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PubMed1988

Neuropharmacological analysis of the role of indoleamine-accumulating amacrine cells in the rabbit retina.

In order to elucidate the role of putative indoleaminergic amacrine cells in visual processing, we have employed pharmacological agents specific for the two classes of serotonin receptor, 5-HT2 and 5-HT1, which have been identified in both the retina and brain. Perfusion of the rabbit retina with 5-HT2 selective antagonists decreases the ON-excitation of all classes of ganglion cell as well as the spontaneous activity of these cells. The effect on OFF-responses depends on the cell type: OFF-excitation of center-surround brisk and sluggish cells is increased or not affected by these drugs, but OFF excitation of ON/OFF direction selective cells is reduced. No disruption of the trigger features of direction selective or orientation selective cells was discovered, suggesting that indoleaminergic amacrine cells do not play a role in the generation of the complex properties of these cells. 5-HT1 receptors are heterogeneous and classified as a, b, or c subtypes. Since no selective antagonists are available for these sites, we have employed specific agonists. The most specific of these are for the 5-HT1A receptor. Perfusion with these agonists had physiological effects similar to those with perfusion of 5-HT2 antagonists. Thus, we have suggested that these two classes of serotonin receptors mediate opponent processes in the neural pathway. Since indoleaminergic cells make reciprocal synaptic connections with rod bipolar cell terminals, which are depolarizing in the rabbit retina, we hypothesize that 5-HT2 receptors facilitate the synaptic transmission from the depolarizing rod bipolar cell thus facilitating ON-excitation in the retinal network while 5-HT1A receptors mediate an inhibitory process. Similar self-opponent processing appears to take place in the hypothalamic and hippocampal serotonergic systems as well as in the dopaminergic retinal system. Thus, it is likely that this organization is a general feature of monoamine signal transmission in the central nervous system.

Animals↗

PubMed2000

Gastric emptying rate of solids is reduced in a group of ileostomy patients.

Feedback inhibition from the colon acts as a potent inhibitor of gastrointestinal motility via an array of gut peptides and neural pathways. The effect of total colonectomy on gastric emptying was assessed in five healthy ileostomy patients (<5 cm ileal resection) and five matched controls. Each subject consumed two isoenergetic test meals of contrasting fat-carbohydrate ratio in random order. Emptying of solids was measured using the [13C]octanoic acid breath test, and liquid emptying was assessed after oral dosing with paracetamol. Ileostomist subjects exhibited an increased half-emptying time for solids (P = 0.047), which included components of an increased gastric lag time (P = 0.004) and a reduction in the linear emptying rate (P = 0.003). There was no difference in the pattern of liquid emptying between subject groups. In conclusion, the gastric emptying rate of solids was reduced in ileostomy patients compared with controls.

Adult↗

PubMed2000

Role of capsaicin-sensitive nerves in gastric and hepatic injury induced by cold-restraint stress.

The role of capsaicin-sensitive afferent fibers on cold-restraint stress-induced gastric and hepatic injury was examined at the macroscopic and ultrastructural levels. Wistar albino rats were treated with capsaicin either locally (intragastric, perivagal, and periceliac) or systemically (neonatal, intraperitoneal). Perineural and neonatal treatment with capsaicin was used to denervate afferent fibers, while intragastric capsaicin treatment would have activated mucosal afferent fibers just before the stress exposure. Capsaicin decreased significantly the formation of macroscopic gastric lesions caused by stress in all treatment groups. At the electron microscopic level, however, denervation of vagal afferent fibers with capsaicin was most effective in prevention of cellular injury in gastric mucosa. In the liver, systemic denervation of afferent fibers completely inhibited stress-induced cellular damage, while denervation of afferent fibers in vagus and splanchnic nerve was partially effective. Central neural pathways sensitive to capsaicin may mediate formation of both gastric and hepatic injury resulting from stress.

Animals↗

PubMed2001

Objective assessment of cognitive factors involved in visceral perception by using event-related cerebral evoked responses to esophageal target stimulation in man.

