PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “STIMULATION AND STIMULI”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 199 records · Page 11Linked to original sources

[Nonspecific signal conduction modification in the cat ventrobasal thalamus].

Evoked unit activity of 83 neurons in the nuclei of ventralis posterior lateralis (VPL) in response to forelimb stimulation combined with the conditioning stimulation of the thalamic centrum medianum (CM) was examined in acute experiments on listenon-immobilized adult cats under nembutal anesthesia (20 mg/kg). 65 neurons responded to the peripheral stimulation with a latency of 5--7 ms (short-latent), the rest 18 neurons responded with a latency of 8--18 ms (long-latent). In 11 cases, the evoked responses with a latency of 2--8 ms were recorded under stimulation of CM with single stimuli. The conditioning stimulation of CM (patches of 4--5 impulses with a frequency of 200--250 Hz) resulted in the inhibition of evoked responses of 26 neurons to the testing stimuli applied to the forelimb over an interval of 20 to 180 ms. The maximum inhibitory effect under CM stimulation was demonstrated in long-latency neurons of VPL.

Animals↗

Nicotine stimulates expression of the PNMT gene through a novel promoter sequence.

Transcription of the gene encoding the epinephrine-synthesizing enzyme phenylethanolamine N-methyltransferase (PNMT, E.C. 2.1.1.28) accelerates in response to hormonal and neural stimuli. Cholinergic stimulation through neuronal nicotinic receptors constitutes the primary means for neural regulation of PNMT expression in the adrenal medulla (AM). Therefore, the regulatory sequence conveying responsiveness of the PNMT gene to nicotinic stimuli has been characterized in the 5' upstream region of the rat PNMT promoter. Functional analyses using nested deletion and substitution mutations of the PNMT promoter map the nicotine responsive region to a sequence spanning -633 to -595 bp, designated the PNMT nicotine-responsive element (NicRE). Sequences at the 5' (-633 to -620) and 3' (-599 to -595) ends of this region are essential to convey nicotine responsiveness to PNMT promoter constructs expressed in primary bovine chromaffin cells and in selected lines derived from mouse pheochromocytomas and human neuroblastomas. Profiles of nuclear proteins associating with PNMT promoter sequences also change following nicotine treatment of these cells. Electrophoretic mobility shift and DNase I footprinting analyses distinguish multiple sites of DNA-protein interactions within the NicRE region. Because the PNMT promoter does not contain a cAMP responsive element (the site through which nicotine stimulation is mediated for other catecholamine-synthesizing and AM genes), the NicRE of the PNMT gene must therefore be distinct. Thus, nicotinic cholinergic stimuli appear to regulate expression of the epinephrine-synthesizing gene PNMT through a previously uncharacterized regulatory element.

Adrenal Glands↗

Stereoselectivity of S- and R-sulpiride for pre- and postsynaptic dopamine receptors in the canine kidney.

The stereoselectivity of S (S)- and R (R)-sulpiride for the pre-(prereceptor) and post (postreceptor) synaptic dopamine receptors has been examined in various tissues. In the present study, the effects of S and R on the pre- and postreceptor in the canine kidney were investigated. The left renal artery of pentobarbital-anesthetized dogs was exposed and mean arterial pressure and renal blood flow were monitored. Vasoconstrictor stimuli [nerve stimulation: 1-8 Hz, 2 msec, 10-20 V, 5 sec; norepinephrine: 0.25-1.0 micrograms i.a.] were produced before and during graded doses of dopamine (DA: 0.3-2.4 micrograms/kg/min i.a.) administration. After a 15-minute recovery period, vasoconstrictor stimuli were repeated before and during the reinfusion of DA at the 2.4-micrograms/kg/min dose. While continuing DA, S or R (0.06-15.6 micrograms/kg/min) was administered and vasoconstrictor stimuli were repeated. DA antagonized the response to nerve stimulation but not norepinephrine (P less than .05). This effect of DA was antagonized by S at a dose of 0.12 micrograms/kg/min but not R. S and R alone did not affect the response to nerve stimulation. In dogs pretreated with phenoxybenzamine (5 mg/kg i.a.), DA produced a decrease in renal vascular resistance (P less than .05) and a dose of 15.6 micrograms/kg/min of either S or R was required to block this effect of DA. Therefore, S is 130 times more stereoselective for the prereceptor, whereas S and R are equipotent at the postreceptor in the canine kidney.

