Electrical stimulation of the septum and hypothalamus as conditioned stimuli in the rabbit.
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Animals↗
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[The role of Schaffer's collaterals in the sensory responses of the neurons of hippocampal field CA1].
In experiments with extracellular recording from the field CA1 pyramidal neurons in unanaesthetized rabbits the functional role of the Schaffer's collaterals (Sc) was investigated. Simultaneous presentation of sensory stimuli and Sc stimulation uniformly resulted in increase in duration of the post-excitatory inhibitory phase. In experiments with electrolytic lesion of the CA3 in the hippocampal segment, where recording from the CA1 was performed, background neuronal activity was normal. Reactions to sensory stimuli were preserved and had typical of the CA1 differentiated characteristics. The number of neurons with inhibitory responses to sensory stimuli was reduced. Habituation of responses was almost absent. Gradual increase in reactions duration up to prolonged increase of the background activity level was observed with repeated presentations of the stimuli. It is suggested that the influences of the field CA3 (through Sc) are not necessary for organization of sensory reactions in the CA1, but somehow participate in their limitation and inhibition.
Animals↗
The role of G-proteins in the activation of human leukocytes by particulate stimuli to produce reactive oxygen metabolites.
Effects of pertussis toxin (PTX), cholera toxin (CTX) and an anhydrolyzable GTP analogue, GTP gamma S, on the levels of free intracellular calcium ([Ca2+]i) and the production of reactive oxygen metabolites (ROM) in human polymorphonuclear leukocytes (PMNL) were studied during cell activation. Cells were stimulated by particulate stimuli, quartz or chrysotile, and soluble stimuli, formyl-methionyl-leucyl-phenylalanine (fMLP) or phorbol myristate acetate (PMA). Pretreatment of PMNL with PTX decreased fMLP-induced elevations of [Ca2+]i but not those induced by quartz or chrysotile. CTX, in turn, decreased both quartz- and fMLP-induced elevations of [Ca2+]i. Likewise, PTX inhibited only fMLP-induced production of ROM, whereas CTX inhibited also those induced by quartz, chrysotile or fMLP. PTX or CTX did not, however, have an impact on PMA-induced production of ROM. GTP gamma S alone did not elevate [Ca2+]i or amplify fMLP-, quartz- or chrysotile-induced [Ca2+]i elevation. However, GTP gamma S alone increased the production of ROM and amplified ROM production induced by fMLP and quartz. The present results suggest that a CTX-sensitive G-protein may be involved in quartz-induced PMNL activation whereas an fMLP-induced neutrophil activation may be regulated by G-proteins sensitive to both PTX and CTX. The involvement of G-protein in chrysotile-induced leukocyte activation is not likely. There may be, however, a relationship between G-protein-mediated cell signalling and quartz-induced production of reactive oxygen metabolites in these cells.
Adult↗
Inhibition of sensory responses of cat inferior olive neurons produced by stimulation of red nucleus.
1. The sensory responsiveness of cells in the inferior olive is known to be suppressed during certain phases of active movement. These experiments were designed to test the possibility that activity in the rubrospinal pathway contributes to this suppression. We recorded from cells sensitive to light touch located in one of the divisions of the inferior olive, the rostral dorsal accessory olive (rDAO), in cats anesthetized with pentobarbitol sodium. Responsiveness to peripheral stimuli was tested during and after trains of conditioning stimuli delivered to the rubrospinal pathway. 2. All 44 cells in our sample of rDAO neurons showed an inhibition of responsiveness to peripheral stimuli after conditioning stimulation of the rubrospinal pathway. Typical conditioning trains consisted of 0.2-ms pulses at 200 Hz for 100 ms. The mean current required for a reduction in firing probability to 0.5 was 31 microA. Slight increases in intensity often completely inhibited responses to peripheral stimuli. 3. Inhibition of responsiveness showed a delayed time course. Peak inhibition occurred approximately 50 ms after the last pulse in the conditioning train. In many cases there was no demonstrable inhibition during the conditioning train. Increases of train frequency, train duration, or stimulus intensity produced stronger and broader periods of olivary inhibition. 4. The lowest threshold points for eliciting rDAO inhibition coincided with either the magnocellular red nucleus (RNm) or the rubrospinal tract (RST). Stimulation at RST sites produced inhibition of responses in the contralateral but not in the ipsilateral rDAO. Transection of the RST in the upper brain stem blocked the inhibition produced by red-nucleus stimulation without altering the inhibition produced by tract stimulation caudal to the transection. The inhibitory effects thus appear to be caused by activation of the rubrospinal pathway. 5. The inhibitory timing observed in this study may be appropriate for explaining the suppression of olivary responsiveness to contact that has been observed in awake animals. Bursts of movement-related, red nucleus discharge often cease approximately 50 ms before the end of movement. This timing would allow peak inhibition to develop at approximately the time of contact with an object at the end of a goal-directed limb movement.
