NEUROGENIC PATHWAYS CONCERNED IN REFLEX VASODILATATION IN THE HAND WITH ESPECIAL REFERENCE TO STIMULI AFFECTING THE AFFERENT PATHWAY.
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Afferent Pathways↗
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Differential role of inhibition in habituation of two independent afferent pathways to a common motor output.
Many studies of the neural mechanisms of learning have focused on habituation, a simple form of learning in which a response decrements with repeated stimulation. In the siphon-elicited siphon withdrawal reflex (S-SWR) of the marine mollusk Aplysia, the prevailing view is that homosynaptic depression of primary sensory afferents underlies short-term habituation. Here we examined whether this mechanism is also utilized in habituation of the tail-elicited siphon withdrawal reflex (T-SWR), which is triggered by an independent, polysynaptic afferent pathway that converges onto the same siphon motor neurons (MNs). By using semi-intact preparations in which tail and/or siphon input to siphon MNs could be measured, we found that repeated tail stimuli administered in the presence of a reversible conduction block of the nerves downstream of the tail sensory neurons (SNs) completely abolished the induction of habituation. Subsequent retraining revealed no evidence of savings, indicating that the tail SNs and their immediate interneuronal targets are not the locus of plasticity underlying T-SWR habituation. The networks closely associated with the siphon MNs are modulated by cholinergic inhibition. We next examined the effects of network disinhibition on S-SWR and T-SWR habituation using an Ach receptor antagonist d-tubocurarine. We found that the resulting network disinhibition disrupted T-SWR, but not S-SWR, habituation. Indeed, repeated tail stimulation in the presence of d-tubocurarine resulted in an initial enhancement in responding. Lastly, we tested whether habituation of T-SWR generalized to S-SWR and found that it did not. Collectively, these data indicate that (1) unlike S-SWR, habituation of T-SWR does not involve homosynaptic depression of SNs; and (2) the sensitivity of T-SWR habituation to network disinhibition is consistent with an interneuronal plasticity mechanism that is unique to the T-SWR circuit, since it does not alter S-SWR.
Afferent Pathways↗
Multiplicity of the afferent pathways mediating the exercise pressor reflex.
The cardiovascular responses to isometric contraction of the triceps surae muscle of one leg were determined before and after transecting the ipsilateral L7 or L6 and S1 spinal roots. Sectioning only the L7 spinal root slightly attenuated the pressor, but not the heart rate response induced by skeletal muscle contraction, while cutting the L6 and S1 spinal roots (L7 intact) had no effect on the cardiovascular changes. This indicates that there is multiplicity in neural afferent pathways that mediate the exercise pressor reflex.
Animals↗
A P2X receptor-mediated nociceptive afferent pathway to lamina I of the spinal cord.
Of the six lamina regions in the dorsal horn of the spinal cord, lamina I is a major sensory region involved in nociceptive transmission under both physiological and pathological conditions. While P2X receptors have been shown to be involved in nociception, it remains unknown if P2X receptors are involved in nociceptive transmission to lamina I neurons. Using rat spinal cord slice preparations and patch-clamp recordings, we have demonstrated that the excitatory synaptic transmission between primary afferent fibers and lamina I neurons is significantly affected by ATP and alpha,beta-methylene-ATP. The synaptic effects of them include the increases of the frequency of both miniature excitatory postsynaptic currents (mEPSCs) and spontaneous EPSCs (sEPSCs), and decreases of evoked EPSCs (eEPSCs). These effects were blocked by pyridoxalphosphate-6-azophenyl-2', 4'-disulfonic acid (PPADS, 10 microM) and suramin (30 microM). In the neurons for which ATP and alpha,beta-methylene-ATP had effects on mEPSCs, sEPSCs and eEPSCs, capsaicin produced similar synaptic effects. Our results indicate that P2X receptors are expressed on many afferent fibers that directly synapse to lamina I neurons. Furthermore, these P2X receptor-expressing afferent fibers are capsaicin-sensitive nociceptive afferents. Thus, this study reveals a P2X receptor-mediated nociceptive afferent pathway to lamina I of the spinal cord and provides a new insight into the nociceptive functions of P2X receptors.
Adenosine Triphosphate↗
[Analgesic effect of pentazocine and its action on nociceptive afferent pathway].