Animals↗

Similar increases in extracellular lactic acid in the limbic system during epileptic and/or olfactory stimulation.

Previous studies have shown that physiological stimulation of brain activity increases anaerobic glucose consumption, both in humans and in experimental animals. To investigate this phenomenon further, we measured extracellular lactate levels within different rat brain regions, using microdialysis. Experiments were performed comparing the effects of natural, physiological olfactory stimulation of the limbic system with experimental limbic seizures. Olfactory stimulation was carried out by using different odors (i.e. both conventional odors: 2-isobutyl-3-methoxypyrazine, green pepper essence; thymol; and 2-sec-butylthiazoline, a sexual pheromone). Limbic seizures were either induced by systemic injection of pilocarpine (200-400 mg/kg) or focally elicited by microinfusions of chemoconvulsants (bicuculline 118 pmol and cychlothiazide 1.2 nmol) within the anterior piriform cortex. Seizures induced by systemic pilocarpine tripled lactic acid within the hippocampus, whereas limbic seizures elicited by focal microinfusion of chemoconvulsants within the piriform cortex produced a less pronounced increase in extracellular lactic acid. Increases in extracellular lactate occurring during olfactory stimulation with the sexual pheromone (three times the baseline levels) were non-significantly different from those occurring after systemic pilocarpine. Increases in lactic acid following natural olfactory stimulation were abolished both by olfactory bulbectomy and by the focal microinfusion of tetrodotoxin, while they were significantly attenuated by the local application of the N-methyl-D-aspartate antagonist AP-5. Increases in hippocampal lactate induced by short-lasting stimuli (olfactory stimulation or microinfusion of subthreshold doses of chemoconvulsants, bicuculline 30 pmol) were reproducible after a short delay (1 h) and cumulated when applied sequentially. In contrast, limbic status epilepticus led to a long-lasting refractoriness to additional lactate-raising stimuli and there was no further increase in lactate levels when the olfactory stimulation was produced during status epilepticus. Increases in lactic acid following olfactory stimulation occurred with site specificity in the rhinencephalon (hippocampus, piriform and entorhinal cortex) but not in the dorsal striatum. Site specificity crucially relied on the quality of the stimulus. For instance, other natural stimuli (i.e. tail pinch) produced a similar increase in extracellular lactate in all brain areas under investigation. The major conclusion of this work is that the presentation of an odor known to be a rat pheromone results in lactate production as great as that induced by the systemic convulsant pylocarpine (maximum: 2.286+/-0.195 mM and 1.803+/-0.108 mM, respectively). This supports the notion that the great magnitude of lactate production known to accompany seizures can result from the intensified neural activity per se ("aerobic gycolysis"), not merely from local anoxia or other pathological changes.

2-Amino-5-phosphonovalerate↗

Role of the thalamus in the bilateral regulation of dopaminergic and GABAergic neurons in the basal ganglia.

