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Evidence for corticotropin-releasing factor, neurotensin, and somatostatin in the neural pathway from the central nucleus of the amygdala to the parabrachial nucleus.

The central nucleus of the amygdala (CNA) and the parabrachial nucleus of the pons (PBN) are included within a group of brain nuclei involved in autonomic responses. Previous studies have shown that the CNA sends a considerable projection to the PBN and that both nuclei contain neurons immunoreactive to many different peptides. In the present study, we used the combined retrograde fluorescence-immunofluorescence method to determine whether the CNA projection to the PBN contains any of the following neuropeptides: corticotropin-releasing factor (CRF), neurotensin (NT), somatostatin (SS), and enkephalin (ENK). Following injections of fluorescent dye into the PBN, neurons within both lateral and medial subdivisions of the CNA were retrogradely labeled. A significant percentage of CRF (54-66%)-, NT (40-53%)-, and SS (31-50%)-immunoreactive neurons were retrogradely labeled, predominantly within the lateral CNA. Enkephalin-immunoreactive neurons were never retrogradely labeled, although they were often found adjacent to retrogradely labeled neurons. Our results show that the lateral CNA is a major source of CRF, NT, and SS terminals within the PBN. Neurons in the medial CNA also provide a significant contribution to the CNA-PBN pathway, but their chemical nature remains to be determined. We conclude that CRF, NT, and SS are important putative neurotransmitters in the CNA's regulation of PBN function. This CNA-PBN peptidergic pathway may participate in stress-related cardiovascular and respiratory responses.

Amygdala

Poliovirus spreads from muscle to the central nervous system by neural pathways.

A transgenic mouse model was used to address an unsolved question in the pathogenesis of poliomyelitis: how poliovirus invades the central nervous system (CNS). LD50 values for intramuscular and intracerebral inoculation of poliovirus in transgenic mice expressing poliovirus receptors (TgPVR mice) were similar. After intramuscular inoculation with poliovirus, paralysis was observed first in the inoculated limb. In contrast, localization of initial paralysis to the inoculated limb was not observed in normal mice inoculated intramuscularly with the mouse-adapted P2/Lansing poliovirus strain. After intramuscular inoculation, infectious poliovirus was first detected in the inferior segment of the spinal cord, then in the superior spinal cord and the brain. Sciatic nerve transection blocked poliovirus spread to the spinal cord after inoculation into the hindlimb footpad of TgPVR mice. These results demonstrate that in TgPVR mice, poliovirus spreads from muscle to the CNS through nerve pathways and that expression of the poliovirus receptor plays an important role in viral spread by this route.

Animals

An HRP study of neural pathways to neocortical olfactory areas in monkeys.

Afferent fiber projections to the two orbitofrontal olfactory areas of monkeys were studied using the horseradish peroxidase (HRP) technique. After injections of HRP into the lateroposterior (LPOF) or centroposterior (CPOF) area of the orbitofrontal cortex, some differences were found in the distribution of labeled cells between the projections to the LPOF and CPOF. These results, along with those of previous electrophysiological investigations, suggest the following conclusions: (1) the extrathalamic olfactory pathway to the LPOF identified by Tanabe et al. has relay neurons primarily in the substantia innominata and the amygdala and, secondarily, in the prorhinal cortex and the hypothalamus; (2) direct fibers to the LPOF from the amygdala and the prorhinal cortex pass through the areas ventral to the thalamus; (3) the transthalamic olfactory pathway to the CPOF identified by Yarita et al. has relay neurons concentrated primarily in the magnocellular portion of the mediodorsal nucleus of the thalamus.

Animals

[Neural pathway of Powassan virus spread in the central nervous system of white mice].