Animals↗
Three-dimensional organization of optokinetic responses in the rabbit.
1. Three-dimensional rotations of both eyes were measured in alert rabbits during optokinetic stimulation about axes lying in the horizontal plane or about an earth-vertical axis, with either one or both eyes viewing the stimulus. Optokinetic stimulus speed was 2 degrees /s, either continuous or alternating in polarity (triangular stimulus). In addition to the gains of the responses, the orientations of the response axes relative to the stimulus axes were determined. 2. In comparison to the response to constant-speed optokinetic stimulation about the vertical axis, the response to constant-speed optokinetic stimulation about horizontal axes was characterized by the lack of a speed buildup. In many cases, slow phase tracking was good as long as the eye was within the central oculomotor range but deteriorated when eye deviation became more eccentric and fast phases failed to be generated. These features suggest that the optokinetic reflex about horizontal axes functions as a position-control system, rather than as a velocity-control system. 3. Binocular optokinetic stimulation at constant speed (2 degrees/s) about the roll axis (0 degrees azimuth horizontal axis) elicited disconjugate responses. Although the gain of the response was not significantly different in the two eyes (0.38 for downward and 0.44 for upward stimulation), the response axes of the two eyes differed by as much as 51 degrees. 4. Monocular, horizontal axis optokinetic stimulation at constant speed elicited responses that were grossly dissociated between the two eyes. The magnitude of the responses was anisotropic in that it varied with the azimuthal orientation of the stimulus axis; the maximum gain for each eye (0.41 for the seeing and 0.33 for the covered eye) was at 135 degrees azimuth for each eye. The axis orientation and direction (sense of rotation) of the optokinetic stimulus eliciting the maximal response for each eye coincided with the optic flow normally associated with the maximal excitation of the corresponding ipsilateral anterior canal. 5. Binocular, triangular optokinetic stimulation with small excursions (+/- 10 degrees), which avoided the saturation problems of constant-speed stimulation, elicited adequate responses without systematic directional asymmetries. Gain was approximately 0.9 for all stimulus axis orientations in the horizontal plane. 6. During monocular stimulation with triangular stimuli, the response of the seeing eye showed a gain of approximately 0.5 for all orientations of the stimulus axis. In contrast, the covered eye showed anisotropic responses, with a maximum gain of approximately 0.5 during stimulation of the seeing eye about its 45 degree axis.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Alteration of activity of single neurons in the nucleus centrum medianum following stimulation of the peripheral nerve and application of noxious stimuli.
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Animals↗
Activation of glucose transport by AMP-activated protein kinase via stimulation of nitric oxide synthase.