In halothane-anaesthetized cats implanted with several push-pull cannulae the release of dopamine from nerve terminals and dendrites of the two nigrostriatal dopaminergic pathways is shown to be asymmetrically or symmetrically regulated bilaterally when dopaminergic or GABAergic drugs are infused into one side of the nigra. Nigrothalamic GABAergic neurons may intervene in the asymmetrical regulation, as sagittal section of the thalamic massa intermedia blocks the contralateral effects induced by dopaminergic drugs. The role of thalamic nuclei in the bilateral regulation of dopamine and GABA release in the caudate nucleus and substantia nigra is further demonstrated by studies showing that (1) electrical stimulation of thalamic motor nuclei induces bilateral asymmetrical changes in dopamine release resembling the changes evoked by unilateral sensory stimuli or stimulation of cerebellar nuclei; (2) electrical stimulation of intralaminar or some midline thalamic nuclei leads to bilateral (or contralateral) symmetrical changes in dopamine release, some of these effects being comparable to those induced by unilateral stimulation of the motor cortex; (3) unilateral lesions of motor or intralaminar thalamic nuclei reverse the changes in GABA release in the contralateral caudate nucleus or substantia nigra induced by unilateral infusion of muscimol into the nigra; and (4) unilateral infusion of GABA into thalamic motor nuclei induces bilateral symmetrical regulation of dopamine release in caudate nuclei by means of presynaptic facilitatory influences.

Animals↗

Autonomic influences on colorectal motility and pelvic surgery.

The nervous control of the motility of the human distal bowel was investigated by two physiological studies of electrical stimulation of sacral parasympathetic outflow in patients with high spinal injuries and in patients with intractable constipation following pelvic surgery. Identical and reproducible motility responses of the left colon, rectum, and anal sphincters were obtained by sequential electrical stimulation of anterior sacral roots S2, S3, and S4 in patients with spinal injury. S2 stimulation provoked isolated low-pressure colorectal contractions. S3 stimulation initiated frequency-dependent high-pressure colorectal motor activity which appeared peristaltic and was enhanced with repetitive stimuli. S4 stimulation increased colonic and rectal tone. Quantitative responses were maximal at the splenic flexure and rectum. Pelvic floor activity was stimulated in increasing magnitude from S2 to S4. These results of distal bowel motility were achieved by an implanted Brindley stimulator. A newer generation of externally active stimulators are envisaged for the control of lower bowel in fecal incontinence. Women with intractable constipation following hysterectomy had significantly increased rectal volume and compliance together with deficits of rectal sensory function. Following stimulation with Prostigmine (neostigmine) a colorectal motility gradient was paradoxically reversed in the patients following hysterectomy, thus constituting a functional obstruction. Denervation supersensitivity was demonstrable in 2 patients tested with carbachol provocation. These findings suggest dysfunction in the autonomic innervation of the hindgut in some patients following hysterectomy.

Adult↗

Impaired bronchomotor responses to field stimulation in guinea-pigs with cisplatin-induced neuropathy.

Pre-treatment with cisplatin (3 mg/kg) i.p. once a day over 6 days induced sensory neuropathy as confirmed by femoral nerve conduction velocity test and significantly decreased contractions induced by electrical field stimulation (100 stimuli, 20 V, 0.1 ms, 20 Hz) in isolated main bronchial rings from guinea-pigs. The field stimulation-induced non-adrenergic, non-cholinergic (NANC) relaxations, however, were amplified in rings from animals with cisplatin neuropathy. The NANC relaxation response was completely blocked by 30 microM N(G)-nitro-L-arginine methyl ester in preparations from both control and cisplatin-treated animals. Superoxide dismutase (40 units/ml) was without effect on NANC relaxation in control rings, however, it substantially decreased NANC relaxation in preparations from animals with cisplatin neuropathy. These results show that cisplatin-induced sensory neuropathy is accompanied by attenuation of neural bronchoconstriction and an enhanced NANC relaxation. The latter is in part attained by an increased peripheral superoxide production.

Animals↗

Action of brain stem reticular afferents on lagged and nonlagged cells in the cat lateral geniculate nucleus.