Electron microscopic investigation of the brains and lumbar spinal cords of adult albino mice infected with Powassan virus was carried out. Virus particles were found within all parts of neurons (perikarya, dendrites, axon), as well as within synaptic apparatus and intercellular gaps of the central nervous tissue. The possibility of the virus spread both throughout the cytoplasm of nerve cells and their processes and the extracellular spaces of the brain was confirmed. Localization of virions within neurons, synapses and myelinated fibers of the spinal cord after intracerebral inoculation suggests that virus spread in the CNS can occur through the CNS parenchyma and also through the nervous conduction pathways. The possible mechanisms of virus dissemination in the CNS of albino mice with experimental Powassan virus encephalomyelitis are discussed.

Animals

Neural pathways for the control of birdsong production.

As in humans, song production in birds involves the intricate coordination of at least three major groups of muscles: namely, those of the syrinx, the respiratory apparatus, and the upper vocal tract, including the jaw. The pathway in songbirds that controls the syrinx originates in the telencephalon and projects via the occipitomesencephalic tract directly upon vocal motoneurons in the medulla. Activity in this pathway configures the syrinx into phonatory positions for the production of species typical vocalizations. Another component of this pathway mediates control of respiration during vocalization, since it projects upon both expiratory and inspiratory groups of premotor neurons in the ventrolateral medulla, as well as upon several other nuclei en route. This pathway appears to be primarily involved with the control of the temporal pattern of song, but is also importantly involved in the control of vocal intensity, mediated via air sac pressure. There are extensive interconnections between the vocal and respiratory pathways, especially at brain-stem levels, and it may be these that ensure the necessary temporal coordination of syringeal and respiratory activity. The pathway mediating control of the jaw appears to be different from those mediating control of the syrinx and respiratory muscles. It originates in a different part of the archistriatum and projects upon premotor neurons in the medulla that appear to be separate from those projecting upon the syringeal motor nucleus. The separateness of this pathway may reflect the imperfect correlation of jaw movements with the dynamic and acoustic features of song. The brainstem pathways mediating control of vocalization and respiration in songbirds have distinct similarities to those in mammals such as cats and monkeys. However, songbirds, like humans, but unlike most other non-songbirds, have developed a telencephalic vocal control system for the production of learned vocalizations.

Animals

Influence of neural pathways on the pyrexial response to surgical trauma.

Epidural analgesia inhibits several metabolic effects of trauma. Some of these effects are generated by the endogenous fever mediator interleukin-1. Postoperative fever was therefore studied in 52 patients, 25 of whom had had epidural analgesia and 27 general anaesthesia. Transvesical prostatectomy was used as standard surgical trauma. Most of the patients had postoperative temperature rise exceeding 0.5 degree C, but the rise was not influenced by epidural analgesia. These data suggest that the release of endogenous fever mediator is not under control of afferent pathways from the region of trauma. The findings are also consistent with regulation of interleukin-1 release which is independent of adrenal stimulation, cyclic AMP or beta-endorphin, as epidural analgesia prevents postoperative increase of these hormones.

Aged

Lack of modulation of pituitary hormone stress response by neural pathways involving opiate receptors.

To evaluate the role of the opiate-like peptidergic pathways in modulating the pituitary hormone response to stress, we measured the GH, PRL, and cortisol responses to hypoglycemia and exercise in normal subjects with and without pretreatment with naloxone, given in the centrally active dose of 0.4 mg iv. Basal serum levels of GH, PRL, and cortisol were not changed significantly by prior naloxone administration. The maximum incremental response of GH to exercise was significantly blunted (13.1 +/- 1.6 vs. 6.0 +/- 1.4; P less than 0.001) by prior naloxone administration. Pretreatment with naloxone did not affect the responses of GH, PRL, or cortisol to hypoglycemia or the PRL response to L-dopa. On the basis of these studies we conclude that the opiate-like peptidergic pathways are not important in the regulation of basal levels of GH, PRL, and cortisol and have only a modest modulating influence on the stress-induced release of the hormones, which may be obscured in the face of severe stress.

Female

Neural pathways to lower urinary tract identified by retrograde axonal transport of horseradish peroxidase.

