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Functional organization of trigeminal subnucleus interpolaris: nociceptive and innocuous afferent inputs, projections to thalamus, cerebellum, and spinal cord, and descending modulation from periaqueductal gray.

In view of continuing uncertainties concerning the organization, afferent inputs, and projection sites of neurons in the subnucleus interpolaris of the trigeminal (V) spinal tract nucleus, the characteristics of 222 single neurons in and adjacent to the subnucleus were examined electrophysiologically in adult cats anesthetized with chloralose. Neurons were tested for orthodromic responsiveness to a variety of stimuli that included nonnoxious tactile stimuli, noxious mechanical and radiant-heat stimuli, and graded electrical stimulation of the skin, mucosa, tooth pulp, and masseter nerve. Antidromic activation techniques were also used to determine if the functionally identified neurons projected directly to the contralateral posterior thalamus, ipsilateral cerebellum, or cervical spinal cord. In addition, the periaqueductal gray matter (PAG) was stimulated to test for conditioning influences from the PAG on orthodromic responses to noxious and nonnoxious oral-facial stimuli. Interpolaris neurons were somatotopically arranged in subnucleus interpolaris in a pattern conforming in general to the medially facing, inverted-head representation characteristic of other parts of the V brain stem sensory nuclear complex. On the basis of their responsiveness to cutaneous stimuli, the neurons could be functionally classified as either cutaneous nociceptive or low-threshold mechanoreceptive (LTM) neurons. The LTM neurons constituted the major neuron type, accounting for over 75% of our neuron sample. Most of them had a localized mechanoreceptive field of less than 100 mm2 in area that was restricted to one V division, and they had skin-evoked response latencies indicative of afferent input predominantly from A-beta cutaneous afferents. A population of nociceptive neurons was also encountered in the lateral, marginal region of interpolaris and at its medial or ventral border with the reticular formation. These neurons were of two types: nociceptive-specific (NS) neurons, which did not respond to nonnoxious stimuli but which required noxious stimuli for their activation; and wide dynamic range ( WDR ) neurons, which responded to both noxious and nonnoxious stimuli applied to the facial skin. Most had an ipsilateral receptive field that was greater than 100 mm2 in area and that often involved two or three V divisions. Their properties generally conformed to those previously described for nociceptive neurons in the medullary dorsal horn (V subnucleus caudalis) and spinal cord dorsal horn. Interpolaris neurons of all classes (LTM, WDR , and NS) were found to have direct axonal projections to the thalamus, cerebellum, and spinal cord.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

Single fibre motor evoked potentials to brain, spinal roots and nerve stimulation. Comparisons of the 'central' and 'peripheral' response jitter to magnetic and electric stimuli.

Single fibre motor evoked potentials to magnetic and electric non-invasive stimulation of brain, spinal cord and peripheral nerve were recorded in 8 healthy volunteers. The 'central motor jitter' and the 'peripheral motor jitter' were respectively calculated and a comparison between the magnetic and electric modalities was made. The highest degree of latency variability was observed for both magnetic and electric central motor jitter, whilst the peripheral motor jitter to nerve stimulation was as low as the neuromuscular one (range 16-60 microsecond). The magnetic 'central motor jitter' (range 94-1024 microsecond) was much larger than the electric one (range 55-280 microsecond), which was in the order of jitter calculated on H-reflex studies; moreover, the former was organized in a bi- or trimodal distribution. On the contrary, no significant differences were observed between the two modalities when the jitter to nerve stimulation was taken into account. Possible contributions of corticocortical circuitries containing several synaptic interruptions during magnetic as opposed to electric transcranial stimulation, is discussed.

Adult↗

Induction of atrial natriuretic factor and myosin light chain-2 gene expression in cultured ventricular myocytes by electrical stimulation of contraction.