1. The A-laminae of the cat lateral geniculate nucleus (LGN) contain two distinct groups of relay neurons: lagged and nonlagged cells. The groups differ in the pattern, timing, and amplitude of response to flashing spots. At spot onset, nonlagged cells discharge at short latency with an excitatory transient; in lagged cells this transient is supplanted by an inhibitory dip and a delayed latency to discharge. At spot offset, lagged cell discharge decays more slowly than in nonlagged cells. Here we have investigated the facilitatory influence of the brain stem reticular formation on the response properties of lagged X-cells (XL) and nonlagged X- and Y-cells (XN and YN). We were particularly interested in whether the inhibitory dip and sluggish response of lagged cells could be reversed during brain stem activation and the cells induced to respond like nonlagged cells. The peribrachial region (PB) of the pontine reticular formation was stimulated electrically with the use of 1,100-ms-long pulse trains that were paired with flashing spot stimuli. 2. Stimulation of PB led to an increase in the amplitude of visually evoked discharge in lagged and nonlagged cells. Compared with their response to spot stimulation alone, the average PB-evoked increase in mean discharge rate was greater than 50% in both groups. The mean discharge rate during PB plus spot stimulation was somewhat higher for XN-cells than for YN- and XL-cells, reflecting the relatively higher discharge rate among XN-cells during spot stimulation alone. 3. Two measures of response timing characterize lagged and nonlagged cells: latency to half-maximal discharge at spot onset (half rise) and latency to half-minimal discharge at spot offset (half fall). Among XN- and YN-cells, PB stimulation had no significant effect on these two latencies; among XL-cells, both latencies were reduced by 43 and 35%, respectively, on average. 4. During spot stimulation alone, all lagged cells were distinguishable from all nonlagged cells in having half-rise and half-fall latencies greater than 60 ms. Despite the reduction among XL-cells in these 2 latencies during PB stimulation, all but 2 of the 40 XL-cells maintained laggedlike latencies. The majority (95%) of XL-cells remained unambiguously lagged on these measures during brain stem stimulation. 5. During spot stimulation alone, 30 of 40 XL-cells tested displayed a prominent and often long-lasting inhibitory dip in discharge starting approximately 45 ms after spot onset. During PB stimulation only three cells lost the dip.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Facilitation of female reproductive behavior from mesensephalic central gray in the rat.

Electrical stimulation in the mesencephalic central gray (CG) and adjacent subtectum through chronically implanted electrodes in free-moving estrogen-primed ovariectomized female rats elicited a rapid and large facilitation of the lordosis reflex in response to either male mounts or manula cutaneous stimuli. Unilateral stimulation was sufficient for this effect. The facilitation increased in a graded manner to increased stimulus intensity, and was optimally evoked by stimuli delivered at 50--150 Hz. Facilitation disappeared rapidly following the end ot electrical stimulation, and within 15 min, reflex performance returned to the prestimulation level. Lordosis facilitation appeared when no aversive responses occurred; stimulation with comparable parameters at the lateral edge of CG or in the mesencephalic reticular formation often resulted in postural changes or aversive responses but was not able to facilitate lordosis. Lordosis refelx facilitation was probably mediated by projections descending from neurons in and around the CG, and represents stimulation of a functional link between ascending somatosensory and descending motor systems for the control of lordosis behavior.

Animals↗

Responsiveness of human nasal mucosa to trigeminal stimuli depends on the site of stimulation.

There is evidence that functionally different areas can be distinguished within the nasal mucosa with regard to stimulation site and stimulus properties. The aim of the present study was the comparison of electrophysiological and psychophysical measures obtained in response to mechanical and chemosomatosensory stimulation of two different regions of the nasal mucosa. A total of 40 volunteers participated in this study (age range 21-36 years). Chemosomatosensory event-related potentials (ERPs) were recorded using gaseous CO2 as stimulant, while somatosensory ERPs were recorded in response to intranasal mechanical stimuli (air puffs). Stimuli were released to the anterior portion and to the posterior portion of the nasal cavity. A significant interaction between stimulus properties and site of stimulation could be detected after analysis of ERP parameters and intensity ratings. Thus, the chemosensory stimulus was perceived as stronger in the anterior portion of the nasal cavity whereas this was not the case for mechanosensory stimuli. In addition, mechanosensory stimuli were found to evoke ERPs with shorter latencies. These results underline the idea that the respiratory mucosa should not be seen as a homogeneous tissue. It exhibits varying sensitivities to trigeminal stimulation depending on stimulus quality and site of stimulation. Hence, perception of chemosensory stimuli seems to be most accurate in the anterior portion of the nasal cavity, while sensitivity to mechanical stimuli appears to be highest in the posterior portion. In addition, these differences within the respiratory mucosa may contribute to differences in the perception of orthonasal and retronasal odorous stimulation.