Evoked potential (EP) studies provide an objective measure of the neural pathways involved with perception of gastrointestinal stimulation. The effects of cognitive factors, such as anticipation or awareness, on EP responses are not known. We compared the EP response to esophageal electrical stimulation with the cortical activity associated with target detection and anticipation of the same stimulus. In 12 healthy men (26.8+/-6 years old), esophageal electrical stimulation (0.2 Hz, 0.2 msec, 15 mA) was applied, and the EP recorded using scalp electrodes. A computerized model of randomly applied target stimuli (1:5 ratio) was used to separately record the EP associated with stimulation and the event-related cognitive EP associated with a dual task-related or anticipated stimulation approach. A periodic electrical stimulus represented the nontarget stimulus and a second electrical impulse (oddball model) or an omitted stimulus (anticipatory model) the target stimulus. The event-related cognitive EP responses were also compared with standard and anticipatory auditory P300 evoked potentials. The esophageal and auditory oddball stimulus approach elicited event-related P300EP in all subjects. P300EP associated with electrical stimulation had a longer peak latency (P < 0.0001) and smaller amplitude than those obtained with auditory stimulation. Anticipatory evoked potentials could be obtained by electrical skipped stimulation in 8 of 12 subjects. These EP were similar to those obtained with omitted auditory target stimulation, although of significantly smaller amplitude than auditory standard P300EP (P < 0.001). In conclusion, the brain response associated with directed effortful processing of discriminate esophageal stimuli consists of a large event-related potential (P300EP). Anticipatory stimulation produces a similar event-related cortical response, which is associated with attention to and awareness of the actual stimulus. The P300EP to gastrointestinal stimuli may provide an objective and powerful electrophysiological tool for the assessment of the cognitive factors associated with visceral perception.

Adult↗

PubMed2001

Structure of cell clusters formed in cultures of dissociated human embryonic brain.

Cell clusters in a culture of dissociated brain from human fetuses at 8-12 weeks gestation in a serum-free growth medium were studied by immunohistochemical methods and electron microscopy. Heterogeneity of cell population in culture was demonstrated. Despite the influence of proliferation-stimulating factors, cell clusters contained not only nestin-immunopositive stem cells, but also beta-tubulin-, vimentin-, and GFAP-positive cells differentiating by the neural pathway. Stem cells were localized on the surface of clusters. The percentage of stem cells in large clusters was lower than in small clusters.

Brain↗

PubMed2004

A comparative study of the effects of electroacupuncture and moxibustion in the gastrointestinal motility of the rat.

We compared the outcomes of the stimulation of specific sets of acupoints with either acupuncture or moxibustion over peristalsis. Twenty-five plastic beads were orally administered in the stomach of the rats and 90 min later animals were sacrificed, the stomach and small intestine were opened, and the number of beads remaining in each segment was counted. Forty rats were immobilized for 20 min and stimulated at either abdominal or hindlimbs acupoints, with either electroacupuncture or moxibustion. Under this restraint (stress) condition electroacupuncture at hindlimb points or moxibustion at abdominal points significantly enhanced gastric emptying (P < 0.02) as well as intestinal motility compared with animals subjected only to immobilization and not stimulated with electroacupuncture or moxibustion. We conclude that the effects of different acupoints and modes of stimulation (electrical vs. moxibustion) over gastrointestinal motility in rats subjected to restraint-induced stress is not uniform and discuss the different neural pathways underlying these differences.

Analysis of Variance↗

PubMed2000

Role of endogenous nitric oxide in asthma.

Endogenous nitric oxide (NO) is an ubiquitous signaling molecule with important regulatory functions such as regulation of blood pressure, neurotransmission, and host and immune defense. In the respiratory tract, NO is formed and released by various sources including endothelial and epithelial cells, nerves, airway smooth muscle, and inflammatory cells. Recent evidence suggests that endogenous NO is the neurotransmitter of the nonadrenergic noncholinergic inhibitory (iNANC) system, the only bronchorelaxant neural pathway of human airways. A number of studies also suggest that in some species epithelium-derived NO accounts for the functional bronchoprotective role of the so-called epithelium-derived relaxing factor. In human airways, endogenous NO counteracts the bronchoconstriction induced by pharmacologic stimuli such as bradykinin, histamine, and methacholine. On the basis of these and other observations, it is suggested that a reduced synthesis and/or activity of endogenous NO may contribute to the pathogenesis of airway hyperresponsiveness that characterizes asthma and other respiratory disorders. This short paper summarizes the activities of endogenous NO in the airways of experimental animals and man, and discusses the evidence supporting the view that NO confers bronchoprotection.

