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Branchial innervation.

Inspection of the dorsal end of fish gills reveals an impressive set of nerve trunks, connecting the gills to the brain. These trunks are branches of cranial nerves VII (the facial) and especially IX (the glossopharyngeal) and X (the vagus). The nerve trunks carry a variety of nervous pathways to and from the gills. A substantial fraction of the nerves running in the branchial trunks carry afferent (sensory) information from receptors within the gills. There are also efferent (motor) pathways, which control muscles within the gills, blood flow patterns and possibly secretory functions. Undertaking a more careful survey of the gills, it becomes evident that the arrangement of the microanatomy (particularly the blood vessels) and its innervation are strikingly complex. The complexity not only reflects the many functions of the gills but also illustrates that the control of blood flow patterns in the gills is of crucial importance in modifying the efficiency of its chief functions: gas transfer and salt balance. The "respiratory-osmoregulatory compromise" is maintained by minimizing the blood/water exchange (functional surface area of the gills) to a level where excessive water loss (marine teleosts) or gain (freshwater teleosts) is kept low while ensuring sufficient gas exchange. This review describes the arrangement and mechanisms of known nervous pathways, both afferent and efferent, of fish (notably teleosts) gills. Emphasis is placed primarily on the autonomic nervous system and mechanisms of blood flow control, together with an outline of the afferent (sensory) pathways of the gill arches.

Animals↗

A second hypothalamic nucleus receiving retinal input in man: the paraventricular nucleus.

A retinofugal projection to the suprachiasmatic nucleus of the hypothalamus has been described in man by means of a newly developed staining technique (PPD) for tracing degenerated fibers in the human brain. We applied the PPD method to the chiasmal/hypothalamic area of human autopsy brains from patients who had incurred prior optic nerve damage. We followed degenerated fibers from the optic nerve through the optic chiasm and the optic tract. At the optic chiasm/tract junction, some fibers were seen to diverge and to form an optic fascicle which traversed the lateral preoptic-anterior hypothalamic area towards the third ventricle. These degenerated fibers terminated in the paraventricular nucleus of the hypothalamus. We suggest that there are at least two retinohypothalamic pathways in man. Some of the neuroendocrine imbalances in blind persons may be attributed to the disruption of the retinal input to the paraventricular and suprachiasmatic nuclei of the hypothalamus. These retinohypothalamic pathways may be the anatomical substrates for light/dark entrainment of human neuroendocrine and autonomic regulatory processes.

Adult↗

[Effects of the autonomic nervous system in supraventricular arrhythmia].

Influences of the autonomic nervous system may cause modifications of the initiation, continuation and discontinuation of supraventricular rhythm disturbances. Whether or not clinically relevant bradycardia syndromes (such as the hypersensitive carotid sinus syndrome and the sick sinus syndrome) also may exist primarily on a functional basis, remains to be proven. Organic pathology, whether it is clinically apparent or not, probably provides the basis for the activation of influences on the autonomic nervous system. In atrial fibrillation and atrial flutter the influence of the autonomic nervous system is apparent in a form of the vagotonically and sympathotonically evoked paroxysms. In the case of persistent atrial fibrillation vagal and sympathotonically transmitted changes in the AV-dromotropy determine the mode of heart rate. Junctional re-entry tachycardias and re-entry tachycardias under the influence of accessory pathways, are potentially triggered by mechanisms, as transmitted by the autonomic nervous system. Furthermore, such autonomic influences are responsible for changes in the conducting velocity and the refractory properties, as produced by parallel conducting pathways. Hemodynamic changes themselves, which are induced at the very beginning of the tachycardia, may activate other electrophysiological mechanisms and thereby cause a modification in the type of tachycardia in question.

Arrhythmias, Cardiac↗

Review of therapeutic modalities acting directly via central pathways.

