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PubMed2003

Nitric oxide (NO) and obstructive sleep apnea (OSA).

Nitric oxide (NO) and obstructive sleep apnea are inseparable. Obstructive sleep apnea could be described as the intermittent failure to transport the full complement of nasal NO to the lung with each breath. There NO matches perfusion to ventilation. NO is utilized by the efferent pathways that control the unequal, inspiratory battle between the pharyngeal dilators and the closing negative pressures induced by the thoracic musculature. Recurrent cortical arousals are a major short-term complication, and the return to sleep after each arousal uses NO. The long-term complications, namely hypertension, myocardial infarction, and stroke, might be due to the repeated temporary dearth of NO in the tissues, secondary to a lack of oxygen, one of NO's two essential substrates.

Arousal↗
PubMed2005

Intravesical therapy for overactive bladder.

Overactive bladder and urgency incontinence are common conditions generally treated with oral anticholinergic therapy. Despite the development of new antimuscarinic agents, many patients do not tolerate or fail to respond to oral therapy. Intravesical instillation therapy can provide an alternative method of managing bladder overactivity. Intravesical instillation of anticholinergics such as oxybutynin and atropine can achieve cholinergic blockade without producing systemic side effects. Botulinum A toxin injected directly into the detrusor has been shown in preliminary studies to increase bladder capacity and decrease uncontrolled bladder contractility for up to 6 months. Intravesical local anesthetics such as lidocaine and bupivacaine block the conduction of unmyelinated C fibers and when administered into the bladder, lead to an increase in functional bladder capacity. Intravesical capsaicin and resiniferatoxin also affect afferent innervation by blocking C-fiber afferents, leading to decreased bladder contractility and increased bladder capacity. Intravesical instillation therapy can provide an alternative treatment for the management of overactive bladder.

Administration, Intravesical↗
PubMed2005

Hemiballismus.

Hemiballismus is the most dramatic movement disorder seen in clinical practice. Its emergence points to a structural lesion or metabolic dysfunction in the region of the subthalamic nucleus, its afferent or efferent pathways, or interconnected deep brain nuclei, usually on the side contralateral to the movements. Any focal process may be to blame, but elderly sufferers generally have had vascular events, whereas the etiology is infectious or inflammatory in younger patients. Severe nonketotic hyperglycemia is another important cause of hemiballismus in the elderly. Hemiballismus patients require treatment both for the underlying etiology of the movement and for the movements themselves. There are no large controlled clinical trials to guide anti-ballismus therapy. However, dopamine receptor blocking agents have an established track record in suppressing choreic and ballistic movements, and are first-line agents for acute treatment. Standard neuroleptics such as haloperidol and perphenazine are started at low doses and titrated as tolerated until the movements are controlled. Atypical antipsychotics such as risperidone and clozapine have been used in small series and may have a reduced risk of extrapyramidal side effects. Catecholamine-depleting agents such as reserpine and tetrabenazine may be considered when long-term therapy is required. Other pharmacologic agents have met with varying success. The course of hemiballismus may be complicated by exhaustion, injury, or metabolic disorders, but with good supportive care, acute survival is good, and long-term survival reflects the prognosis of the underlying etiology. In time, the ballistic movements themselves tend to subside allowing withdrawal of drugs in many cases. When movements persist, stereotactic functional neurosurgical procedures may be considered in good surgical candidates.

Journal Article↗
PubMed1976

Electrophysiological evidences for possible participation of periventricular neurons in anterior pituitary regulation.

Unit activity of neurons in the periventricular area of the third ventricle (PVA), in which the organum vasculosum laminae terminalis is included, was recorded in female rats in proestrus. The units were antidromically driven by electrical stimulation of the arcuate-median eminence region (ARC-ME). In the antidromic responses, a notch was generally observed in the rising phase of the driven wave, and fractionation of A- and B-components at the notch was readily elicited by applying repetitive stimulatory pulses at frequencies higher than 10 Hz, or successive double pulses with intervals less than 3.5 msec. At the same time, ARC-ME efferents to the PVA were suggested by orthodromic responses in the PVA to ARC-ME stimulation. Occasionally, anti- and orthodromic responses appeared in one electrode, indicating a proximate distribution of these two types of neurons in the PVA. Repetitive stimulation of the ARC-ME at 50 Hz facilitated the orthodromically driven units, whereas antidromically driven units were inhibited. This seems to imply that the orthodromic responses might be recorded from an inhibitory interneuron in the ARC-ME efferent pathway to the PVA, judging from the identical time course of the responses of the two types of the units. Both the anti- and orthodromically driven units were tested with microiontophoresis of LH-RH, TRH, LH, FSH and prolactin. Orthodromically driven units showed no response to microiontophoresis of any hormone. In the antidromically driven units, microiontophoresis of LH-RH and FSH elicited inhibition in 15 and 18% of the tests, and facilitation was seen in 15-25% of the tests in response to LH, TRH and prolactin. The demonstration that local application of hypothalamic and pituitary hormones exerts direct effects on the activity of the PVA neurons which send their axons directly to the ARC-ME, provides additional evidence that the PVA may participate in anterior pituitary regulation.