Animals↗

PubMed2001

Sensorimotor control of knee stability. A review.

Traditionally, the concept of joint stability considered the displacement (or subluxation) of two bones relative to each other as the measurement index, and attributed the preservation of such stability in its physiologic range to the various ligaments associated with the joint. Although the ligaments are indeed the major restraints of any joint, the significant contribution of the musculature toward joint stability had been grossly overlooked or neglected until the last 15 years. The value and importance of muscular activity in that role becomes immediately apparent if one performs even a superficial functional comparison of muscles and ligaments. Ligaments are passive viscoelastic structures, whereas muscles are dynamic viscoelastic organs. The viscoelastic effects of the ligaments are activated and applied strictly upon the geometric and kinematic configuration of the joint traversing through its range of motion according to fixed force-displacement relationships. The musculature, however, can apply passive viscoelastic effects to the joint when not active (passive tone) and variable dynamic viscoelastic effects when contracting under voluntary or reflexive control, and at any desirable point in the range of motion and in response to joint speed, external load, gravity, pain, and so forth, while executing the functional objective of the movement set by the individual. Preservation of joint stability cannot be ascribed to the ligaments alone, but should be considered as a synergistic function in which bones, joint capsules, ligaments, muscles, tendons, and sensory receptors and their spinal and cortical neural projects and connections function in harmony. The objective of this report is to first review the anatomy and physiology of the various mechanoreceptors and their neural pathways about the joint, and describe some of the current concepts of the reflex arcs elicited by such receptors, with special emphasis on biomechanical outcomes relative to stability. The role of the musculature in maintaining stability while controlling joint motion is then reviewed, with data obtained from experiments performed on humans and animals. Finally, some clinical findings from patients with anterior cruciate ligament deficiency using a brace that simulates the ligament-muscle functions is described.

Anterior Cruciate Ligament Injuries↗

PubMed1978

Reaction times and evoked potentials as indicators of hemispheric differences for laterally presented name and physical matches.

Letter pairs, which could be name matches, physical matches, or mismatches, were presented at fixation or 2.5 degrees left or right of fixation. During different experimental sessions, the locations and the types of matches were fixed (and therefore known in advance by the subject) or were randomized. Right visual field superiority in reaction time occurred for name matches only when location was randomized, and then the extent of the superiority depended on whether the types of match called for were predictable. Evoked potentials to the letter pairs during this task revealed hemispheric and neural pathway differences that were independent of expectancy condition. Right hemisphere responses were larger than left. For some components, amplitudes were smaller and latencies were shorter for direct than for indirect projection of stimuli to each cerebral hemisphere. Indirect-direct differences in P300 amplitude varied for each cerebral hemisphere according to whether a physical or name match occurred. The P130 and N170 components manifested hemispheric differences that depended on whether the two letters of a pair were in the same or different cases.

Adult↗

PubMed2001

Paternal behavior is associated with central neurohormone receptor binding patterns in meadow voles (Microtus pennsylvanicus).

Paternal and nonpaternal voles (microtus) have different arginine-vasopressin (AVP) and oxytocin (OT) receptor patterns in the extended amygdala, a neural pathway associated with parental behavior. Using receptor autoradiography, the authors examined whether AVP and OT receptor patterns were associated with facultative paternal behavior in either sexually and parentally inexperienced or experienced meadow voles (Microtus pennsylvanicus). Experienced, in contrast to inexperienced, males had less AVP binding in the lateral septum (LS), more AVP binding in the anterior olfactory nucleus (AON), and more OT binding in the AON, bed nucleus of the stria terminalis, LS, and lateral amygdala. Thus, specific AVP receptor patterns, which co-occur with paternal care in consistently paternal voles, also may be associated with paternal care (when present) in typically nonpaternal species. This study also demonstrated a possible relationship between OT receptor patterns and paternal state in male mammals.

Amygdala↗

PubMed2003

Novel tastes elevate c-fos expression in the central amygdala and insular cortex: implication for taste aversion learning.

