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Cannabinoid inhibition of guinea-pig intestinal peristalsis via inhibition of excitatory and activation of inhibitory neural pathways.

Since activation of cannabinoid CB1 receptors inhibits gastrointestinal transit in the mouse, this study analyzed the action of the cannabinoid receptor agonist methanandamide on distension-induced propulsive motility. Peristalsis in luminally perfused segments of the guinea-pig isolated ileum was elicited by a rise of the intraluminal pressure. The pressure threshold at which peristaltic contractions were triggered was used to quantify drug effects. Methanandamide (0.1-3 microM) inhibited peristalsis as deduced from a concentration-related increase in the peristaltic pressure threshold, an action that was prevented by the CB1 receptor antagonist SR141716A (1 microM) per se, which had no effect on peristalsis. The distension-induced ascending reflex contraction of the circular muscle was likewise depressed by methanandamide in a SR141716A-sensitive manner, whereas indomethacin-induced phasic contractions of the circular muscle were left unchanged by methanandamide. The anti-peristaltic action of methanandamide was inhibited by apamin (0.5 microM), attenuated by N-nitro-L-arginine methyl ester (300 microM) and left unaltered by suramin (300 microM), pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (150 microM) and naloxone (0.5 microM). It is concluded that methanandamide depresses intestinal peristalsis via activation of CB1 receptors on enteric neurons, which results in blockade of excitatory motor pathways and facilitation of inhibitory pathways operating via apamin-sensitive K+ channels and nitric oxide.

Animals↗

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↗

Neural pathways mediating vaginal function: the vagus nerves and spinal cord oxytocin.

The initial observations, made in our laboratory with Knut Larsson, of the ability of vaginocervical stimulation (VCS) to block withdrawal responses to foot pinch in rats has led to findings of multiple behavioral, autonomic, and neuroendocrine effects of this potent stimulus in rats and also in women. It has led to an understanding of: (1) the neuroanatomical and neurochemical basis of a novel and potent pain-blocking mechanism; (2) likely neuroanatomical pathways mediating both the Ferguson reflex and a specific autonomic response - the pupil-dilating effect of VCS; (3) a role for oxytocin as a putative central nervous system neurotransmitter that stimulates autonomic sympathetic preganglionic neurons within the spinal cord; and (4) a novel pathway that can convey sensory activity from the cervix, adequate to induce orgasm, via the vagus nerves. This latter pathway bypasses the spinal cord and projects directly to the medulla oblongata, and thus can convey genital afferent activity despite complete spinal cord injury at any level.

Animals↗

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↗

Transneuronal tracing of neural pathways controlling an abdominal muscle, rectus abdominis, in the ferret.

Abdominal muscles participate in generating a large number of behaviors and reflex responses, including expiration, coughing, sneezing, vomiting, postural control, production of speech, straining, facilitation of venous return to the heart, and reaction to vestibular stimulation. However, the only premotor neurons that have been conclusively shown to influence abdominal motoneurons are located in nucleus retroambiguus, the expiratory region of the caudal ventral respiratory group. In the present study, the neural circuitry controlling the activity of one abdominal muscle, rectus abdominis, was mapped using the transneuronal tracer pseudorabies virus (PRV) in the ferret. Injections of PRV into rectus abdominis labeled large presumed motoneurons in the ventral horn of T12-L4, and smaller presumed interneurons that were scattered in laminae VII, VIII, IX, and X of T4-L4. In addition, neurons in several areas of the medulla and caudal pons, including the retroambigual nucleus, medial and ventromedial reticular formation, nucleus prepositus hypoglossi, vestibular nuclei, and raphe nuclei, were infected by transynaptic passage of PRV from rectus abdominis motoneurons. Thus, the multifunctional roles of abdominal muscles appear to be coordinated by premotor neurons located in both the spinal cord and several regions of the brainstem.

Animals↗

Dissociable neural pathways are involved in the recognition of emotion in static and dynamic facial expressions.

Facial expressions of emotion powerfully influence social behavior. The distributed network of brain regions thought to decode these social signals has been empirically defined using static, usually photographic, displays of such expressions. Facial emotional expressions are however highly dynamic signals that encode the emotion message in facial action patterns. This study sought to determine whether the encoding of facial expressions of emotion by static or dynamic displays is associated with different neural correlates for their decoding. We used positron emission tomography to compare patterns of brain activity in healthy men and women during the explicit judgment of emotion intensity in static and dynamic facial expressions of anger and happiness. Compared to judgments of spatial orientation for moving neutral facial expressions, the judgment of anger in dynamic expressions was associated with increased right-lateralized activity in the medial, superior, middle, and inferior frontal cortex and cerebellum, while judgments of happiness were associated with relative activation of the cuneus, temporal cortex, and the middle, medial, and superior frontal cortex. In contrast, the perception of anger or happiness in static facial expressions activated a motor, prefrontal, and parietal cortical network previously shown to be involved in motor imagery. The direct contrast of dynamic and static expressions indicated differential activation of visual area V5, superior temporal sulcus, periamygdaloid cortex, and cerebellum for dynamic angry expressions and differential activation of area V5, extrastriate cortex, brain stem, and middle temporal cortical activations for dynamic happy expressions. Thus, a distribution of neural activations is related to the analysis of emotion messages in the nearly constant biological motion of the face and differ for angry and happy expressions. Static displays of facial emotional expression may represent noncanonical stimuli that are processed for emotion content by mental strategies and neural events distinct from their more ecologically relevant dynamic counterparts.

Adult↗

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↗

Cellular distribution and bioactivity of the key steroidogenic enzyme, cytochrome P450side chain cleavage, in sensory neural pathways.