Nociceptive stimulus was applied to the skin of adult cats by pinching with a serrated forceps or by radiant heat with Pain meter. This stimulation caused motor or emotional responses such as movements of the head and trunk, vocalization, escape and attack. After the administration of pentazocine, these responses disappeared and the animals behaved normally. Analgesic action appeared approximately 15 min after the administration and lasted more than 90 min. Effects of pentazocine on pain-afferent pathways were studied and the evoked potential was recorded by tibial nerve stimulation. Though pentazocine did not influence the evoked potential recorded from somatic sensory area I and mesencephalic central gray, the evoked potential in pre-central association area, nucleus centralis lateralis, nucleus suprageniculatus-limitans and reticularis pontis caudalis was reduced by pentazocine.
Afferent Pathways↗
Octreotide reduces perception of rectal electrical stimulation by spinal afferent pathway inhibition.
Octreotide reduces perception of rectal distension in normal volunteers and irritable bowel patients. To localize octreotide's site of action, perceptual and evoked potential responses to rectal electrical stimulation were tested in seven normal volunteers after double-blind octreotide (100 micrograms 2) or placebo. After octreotide, the currents needed to elicit threshold perception of square-wave impulses delivered to the rectum were 29% higher than after placebo. When electrical stimulation was delivered at constant currents 50% above threshold, rectal perception scores were significantly reduced after octreotide compared with placebo. Rectal electrical stimulation led to characteristic and reproducible cerebral evoked potentials. Octreotide had no effect on latencies, but reduced peak-to-peak amplitudes by 35% compared with placebo. Rectal electrical stimulation also led to characteristic and reproducible spinal evoked potentials. Octreotide had no effect on spinal latencies, but reduced peak-to-peak amplitudes by 51%. In conclusion, octreotide reduces perception of rectal electrical stimulation, which is associated with inhibition of cerebral and spinal evoked potential amplitude, indicating effects on spinal afferent pathways.
Adult↗
Functional integration of fetal cortical grafts into the afferent pathway of the rat somatosensory cortex (SmI).
The somatosensory area of fetal (E15-16) Sprague-Dawley rat neocortex was implanted into the barrel receptor area of adult first somatosensory cortex (SmI) to determine if it could be integrated into the host vibrissa-cortical pathway. Functional integration was tested 3-6 months later using the 2-deoxyglucose [44,45] (2-dg) method for estimation of glucose utilization. A variety of control grafts (cerebellum in SmI cortex, neocortex outside the host SmI cortex and appropriately placed neocortex in non-stimulated hosts) all had uniform 2-dg uptake (70 +/- 10 mumol/100 g/min) throughout each graft which averaged 42% less than non-stimulated host SmI cortex (121 +/- 6 mumol/100 g/min; p less than 0.001) but was 3-fold greater than white matter (24.8 +/- 3.1 mumol/100 g/min; p less than 0.001). In appropriately placed neocortical grafts, vibrissal stimulation produced 125% greater average 2-dg uptake (157 +/- 19 mumol/100 g/min) than control grafts (p less than 0.01). Such appropriately placed and stimulated neocortical grafts also contained focal areas of increased 2-dg uptake which were 43% greater than average graft uptake. These data suggest that fetal neocortical grafts were functionally integrated into the physiologically relevant afferent pathways of adult host brains.
Afferent Pathways↗
Antimuscarinic agents exhibit local inhibitory effects on muscarinic receptors in bladder-afferent pathways.
OBJECTIVES: To investigate the potential of antimuscarinic agents for sensory mechanisms in overactive bladder using intravesical instillation. METHODS: Antimuscarinic agents were instilled intravesically in rats using two protocols. In the high-dose protocol, 5 mg atropine, oxybutynin, and dimethindene (M2-selective muscarinic receptor antagonist) were instilled into the bladder, and cystometric parameters, such as bladder capacity, intercontraction interval, pressure threshold, and maximal voiding pressure were monitored. In the low-dose protocol, 0.1 and 0.5 mug/mL oxybutynin, trospium, tolterodine, and dimethindene were continuously infused into the bladder. The doses chosen were based on the calculated urine-excreted concentrations of trospium typically achieved from human oral treatment of 40 mg/day. The effect of carbachol with and without the low-dose agents was then assessed. RESULTS: With the high-dose protocol, bladder capacity, intercontraction interval, and pressure threshold were increased when atropine and oxybutynin were instilled, but not when dimethindene was used. The maximal voiding pressure was not affected by any of the agents tested. In the low-dose protocol, none of the cystometric parameters were altered with antimuscarinic agents alone. The intercontraction interval decreased with intravesical carbachol (65% +/- 0.1% compared with baseline), but this was prevented with concomitant antimuscarinic agents. CONCLUSIONS: We have separated the local inhibitory effects of antimuscarinic agents during the storage phase from a decrease in voiding pressure. Intravesical instillation of antimuscarinic agents at clinically meaningful concentrations also suppressed carbachol-induced bladder overactivity. Antimuscarinic agents may be effective in treating overactive bladder, not only by suppression of muscarinic receptor-mediated detrusor muscle contractions, but also by blocking muscarinic receptors in bladder-afferent pathways.