Glucose transport in skeletal muscle is stimulated by two distinct stimuli, insulin and exercise. The mechanism by which exercise stimulates glucose transport is not known, although it is distinct from the insulin-mediated pathway. Recently, it has been shown that AMP-activated protein kinase (AMPK) is activated by exercise in skeletal muscle, whereas pharmacological activation of AMPK by 5-amino-4-imidazolecarboxamide riboside (AICAR) leads to increased glucose transport. It has been postulated, therefore, that AMPK may be the link between exercise and glucose transport. To address this, we have examined the signaling pathway involved in the stimulation of glucose uptake after activation of AMPK. Here we show that activation of AMPK by AICAR in rat muscle and mouse H-2Kb muscle cells activates glucose transport approximately twofold. AMPK in H-2Kb cells is also activated by hyperosmotic stress and the mitochondrial uncoupling agent, dinitrophenol, both of which lead to increased glucose transport. In contrast, insulin, which activates glucose transport two- to-threefold in both rat muscle and H-2Kb cells, has no effect on AMPK activity. A previous study has shown that AMPK phosphorylates and activates endothelial nitric oxide synthase (NOS). We show here that NOS activity in H-2Kb cells is activated after stimulation of AMPK by AICAR. Treatment of H-2Kb cells or rat muscle with NOS inhibitors completely blocks the increase in glucose transport after activation of AMPK. In addition, an inhibitor of guanylate cyclase also blocks activation of glucose transport by AICAR in H-2Kb cells. These results indicate that activation of AMPK in muscle cells stimulates glucose transport by activation of NOS coupled to downstream signaling components, including cyclic GMP.
Adenosine Monophosphate↗
Arginine vasopressin as a central neurotransmitter.
Anatomical and electrophysiological studies have revealed a widespread innervation of the brain by arginine vasopressin (AVP)-containing fibers. There is evidence that these central AVP pathways may be activated simultaneously with endocrine pathways. Stimulation of hypothalamic nuclei that contain AVP cell bodies causes changes in electrical activity of neurons in areas receiving AVP projections; in these same regions, release of immunoreactive AVP can be detected in response to appropriate stimuli or hypothalamic stimulation. These parts of the brain have also been shown to contain AVP receptors, and application of AVP to cells in these areas alters spontaneous activity or modifies the responses to other transmitters. AVP appears to act as a neurotransmitter involved in the central control of the cardiovascular, renal, and thermoregulatory systems. AVP may act centrally to coordinate autonomic and endocrine responses to homeostatic perturbations.
Animals↗
A comparison of hemodynamic and neural responses in cat visual cortex using complex stimuli.
We compare fMRI-BOLD responses in anesthetized cats with local field potentials (LFPs), aggregate high-frequency responses (analog-Mua) and spiking activity recorded in primary and higher visual cortex of alert animals. The similarity of the activations in these electrophysiological signals to those in the BOLD is quantified by counting recording sites where different stimuli elicit the same relative activation as in the imaging experiments. Using artificial stimuli, a comparison of BOLD and LFP strongly depends on the frequency range used. Stimulating with complex or natural stimuli reduces this frequency dependence and yields a good match of LFP and BOLD. In general, this match is best between 20 and 50 Hz. The measures of high-frequency activity behave qualitatively different: the responses of the analog-Mua match those of the LFP; the spiking activity shows a low concordance with the BOLD signal. This dissociation of BOLD and spiking activity is most prominent upon stimulation with natural stimuli.
Animals↗
[Glucocorticosteroid, catecholamine and protein-bound iodine (PBI) plasma levels in swine following electrocutaneous stimulation].
Application of electrocutaneous stimuli for short-time excitation of swine, accompanied by high locomotor activity, led in animals weighing between 30 kg and 45 kg to steep rises of catecholamine and glucocorticosteroid plasma concentrations, while little change was recordable from protein-linked iodine. Increase in plasma glucose and RQ in animals with higher rises in plasma-borne catecholamines and glucocorticoids was higher than that in animals with lower catecholamine deflection. Both the results reported in this paper and findings obtained from other studies into swine are likely to suggest major involvement of the sympathico-adrenomedullary system in the buildup of transport stress. Interdependence was found to exist between the intensity of the adrenergic reaction, on the one hand, and rises in plasma glucose and RQ as well as drop of pH, on the other. Those findings from various tests seem to support the conclusion that under conditions of severe excitation and high locomotor activity the differentiated resistance of swine to stress is atributable to different intensities of sympathico-adrenergic reaction of the animal concerned.