Adult↗

Temporal analysis of cortical mechanisms for pain relief by tactile stimuli in humans.

The mechanisms by which vibrotactile stimuli relieve pain are not well understood, especially in humans. We recorded cortical magnetic responses to paired noxious (intra-epidermal electrical stimulation, IES) and innocuous (transcutaneous electrical stimulation, TS) stimuli applied to the back at a conditioning-test interval (CTI) of -500 to 500 ms. Results showed that IES-induced responses were remarkably attenuated when TS was applied 20-60 ms later and 0-500 ms earlier than IES (CTI = -60 to 500 ms). Since the signals evoked by IES reached the spinal cord (CTI = -60 to -20 ms conditions) and the cortex (-60 and -40 ms condition) earlier than those evoked by TS, the present results indicate that cortical responses to noxious stimuli can be inhibited by innocuous tactile stimuli at the cortical level, with minimal contribution at the spinal level.

Adaptation, Physiological↗

Measuring threshold of reinforcing brain stimulation by the method of constant stimuli.

A new method for measuring threshold of reinforcing electrical brain stimulation is described and results of a parametric study using this method are presented. Two groups of rats were trained under a concurrent FR-CRF (fixed ratio-continuous reinforcement) schedule of reinforcement provided by electrical stimulation of the lateral hypothalamus. The invariant intermittent FR schedule of reinforcement was used to maintain a baseline of behavior while a superimposed concurrent CRF schedule was used to measure reinforcement magnitude by varying the intensity of the CRF stimulus between zero and a maximum. Increasing and decreasing stimulus intensity on the CRF schedule leads to a gradual disappearance, respectively reappearance, of post-reinforcement pauses (PRPs) on the concurrent FR schedule, providing a criterion for changeover in schedule control, and thus, for threshold of reinforcement. To illustrate the measurement of threshold according to psychophysical requirements of the Method of Constant Stimuli, different CRF intensities were given in a randomized order. In one group of animals FR and CRF stimuli were given through the same electrode. Another group received FR and CRF stimuli through separate electrodes implanted in different hemispheres of the brain. For both groups the duration of the PRP was used as the dependent variable. The data of both groups showed a high negative correlation between the intensity of the CRF stimulus and the duration of the PRP, which is consistent with the results of experiments in which a Method of Limits procedure was used. On the basis of this relationship between CRF current intensity and PRP duration a threshold for reinforcing brain stimulation was calculated.

Animals↗

Spinal dorsal horn neuron response to mechanical stimuli is decreased by electrical stimulation of the primary motor cortex.

Motor cortex stimulation (MCS) has been used clinically as a tool for the control for central post-stroke pain and neuropathic facial pain. The underlying mechanisms involved in the antinociceptive effect of MCS are not clearly understood. We hypothesize that the antinociceptive effect is through the modulation of the spinal dorsal horn neuron activity. Thirty-two wide dynamic range spinal dorsal horn neurons were recorded, in response to graded mechanical stimulation (brush, pressure, and pinch) at their respective receptive fields, while a stepwise electrical stimulation was applied simultaneously in the motor cortex. The responses to brush at control, 10 V, 20 V, and 30 V, and recovery were 11.5+/-1.6, 12.1+/-2.6, 11.1+/-2.2, 10.5+/-2.1, and 13.2+/-2.5 spikes/s, respectively. The responses to pressure at control, 10 V, 20 V, and 30 V, and recovery were 33.2+/-6.1, 22.9+/-5.3, 20.5+/-5.0, 17.3+/-3.8, and 27.0+/-4.0 spikes/s, respectively. The responses to pinch at control, 10 V, 20 V, and 30 V, and recovery were 37.2+/-6.4, 26.3+/-4.7, 25.9+/-4.7, 22.5+/-4.3, and 35.0+/-6.2 spikes/s, respectively. It is concluded that, in the rat, electrical stimulation of the motor cortex produces significant transient inhibition of the responses of spinal cord dorsal horn neurons to higher intensity mechanical stimuli without affecting their response to an innocuous stimulus.