Acetylcholine↗
The spinal cord ventral root: an afferent pathway of the hind-limb pressor reflex in cats.
1. In anaesthetized cats the sciatic nerve was cut and the central end was stimulated at a high frequency and voltage. This caused an increase in arterial blood pressure and a rise in heart rate. The pressure response was diminished by dorsal root section but not completely eliminated until ventral root section (L4-S3). The tachycardia response was abolished by dorsal root section alone. 2. In other cats capsaicin was injected intra-arterially into the hind limb, causing elevations in both blood pressure and heart rate. Similar to the sciatic nerve stimulation experiments, the pressor response was principally reduced by dorsal root section but was further significantly decreased by ventral root section (L1-S3). The rise in heart rate was prevented by dorsal root section alone. 3. It is concluded that, in cats, the afferent pathway of the pressor response to sciatic nerve stimulation and to hind-limb capsaicin injection are conducted principally in the dorsal roots but also to a small extent in the ventral roots of the spinal cord. Although the tachycardia response appears to be conducted only through the dorsal roots, it is possible that at lower resting heart rates and by stimulation of a large population of the unmyelinated skeletal muscle afferents, the ventral root is a functional pathway.
Afferent Pathways↗
A model of status epilepticus based on electrical stimulation of hippocampal afferent pathways.
A new model of status epilepticus has been developed in the unanesthetized rat. The model involves repetitive tetanic stimulation of hippocampal afferent pathways. Pulse trains were delivered according to a fixed schedule (0.2 to 0.4-ms monophasic rectangular pulses, 20 Hz, stimulus current adjusted for maximal synaptic response in area CA3 of the hippocampus, 10-s train duration, 30-s intertrain interval) through electrodes chronically implanted in the angular bundle or fimbria. CA3 pyramidal cells responded to each stimulus in the train with little or no decrement. When 10 consecutive trains each produced 30 s of hippocampal afterdischarge, stimulation was terminated and self-sustained electrographic seizure activity was monitored. This procedure was repeated until it yielded at least 15 min of self-sustained seizure activity. Status epilepticus occurred in about 85% of subjects within less than 7 h. Self-sustained electrographic seizures were associated with limbic motor seizures and with brain lesions that resembled Ammon's horn sclerosis. This model holds promise for analyzing the biochemical and physiological bases of seizures, status epilepticus, and neuronal cell death, because the timing of these events during the stimulation protocol is fairly predictable and because seizures are self-sustaining without the need drugs, toxins, or prior kindling.
Animals↗
The effect of spreading cortical depression on activity of subcortical relay nuclei of specific afferent pathways.
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Afferent Pathways↗
Rectal heat thresholds: a novel test of the sensory afferent pathway.
PURPOSE: Currently, rectal sensation may be measured by balloon distention or mucosal electrostimulation. This study investigated the application of a graded heat stimulus to the rectum using a novel thermal probe as a further method of evaluating rectal sensory afferent mechanisms. METHODS: A thermal probe specially designed in our institution was used to test rectal heat sensitivity in 31 healthy subjects. This was compared with all other standard anorectal physiologic measurements. Repeatability studies were also performed. RESULTS: Heat stimulation of the mid rectum elicited sensory responses in all subjects. The most common reported response was not heat but a sharp or prickling sensation. The median rectal heat threshold was similar in males (median, 47 degrees C; range, 44-50 degrees C) compared with females (median, 45 degrees C; range, 43-50 degrees C; P > 0.05). There was a high degree of repeatability with rectal heat and balloon distention thresholds, but not electrostimulation thresholds. A strong correlation was found between rectal heat thresholds and defecatory desire (r = 0.71; P < 0.001) and maximum tolerable volumes (r = 0.8; P < 0.001) measured with balloon distention. CONCLUSION: This is the first demonstration of a repeatable sensory response to heat stimulation in the rectum of normal subjects. Strong correlation between heat thresholds and balloon distention to maximum tolerable volumes and defecatory desire suggest common sensory afferent pathway excitation. Heat stimulation is a simple technique that has a high degree of repeatability and may be an objective assessment of polymodal nociceptor function in the rectum.