A new technique for tracing nerve fibers supplying specific organs by retrograde axonal transport of the enzyme horseradish peroxidase (HRP) was used to determine the innervation of various segments of the lower urinary tract. HRP was injected at the level of the bladder neck, postprostatic urethral segment, pelvic nerve, pudendal nerve, and pelvic floor musculature to determine precise nerve supply to each site, as well as possible overlap. The technique determines the exact spinal level of innervation, as well as the number of nuclei directly related to the motor neuron axons supplying innervation to each particular site. Representation of these nuclei at various levels of the spinal cord was shown in various serial sections obtained after the injection of HRP. This technique is accurate and precise; it is valuable in establishing exact neural anatomic connections between the central nervous system and target organs.

Anal Canal

Neural pathways associated with hypothalamically elicited attach behavior in cats.

Small electrolytic lesions were made in cats through electrodes, which, when stimulated, elicited either quiet biting attack or affective paw strike attack upon rats. The Nauta method for impregnating degenerating axoplasm was used to reveal that degeneration resulting from lesions at quiet attack sites followed largely along the course of the medial forebrain bundle, while the degeneration after lesions of affective attack sites was concentrated more heavily in the periventricular system.

Aggression

Neural pathways from thalamus associated with regulation of aggressive behavior.

Small electrolytic lesions were made through electrodes in the thalamus of cats at sites where electrical stimulation elicited attack on a rat. Staining by modified Nauta reduced silver methods revealed that significant degeneration passed caudally from the lesions and entered the midbrain dorsal central gray region. Electrical stimulation of this dorsal midbrain region elicited attack on a rat, and destruction of this region suppressed the attack elicited by thalamic stimulation.

Aggression

Mapping of functional neural pathways by autoradiographic survey of local metabolic rate with (14C)deoxyglucose.

An enzymatic preparation from human brain converts tryptamine to tryptoline (9H-1,2,3,4-tetrahydropyrido(3,4-b)indole) in the presence of 5-methyltetrahydrofolic acid. Similarly, N-methyltryptamine and 5-hydroxytryptamine yield 1-methyltryptoline and 5-hydroxytryptoline, respectively. Neither in vitro nor in vivo formation of these compounds by human tissues has been described.

Animals

Neural pathways mediating the corneal blink reflex and Bell's phenomenon in the cat.

Two central projections from the corneal representation of the sensory trigeminal complex in the cat were demonstrated with horseradish peroxidase, autoradiographic and Golgi methods: (1) to the dorsal subdivision of the ipsilateral facial nucleus that innervates the orbicularis oculi muscle; and (2) to the bordering area between the contralateral central gray matter and the oculomotor nucleus, which receives dendrites of the oculomotor cells innervating the contralateral superior rectus muscle. These two routes probably mediate early responses of the corneal blink reflex and Bell's phenomenon, respectively.

Animals

PKA isoforms, neural pathways, and behaviour: making the connection.

In mammals, the cAMP-dependent protein kinase (PKA) family of enzymes is assembled from the products of four regulatory and two catalytic subunit genes, all of which are expressed in neurons. Specific isoforms of PKA display differences in biochemical properties and subcellular localization, but it has been difficult to ascribe specific physiological functions to any given isoform. The recent development of gene knockout and transgenic mouse models has allowed for a more integrated examination of the in vivo roles of specific PKA isoforms in gene expression, synaptic plasticity, and behaviour.

Animals

Neural pathway involved in the excitation of motoneurones to jaw-opening muscles by stimulation of the orbital cerebral cortex in the cat.

The pathway and synaptic basis for the efferent discharge in the digastric nerve evoked by stimulation of the orbital cortex were studied in cats anesthetized with alpha-chloralose. Transection of the brain stem at the boundary between the pons and the medulla oblongata abolished discharge. Intracellular recording from anterior digastric motoneurones revealed that the orbital cortical stimulation evoked excitatory post-synaptic potentials with a latency that was longer by one synaptic delay than that of spike potentials evoked in medial bulbar reticular neurones making a direct excitatory projection to anterior digastric motoneurones. It was concluded that the excitatory effects was mediated by the medial bulbar reticular formation.