While hormonal stimuli and mechanical stretch can induced cardiac-specific gene expression and in some cases cellular hypertrophy, the relationship between myocyte contraction frequency, gene expression, and myocyte growth has not been well characterized. In this study a new model system was developed in which cultures of neonatal rat ventricular myocytes were subjected to long term pacing of contractions with pulsatile electrical stimulation. Myocytes submitted to electrical stimulation for 3 days displayed dramatic increases in cellular size and myofibrillar organization, and a 5-10-fold increase in the expression of the cardiac genes atrial natriuretic factor and myosin light chain-2. Atrial natriuretic factor expression induced by electrical stimulation of contractions was inhibited by nifedipine or W7, indicating a dependence on calcium influx and calmodulin activity. Phosphoinositide hydrolysis and cAMP formation were not affected by electrical stimulation suggesting that gene induction occurred independently of the activation of protein kinases C or A above basal levels. These findings show that the cellular events associated with contraction, such as changes in cytoplasmic free calcium levels and/or cellular stretch, may serve as important determinants of myocyte growth and cardiac gene expression.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Comparative investigation of retinal responses to brief light stimuli: 2-amino-4-phosphonobutyrate studies--II. Turtle retina (Emys orbicularis).

1. Electroretinogram (ERG) and responses of single ganglion cells to 75 microseconds light flashes, presented on two different backgrounds, were studied. Additionally, stimulation with long lasting stimuli (ordinarily 5 sec ON-, 15 sec OFF-) was used. 2. 2-amino-4-phosphonobutyrate (APB) at a concentration of 450 microM on average was used to separate OFF- from ON- channels. It is known, that in other species APB selectively blocks the activity of ON- channel only. 3. The existence of APB- sensitive membrane receptors was demonstrated in the turtle retina. As in other species, APB abolished the ERG b-wave and enhanced the d-wave, when long lasting stimulation was used. 4. By means of APB, two components were shown to exist in the ERG positive wave in response to a flash. APB abolished the first component and did not influence or enhanced the second one. 5. By means of APB, one or two components in the impulse activity in response to flash were demonstrated, depending on the type of ganglion cell (ON-, OFF- or ON-OFF). The latency of the first component was 70 msec and the latency of the second one 210 msec on average. APB abolished the first component, and enhanced the second one. 6. The data obtained show that both ON- and OFF- channels take part in the generation of the turtle retinal responses to brief stimuli. 7. Based on the results obtained, some peculiarities of the network organization of the ganglion cells' receptive fields are discussed.

Action Potentials↗

Morning to evening changes of human pituitary and adrenal responses to specific stimuli.

We performed a combined stimulation test with the simultaneous application of GnRH (100 micrograms), TRH (200 micrograms) and ACTH (10 micrograms) in 10 healthy adult males at two opposite clock timing, i.e. at 09:00 and 21:00 h. Pituitary (gonadotropins, PRL, TSH) and adrenal (cortisol, aldosterone, progesterone) hormones showed a common trend of enhanced responsiveness to the evening challenge. Differences reached statistical significance in the case of cortisol, aldosterone, PRL and FSH. These findings suggest that the responsiveness of some pituitary and adrenocortical hormones to specific stimuli is physiologically different in humans as a function of the clock timing, being higher in the evening than in the morning. From the clinical standpoint, however, differences in the magnitude of responses were not enough to recommend provocative testing at a particular clock time, at least for routine diagnostic purposes.

Adrenal Glands↗

Response patterns to noxious and non-noxious stimuli in rostral trigeminal relay nuclei.

Postimulus time histogram analysis of second-order neuron responses in rostral trigeminal relay nuclei of cat demonstrated characteristic firing patterns after noxious (tooth pulp) and non-noxious (tooth tap) stimuli. The response to noxious stimulation was prolonged and frequently bimodal while the response to non-noxious stimulation was brief. The same neurons were fired by electrical stimuli applied directly to nucleus caudalis but with longer latencies suggesting a contributory role of nucleus caudalis to the characteristic prolonged bimodal response pattern to noxious stimuli. Interacting noxious and non-noxious stimuli using condition-test sequences demonstrated further stimulus mode-related changes in firing patterns. Electrical conditioning stimuli in nucleus caudalis reduced some responses while strychnine sulfate applied into nucleus caudalis augmented the responses evoked in rostral nuclei by both noxious and non-noxious peripheral stimuli. Nucleus caudalis appeared to contain elements which may modulate activity in rostral trigeminal nuclei by either augmenting or reducing specific firing patterns of second-order neurons in rostral relay nuclei.

