in the autonomic, neuroendocrine, and behavioral responses to glucoprivation, yet the functions of the individual...
Brainstem catecholaminergic neurons play key roles in the autonomic, neuroendocrine, and behavioral responses to glucoprivation, yet the functions of the individual groups are not fully understood. Adrenergic C3 neurons project widely throughout the brain, including densely to sympathetic preganglionic neurons in the spinal cord, yet their function is completely unknown. Here we demonstrate in rats that optogenetic stimulation of C3 neurons induces sympathoexcitatory, cardiovasomotor functions. These neurons are activated by glucoprivation, but unlike the C1 cell group, not by hypotension. The cardiovascular activation induced by C3 neurons is less than that induced by optogenetic stimulation of C1 neurons; however, combined stimulation produces additive sympathoexcitatory and cardiovascular effects. The varicose axons of C3 neurons largely overlap with those of C1 neurons in the region of sympathetic preganglionic neurons in the spinal cord; however, regional differences point to effects on different sympathetic outflows. These studies definitively demonstrate the first known function of C3 neurons as unique cardiovasomotor stimulatory cells, embedded in the brainstem networks regulating cardiorespiratory activity and the response to glucoprivation.
Topics: Action Potentials; Adrenergic Fibers; Animals; Brain Stem; Glucose; Heart; Homeostasis; Male; Rats; Rats, Sprague-Dawley; Sympathetic Nervous System
PubMed: 25378174
DOI: 10.1523/JNEUROSCI.3179-14.2014