Action Potentials↗
PubMed1979

Cardio-inhibitory mechanism in the gigantocellular reticular nucleus of the medulla oblongata.

A cardio-inhibitory mechanism was localized in the ventral part of the medullary gigantocellular reticular nucleus (GRN) in chloralose--urethane anesthetized cats. Stimulation of this mechanism produced an average 58.9% reduction of the heart rate (calculated from 55 responsive points having more than 40% reduction) associated mostly with hypotension, or no change or occasionally a slight increase of the arterial blood pressure. Midcollicular decerebration did not affect this bradycardia. The bradycardia following GRN stimulation of either side by a pair of symmetrically placed electrodes was reduced slightly but equally by: (1) sectioning either side of the vagus nerve; (2) hemisection at a level 4 mm rostral of the obex on either side; or (3) partial destruction of the dorsal motor (DM) and solitary (SN) nuclei on either side. Additional section of the vagus nerve on the opposite side completely abolished the bradycardiac response. Besides, the GRN bradycardia was also slightly but equally attenuated by making a midline bisection in a length extending from 10 to 4 mm rostral of the obex. Additional section of the vagus nerve on either side abolished completely only the bradycardia following electrical stimulation of the GRN on the same side, while that following electrical stimulation of the GRN on the opposite side remained unaffected. On the other hand, the GRN bradycardia was not affected by simply making a caudal midline bisection in a length extending from 3 or 4 mm rostral to 2 mm caudal of the obex. The results suggest: (1) the ventral part of the GRN is a cardio-inhibitory mechanism independent of the higher center; (2) the efferent pathway descends both ipsilaterally and contralaterally and makes synaptic relay in the areas of DM and/or SN and finally exits via the vagus nerves; (3) the fibers decussate rostral to the level 4 mm rostral of the obex; and (4) both ipsilateral and contralateral descending fibers appeared to exert the same degree of suppressive influence in the heart rate.

Animals↗
PubMed1984

Neuropeptide Y in the stria terminalis: evidence for an amygdalofugal projection.

Lesions of the stria terminalis in the rat brain indicate that neuropeptide Y, a recently isolated peptide of the pancreatic polypeptide family, projects rostrally in an efferent pathway from the amygdaloid complex. Marked depletions of NPY-immunoreactivity observed by immunocytochemistry were apparent in the laterobasal septum and suprachiasmatic nucleus of the hypothalamus, but most markedly in rostrolateral regions of the bed nucleus of the strial terminalis.

Amygdala↗
PubMed1984

Electrolytic lesions of the substantia innominata and lateral preoptic area attenuate the 'supersensitive' locomotor response to apomorphine resulting from denervation of the nucleus accumbens.

Apomorphine-stimulated locomotion in the rat is greatly enhanced following destruction of dopamine terminals in the nucleus accumbens (NA) with 6-hydroxydopamine (6-OHDA). While this augmented response is ascribed to the action of the dopamine stimulant apomorphine on supersensitive receptors within the NA, little is known regarding the mechanisms by which increased receptor stimulation within the NA influences lower motor circuitry to produce changes in locomotion. In this study, we examined apomorphine-stimulated locomotion in 6-OHDA-infused rats following electrolytic damage to the terminal region of first-order NA efferent fibers within the substantia innominata and lateral preoptic area. This damage greatly diminished the locomotor response to apomorphine in 6-OHDA-infused animals, but did not diminish locomotion in vehicle-infused animals. Destruction of dopamine terminals within the NA has also been reported to enhance the place-preference response to apomorphine in rats. Damage to the substantia innominata and lateral preoptic area significantly decreased the place-preference for apomorphine-paired environments in 6-OHDA-infused animals, but did not alter place-preference responses in vehicle-infused animals. Our results indicate that the efferent pathway from the NA to the substantia innominata and lateral preoptic area serves as an important output of mesolimbic activity into motor circuitry involved in the expression of apomorphine-stimulated locomotion and place-preference.