Adolescent↗
Sensory processing in a thermal afferent pathway.
Extracellular recordings were made from cold-receptive afferent fibers in the trigeminal ganglion of rats anesthetized with halothane. By applying a standardized series of steady or changing temperatures to the receptive fields, we recorded the static and dynamic responses of the afferents. Comparable recordings were made from neurons in the marginal layer of the caudal trigeminal nucleus onto which the cold fibers synapse. The static and dynamic responses of the afferent fibers were reproduced faithfully by the second-order neurons, but at a much higher level of activity. Ganglionectomy silenced the second-order cells. Their continuous high level of activity appears to depend on the tonic input from the afferent fibers and not on any intrinsic circuits in the medulla.
Afferent Pathways↗
Cranial visceral afferent pathways through the nucleus of the solitary tract to caudal ventrolateral medulla or paraventricular hypothalamus: target-specific synaptic reliability and convergence patterns.
Cranial visceral afferents activate central pathways that mediate systemic homeostatic processes. Afferent information arrives in the brainstem nucleus of the solitary tract (NTS) and is relayed to other CNS sites for integration into autonomic responses and complex behaviors. Little is known about the organization or nature of processing within NTS. We injected fluorescent retrograde tracers into two nuclei to identify neurons that project to sites involved in autonomic regulation: the caudal ventrolateral medulla (CVLM) or paraventricular nucleus of the hypothalamus (PVN). We found distinct differences in synaptic connections and performance in the afferent path through NTS to these neurons. Anatomical studies using confocal and electron microscopy found prominent, primary afferent synapses directly on somata and dendrites of CVLM-projecting NTS neurons identifying them as second-order neurons. In brainstem slices, afferent activation evoked large, constant latency EPSCs in CVLM-projecting NTS neurons that were consistent with the precise timing and rare failures of monosynaptic contacts on second-order neurons. In contrast, most PVN-projecting NTS neurons lacked direct afferent input and responded to afferent stimuli with highly variable, intermittently failing synaptic responses, indicating polysynaptic pathways to higher-order neurons. The afferent-evoked EPSCs in most PVN-projecting NTS neurons were smaller and unreliable but also often included multiple, convergent polysynaptic responses not observed in CVLM-projecting neurons. A few PVN-projecting NTS neurons had monosynaptic EPSC characteristics. Together, we found that cranial visceral afferent pathways are structured distinctly within NTS depending on the projection target. Such, intra-NTS pathway architecture will substantially impact performance of autonomic or neuroendocrine reflex arcs.
Action Potentials↗
Release of glutamate and aspartate from the visual cortex of the cat following activation of afferent pathways.
To test the possibility that glutamate (Glu) and aspartate (Asp) are transmitters at geniculo-cortical synapses in the visual cortex of the cat, we studied the release of amino acids from the striate cortex consequent upon visual and electrical stimulation of the dorsal lateral geniculate nucleus (LGN) and of the optic tract, using push-pull cannulae. We perfused a discrete region that included layer IV of the cortex with an artificial cerebrospinal fluid (aCSF) and analysed the amino acid content of these perfusates by high-performance liquid chromatography (HPLC). Significant increases only of Glu and Asp were obtained among all 17 amino acids measured, except for gamma-aminobutyric acid (GABA), during electrical stimulation of the afferent pathways. Visual stimulation by stroboscopic diffuse flashes of light increased the level of Glu released, but did not change that of Asp significantly. The level of GABA released did not change during diffuse flash stimulation, suggesting that the increase in Glu was not derived from cortical neurons. The increases in release of Glu/Asp were not seen when the perfusion medium was replaced with a Ca2(+)-free, high-Mg2(+)-containing solution. The basal (resting) release of Glu/Asp in the absence of stimulation also was decreased during perfusion with Ca2(+)-free/high-Mg2+ solutions. Intraocular injections of a sodium channel blocker, tetrodotoxin (TTX), resulted in a remarkable decrease in the basal release of Glu. These results suggest that Glu is released as in excitatory synaptic transmitter at least from terminals of geniculo-cortical afferents and Asp from axons of a certain type of visual cortical neuron.
Animals↗
[Activity of neurons of the anterior thalamic nuclei after elimination of afferent pathways from the hippocampus and limbic cortex].