Animals↗

Electrocortical, autonomic, and subjective responses to rhythmic audio-visual stimulation.

The present study was designed to test the hypothesis that varying sensory input can affect mood, autonomic arousal, and electrocortical activity. Twenty right-handed males were exposed to three rhythmic audio-visual stimulation programs, with either a high intensity and variety of stimuli (program H), a low stimulation (program L) or with a transient from high to low (program HL). Multichannel EEG, heart rate, and skin conductance were recorded continuously, and after each trial mood was rated on a bipolar adjective list. EEG data were subjected to FFT dipole approximation procedure, and dipole locations and field strength (Global Field Power) were analyzed for the frequency bands theta, alpha, and beta 1. Mood ratings clearly differed between programs H and HL, with highest values of arousal after H. Programs L and HL decreased autonomic arousal, whereas H induced deactivating as well as activating effects. Field strength of the alpha band decreased similarly during all programs. Dipole sources were located more to the left in the alpha band and more to the right in the beta 1 band during all programs as compared with baseline. Therefore, programs affected mood and autonomic variables differently, but not electrocortical variables. The higher activation of the right hemisphere during all programs is interpreted as an indication that audio-visual stimulation does induce changes in the brain, such as are commonly found in altered states of consciousness.

Acoustic Stimulation↗

Learning about sex: conditioning of partner preference: theoretical comment on Coria-Avila et Al. (2005).

Sexual partner preference in female rats has been difficult to establish experimentally because the vaginocervical stimulation the female receives during the preference test can be rewarding or aversive depending on the context. G. A. Coria-Avila, A. J. Ouimet, P. Pacheco, J. Manzo, and J. G. Pfaus (2005) reported that female rats can be conditioned to show partner preference for a male that is scented with a sexually neutral odor if they are mated repeatedly with that male in a paced mating test. These results suggest that establishment of a partner preference depends on rewarding characteristics of the vaginocervical stimulation the female receives during an initial mating and that selection of a sexual partner can be determined by olfactory stimuli associated with that stimulation. These results are discussed within the context of the appetitive-consummatory construct of sexual behavior and the evolutionary significance of conditioned partner preference.

Animals↗

GABAB receptors mediate frequency-dependent depression of excitatory potentials in rat perirhinal cortex in vitro.

Excitatory synaptic transmission in the perirhinal cortex exhibits marked homosynaptic paired pulse depression (PPD) at inter-pulse intervals between 100 and 1000 ms, being maximal at 200 ms. Additionally, there is greater PPD with stimulation of the pathway from the temporal cortex side than with stimulation of the pathway from the entorhinal cortex side. We establish that this frequency-dependent depression relies on the activation of GABAB (gamma-aminobutyric acid) receptors. PPD in both temporal and entorhinal pathways is abolished by either of the selective GABAB receptor antagonists, 3-N[1-(S)-(3, 4-dichlorophenyl)ethyl]amino-2-(S)-hydroxypropyl-p-benzyl-phosphinic acid (CGP55845A) or 3-amino-propyl(diethoxymethyl)phosphinic acid (CGP35348). Barium which blocks G-protein-coupled, inwardly rectifying potassium channels, does not block PPD. Heterosynaptic depression mediated by GABAB receptors was also observed. The depression of the entorhinal pathway by stimulation of the temporal pathway is greater than depression of the temporal pathway by stimulation of the entorhinal pathway. Moreover, PPD increases with stimulus strength and the depression is enhanced by short trains of stimuli, consistent with stronger stimulation resulting in more GABA reaching GABAB receptors on excitatory glutamatergic synapses. Synaptic activation of GABAB receptors may be important in regulating excitability in a frequency-dependent manner with maximal depression occurring at approximately 5 Hz, which approximates to the theta rhythm. That homosynaptic and heterosynaptic depression by stimulation of the temporal pathway is greater than by stimulation of the entorhinal pathway suggests that activation of temporal feedforward connections to the perirhinal cortex can dominate the GABAergic control of synaptic activity within the perirhinal cortex.