11-Hydroxycorticosteroids↗
Organization of visual inputs to interneurons of lateral geniculate nucleus of the cat.
1. Two groups of interneurons that are involved in the organization of the lateral geniculate nucleus (LGN) are described. The cell bodies of one group lie within the LGN; these units are referred to as intrageniculate. The cell bodies of the other group are found immediately above the LGN at its border with the perigeniculate nucleus; these units are referred to as perigeniculate. 2. Intrageniculate interneurons have center-surround receptive fields that resemble those of relay (principal) cells. They can be subdivided into brisk or sluggish and sustained or transient categories. They are stimulated transsynaptically from the visual cortex and have a characteristic variation in the latency of their spike response to such stimulation both at threshold and for suprathreshold stimuli. The pathway for this stimulation appears to be via cortical efferents to the LGN. Intrageniculate interneurons receive direct, monosynaptic retinal inputs, as determined by recording simultaneously from such interneurons and from the ganglion cells which provide excitatory input to them. Similar to relay cells, they are shown to have one or two major ganglion cell inputs. 3. Perigeniculate interneurons are generally binocularly innervated and give on-off responses to small spot stimuli throughout their receptive field. They respond well to rapid movement of large targets. They respond to electrical stimulation of the retina with a spike latency that falls between that of brisk transient and brisk sustained relay cells. This latency is one synaptic delay longer than that of brisk transient relay cell activation and suggests that they are excited by axon collaterals of these relay cells. Electrical stimulation of the visual cortex is also consistent with this model; the latency of the response of perigeniculate interneurons is approximately one synaptic delay longer than the latency of the response of brisk transient relay cells. 4. The interneuronal pathways described are consistent with proposed circuits that subserve the generation of IPSPs that arise in response to optic nerve and visual cortical stimulation. We now show that such inhibition has feed-forward (intrageniculate) and feed-back (perigeniculate) components that are mediated by two different classes of geniculate interneurons. It is suggested that the intrageniculate interneurons are involved in precise, spatially organized inhibition and that the perigeniculate interneurons are part of a more general, diffuse inhibitory system that modulates LGN excitability.
Animals↗
[Morphofunctional interrelationships between the hippocampus and hypothalamus in rats].
Evoked reactions of the hypothalamic arcuate and medial preoptic nuclei neurons were recorded when the hippocampus was stimulated by single stimuli in anaesthetized rats. In the arcuate nucleus phasic responses and primary inhibition were found to be dominant and in the medial preoptic nucleus--both phasic and nonspecifical responses. After injection of the horseradish peroxidase into the stimulated hippocampal region stained cells were found in the nuclei of the mammillary complex, mediobasal hypothalamus and in the medial preoptic nucleus. Groups of stained neurons were observed in the periphery of ventro- and dorsomedial, lateral and mammillary nuclei of the hypothalamus. In all the studied structures, except the medial mammillary nucleus, reticular-like cells were found alongside with spindle-like and triangle neurons. The data obtained are discussed in connection with the problem of hypothalamo-hippocampal interaction.
Animals↗
[Effect of motor stimulation and stretching on afferent activity of the neuromuscular spindle isolated from the frog].
The arrangement of muscle spindles in m. ext. long. dig. IV has been examined by microdissection. It is confirmed that spindle systems generally appear to consist of individual receptors. Stimulation effects of fast motor fibres (conduction velocities greater than 12 m/sec) on the spindles of the same muscle were studied. Receptors were isolated with their nerves and the appropriate spinal roots, the latter ones were used for stimulating efferent fibres and recording sensory discharges. Single shocks to the ventral root filaments caused afferent responses ranging from a single action potential to a train of impulses. During repetitive stimulation (train of stimuli at frequency of 10 to 150/sec) a marked increase in afferent activity was found. Afferent activity could be driven by the frequency of stimuli ("driving") and the stimulus/action potentials ratio varied from 1:1 to 1:3 or more. The rate of sensory discharge depended on the frequency of stimuli: the maximum effect, was attained at 30 to 50 stimuli/sec and, in the most responsive receptors, up to 80 stimuli/sec. Slight increases of the initial lengths of the receptors caused facilitation of sensory responses to motor stimulation. Moreover, impairing effects, which appear during sustained or high-frequency stimulation, possibly related to fatigue in intrafusal neuromuscular transmission, could be relieved by increasing the initial length. The repetitive stimulation of fast fusimotor fibres increased both dynamic and static responses and also raised the afferent activity after a period of stretching, when usually a depression occurs; these effects varied according to the preparation, its initial tension and the frequency of stimulation. The main feature of the examined motor fibres, when stimulated, is the constant excitatory action on muscle spindle static response. Results are discussed. It is suggested that the different characteristics of intrafusal muscle fibres, the receptor initial tension and the frequency of motor units discharges, may together affect muscle spindles static or dynamic performance.