The brain influences arterial pressure through central mediation of a variety of neurotransmitters, including norepinephrine, and translates this action into changes in peripheral autonomic tone. Two opposed adrenergic systems have been described in brain: a hypothalamic pathway in which adrenergic receptor stimulation raises arterial pressure and a brainstem pathway related to the baroreflex arc in which adrenergic receptor stimulation lowers arterial pressure. Antihypertensive drugs with primarily central effects, including clonidine and alpha methyldopa, act as alpha 2 adrenoceptor agonists. The central receptor involved in their antihypertensive action is of the alpha 2 type but is located postsynaptically. Activation of this receptor by either clonidine or alpha methylnorepinephrine, a metabolite of alpha methyldopa, engages the depressor pathway in the brainstem and leads to a decrease in norepinephrine release and a reduction in peripheral sympathetic tone. Clonidine and alpha methyldopa share a similar pattern of peripheral effects, including reductions in preganglionic sympathetic nerve traffic, bradycardia, decreases in plasma renin activity, reductions in blood pressure in the supine position and adverse effects such as depression, sedation and bad dreams. Because of the frequency and severity of these side effects, there is an ongoing search for new centrally acting antihypertensive agents which might be better tolerated.

Adrenergic beta-Antagonists↗

Leptin activates distinct projections from the dorsomedial and ventromedial hypothalamic nuclei.

Leptin has profound effects on feeding, metabolism, and neuroendocrine status. Evidence indicates that the hypothalamus coordinates these responses, though the specific brain pathways engaged by leptin remain obscure. The paraventricular nucleus of the hypothalamus (PVH) regulates pituitary gland function and feeding, and innervates autonomic preganglionic neurons, making it a candidate to regulate many of the responses to leptin. The subparaventricular zone, an anterior hypothalamic region receiving dense innervation from the suprachiasmatic nucleus, is thought to integrate circadian and metabolic information. We investigated the distribution of neurons in the rat brain activated by leptin administration that also project to the PVH or the subparaventricular zone by coupling immunohistochemistry for Fos with retrograde transport of cholera toxin-b. Intravenous leptin characteristically activated several cell groups including the ventromedial hypothalamic nucleus, the dorsomedial hypothalamic nucleus (DMH), and the PVH. When tracer injections were centered in the subparaventricular zone, many double-labeled cells were observed in the dorsomedial subdivision of the ventromedial hypothalamic nucleus. This projection may provide an anatomic substrate for integration of metabolic and circadian information to regulate the hypothalamo-pituitary axis. When cholera toxin-b injections were centered in the PVH, many double-labeled cells were found within the caudal DMH. Hence, activation of specific neuroendocrine and autonomic elements of the PVH may be triggered by leptin-activated afferents arising in the DMH. Our results demonstrate that a discrete set of hypothalamic pathways may underlie leptin's autonomic, endocrine, and behavioral effects.

Animals↗

The human nucleus of the solitary tract: visceral pathways revealed with an "in vitro" postmortem tracing method.

Visceral relay neurons in the nucleus of the solitary tract (NTS) regulate behavior and autonomic reflex functions. NTS projections have been extensively characterized in animal studies but not in humans. For the first time, NTS fiber trajectories in the human medulla oblongata were revealed with an "in vitro" postmortem tracing method. Local intramedullary pathways were labeled by direct pressure injections of free horseradish peroxidase centered on the medial subnucleus at a level adjacent to true obex. Labeled elements were resolved by peroxidase histochemistry as a dark brown intracellular reaction product. A prominent transtegmental system of axons emerged from the NTS injection sites and entered the intermediate reticular zone, a region corresponding to an autonomic reflex center in other mammals. A medial system of axons arched across the dorsomedial reticular formation toward the dorsal medullary raphe and projected ventrally toward the nucleus gigantocellularis. A small lateral fiber trajectory coursed towards the dorsomedial zone of spinal trigeminal nucleus caudalis. Presumptive terminals appeared as dustings of fine punctate processes within the NTS, dorsomotor nucleus and reticular formation. NTS projections in humans resemble those identified in other mammals including primates. Axonal tracing studies predict that visceral impulses in humans may transmit over evolutionarily conserved pathways involved in autonomic feedback control and stress adaptation.

Adult↗

Early stages in the organization of cardiovascular control.