Animals↗

Transcranial magnetic stimulation in clinical practice.

Transcranial magnetic stimulation allows a non-invasive and painless stimulation of the human brain and cranial nerves. The method is in use since 1985. Transcranial magnetic stimulation can use single stimuli, pairs of stimuli separated by different intervals (to the same or to several brain areas), or trains of repetitive stimuli at various frequencies. Single stimuli give rise to motor evoked potentials that have clinical use and serve diagnostic and prognostic purposes. Repetitive transcranial magnetic stimulation can modify excitability of cerebral cortex. Repetitive transcranial magnetic stimulation has opened a new field of investigation of the neural circuitry, and is developing into a therapeutic tool. This general review considers basic principles of transcranial magnetic stimulation, discusses methodological aspects and techniques, and analyses their utility in clinical practice.

Brain↗

Vascular endothelial cell proliferation: regulation of cellular polyamines.

OBJECTIVE: The aims were to investigate the requirement for and regulation of cellular polyamines during vascular endothelial cell proliferation. METHODS: Proliferation of cultured bovine pulmonary artery endothelial cells was determined after cellular polyamine depletion. In addition, polyamine synthesis and uptake mechanisms were examined in the presence and absence of trophic stimuli and density dependent inhibition of cell proliferation. RESULTS: Serum stimulated, subconfluent cells ceased cell division following the inhibition of ornithine decarboxylase (ODC), a rate limiting enzyme for polyamine biosynthesis. The addition of 10 microM putrescine, the product of the enzyme reaction catalysed by ODC, completely reversed the inhibition of cell growth. Serum deprivation reduced cytosolic ODC activity to near non-detectable levels. Readdition of 10% fetal bovine serum (FBS) resulted in transient increases in ODC activity which preceded DNA synthesis and mitosis. Basic fibroblast growth factor also stimulated ODC activity in a dose dependent manner with levels approximating the maximum obtainable with FBS. In contrast, platelet derived growth factor and epidermal growth factor did not stimulate ODC activity. Finally, mitogenic stimuli did not induce ODC activity in density arrested cells. The uptake of radiolabelled putrescine from the cell medium was time dependent and saturable. Kinetic studies from dividing cells revealed a single transport component for putrescine uptake [maximum rate of uptake (Vmax) = 11.2(SEM 2.0) pmol.10(5) cells-1.h-1; Michaelis constant (Km) = 1.1(0.3) microM]. Putrescine uptake by density arrested cells was characterised by a 57% decrease in Vmax with no change in Km. Readdition of FBS to serum deprived subconfluent cells, in the presence of ODC inhibitors, resulted in a rapid increase in the rate of putrescine uptake with Vmax increasing by 533% over FBS alone by 48 h. DISCUSSION: These data suggest that polyamines are essential for endothelial cell proliferation and that synthesis and uptake mechanisms are regulated according to cell growth.

Animals↗

Sympathetic hyperactivity during hypothalamic stimulation in spontaneously hypertensive rats.

To determine whether sympathetic hyperactivity of hypothalamic origin contributes to keep blood pressures high in spontaneous hypertension, aortic pressures and sympathetic nerve spike potentials were recorded during electrical stimulation of the posterior hypothalamus in urethane-anesthetized normotensive or hypertensive rats. Basal sympathetic nerve activity was higher in spontaneously hypertensive rats than in either normotensive or deoxycorticosterone acetate-salt hypertensive ones even before stimulation began. Blood pressure elevations produced by hypothalamic stimulation were always preceded by substantial increases in amplitude and rate of neural firing. Changes in amplitude could not be quantified, but rates of neural firing accelerated much more in spontaneous hypertensives than in normotensives during stimulation with 50- and 100-muA currents. Similar differences between deoxycorticosterone acetate-salt hypertensives and either normotensives or spontaneous hypertensives were not statistically significant. Nerve activity invariably became quiescent immediately after hypothalamic stimulation was discontinued, and recovery from this poststimulatory inhibition was faster in spontaneously hypertensive than in normotensive rats. Although spontaneous hypertensives generally also had stronger pressor responses to various sympathomimetic stimuli, responses to hypothalamic stimulation were enhanced to a greater extent than those to either norepinephrine or sympathetic nerve stimulation. Because this selectivity indicates participation of mechanisms other than augmented cardiovascular reactivity, further enhancement of responsiveness to hypothalamic stimuli was attributed to the associated increase in sympathetic nerve firing. These results are in accord with the hypothesis that the blood pressure elevation in rats with established spontaneous hypertension is a result, at least in part, of sympathetic hyperactivity emanating from the posterior hypothalamus.

