SI neuron response variability is stimulus tuned and NMDA receptor dependent.
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Skin brushing stimuli were used to evoke spike discharge activity in single skin mechanoreceptive afferents (sMRAs) and anterior parietal cortical (SI) neurons of anesthetized monkeys (Macaca fascicularis). In the initial experiments 10-50 presentations of each of 8 different stimulus velocities were delivered to the linear skin path from which maximal spike discharge activity could be evoked. Mean rate of spike firing evoked by each velocity (MFR) was computed for the time period during which spike discharge activity exceeded background, and an across-presentations estimate of mean firing rate (MFR) was generated for each velocity. The magnitude of the trial-by-trial variation in the response (estimated as CV; where CV = standard deviation in MFR/MFR) was determined for each unit at each velocity. MFR for both sMRAs and SI neurons (MFRsMRA and MFRSI, respectively) increased monotonically with velocity over the range 1-100 cm/s. At all velocities the average estimate of intertrial response variation for SI neurons (CVSI) was substantially larger than the corresponding average for sMRAs (CVsMRA). Whereas CVsMRA increased monotonically over the range 1-100 cm/s, CVSI decreased progressively with velocity over the range 1-10 cm/s, and then increased with velocity over the range 10-100 cm/s. The position of the skin brushing stimulus in the receptive field (RF) was varied in the second series of experiments. It was found that the magnitude of CVSI varied systematically with stimulus position in the RF: that is, CVSI was lowest for a particular velocity and direction of stimulus motion when the skin brushing stimulus traversed the RF center, and CVSI increased progressively as the distance between the stimulus path and the RF center increased. In the third series of experiments, either phencylidine (PCP; 100-500 microg/kg) or ketamine (KET; 0.5-7.5 mg/kg) was administered intravenously (iv) to assess the effect of block of N-methyl-D-aspartate (NMDA) receptors on SI neuron intertrial response variation. The effects of PCP on both CVSI and MFRSI were transient, typically with full recovery occurring in 1-2 h after drug injection. The effects of KET on CVSI and MFRSI were similar to those of PCP, but were shorter in duration (15-30 min). PCP and KET administration consistently was accompanied by a reduction of CVSI. The magnitude of the reduction of CVSI by PCP or KET was associated with the magnitude of CVSI before drug administration: that is, the larger the predrug CVSI, the larger the reduction in CVSI caused by PCP or KET. PCP and KET exerted variable effects on SI neuron mean firing rate that could differ greatly from one neuron to the next. The results are interpreted to indicate that SI neuron intertrial response variation is 1) stimulus tuned (intertrial response variation is lowest when the skin stimulus moves at 10 cm/s and traverses the neuron's RF center) and 2) NMDA receptor dependent (intertrial response variation is least when NMDA receptor activity contributes minimally to the response, and increases as the contribution of NMDA receptors to the response increases). (+info)
Lack of AMPA receptor desensitization during basal synaptic transmission in the hippocampal slice.
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Excitatory postsynaptic currents in the CA1 region of rat hippocampal slices are mediated primarily by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in response to synaptically released glutamate. Outside-out patches from pyramidal cells in this region have shown that AMPA receptors are desensitized by short (1 ms) pulses of glutamate. We have taken a number of approaches to ask whether synaptic receptors desensitize in response to synaptically released glutamate in the slice. Recordings with paired pulses and minimal stimulation conditions that are presumably activating only a single release site do not show evidence for desensitization. Furthermore, cyclothiazide, a drug that blocks desensitization, does not alter paired-pulse ratios even under conditions of high probability of release, which should maximize desensitization. These results suggest that synaptic receptors do not desensitize in response to synaptically released glutamate during basal synaptic transmission. (+info)
Contribution of the cerebellar flocculus to gaze control during active head movements.