Our studies have revealed a number of unexpected characteristics of the immature cardiovascular system of the infant rat. Sympathetic and parasympathetic divisions of the autonomic system appear to have different timetables for the development of tonic and phasic activities. These different timetables of development result in unusual physiological organizations at particular stages in postnatal life. We have described some of the features of one of these: the infant rat's cardiac rate responses in the second week after birth include a high resting rate, decreased rates in response to several (but not all) forms of activation, and two forms of phasic activity, a bradycardia and a tachycardia, that are related to naturally occurring behavioral states and have not been described in adults. The nature of this age-specific autonomic organization was explored further and found to be embedded in the infant's relationship with its mother and in her role as a supplier of nutrient in particular. The mechanisms by which nutrient intake regulates autonomic cardiovascular control during this stage of life have been partially explored by analytic experiments and the results are described along with the possible adaptive value of this regulatory system.

Afferent Pathways↗

Neurofibromatosis 1 (NF1) heterozygosity results in a cell-autonomous growth advantage for astrocytes.

Individuals with neurofibromatosis 1 (NF1) develop low-grade astrocytomas at an increased frequency. To gain insight into the function of the Nf1 gene product as a growth regulator for astrocytes, we examined mice heterozygous for a targeted Nf1 mutation. In our previous studies, we demonstrated increased numbers of proliferating astrocytes in Nf1 heterozygote (Nf1+/-) mice in vivo. We now show that cultured Nf1+/- astrocytes exhibit a cell-autonomous growth advantage in vitro associated with increased p21-ras pathway activation. Furthermore, we demonstrate that Nf1+/-;wild-type N-ras mice have a similar astrocyte growth advantage in vitro and in vivo as either oncogenic N-ras or Nf1+/-; oncogenic N-ras mice. Lastly, mice heterozygous for targeted defects in both Nf1 and p53 as well as Nf1 and Rb exhibit 3- and 2.5-fold increases in astrocyte proliferation in vivo, respectively, suggesting that abnormalities in Nf1- and p53/Rb-regulated pathways cooperate in the heterozygous state to confer a growth advantage for brain astrocytes. Collectively, these results provide evidence for a cell-autonomous growth advantage in Nf1+/- astrocytes and suggest that some of the brain pathology in individuals with NF1 might result from reduced, but not absent, NF1 gene function.

Animals↗

Noncell- and cell-autonomous G-protein-signaling converges with Ca2+/mitogen-activated protein kinase signaling to regulate str-2 receptor gene expression in Caenorhabditis elegans.

In the sensory system of C. elegans, the candidate odorant receptor gene str-2 is strongly expressed in one of the two AWC neurons and weakly in both ASI neurons. Asymmetric AWC expression results from suppression of str-2 expression by a Ca2+/MAPK signaling pathway in one of the AWC neurons early in development. Here we show that the same Ca2+/MAPK pathway promotes str-2 expression in the AWC and ASI neurons together with multiple cell-autonomous and noncell-autonomous G-protein-signaling pathways. In first-stage larvae and adult animals, signals mediated by the Galpha subunits ODR-3, GPA-2, GPA-5, and GPA-6 and a Ca2+/MAPK pathway involving the Ca2+ channel subunit UNC-36, the CaMKII UNC-43, and the MAPKK kinase NSY-1 induce strong str-2 expression. Cell-specific rescue experiments suggest that ODR-3 and the Ca2+/MAPK genes function in the AWC neurons, but that GPA-5 and GPA-6 function in the AWA and ADL neurons, respectively. In Dauer larvae, the same network of genes promotes strong str-2 expression in the ASI neurons, but ODR-3 functions in AWB and ASH and GPA-6 in AWB. Our results reveal a complex signaling network, encompassing signals from multiple cells, that controls the level of receptor gene expression at different developmental stages.

Animals↗

Prefrontal cortex in the rat: projections to subcortical autonomic, motor, and limbic centers.