Action Potentials↗

[Amino acids as olfactory stimuli in the Rana temporaria].

Stimulation of the olfactory receptors in the frog by 10(-3) and 10(-4) M solutions of 22 amino acids results in generation of slow potential and evoked waves in the olfactory bulb. The amplitude, duration and area of the slow potential, as well as the frequency of onset of the induced waves served as an index of effectiveness of the amino acids. All the amino acids were shown to be the effective stimuli, the irreplaceable ones being more effective as compared with the replaceable amino acids. Among the former, basic amino acids (lysine, histidine, arginine) were most effective.

Amino Acids↗

Diencephalic neuronal activity during acquisition and ingestion of food in sheep.

Single unit recordings were made in the lateral hypothalamic region and ventrobasal thalamus in conscious sheep during presentation of food and feeding. Unit responses to all aspects of testing were observed between the two areas. However, analysis of the data revealed a functional division of unit types between the two regions. Unit responses specific to the sight of food, to the approach of food to the mouth, and during ingestion of food were observed in the lateral hypothalamic area, but not the ventrobasal thalamus. These responses were not associated with specific or generalized movements, non-specific arousal, with olfactory stimulation, or with other oral stimuli. Units responding in association with specific mouth movements or somatosensory stimulation of the face or mouth-parts were observed in the ventrobasal thalamus but not in the lateral hypothalamic area. In the case of movement-related activity, the response was independent of the stimulus inducing the movement, food and non-food stimuli being equally effective. This was also true of the somatosensory responses observed. Two possibilities in relation to this functional division are discussed. Firstly, that the ventrobasal thalamus receives oral sensory afferents which may be associated with the thalamic area for taste. Secondly, that the activity of hypothalamic cells recorded in the sheep is consistent with a role for this area of the brain in the guidance and control of ingestive behaviour in ruminant as well as non-ruminant species.

Animals↗

Rate-dependent change in dispersion of repolarisation during ventricular pacing in man.

The difference between the end of monophasic action potentials recorded in the outflow tract of right ventricle and the T-wave on the surface electrocardiogram was measured as an estimate for disparity of termination of repolarisation. It was measured during right ventricular pacing at three basic cycle lengths 500, 600 and 700 msec and programmed stimulation with single extra stimuli in 15 patients with coronary arterial disease. The disparity of termination of repolarisation was rate dependent, showing increased values when stimulated at cycle length of 700 ms compared to 600 msec (P less than 0.005) and 500 ms (P less than 0.001). Premature stimulation revealed three different modes in changes of dispersion: in six patients the premature dispersion was increased at the shortest coupling intervals from the effective refractory period. It was unchanged compared to basic values in four, and in the rest of the patients the premature dispersion was reduced at the shortest coupling intervals. These results show that the dispersion of recovery of repolarisation increases at the lower stimulation frequencies. Premature dispersion is not always increased in the closest proximity to V-ERP during programmed ventricular stimulation in patients with ischemic heart disease.

Action Potentials↗

Gustatory evoked potentials in man.