Action Potentials↗

Secondary epileptogenesis in frog forebrain: effect of inhibition of protein synthesis.

Secondary epileptogenesis was induced in the hippocampal cortex of the paralyzed bullfrog by means of localized, unilateral, intermittent electrical stimulation (kindling). Stimuli were designed to yield a brief but definite after-discharge. In control animals a progressive increase in after-discharge duration occurred at the 1 degree (stimulated) site and then at the 2 degrees site (contralateral hippocampus). Spontaneous epileptiform potentials (SEP's) occurred between stimuli, eventually independently on both sides. Cycloheximide (50 mg/kg) caused 88-99% reduction in protein synthesis, measured by 14C-leucine incorporation into brain protein. Cycloheximide-treated animals revealed no evidence of progressive prolongation of after-discharge duration when subjected to the kindling procedure (p = 0.1205 X 10(-7)). SEP's were reduced in the cycloheximide-treated animals, and confined to 1 degree hemisphere (p = 0.6 X 10(-10)). Since cycloheximide did not disturb normal electrogenesis or disrupt the after-discharges, this experiment distinguishes processes dependent upon electrical events from those requiring macromolecular synthesis. Protein synthesis seems critical to the emergence of spontaneous and autonomous epileptiform behavior of neural aggregates.

Animals↗

Analysis of polyunsaturated aminophospholipid molecular species using isotope-tagged derivatives and tandem mass spectrometry/mass spectrometry/mass spectrometry.

When aminophospholipids with only saturated and monounsaturated fatty acids esterified to the glycerol backbone were labeled with isotopically enriched N-methylpiperazine acetic acid N-hydroxysuccinimide ester reagents, it was found that they could be readily detected as N-methylpiperazine-amide-tagged aminophospholipids using a precursor scan of the stable isotope reporter ion (m/z 114-117) formed by tandem mass spectrometry/mass spectrometry. However, it was found in the current study that these precursor ion scans are not useful in determining the changes of aminophospholipids with polyunsaturated fatty acids (PUFAs) esterified to the glycerol backbone due to the presence of interfering ions in the reporter ion region. Therefore, a method was developed using tandem mass spectrometry/mass spectrometry/mass spectrometry (MS(3)) to obtain reporter ion ratios that were not distorted by interfering ions present in the collision-induced dissociation spectra of nontagged aminophospholipids with PUFAs. This new MS(3) method for N-methylpiperazine- amide-tagged aminophospholipids was used to examine the fate of diacyl, ether, or plasmalogen glycerophosphoethanolamine (GPEtn) species after exposure of human polymorphonuclear leukocytes to A23187 and granulocyte macrophage-colony-stimulating factor/formyl-methionyl-leucyl-phenylalanine stimuli, which can induce eicosanoid biosynthesis, to follow those GPEtn molecular species which were the source of arachidonic acid released. Upon stimulation of the human polymorphonuclear leukocyte, it was found that the abundant arachidonoyl GPEtn plasmalogen molecular species were uniquely reduced in relative content compared to ether or diacyl species and this subclass of GPEtn may be a source of the arachidonic acid converted to leukotrienes by the 5-lipoxygenase pathway activated in this cell.

Calcimycin↗

Regulation of the oxidative response of human granulocytes to chemoattractants. No evidence for stimulated traffic of redox enzymes between endo and plasma membranes.