This paper describes the quantitative areal and laminar distribution of identified neuron populations projecting from areas of prefrontal cortex (PFC) to subcortical autonomic, motor, and limbic sites in the rat. Injections of the retrograde pathway tracer wheat germ agglutinin conjugated with horseradish peroxidase (WGA-HRP) were made into dorsal/ventral striatum (DS/VS), basolateral amygdala (BLA), mediodorsal thalamus (MD), lateral hypothalamus (LH), mediolateral septum, dorsolateral periaqueductal gray, dorsal raphe, ventral tegmental area, parabrachial nucleus, nucleus tractus solitarius, rostral/caudal ventrolateral medulla, or thoracic spinal cord (SC). High-resolution flat-map density distributions of retrogradely labelled neurons indicated that specific PFC regions were differentially involved in the projections studied, with medial (m)PFC divided into dorsal and ventral sectors. The percentages that WGA-HRP retrogradely labelled neurons composed of the projection neurons in individual layers of infralimbic (IL; area 25) prelimbic (PL; area 32), and dorsal anterior cingulate (ACd; area 24b) cortices were calculated. Among layer 5 pyramidal cells, approximately 27.4% in IL/PL/ACd cortices projected to LH, 22.9% in IL/ventral PL to VS, 18.3% in ACd/dorsal PL to DS, and 8.1% in areas IL/PL to BLA; and 37% of layer 6 pyramidal cells in IL/PL/ACd projected to MD. Data for other projection pathways are given. Multiple dual retrograde fluorescent tracing studies indicated that moderate populations (<9%) of layer 5 mPFC neurons projected to LH/VS, LH/SC, or VS/BLA. The data provide new quantitative information concerning the density and distribution of neurons involved in identified projection pathways from defined areas of the rat PFC to specific subcortical targets involved in dynamic goal-directed behavior.

Animals↗

Psychosomatics and psychopathology: looking up and down from the brain.

The autonomic nervous system (ANS) plays a role in a wide range of somatic and mental diseases. Using a model of neurovisceral integration, this article describes how autonomic imbalance and decreased parasympathetic tone in particular may be the final common pathway linking negative affective states and conditions to ill health. The central nervous system (CNS) network that regulates autonomic balance (central autonomic network, CAN) is closely related and partially overlaps with networks serving executive, social, affective, attentional, and motivated behavior (anterior executive region, AER; and Damasio's [Damasio, A.R., 1998. Emotion in the perspective of an integrated nervous system. Brain Res. Rev. 26, 83-86.] 'emotion circuit'). A common reciprocal inhibitory cortico-subcortical neural circuit serves to regulate defensive behavior, including autonomic, emotional and cognitive features. This inhibitory cortico-subcortical circuit may structurally, as well as functionally, link psychological processes with health-related physiology. When the prefrontal cortex is taken 'offline' for whatever reason, parasympathetic inhibitory action is withdrawn and a relative sympathetic dominance associated with disinhibited defensive circuits is released, which can be pathogenic when sustained for long periods. This state is indicated by low heart rate variability (HRV), which is a marker for low parasympathetic activation and prefrontal hypoactivity. Consistent with this, HRV is associated with a range of psychological and somatic pathological conditions, including immune dysfunction. Finally, we discuss supportive evidence from recent studies of the reflexive startle blink, attention and working memory, which shows that low HRV predicts hypervigilance and inefficient allocation of attentional and cognitive resources.

Animals↗

Ribbon networks for modeling navigable paths of autonomous agents in virtual environments.

This paper presents the Environment Description Framework (EDF) for modeling complex networks of intersecting roads and pathways in virtual environments. EDF represents information about the layout of streets and sidewalks, the rules that govern behavior on roads and walkways, and the locations of agents with respect to navigable structures. The framework serves as the substrate on which behavior programs for autonomous vehicles and pedestrians are built. Pathways are modeled as ribbons in space. The ribbon structure provides a natural coordinate frame for defining the local geometry of navigable surfaces. EDF includes a powerful runtime interface supported by robust and efficient code for locating objects on the ribbon network, for mapping between Cartesian and ribbon coordinates, and for determining behavioral constraints imposed by the environment.

Algorithms↗

Distribution of c-fos mRNA in the brain following intracerebroventricular injection of nitric oxide (NO)-releasing compounds: possible role of NO in central cardiovascular regulation.