Afferent Pathways↗
Cerebellar stimulation modulates thalamic noxious-evoked responses.
Parafascicular (PF) neurons responding to noxious stimuli and focal electrical stimulation of midbrain, diencephalon, and hypothalamic nuclei, which send projections to PF, modulates the PF spontaneous and noxious-evoked responses. Some cerebellar efferents ascend to PF. This investigation attempted to study the effect of cerebellar stimulation on spontaneous and noxious-evoked PF neuronal activity in rats. It was observed that 26% (73/280) of PF neurons responded to a noxious stimulus. The PF neuronal population exhibits two cell types according to their response pattern following the noxious stimulus. One type of PF neurons were excited (n = 53) and were classified as nociceptive-on cells. The second type of PF neurons responded to noxious stimulus by a decrease in the ongoing firing rate (n = 20) and were classified as nociceptive-off cells. The responses of these two types of nociceptively identified cells were tested following cerebellar lateral nucleus stimulation (Lat.N.S.) utilizing several current intensities. Lat.N.S. with lower intensities (0.1-0.2 mA) elicited suppression of both spontaneous and nociceptive-evoked discharges of the nociceptive-on neurons, although higher intensities (0.4-0.6 mA) elicited excitation on both discharges of this type of neuron. In contrast, Lat.N.S. induced a monophasic intensity-dependent suppression of both the spontaneous and the nociceptive-evoked discharges of the nociceptive-off neurons. The results indicate that Lat.N.S. modulates the nociceptive-evoked responses of PF neurons. The possible role and related pathways of cerebellum in modulating noxious input were discussed.
Animals↗
Stimulation of cholesterol side-chain cleavage enzyme activity by cAMP and hCG in MA-10 Leydig tumor cells.
Using a cloned Leydig tumor cell line (designated MA-10), we have studied the activity of cholesterol side-chain (CSCC) enzyme, the rate-determining step in steroidogenesis, in mitochondria isolated from cells pretreated either with human chorionic gonadotropin (hCG) or dibutyryl cyclic adenosine monophosphate (dbcAMP). Results showed a slight but significant increase in CSCC activity with treatment by cAMP (25% increase) and hCG (60% increase), as compared to mitochondria isolated from nontreated control cells. However, this stimulation of CSCC activity appears to be of limited significance when compared to the approximately 1000-fold or greater increase observed in progesterone production in the presence of hCG or dbcAMP. On the other hand, unstimulated MA-10 cells or isolated mitochondria efficiently converted 25-hydroxycholesterol and 22R-hydroxycholesterol into progesterone, and this conversion was not affected by cycloheximide. The addition of cholesterol to intact cells or to isolated mitochondria did not affect progesterone production. Our observations clearly indicate that given the proper hydroxy substrates (22R-hydroxycholesterol or 25-hydroxycholesterol), MA-10 Leydig cells are able to convert them into progesterone without any stimulation by steroidogenic stimuli, i.e. cAMP or hCG. Since MA-10 Leydig cells can efficiently convert 22R-hydroxycholesterol--an intermediate in CSCC reaction--into progesterone, these results suggest that the key regulatory step in the mechanism of trophic hormone-stimulated steroid production is the first hydroxylation step of the 3 sequential monooxygenation reactions involved in the conversion of cholesterol to pregnenolone.