Taste novelty strongly modulates the speed and strength of taste aversion conditioning. To identify molecular signals responsive to novel tastes, immunostaining for c-fos protein (Fos-like immunoreactivity [FLI]) was used to mark neurons that responded differentially to taste novelty. Novel saccharin induced larger increases in FLI than familiar saccharin. This pattern was seen in central amygdala and insular cortex, but not in basolateral amygdala, parabrachial nucleus, or nucleus of the solitary tract. Other parameters known to influence aversion learning were tested for effects on FLI. Manipulations known to reduce the strength of learning blunted the FLI response, supporting the idea that FLI marks neural pathways critical to taste processing during acquisition, and that c-fos expression is a key transcriptional event underlying this plasticity.

Amygdala↗

PubMed1998

Corticofugal modulation of the midbrain frequency map in the bat auditory system.

The auditory system, like the visual and somatosensory systems, contains topographic maps in its central neural pathways. These maps can be modified by sensory deprivation, injury and experience in both young and adult animals. Such plasticity has been explained by changes in the divergent and convergent projections of the ascending sensory system. Another possibility, however, is that plasticity may be mediated by descending corticofugal connections. We have investigated the role of descending connections from the cortex to the inferior colliculus of the big brown bat. Electrical stimulation of the auditory cortex causes a downward shift in the preferred frequencies of collicular neurons toward that of the stimulated cortical neurons. This results in a change in the frequency map within the colliculus. Moreover, similar changes can be induced by repeated bursts of sound at moderate intensities. Thus, one role of the mammalian corticofugal system may be to modify subcortical sensory maps in response to sensory experience.

Animals↗

PubMedDate not supplied

Autoradiographic distribution of substance P receptors in rat central nervous system.

Among various neuropeptides present in the central nervous system (CNS), substance P, an undecapeptide, is of great interest as a putative pain neurotransmitter. Substance P is present within numerous intrinsic neural pathways throughout the CNS. Several groups have attempted to label substance P receptors on brain membranes by ligand binding techniques; only one study used native 3H-labelled substance P as the ligand and the precise anatomical distribution of substance P receptors has not yet been described. Here we report the autoradiographic localization of 3H-labelled substance P receptors in rat brain using the in vitro autoradiographic technique developed recently. 3H-substance P binds specifically to an apparently single class of sites on slide-mounted brain sections (Kd = 0.52 nM; Bmax = 21.6 fmol per mg protein). The ligand selectivity pattern suggests that 3H-substance P binding sites are similar to those found in other assays. 3H-substance P receptors are highly concentrated in the external layers of the olfactory bulb, medial amygdala, dentate gyrus, superior colliculus, dorsal parabrachial nucleus and locus coeruleus, with moderate densities being found in the nucleus accumbens, striatum, periaqueductal grey and subiculum. The distribution of 3H-substance P receptors suggests that substance P is probably involved in the control of sensory processes such as pain, vision, audition and olfaction.

Animals↗

PubMedDate not supplied

Modulation of stress-induced ACTH release by corticotropin-releasing factor, catecholamines and vasopressin.

The stress-induced release of ACTH is believed to involve the activation of several humoral and neural pathways, including corticotropin-releasing factor (CRF), catecholamines and vasopressin. The essential role of CRF was supported by our observation that immunoneutralization of this releasing factor significantly lowers plasma ACTH levels of ether-stressed rats. However, the presence of a small but measurable residual ACTH secretion suggested the possible involvement of factors other than CRF in the stress response. We report here that pretreatment with a vasopressin antagonist decreases the plasma ACTH levels of ether-stressed rats in later (10-20 min), but not earlier (0-10 min), phases of ether stress. The ganglionic blocker chlorisondamine, inhibits ACTH release during both phases of the response to ether by 40-60% when used alone, and by 100% when administered with anti-CRF antibody. These results support a role of CRF, catecholamines and vasopressin in mediating ACTH release by ether stress.

Adrenocorticotropic Hormone↗

PubMed1994

Mapping motor representations with positron emission tomography.

Brain activity was mapped in normal subjects during passive observation of the movements of an 'alien' hand and while imagining grasping objects with their own hand. None of the tasks required actual movement. Shifting from one mental task to the other greatly changed the pattern of brain activation. During observation of hand movements, activation was mainly found in visual cortical areas, but also in subcortical areas involved in motor behaviour, such as the basal ganglia and the cerebellum. During motor imagery, cortical and subcortical areas related to motor preparation and programming were strongly activated. These data support the notion that motor learning during observation of movements and mental practice involves rehearsal of neural pathways related to cognitive stages of motor control.