We injected nitric oxide (NO)-releasing compounds and NO synthase (NOS) inhibitors into the brains of conscious, freely moving rats and measured the effects on mean arterial blood pressure (MAP) and heart rate, as well as on the expression of c-fos mRNA, neuronal NOS (nNOS) mRNA and NADPH-diaphorase, an indicator of NOS activity. When administered i.c.v., the NO donor, NOC-18, caused a significant fall in MAP and heart rate, whereas the NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), induced a significant rise in MAP. The same dose of NOC-18 or L-NAME when administered i.v. did not affect MAP and heart rate. Centrally administered NOC-18 induced c-fos mRNA expression in several regions of the brain involved in the baroreceptor response, including the nucleus of the solitary tract, the area postrema and the rostral ventrolateral medulla, as well as areas involved in the integration of autonomic, neuroendocrine and behavioural responses, including the medial preoptic area, the organum vasculosum lamina terminalis, the bed nucleus of stria terminalis, the paraventricular nucleus (PVN), the supraoptic nucleus (SON), the central nucleus of amygdala (CeA) and the locus coeruleus. Most of the areas that expressed c-fos also contained nNOS mRNA and/or NADPH-d-positive neurones and fibres. i.c.v. injection of L-NAME induced c-fos mRNA expression in PVN, SON, locus coeruleus and NTS, suggesting a tonic inhibition of neuronal activity by NO or stimulation of neuronal activity by endogenous NO. i.v. injection of NOC-18 or L-NAME did not induce any significant c-fos mRNA expression in rat brain. These results demonstrate that NO acts directly in the brain to reduce the systemic blood pressure, and that the endogenous NO pathway may play a role in cardiovascular and autonomic regulation by modulating neuronal activities in discrete regions of the brain.

Amygdala↗

Sequential changes in autonomic regulation of cardiac myocytes after in vivo endotoxin injection in rat.

We report that in vivo injection of endotoxin (EDTX, 6 mg. kg(-)(1)) induces cardiovascular alterations in rats that closely mimic the clinical situation, as assessed by in vivo hemodynamic measurements in anesthetized and conscious, chronically instrumented animals. The patch-clamp technique was used to characterize the L-type calcium current (I(Ca)) and its autonomic regulation in isolated cardiac myocytes. The density of I(Ca) progressively decreased at 12 and 36 h after EDTX injection. However, the dihydropyridine (+/-)Bay K 8644 (100 nM) enhanced I(Ca) to levels similar to those in control and EDTX-treated myocytes. In addition, the net stimulatory effect of a beta-adrenergic agonist (isoproterenol) on I(Ca) was increased 12 h after EDTX injection. This change in the beta-adrenergic effect declined 24 h later. The potentiation in the beta-adrenergic stimulation of I(Ca) was mimicked by L858051 (10 microM), a direct activator of adenylyl cyclase, but not by IBMX (200 microM), a phosphodiesterase inhibitor. Besides, the antiadrenergic effect of acetylcholine on I(Ca) was unchanged 12 h after EDTX injection, but increased 36 h after EDTX injection. These results support the hypothesis that time-dependent changes in the adenylyl cyclase pathway in cardiac myocytes may contribute, via the autonomic regulation of I(Ca), to the severity of myocardial dysfunction during sepsis.

1-Methyl-3-isobutylxanthine↗

Co-localization and plasticity of transmitters in peripheral autonomic and sensory neurons.

Immunohistochemical studies have shown that most peripheral autonomic and sensory ganglia are heterogeneous, consisting of several populations of neurons which can be distinguished by their content of peptide and non-peptide transmitters, and transmitter-associated enzymes. Many neurons contain several different potential transmitters, especially neuropeptides. Some neuropeptides have been localized in more than one population of autonomic and sensory neurons. However, the peptide often occurs together with a distinctive combination of additional transmitters in each neuronal class. The precise combination of transmitters found in any individual neuron is highly correlated with the peripheral target of the neuron. This indicates that immunohistochemically defined neuronal populations represent distinct functional classes of neurons. In an increasing number of cases, many of the potential transmitters contained in a particular neuron have been shown to be released from the nerve terminals, and to contribute to presynaptic or postsynaptic effects of nerve activation. Despite this association between the combination of potential transmitters contained in a neuron, and the function of the neuron, not all transmitters or transmitter-associated enzymes are expressed equally at all times in the life of a neuron: the levels of some substances change dramatically during development; some are detected only after experimental alteration of the environment of the developing or mature neurons. Taken together, these results indicate that, during development, pathway-specific information influences the differentiation of peripheral autonomic and sensory neurons. Furthermore, the expression of neuropeptides and transmitter-associated enzymes in a particular neuron appears to be under continuous regulation. These phenomena demonstrate the complexity and precision involved in development and maintenance of the peripheral autonomic and sensory nervous systems.