Experiments were performed to probe the role of exocytotic and endocytotic processes in the regulation of the human granulocyte O-2-generating system. Analytical subcellular fractionation studies indicated that 25-30% of the total cellular b-cytochrome and 8-10% of the flavin co-sedimented with plasma membrane markers, irrespective of stimulation of the cells by the chemoattractants N-formyl-Met-Leu-Phe (FMLP) or C5a. Phorbol myristate acetate stimulation resulted in significant translocation of b-cytochrome but not flavin from the specific granule/Golgi to the plasma membrane-enriched fractions. These results indicated that approximately 3.1 X 10(5) flavin and 0.8-1 X 10(6) b-cytochrome molecules are present in the plasma membrane of an isolated unstimulated human granulocyte and that these levels are invariant upon stimulation with chemoattractants. Maximal instantaneous rates of O-2 generation by cells in these preparations, however, were equivalent for all the stimuli. Since stimulation of granulocytes by phorbol myristate acetate, FMLP, or C5a results in exocytosis and/or endocytosis, then the role of these processes in regulating stimulated O-2 production by controlling the content of plasma membrane redox enzymes is questionable. This conclusion was supported by observations made with cytoplasts, which do not have an intracellular reserve of granules. Cytoplasts prepared from granulocytes produced O-2 at equivalent rates as their parent cells on a per unit surface area basis. These results suggest: 1) that stimulation of granulocytes with chemotactic peptides leads to full generation of O-2 at the cell surface without exocytotic recruitment of additional b-cytochrome and flavoprotein from the cytoplasmic compartment; 2) that these redox enzymes are not internalized along with chemoattractant receptors; and 3) that traffic of these redox enzymes between endo- and plasma membranes is not involved in the regulation of O-2 production in suspensions of human granulocytes stimulated by chemoattractants.

Cell Fractionation↗

A two-dimensional simulation of the effects of late stimulation on a cardiac action potential.

The response of cardiac tissue to a stimulus delivered late in the action potential (AP) is important in studies of defibrillation and certain models of ischemia in which reentrant trajectories produce such stimulation. Such stimuli are often strong and delivered in complex spatial arrangements. In this work a two-dimensional computer simulation of a thin, flat layer of cardiac tissue subjected to rather small sizes of late stimulation delivered at a simple point has been performed. The calculation covered a plane of 95 x 140 space units of 72 u each and the stimulus was near the center. The Drouhard and Roberge version of the physiological routine due to Beeler and Reuter was used in an anisotropic bidomain model of the tissue. Late stimuli of either polarity were applied from 150 to 250 msec after initiation of the AP. Depolarizing (positive) voltage stimuli produced small positive voltage peaks, narrowly localized in space, which decayed with a time constant of 8 to 10 msec. Repolarizing (negative) stimuli, if not applied too late in the AP, produced, after a variable delay, a depolarizing fast sodium peak, which was also positive and spatially quite localized. It decayed quickly so that little effect on the AP duration was found. Since stimuli were of limited size and spatial extent in this study the small effects found here are expected but they indicate that major effects from late stimulation require strong pulses and/or large electrode arrays.

Action Potentials↗

Dopaminergic inhibition from substantia nigra of caudate neurons activated by cortical stimulation.

Studies were performed to elucidate the role of dopamine originating in the pars compacta of the substantia nigra (SN) on caudate nucleus (CN) neurons receiving input from the motor cortex using cats anesthetized with alpha-chloralose. Activation with cortical stimulation was observed in 50 CN neurons, five out of which also excited by SN stimulation. Conditioning stimuli applied to the SN, 30 msec preceding the test stimulus to the cortex, produced a significant inhibition of spike generation upon cortical stimulation in 28 out of 45 neurons tested and did not affect the remaining 17 neurons. The mean spike number of the 45 neurons was significantly reduced with SN conditioning stimulation. When dopamine up to 200 nA was iontophoretically applied to CN neurons, there was a significant inhibition of the spike generation with cortical stimulation in 9 out of 16 neurons. The mean spike number of the 16 neurons upon cortical stimulation was significantly reduced during dopamine application. In addition, a close correlation was observed between the effects of SN conditioning stimulation and iontophoretic dopamine. These results suggest that dopamine derived from the SN produces an inhibition of CN neurons receiving input from the motor cortex.

Animals↗