Allosteric Regulation↗
Nerve stimulation test in murine experimental autoimmune myasthenia gravis.
Use of the mouse model of myasthenia gravis (murine EAMG), ideally suited for immunological study, has been hampered by the relatively mild character of the disease and by the extended time and effort required for inducing severe disease. Electromyographic measurement of the compound action potential after repetitive stimuli, the nerve stimulation test, was evaluated for its ability to diagnose neuromuscular transmission defects in mice immunized with Torpedo acetylcholine receptor. With the combination of provocative maneuvers and raising of the body temperature, EAMG could be diagnosed in nearly all immunized animals a few weeks after immunization, whereas clinical evaluation of muscle weakness was positive in less than half of immunized mice months after the first immunization. Thus, EMG provides a means of objective evaluation of the disease and attempts at its experimental modification.
Animals↗
The effects of Zn2+ on long-term potentiation of C fiber-evoked potentials in the rat spinal dorsal horn.
Tetanic stimuli of peripheral C fibers produces long-term potentiation (LTP) in the spinal cord, which may contribute to sensitization of spinal pain-sensitive neurons. Zn2+ is widely distributed in the central nervous system and has blocked (LTP) in the hippocampus. The present study examined the effects of Zn2+ on the induction and maintenance of C fiber-evoked LTP in the deep dorsal horn of spinalized rats in vivo. The sciatic nerve was stimulated by tetanic stimuli for inducing LTP. (1) Topical administration of Zinc chloride (15 microM) to the spinal cord 15 min before tetanic stimulation completely blocked the induction of LTP, but not the baseline C responses. When Zn2+ was given 2 h after induction of LTP, no significant effect occurred. (2) Chelation of Zn2+ by disodium calcium ethylene diaminetelraacetate (CaEDTA) (500 microM) resulted in no effect on LTP. (3) Coadministration of Zn2+ (15 microM) and N-methyl-D-aspartic acid (NMDA) (5 microM) significantly attenuated C fiber-evoked potentials, which was prevented by the NMDA receptor antagonist AP-5 (100 microM). The present results showed that Zn2+ may contribute to the modulation of the formation, but not the maintenance, of spinal LTP. NMDA receptors may be involved in Zn2+-induced modulation.
Afferent Pathways↗
Stimulation of afferent fibres of the guinea-pig ureter evokes potentials in inferior mesenteric ganglion neurones.
1. Intracellular recordings were made from neurones of the guinea-pig inferior mesenteric ganglion (IMG) maintained in vitro with both ureters and major nerve trunks attached. Afferent fibres in the ureteric nerve were activated by electrical, chemical and mechanical stimuli. 2. Repetitive stimulation of a ureteric nerve branch evoked a non-cholinergic, synaptic slow excitatory potential (slow EPSP) in 48% of neurons. The amplitude of the slow EPSP was dependent on membrane potential and was decreased by membrane depolarization and increased by hyperpolarization. 3. The slow EPSP was attenuated or abolished by capsaicin (1 microM), which itself depolarized IMG neurones. Substance P (2 microM) or neurokinin A (2 microM) also depolarized IMG neurones and in the presence of these tachykinins the slow EPSP was attenuated or abolished. 4. Distension of the ureter evoked a non-cholinergic slow depolarization in 45% of IMG neurones which was abolished by tetrodotoxin (1 microM) and by capsaicin (1 microM). 5. Chemical stimulation of ureteric afferent nerve terminals by intralumenal perfusions of the ureter with capsaicin (1 microM) produced a slow depolarization in the IMG which was prevented by blocking nerve conduction with TTX. 6. These data demonstrate that electrical stimulation of ureteric afferent fibres produces a non-cholinergic slow EPSP in the IMG. Primary afferent (capsaicin-sensitive) C fibres are also activated by distension of the ureter and evoke a slow depolarization in the IMG. The synaptic mediator of these events is likely to be tachykinin(s) released from capsaicin-sensitive C fibres. These fibres may be mechanosensory and/or nociceptive.
Animals↗