Animals

Neural pathways mediating hypothalamically elicited flight behavior in the cat.

This study has sought to identify hypothalamic pathways mediating flight behavior in the cat. Flight behavior, characterized by an initial pupillary dilatation and followed by vigorous attempts to leap out of the observation chamber, was elicited primarily by electrical stimulation of the medial preoptic region and dorsomedial hypothalamus, and to a lesser extent from the perifornical region. A [14C]-2-deoxyglucose analysis was utilized to examine brain regions functionally activated by stimulation of hypothalamic sites which elicited flight behavior. In a second series of experiments, [3H]leucine injected into regions surrounding electrode tips from which flight had previously been elicited, permitted identification of pathways arising from such functionally characterized sites. We describe for the first time pathways arising from the hypothalamus which mediate flight behavior. In spite of individual variation in placement of electrodes eliciting flight, a consistent pattern of labeling was observed following injection of either [14C]-2-deoxyglucose systemically or [3H]amino acids into the hypothalamus. The primary rostral target structures receiving inputs from flight electrode sites included the nuclei of the diagonal band, bed nucleus of the stria terminalis, medial amygdaloid nucleus, lateral septal nucleus, and anterior medial preoptico-hypothalamus. Caudal to the level of stimulation, the principal target nuclei involved the centrum medianum-parafascicular complex and the midbrain central gray substance. Possible roles of these nuclear regions in organization and regulation of flight behavior is discussed.

Amygdala

Sexually dimorphic cell groups in the medial preoptic area that are essential for male sex behavior and the neural pathways needed for their effects.

The research summarized here shows that the two major cell groups of the sexually dimorphic area (SDA) of the gerbil hypothalamus are essential for male sex behavior. Bilateral cell-body lesions of either the medial or lateral SDA virtually eliminate mating in sexually experienced male gerbils given exogenous testosterone. Similar deficits occur when the SDA is bilaterally disconnected from the retrorubral field (RRF) as a result of unilateral cell-body lesions in the SDA and contralateral RRF. The A8 cells of the RRF do not account for this effect. Bilaterally disconnecting the SDA from the caudomedial part of the bed nucleus of the stria terminalis (caudal BSTm) also eliminates sexual activity. Disconnecting the SDA from the medial amygdala does not mimic this effect. Neither does disconnecting the medial amygdala from the caudal BSTm. Thus, caudal BSTm neurons that are essential for mating via connections with the SDA do not simply relay information from the medial amygdala.

Amygdala

Involvement of NO-ergic neural pathway in reflex tracheal dilatation during bronchoconstriction in guinea pigs.

The involvement of NOergic nerve in vagal reflex-mediated tracheal dilatation during bronchoconstriction was investigated using the guinea pig in vivo tracheo-bronchi separated preparation. Inhalation of 0.01% histamine to the bronchial site induced a biphasic, vagal reflex tracheal response, i.e., constriction followed by dilatation slightly after bronchial constriction. The reflex tracheal dilatation was inhibited by 49% by local treatment of the tracheal site with 1% propranolol. The residual dilatation in the presence of atropine and propranolol was significantly inhibited by 1% oxyhemoglobin or 1% carboxy-PTIO, NO scavengers. Cyclic GMP content in the tissue of the tracheal site during the reflex tracheal dilatation significantly increased. The increase in cyclic GMP was reduced by treatment of the tracheal site with 1% N omega-nitro-L-arginine methyl ester. These results support a hypothesis that reflex tracheal dilatation during bronchoconstriction may be mediated by not only adrenergic but also NOergic nerves in guinea pigs.

Administration, Inhalation