Animals↗
PubMed1984

Responses of striatal neurons in the behaving monkey. 2. Visual processing in the caudal neostriatum.

The activity of single neurons was recorded in the tail of the caudate nucleus and adjoining part of the ventral putamen, which receive projections from the inferior temporal visual cortex, in order to investigate the functions of these regions. Of 195 neurons analyzed in two macaque monkeys, 109 (56%) responded to visual stimuli, with latencies of 90-150 ms for the majority of the neurons. The neurons responded to a limited range of complex visual stimuli, and in some cases responded to simpler stimuli such as bars and edges. Typically (in 75% of cases) the neurons habituated rapidly, within 1-8 exposures, to each visual stimulus, but remained responsive to other visual stimuli with a different pattern. This habituation was orientation specific, in that the neurons responded to the same pattern shown in an orthogonal orientation. The habituation was also relatively short-term, in that at least partial dishabituation to one stimulus could be produced by a single intervening presentation of a different visual stimulus. These neurons were relatively unresponsive in a visual discrimination task, having habituated to the stimuli which had been presented in the task on many previous trials. It is suggested on the basis of these results and other studies that these neurons are involved in pattern-specific habituation to repeated visual stimuli, and in attention an orientation to a changed visual stimulus pattern. Changes in attention and orientation to stimuli as a result of damage to the striatum and its afferent and efferent pathways may arise in part because of damage to neurons with responses of this type.

Animals↗
PubMed1984

Decreased catalepsy response to haloperidol in the genetically dystonic (dt) rat.

The rat mutant dystonic displays an autosomal recessive neurological disease characterized by slow, twisting movements of the limbs and trunk. Rats displaying clinical signs also show a decreased behavioral response to the dopaminergic blocker, haloperidol. Investigation of the development of the cataleptic response to haloperidol in the dystonic (dt) rat indicated that the response of the dt rat in the bar test is similar to that of normal littermates until after the appearance of clinical symptoms in the mutants on postnatal day 10. Mutant rats did not differ from their normal littermates in response to another cataleptic agent, morphine. Assessment of the integrity of the nigrostriatal dopamine (DA) system did not indicate the presence of any degenerative process or of any alterations in DA metabolism. No reliable differences were found between normal and dt rats in striatal DA levels or turnover rates; in DA levels in response to gamma-hydroxybutyrolactone; or in the number and affinity of striatal DA muscarinic acetylcholine receptors. Nor did qualitative light microscopic examination of Golgi-impregnated tissue from dt rats indicate the presence of any morphological abnormalities in the striatum. These findings suggest that dystonic symptoms can occur in the absence of an alteration in striatal DA metabolism and that the dt rat may have a defect in a pathway efferent to the striatum.

4-Butyrolactone↗
PubMed1985

Extracranial vasodilation mediated by vasoactive intestinal polypeptide (VIP).

Pooled antisera to vasoactive intestinal polypeptide were used to block neurogenic extracranial vasodilatation elicited from either brainstem (locus coeruleus) or pterygopalatine ganglion stimulation in the cat. Vasodilatation was not inhibited by sham immune sera, or by antisera to bradykinin or substance P. The efferent pathway for vasodilatation from the locus coeruleus traverses the facial nerve (greater superficial petrosal branch) and the pterygopalatine and otic ganglia. Its blockade demonstrates a novel action of a peptide transmitter in the expression of a central neurogenic response.

Animals↗
PubMed1986

Effect of central noradrenaline depletion on corticosterone levels and gastric ulcerations in rats.

Effects of central noradrenergic depletion on the stress responses of rats were explored using the new selective neurotoxin (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4)). Noradrenergic depletion using DSP-4 was followed by a reduction in basal corticosterone levels after 7 days. Three weeks after DSP-4 treatment, animals exhibited less severe and fewer gastric ulcerations than control animals following 23 h immobilization stress, but stress levels of corticosterone were similar for the two groups. No differences could be found in the peripheral gastric levels of noradrenaline between experimental and control animals, while central noradrenaline was reduced to approximately 30% of control levels. The data support previous findings using other methods that central noradrenaline is an important factor in stress-induced gastric ulceration. The peripheral mechanisms for the protective effects of DSP-4 remain to be elucidated, and studies of these may cast light on the efferent pathways between the central nervous system and gastric mucosa which are involved in stress-induced gastric pathology.

Animals↗
PubMed1986

Immunocytochemical localization of glutamate-, glutaminase- and aspartate aminotransferase-like immunoreactivity in the rat deep cerebellar nuclei.