Animals↗

Does a Leu 512 Arg thyrotropin receptor mutation cause an autonomously functioning papillary carcinoma?

In the last decade, studies were first done to determine the frequency of Gsalpha and later thyrotropin receptor (TSHR) mutations in benign autonomously functioning thyroid nodules (AFTN). Different frequencies ranging from 0% to 38% for GSp mutations and from 20% to 86% for TSHR mutations were found. There were only some limited case reports related to TSHR genetic alterations in malignant AFTN. Their role in autonomously functioning thyroid carcinomas is not well established. We present a patient who had thyroidectomy for toxic multinodular goiter and a papillary carcinoma was demonstrated histopathologically. Genomic DNA was isolated from two solid areas in the hot nodule and peripheral leukocytes of the patient. After amplifying the related regions, TSHR and GSalpha genes were analyzed by single-strand conformation polymorphism (SSCP) analysis. The precise localization of the mutations was identified by automatic DNA sequence analysis. An activating mutation of the TSHR gene (Leu 512 Arg) was found in the autonomously functioning papillary carcinoma. It is believed that this mutation causes constitutive activation of the cyclic adenosine monophosphate (cAMP) signal transduction pathway and thereby causes thyrotoxicosis and a hot thyroid nodule in an autonomously functioning papillary carcinoma.

Amino Acid Sequence↗

Electrophysiologic properties of the atrioventricular node in pediatric patients.

OBJECTIVES: The purpose of this study was to characterize anterograde and retrograde properties of the atrioventricular (AV) node in children and to determine the presence of ventriculoatrial (VA) conduction and dual AV node pathways. BACKGROUND: Although AV node reentry is common in adults, it accounts for 13% of pediatric supraventricular tachycardia (SVT). The age-related changes in the AV node with development are poorly understood. The incidence of dual AV node pathways and VA conduction in the pediatric population is unknown. METHODS: Electrophysiologic studies were performed in 79 patients with normal hearts and no evidence of AV node arrhythmias. Patients were classified into two groups by age: group I = 49 patients (0.39 to 12.8 years old, mean [+/- SD] age 8.5 +/- 3.6); group II = 30 patients (13.4 to 20.0 years old, mean age 15.6 +/- 1.8). RESULTS: There was a significant difference (p < 0.05) in the cycle length (CL) at which anterograde AV block occurred between group I (305 +/- 63 ms) and group II (350 +/- 91 ms). Sixty-one percent of children had VA conduction with no age-related differences. There was no significant difference in the mean CL of retrograde VA block (360 ms). The incidence of dual AV node pathways in group I was 15% and 44% in group II (p < 0.05). CONCLUSIONS: These findings suggest that AV node electrophysiology undergoes maturational changes. The increase in AV node reentrant tachycardia in adults may relate to changes in the relative refractoriness and conduction of the AV node or to differences in autonomic input into the AV node that allow dual pathway physiology to progress to SVT.

Adolescent↗

Synaptic transmission in thoracic autonomic ganglia of the dog.

Afferent stimulation of one canine thoracic cardiopulmonary nerve can generate compound action potentials in another ipsilateral cardiopulmonary nerve. These compound action potentials persist after acute decentralization of the middle cervical ganglion, indicating that they result from neural activity in the middle cervical ganglion and thoracic nerves. Changing the frequency of stimulation can alter the compound action potentials, suggesting that temporal facilitation or inhibition occurs in this middle cervical ganglion preparation. The compound action potentials can be modified by stimulation of sympathetic preganglionic fibers and by hexamethonium, atropine, phentolamine, propranolol, and (or) manganese. It thus appears that afferent cardiopulmonary nerves can activate efferent cardiopulmonary nerves via synaptic mechanisms in the stellate and middle cervical ganglia. It also appears that these mechanisms involve adrenergic and cholinergic receptors and are influenced by preganglionic sympathetic fibers arising from the cord.

Action Potentials↗