Adult↗

PubMed1997

Colour tuning in human visual cortex measured with functional magnetic resonance imaging.

The primate retina contains three classes of cones, the L, M and S cones, which respond preferentially to long-, middle- and short-wavelength visible light, respectively. Colour appearance results from neural processing of these cone signals within the retina and the brain. Perceptual experiments have identified three types of neural pathways that represent colour: a red-green pathway that signals differences between L- and M-cone responses; a blue-yellow pathway that signals differences between S-cone responses and a sum of L- and M-cone responses; and a luminance pathway that signals a sum of L- and M-cone responses. It might be expected that there are neurons in the primary visual cortex with response properties that resemble these three perceptual pathways, but attempts to find them have led to inconsistent results. We have therefore used functional magnetic resonance imaging (fMRI) to examine responses in the human brain to a large number of colours. In visual cortical areas V1 and V2, the strongest response is to red-green stimuli, and much of this activity is from neurons receiving opposing inputs from L and M cones. A strong response is also seen with blue-yellow stimuli, and this response declines rapidly as the temporal frequency of the stimulus is increased. These responses resemble psychophysical measurements, suggesting that colour signals relevant for perception are encoded in a large population of neurons in areas V1 and V2.

Brain Mapping↗

PubMed1986

Response of regional cerebral blood flow and oxygen metabolism to thalamic stimulation in humans as revealed by positron emission tomography.

To clarify functional neural pathways originating from the thalamic nucleus ventralis posterolateralis (VPL) in humans, the responses of regional CBF (rCBF) and regional CMRO2 (rCMRO2) to VPL stimulation were investigated by positron emission tomography in five patients who had undergone chronic implantation of electrodes into the VPL for therapeutic purposes. Measurement of rCBF and rCMRO2 under continuous inhalation of C15O2 and 15O2 by steady-state methods revealed significant increases of rCBF and rCMRO2 in the frontal, postcentral, and thalamic regions. The increases in rCBF and rCMRO2 of the postcentral regions were clearly predominant in the stimulated hemisphere insofar as the stimulation produced moderate paresthesia in restricted areas of the body. These results indicate that the VPL relays peripheral somatosensory information, which has previously been demonstrated to be transmitted to the frontal as well as postcentral regions.

Cerebrovascular Circulation↗

PubMed1992

Stimulation of Cl area neurons globally increases regional cerebral blood flow but not metabolism.

We examined the effects of electrical and chemical stimulation of the Cl area of the rostral ventrolateral medulla (RVL) on regional cerebral blood flow (rCBF) and regional cerebral glucose utilization (rCGU) in anesthetized (chloralose), paralyzed (curare) and ventilated rats. rCBF and rCGU were measured using 14C-iodoantipyrine (IAP) and 14C-deoxyglucose (2-DG), respectively, as indicators, with bilateral regional dissection of 11 brain regions. Electrical stimulation of the RVL elicited increases in arterial pressure (AP), heart rate (HR) and plasma concentration of epinephrine (EPI) and norepinephrine (NE). In addition, stimulation of the RVL, but not the adjacent medial longitudinal fasciculus, with AP maintained, increased rCBF (p less than 0.05, n = 6), but not rCGU, bilaterally and symmetrically (134-169% of control) throughout the brain. Bilateral adrenalectomy abolished the increase in plasma EPI elicited by stimulation of the RVL but did not affect resting rCBF (n = 5) or the elevation in rCBF elicited by RVL stimulation (n = 5). Increases in rCBF elicited by RVL stimulation were also unaffected by acute transection of the superior cervical ganglion (p greater than 0.05). Kainic acid (KA) microinjected into the RVL unilaterally (n = 6) at a dose producing sustained elevation in AP (5 nmol in 100 nl), elicited changes in rCBF similar to those elicited by electrical stimulation. We conclude that neurons within the RVL, possibly those of the adrenergic Cl group, can initiate a global cerebrovasodilation, but not an increase in rCGU, largely through neural pathways intrinsic to the brain. The responses may represent activation of networks in RVL mediating circulatory adjustments to hypoxia.

Animals↗