Although the anatomy and the connectivity of the deep cerebellar nuclei have been well documented, little is known about the neurotransmitter systems mediating cerebellar efferent pathways. The present study utilizes immunohistochemical procedures in conjunction with a novel monoclonal antibody specific for carbodiimide-fixed glutamate and polyclonal antisera against glutaminase (GLNase) and aspartate aminotransferase (AATase) to examine the presence of putative excitatory amino acid transmitters in neurons of the deep cerebellar nuclei. Carbodiimide-fixed glutamate-like, GLNase-like and AATase-like immunoreactivities were observed in neurons of the lateral, posterior interpositus, anterior interpositus and medial deep cerebellar nuclei. More neurons were stained with AATase antiserum than with the GLNase antiserum or the monoclonal antibody. These results suggest glutamate, GLNase and AATase are present in neurons of the deep cerebellar nuclei and raise the possibility that glutamate may be an excitatory transmitter in these structures.

Animals↗
PubMed1987

Phenylethanolamine N-methyltransferase-containing neurons in the rostral ventrolateral medulla of the rat. I. Normal ultrastructure.

The electron microscopic localization of the adrenaline-synthesizing enzyme, phenylethanolamine N-methyltransferase (PNMT) was examined in the rostral ventrolateral medulla (RVL) of adult rats. The brains were fixed by perfusion with 3.75% acrolein and 2.0% paraformaldehyde in phosphate buffer. Coronal Vibratome sections through the RVL were immunocytochemically labeled using a rabbit polyclonal antiserum to PNMT and the peroxidase-antiperoxidase method. A semi-quantitative ultrastructure analysis revealed that the perikarya constituted 9% of the total immunoreactive profiles observed in the RVL. The labeled somata were large (18-24 microns) and were characterized by an indented nucleus and abundant cytoplasm with numerous mitochondria. An average of 136.8 +/- 11.6 mitochondria were present per 100 microns2 cytoplasm, which is 38% greater than the numbers found for PNMT-immunoreactive neurons in the nucleus of the solitary tract. Moreover, the labeled somata were often found in direct apposition to the basal lamina of small capillaries and neighboring astrocytic processes. The remaining labeled profiles were neuronal processes of which 72% were dendrites. Both the PNMT-labeled somata and dendrites received primarily symmetric contacts from unlabeled axon terminals. Only a few axons and terminals containing immunoreactivity for PNMT were observed. The axons were both unmyelinated and myelinated. The PNMT-immunoreactive terminals were characterized by a mixed population of vesicles and by the formation of synaptic junctions with both unlabeled dendrites and PNMT-labeled perikarya and dendrites. The ultrastructural morphology and proximity to blood vessels and glia suggest a high metabolic activity and possibly a chemosensory function of PNMT neurons in the RVL. The existence of myelinated and unmyelinated axons could imply that PNMT-containing neurons have different conduction velocities in efferent pathways to the spinal cord or other brain regions. Furthermore, the multiple types of synaptic interactions between labeled and unlabeled axons and dendrites support the concept that adrenergic neurons modulate and are modulated by neurons containing the same or other putative transmitters in the RVL.

Adrenergic Fibers↗
PubMed1987

Intracellular horseradish peroxidase labeling of rapidly firing dorsal raphe projection neurons.

The class of rapidly firing neurons in the dorsal raphe of the rat was examined using extracellular recording and intracellular injection of horseradish peroxidase. Rapidly firing neurons (termed F-cells in this report) continue to fire at high spontaneous rates during intracellular recording. This and their brief (ca. 1 ms) and symmetrical action potentials distinguish them from the slowly firing, presumably serotonergic neurons in dorsal raphe. Intracellular labeling with horseradish peroxidase reveals that F-cells have small (10-15 microns) spherical, multipolar or piriform somata. Somatic spines are sparse or entirely absent. The general form of the dendritic tree is radiant and poorly branching. However, the dendrites of F-cells take two forms, with both forms being present on the same neuron so that besides having a complement of poorly branching dendrites, each F-cell has at least one dendrite with a slightly tufted branching pattern: a short primary dendrite gives rise to 3 or 4 secondary branches. The axons of F-cells project from the nucleus. They align themselves along the trajectories of known dorsal raphe efferent pathways, coursing laterally and ventrorostrally beyond the bounds of the nucleus. Morphometric measurements of retrogradely labeled dorsal raphe projection neurons provide additional evidence that small projection neurons exist.

Action Potentials↗
PubMed1990

Preservation of integrative function in a perfused guinea pig brain.