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The flocculus and ventral paraflocculus are adjacent regions of the cerebellar cortex that are essential for controlling smooth pursuit eye movements and for altering the performance of the vestibulo-ocular reflex (VOR). The question addressed in this study is whether these regions of the cerebellum are more globally involved in controlling gaze, regardless of whether eye or active head movements are used to pursue moving visual targets. Single-unit recordings were obtained from Purkinje (Pk) cells in the floccular region of squirrel monkeys that were trained to fixate and pursue small visual targets. Cell firing rate was recorded during smooth pursuit eye movements, cancellation of the VOR, combined eye-head pursuit, and spontaneous gaze shifts in the absence of targets. Pk cells were found to be much less sensitive to gaze velocity during combined eye-head pursuit than during ocular pursuit. They were not sensitive to gaze or head velocity during gaze saccades. Temporary inactivation of the floccular region by muscimol injection compromised ocular pursuit but had little effect on the ability of monkeys to pursue visual targets with head movements or to cancel the VOR during active head movements. Thus the signals produced by Pk cells in the floccular region are necessary for controlling smooth pursuit eye movements but not for coordinating gaze during active head movements. The results imply that individual functional modules in the cerebellar cortex are less involved in the global organization and coordination of movements than with parametric control of movements produced by a specific part of the body. (+info)
Potassium ions and endothelium-derived hyperpolarizing factor in guinea-pig carotid and porcine coronary arteries.
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Experiments were designed to determine in two arteries (the guinea-pig carotid and the porcine coronary arteries) whether or not the endothelium-derived hyperpolarizing factor (EDHF) can be identified as potassium ions, and to determine whether or not the inwardly rectifying potassium current and the Na+/K+ pump are involved in the hyperpolarization mediated by EDHF. The membrane potential of vascular smooth muscle cells was recorded with intracellular microelectrodes in the presence of N(omega)-L-nitro-arginine (L-NA) and indomethacin. In vascular smooth muscle cells of guinea-pig carotid and porcine coronary arteries, acetylcholine and bradykinin induced endothelium-dependent hyperpolarizations (-18+/-1 mV, n = 39 and -19+/-1 mV, n = 7, respectively). The hyperpolarizations were not affected significantly by ouabain (1 microM), barium chloride (up to 100 microM) or the combination of ouabain plus barium. In both arteries, increasing extracellular potassium concentration by 5 or 10 mM induced either depolarization or in a very few cases small hyperpolarizations which never exceeded 2 mV. In isolated smooth muscle cells of the guinea-pig carotid artery, patch-clamp experiments shows that only 20% of the vascular smooth muscle cells expressed inwardly rectifying potassium channels. The current density recorded was low (0.5+/-0.1 pA pF(-1), n = 8). These results indicate that, in two different vascular preparations, barium sensitive-inwardly rectifying potassium conductance and the ouabain sensitive-Na+/K+ pump are not involved in the EDHF-mediated hyperpolarization. Furthermore, potassium did not mimic the effect of EDHF pointing out that potassium and EDHF are not the same entity in those arteries. (+info)
Comparison of antagonist potencies at pre- and post-synaptic GABA(B) receptors at inhibitory synapses in the CA1 region of the rat hippocampus.
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Synaptic activation of gamma-aminobutyric acid (GABA)B receptors at GABA synapses causes (a) postsynaptic hyperpolarization mediating a slow inhibitory postsynaptic potential/current (IPSP/C) and (b) presynaptic inhibition of GABA release which depresses IPSPs and leads to paired-pulse widening of excitatory postsynaptic potentials (EPSPs). To address whether these effects are mediated by pharmacologically identical receptors the effects of six GABA(B) receptor antagonists of widely ranging potencies were tested against each response. Monosynaptic IPSP(B)s were recorded in the presence of GABA(A), AMPA/kainate and NMDA receptor antagonists. All GABA(B) receptor antagonists tested depressed the IPSP(B) with an IC50 based rank order of potency of CGP55679> or =CGP56433 = CGP55845A = CGP52432>CGP51176>CGP36742. Paired-pulse EPSP widening was recorded as an index of paired-pulse depression of GABA-mediated IPSP/Cs. A similar rank order of potency of antagonism of paired-pulse widening was observed to that for IPSP(B) inhibition. Comparison of the IC50 values for IPSP(B) inhibition and paired-pulse EPSP widening revealed a close correlation between the two effects in that their IC50s lay within the 95% confidence limits of a correlation line that described IC50 values for inhibition of paired-pulse EPSP widening that were 7.3 times higher than those for IPSP(B) inhibition. Using the compounds tested here it is not possible to assign different subtypes of GABA(B) receptor to pre- and post-synaptic loci at GABAergic synapses. However, 5-10 fold higher concentrations of antagonist are required to block presynaptic as opposed to postsynaptic receptors when these are activated by synaptically released GABA. (+info)
Pilocarpine modulates the cellular electrical properties of mammalian hearts by activating a cardiac M3 receptor and a K+ current.