Despite numerous attempts, a satisfactory method of recording gustatory evoked potentials (GEPs) had not been found as yet. This study reports a new stimulation technique by which taste receptors can be stimulated selectively. Gaseous chemical stimuli of an approximately rectangular concentration course were presented to 5 subjects. Acetic acid at different concentrations was used as the stimulant. The EEG was recorded from standard 10/20 positions referred to A1. Taste receptors were activated in a sufficiently synchronous manner to evoke summated slow wave potentials in the central nervous system. Concordant with other cortical evoked potentials, the vertex was the site of the most pronounced deviations of GEPs. Potential amplitudes increased and latencies decreased with rising concentrations. After application of the local anaesthetic tetracaine hydrochloride (10 mg) to the tongue, GEPs and taste sensations were eliminated. In one patient ageusia coinciding with irradiation therapy (36 Gy) was proved by the attenuation of the GEPs. Also GEPs to sweet (chloroform), salty (ammonium chloride) and bitter (thujone) taste sensations were recorded for the first time.

Acetates↗

Habituation and recovery of a slow negative wave of the event-related brain potential.

This study is concerned with the question of whether the late, slow negative wave 2 (SNW2) component of the event-related brain potential is a component of the orienting response (OR). As habituation of the SNW2 would be an argument for such a link with the OR, it was investigated using a variant of the classical repetition/change paradigm. Results supported major claims to be made for a component of the OR: the amplitude of the vertex SNW2 exhibited roughly the typical exponential decline with repeated stimulations (six numeric verbal stimuli presented seriatim in an ascending order) and responded incrementally to a change, at least in a narrow time slot, i.e. it exhibited partial recovery to an out-of-sequence stimulus. These findings were accompanied by similar effects on an exemplary OR component, the skin conductance response, and on such possible components of the OR as heart rate deceleration and the vertex P3 of the event-related brain potential. In so far as OR components should behave in comparable fashion in response to orienting stimuli, it is thus reasonable to suppose that the SNW2 relates to the OR.

Acoustic Stimulation↗

Length changes of the cat soleus muscle under frequency-modulated distributed stimulation of efferents in isotony.

The length changes of the cat soleus muscle have been examined in isotony within closed cycles of the stimulation rate change. Successive stimuli were applied in a cycle to five filaments of the preliminary dissected L7-S1 ventral roots (method of distributed stimulation), maximal rate did not exceed 80-90/s (16-18/s per single filament). At the beginning of a slow linear increase in the rate a muscle began shortening rather quickly, the rate changes without muscle reaction consisted of 5.91 +/- 0.28/s (mean +/- S.E.M.). A substantially linear movement was observed during increase of the input rate up to 40-50/s (i.e. 8-10/s per filament), a further rate increment could evoke a somewhat slowing of the shortening velocity with a distinctive infection of the rate-length curve. During a significant part of the rate decrease phase no movement was seen, the rate range with the absence of muscle lengthening was 29.93 +/- 1.57/s. After such a pronounced period of length fixation, a muscle began to elongate, the steady-state velocity at this part of the movement trajectory was invariably higher as compared with shortening velocity at the leading edge of the cycle. The striking feature of a powerful length clamping seen in active muscle at the phase of rate decrease preceded by previous rate increment allows us to suppose that this strongly non-linear behaviour of muscle might be a main reason for the existence of powerful dynamic components in efferent activity every time when muscle should shorten against external load in a ramp-and-hold fashion. We used the following experimental paradigm to check the assumption. Stimulation began with regular rate of 15/s; then, after transition from isometry to isotony and cessation of movement transients, the rate was raised linearly; after reaching a peak value of 50-90/s, it decreased linearly or exponentially, being afterwards fixed at several different levels between the maximal and initial values of the rate. It was demonstrated that such pattern of stimulation could be effective for a linear transition between two equilibrium lengths, provided that corresponding parameters in modulation signal were chosen in an optimal way. Duration and amplitude of the leading edge of the dynamic component seemed to completely define amplitude and velocity of the ramp phase of movement, parameters of decay to the final steady rate were, on the other hand, important for efficacy of the length clamping at hold phase. It was concluded that hysteresis effects of muscle contraction seemed to be an extremely important nonlinear property of muscle dynamics in producing any transition movements between two steady-states. Thus, oversimplified muscle models, like the spring model based on the isometric length-tension dependencies, seem to be incorrect. Possible mechanisms for the muscle hysteresis and its role in motor control are discussed.

Animals↗