Neurosteroids are steroids produced within the nervous system. Based on behavioural responses evoked in animals by synthetic steroid injections, several studies suggested neurosteroid involvement in important neurophysiological processes. These observations should be correlated only to neuroactive effects of the injected steroids. Neurosteroids mostly control the CNS activity through allosteric modulation of neurotransmitter receptors within concentration ranges used by neurotransmitters themselves. Therefore, neurosteroid production within pathways controlling a neurophysiological process is necessary to consider neurosteroid involvement in that process. Because of the increasing speculation about pain modulation by neurosteroids based on pharmacological observations, we decided to clarify the situation by investigating neurosteroidogenesis occurrence in sensory pathways, particularly in nociceptive structures. We studied the presence and activity of cytochrome P450side chain cleavage (P450scc) in rat pain pathways. P450scc-immunoreactive cells were localized in dorsal root ganglia (DRG), spinal cord (SC) dorsal horn, nociceptive supraspinal nuclei (SSN) and somatosensory cortex. Incubation of DRG, SSN or SC tissue homogenates with [3H]cholesterol yielded the formation of radioactive metabolites including [3H]pregnenolone of which the synthesis was reduced in presence of aminogluthetimide, a P450scc inhibitor. These first neuroanatomical and neurochemical results demonstrate the occurrence of neurosteroidogenesis in nociceptive pathways and strongly suggest that neurosteroids may control pain mechanisms.

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↗

Spinothalamic lamina I neurons selectively sensitive to histamine: a central neural pathway for itch.

We found a class of lamina I spinothalamic tract (STT) neurons selectively excited by iontophoretic histamine. The responses of this class of neurons parallel the pure itching sensation this stimulus elicits in humans, and match the responses of peripheral C-fibers that have similar selectivity. These neurons have distinct central conduction velocities and thalamic projections, indicating that they constitute a unique subset of STT neurons. These findings can explain why a lesion of the lateral STT disrupts itch along with pain and temperature sensations. Our findings provide strong evidence that itch is subserved by specific neural elements both peripherally and centrally.

Animals↗

Neural pathways mediating bilateral interactions between the upper limbs.

The ease with which we perform tasks such as opening the lid of a jar, in which the two hands execute quite different actions, belies the fact that there is a strong tendency for the movements of the upper limbs to be drawn systematically towards one another. Mirror movements, involuntary contractions during intended unilateral engagement of the opposite limb, are considered pathological, as they occur in association with specific disorders of the CNS. Yet they are also observed frequently in normally developing children, and motor irradiation, an increase in the excitability of the (opposite) homologous motor pathways when unimanual movements are performed, is a robust feature of the mature motor system. The systematic nature of the interactions that occur between the upper limbs has also given rise to the expectation that functional improvements in the control of a paretic limb may occur when movements are performed in a bimanual context. In spite of the ubiquitous nature of these phenomena, there is remarkably little consensus concerning the neural basis of their mediation. In the present review, consideration is given to the putative roles of uncrossed corticofugal fibers, branched bilateral corticomotoroneuronal projections, and segmental networks. The potential for bilateral interactions to occur in various brain regions including the primary motor cortex, the supplementary motor area, non-primary motor areas, the basal ganglia, and the cerebellum is also explored. This information may provide principled bases upon which to evaluate and develop task and deficit-specific programs of movement rehabilitation and therapy.

Animals↗

Sensory interactions through neural pathways.

The word "taste" includes olfaction and somatosensory information besides the proper sense of taste. Taste and somatosensory sensitivity are very close and overlapping in most central nervous system projection areas. The objective of the present paper is to review a series of experiments disclosing functional neurophysiological interactions between taste and somatosensory information at different levels.

Animals↗

Structural maturation of neural pathways in children and adolescents: in vivo study.

Structural maturation of fiber tracts in the human brain, including an increase in the diameter and myelination of axons, may play a role in cognitive development during childhood and adolescence. A computational analysis of structural magnetic resonance images obtained in 111 children and adolescents revealed age-related increases in white matter density in fiber tracts constituting putative corticospinal and frontotemporal pathways. The maturation of the corticospinal tract was bilateral, whereas that of the frontotemporal pathway was found predominantly in the left (speech-dominant) hemisphere. These findings provide evidence for a gradual maturation, during late childhood and adolescence, of fiber pathways presumably supporting motor and speech functions.

Adolescent↗

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↗

Separate neural pathways for contour and biological-motion cues in motion-defined animal shapes.

To determine whether contour and biological motion (BM) cues for motion-defined shapes are subserved by two separate mechanisms, we used PET to measure regional cerebral blood flow in nine human subjects. Subjects were scanned in the following four conditions: (1) contour-defined animals with natural movements (running), (2) motion-defined animals in which the contours were removed and dots were placed on the limbs and moving parts (BM; running); (3) drifting static animal shapes (contours); and (4) drifting dots. The results demonstrate that the perception of BM involves the superior frontal gyrus, the precuneus, the fusiform, the lingual and the medial temporal gyri, the inferior parietal lobe, the hippocampal and parahippocampal areas, and the cerebellum. In addition, the anterior cingulate cortex and the amygdala were significantly activated. The perception of contour-defined shapes produced significant elevation of rCBF in some areas similar to the BM condition, namely the fusiform, medial occipital, medial temporal, and lingual gyri. Only the occipital pole and the inferior temporal cortex were specifically activated by contour-defined shapes. These results are congruent with previous findings that the dorsal visual pathway is important for the perception of BM. They further support psychophysical results showing that contour and BM cues for motion-defined animal shapes are processed by independent channels.

Adult↗