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1. Pilocarpine, a muscarinic acetylcholine receptor (mAChR) agonist, is widely used for treatment of xerostomia and glaucoma. It can also cause many other cellular responses by activating different subtypes of mAChRs in different tissues. However, the potential role of pilocarpine in modulating cardiac function remained unstudied. 2. We found that pilocarpine produced concentration-dependent (0.1-10 microM) decrease in sinus rhythm and action potential duration, and hyperpolarization of membrane potential in guinea-pig hearts. The effects were nearly completely reversed by 1 microM atropine or 2 nM 4DAMP methiodide (an M3-selective antagonist). 3. Patch-clamp recordings in dispersed myocytes from guinea-pig and canine atria revealed that pilocarpine induces a novel K+ current with delayed rectifying properties. The current was suppressed by low concentrations of M3-selective antagonists 4DAMP methiodide (2-10 nM), 4DAMP mustard (4-20 nM, an ackylating agent) and p-F-HHSiD (20-200 nM). Antagonists towards other subtypes (M1, M2 or M4) all failed to alter the current. 4. The affinity of pilocarpine (KD) at mAChRs derived from displacement binding of [3H]-NMS in the homogenates from dog atria was 2.2 microM (65% of the total binding) and that of 4DAMP methiodide was 2.8 nM (70% of total binding), consistent with the concentration of pilocarpine needed for the current induction and for the modulation of the cardiac electrical activity and the concentration of 4DAMP to block pilocarpine effects. 5. Our data indicate, for the first time, that pilocarpine modulates the cellular electrical properties of the hearts, likely by activating a K+ current mediated by M3 receptors. (+info)
Effect of acetylstrophanthidin on action potential duration and relation with extracellular potassium in sheep isolated Purkinje fibers.
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AIM: To study the relation between the effect of acetylstrophanthidin on action potential duration (APD) and the extracellular potassium concentration. METHODS: Effect of acetylstrophanthidin (AS 0.15 mmol.L-1) on APD at different extracellular potassium concentrations was studied at the stimulation cycle lengths of 990 and 690 ms in sheep isolated cardiac Purkinje fibers using the standard microelectrode technique. RESULTS: At [K+]o 4.0 mmol.L-1, the biphasic effect of AS on APD appeared obviously. Both APD50 and APD90 were lengthened within the first 10 min of drug exposure. After 10 min, they were shortened at all pacing cycle lengths. On the other hand, at [K+]o 5.4 mmol.L-1, AS only shortened APD markedly without lengthening effect on it. The biphasic and monophasic effects of AS on APD were found at [K+]o 4.0 mmol.L-1 and 5.4 mmol.L-1, respectively. CONCLUSION: The effect of AS on APD was related to the concentration of [K+]o. (+info)
Activity of neurons in human temporal cortex during identification and memory for names and words.
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Extracellular recordings of human temporal cortical neuronal activity during identification and memory for object names or words were obtained from 31 neurons at 18 sites in 12 left language dominant patients undergoing left (10) or right (2) awake craniotomy for epilepsy under local anesthesia. Frequency of activity during identification was compared with perceptual controls, that during the encoding phase of recent memory to identification of the same material. Statistically significant changes in one or more temporal epoch (p < 0.005) of one or more comparisons were present for 27 of the 31 neurons in either hemisphere. Few neurons changed activity in the same direction for both words and names. The instruction to retain an item in recent memory changed activity in most neurons from that during identification of the same material, although the items presented were identical and overtly identified in each task. Any individual neuron usually changed activity in one direction for only one task. There are separate, widely distributed neural networks for identification or recent memory for each type of material. The majority of nearby neurons recorded through the same extracellular microelectrode were related to the networks for different tasks. The temporal characteristics of these changes were also investigated; 31% of the changes were "phasic": temporally related to presentation or response to the item. Most of the remaining neuron changes were sustained throughout a task, often for several minutes. These task-specific sustained changes may reflect effects of thalamo-cortical attentional systems. Individual neurons had both sustained and phasic changes to different tasks. (+info)