The mammalian brain has been one of the most difficult organs to maintain using artificial perfusion. Normal biochemistry, histology, and electrophysiology of the brain have been demonstrated for limited periods in vitro, but it has been more difficult to maintain complex, integrative neuronal activity such as the electroencephalogram (EEG) or programmed motor output. Normal motor output, other than reflex activity, has not previously been demonstrated in a perfused brain preparation. This paper reports the first preservation of normal function in a complete motor network, including intact afferent and efferent pathways, during perfusion of the mammalian brain. The brain, rostral spinal cord and peripheral nervous system of the guinea pig were perfused in situ using an artificial blood containing the oxygen carrier, perfluorotributylamine (FC-43). This preparation was maintained normothermic, whereas many other perfused brain preparations have been maintained hypothermic to prolong viability. Survival was enhanced by the addition of HEPES buffer to the perfusion medium, probably by increasing carbon dioxide transport. The duration of normal EEG was extended to 8 h. Spontaneous respiratory motor output with normal waveform and temporal pattern was recorded from the phrenic nerve for an average of 6 h. The respiratory motor output responded appropriately to blood pCO2, temperature, blood flow, drug concentrations, and electrical stimulation of vagal afferent fibers. This preparation represents a significant advance in the ability to preserve neural function during perfusion, and should offer advantages for studying cellular electrophysiology of intact, functioning neural networks, as well as neurochemistry and neuropharmacology.

Animals↗
PubMed1990

Electrical stimulation of the inferior colliculus at low rates protects the cochlea from auditory desensitization.

The effects of inferior collicular (IC) stimulation on cochlear responses were tested with pulsed electrical trains and with 1 min long continuous bursts. Pulsed trains did not cause any effects at the contralateral cochlea. However, a 1 min burst, containing pulses at low rates, was able to significantly reduce temporary threshold shifts (TTS) in cochlear sensitivity caused by a loud sound exposure. Intracochlear perfusion of hexamethonium blocked this effect. The time course of the hexamethonium blocking action paralleled its blocking action on the cochlear effects of electrical stimulation at the brainstem of an auditory efferent pathway, the crossed olivocochlear bundle (COCB). The protective IC effects were persistent and TTS reductions could be obtained even with a 5 min delay between IC stimulus and the loud sound. However, these persistent protective effects did not appear to occur at the cochlea. Finally, electrical stimulation at the IC ipsilateral to a cochlea exposed to loud sound also reduced TTS, but only by smaller amounts and at higher stimulation rates. Thus the IC appears to provide a strong descending influence that modulates the excitability levels of the olivocochlear nuclei in the brainstem. Both crossed and uncrossed OCB appear to be involved and able to reduce TTS. It is proposed that the protective effects may be due solely to the medial olivocochlear system and possibly only those fibres originating from one of the nuclei of the medial system.

Acoustic Stimulation↗
PubMed1991

Intrinsic connections in cat visual cortex: a combined anterograde and retrograde tracing study.

Area 18 of cat visual cortex was examined for intrinsic axons following small, columnar injections of an anterograde tracer, Phaseolus vulgaris leucoagglutinin (PHA-L). Locally projecting axons radiated from the injection site and branched to form 10-15 discrete, approximately circular patches 500-750 microns in diameter consisting of many bouton-studded terminal arborizations. Labeled fibers and boutons ramified densely in layers I, II/II, V, and VI, and were noticeably less dense in layer IV. Afferent and efferent pathways originating from the same cortical columns were studied by injecting a mixture of PHA-L and wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). Between 10 and 15 patches of cells retrogradely labeled by WGA-HRP surrounded each injection site. Within a patch, labeled cells were found in all layers and included both pyramidal and non-pyramidal cells. The distribution of PHA-L labeling was similar to that obtained when PHA-L was injected alone. Most often, the labeled patches resulting from injections of such mixtures contained both anterograde and retrograde labeling. However, patches consisting of retrograde labeling alone and of anterograde labeling alone were also observed, indicating that the local connections linking neighboring cortical columns were not always reciprocal.

Animals↗
PubMed1993

Characterization of neurons born and incorporated into a vocal control nucleus during avian song learning.

In male zebra finches, song learning is accompanied by the addition of new neurons to Area X, a nucleus necessary for normal song development. We examined whether Area X neurons born after 15 days post-hatch are recruited into the efferent pathway from Area X to the dorsolateral nucleus of the medial anterior thalamus (DLM). Our data suggest that the majority of these new Area X neurons are interneurons and that DLM-projecting neurons are incorporated into Area X prior to song learning.

Animals↗