Neuronal activity of anterior thalamic nuclei AV and AD was analyzed in chronic rabbits after lesion of the fornix-fimbria or its combination with transection of the septum and capsula interna fibers at the rostral prethalamic level. The results were compared with previous data obtained in intact animals and after MTT lesion. Decrease of reactivity to sensory stimuli, "de-specialisation" of reactions (dominance of diffuse tonic effects and disappearance of patterned and phasic reactions) was observed in AV. The degree of the observed changes correlated with the volume of the lesioned limbic afferent pathways. Contrary to that, slight increase of reactivity to sensory stimuli was invariably present in AD. All characteristics of responses were preserved by the AD neurones after any type of limbic deafferentation. Only dynamic changes of reactions (gradual build-up and habituation) were absent in both nuclei after massive limbic deafferentations. The data support a previous conclusion that while AV is indeed an important integral link of the limbic circuit, AD should be regarded as relatively independent structure, introducing sensory information into limbic system and subjected to its secondary modulating influence.
Animals↗
The rubro-bulbospinal path. A descending system known to influence dynamic fusimotor neurones and its interaction with distal cutaneous afferents in the control of flexor reflex afferent pathways.
The inhibitory effect of electrical stimulation in the near-rubral region on polysynaptic segmental as well as ascending pathways activated by the flexor reflex afferents (FRA) in hind limb nerves was studied in chloralose anaesthetized cats. The effective stimulating region totally coincided with the one from which a D zone climbing fibre response may be elicited in the contralateral cerebellar cortex. The descending path was dependent upon an intact dorsolateral spinal funiculus, where also a characteristic volley could be recorded with a surface electrode on short train central stimulation. The suppressive action on the transmission through the FRA pathways was evoked in the absence of a lower lumbar dorsal root potential, and it was concluded that the effect was exerted by postsynaptic inhibition. It was suggested that this descending path, the effects of which resemble those elicited from the dorsal reticulospinal system, is identical to the rubro-bulbospinal path, previously known to influence dynamic fusimotor neurones. The transmission through the FRA pathways was also suppressed by conditioning stimulation of ipsilateral, low threshold distal cutaneous afferents. The time course of this effect was the same as that with central conditioning stimulation. Facilitatory interaction was revealed with double conditioning and it was suggested that the descending path and the distal cutaneous afferents converge upon a common group of interneurones, which postsynaptically inhibit an early (possibly the first one) interneurone in the FRA pathways. As low threshold distal cutaneous afferents supply the primary peripheral input via climbing fibres to the cerebello-cortical D zone, it was concluded that the different stimuli (central or peripheral) which activate a common group of inferior olivary neurones destined for the D zone also activate a common group of segmental inhibitory interneurones. The results are discussed in relation to current concepts of segmental motor control, and it is suggested that the mechanisms studied could be involved in the regulation of stepping.
Afferent Pathways↗
Influences on drugs on evoked potentials in the cat cerebellum: I. Effects of CNS depressants and stimulants on the cerebellar afferent pathways.
The effects of drugs on the potentials evoked by electrical stimulation on the sensorimotor area (SMA), nucleus reticularis tegmenti pontis (PTRN), nucleus reticularis lateralis (LRN), nucleus olivaris inferior (ION), or superficial radial nerve (SR) were investigated in cat cerebellar cortices. Pentobarbital-Na decreased the amplitude of the potentials evoked by all stimulations at every recording site. Pentobarbital-Na remarkably decreased the SMA- or PTRN-stimulation induced evoked potentials in the anterior lobe. Chlorpromazine decreased the amplitude of the potentials evoked by SMA stimulation on the anterior lobe and ipsilateral crus l, and the drug increased it on the posterior lobe and contralateral crus l. With precerebellar nuclei stimulations, chlorpromazine decreased the amplitude of the evoked potentials in cerebellar cortices, whereas SR stimulation-evoked potentials were remarkably increased in amplitude. Meprobamate increased the amplitude of the potentials evoked by precerebellar nuclei or SR stimulation at an early stage and then decreased it. Caffeine, picrotoxin, and strychnine remarkably increased the amplitude of the potentials in cerebellar cortices evoked by all stimulations. Strychnine in particular significantly increased the amplitude of the potentials evoked by SR stimulation. These results strongly indicate that CNS depressants and stimulants affect the cerebellar afferent pathways, probably in an indirect manner.
Animals↗