Neuronal activity in somatosensory cortex of monkeys using a precision grip. III. Responses to altered friction perturbations.
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The purpose of this investigation was to examine the activity changes in single units of the somatosensory cortex in response to lubricating and adhesive coatings applied to a hand-held object. Three monkeys were trained to grasp an object between the thumb and index fingers and to lift and hold it stationary within a narrow position window for 1 s before release. Grip forces normal to the skin surface, load forces tangential to the skin surface, and the displacement of the object were measured on each trial. Adhesive (rosin) and lubricant (petroleum jelly) coatings were applied to the smooth metal surface of the object to alter the friction against the skin. In addition, neuronal activity evoked by force pulse-perturbations generating shear forces and slip on the skin were compared with the patterns of activity elicited by grasping and lifting the coated surfaces. Following changes in surface coatings, both monkeys modulated the rate at which grip forces normal to the skin surface and load forces tangential to the skin surface were applied during the lifting phase of the task. As a result, the ratio of the rates of change of the two forces was proportionately scaled to the surface coating properties with the more slippery surfaces, having higher ratios. This precise control of normal and tangential forces enabled the monkeys to generate adequate grip forces and prevent slip of the object. From a total of 386 single neurons recorded in the hand area of the somatosensory cortex, 92 were tested with at least 1 coating. Cell discharge changed significantly with changes in surface coating in 62 (67%) of these cells. Of these coating-related cells, 51 were tested with both an adhesive and lubricating coating, and 45 showed significant differences in activity between the untreated metal surface and either the lubricant or the adhesive coating. These cells were divided into three main groups on the basis of their response patterns. In the first group (group A), the peak discharge increased significantly when the grasped surface was covered with lubricant. These cells appeared to be selectively sensitive to slip of the object on the skin. The second group (group B) was less activated by the adhesive surface compared with either the untreated metal or the lubricated surface, and they responded mainly to variations in the force normal to the skin surface. These cells provide useful feedback for the control of grip force. The third group (group C) responded to both slips and to changes in forces tangential to the skin. Most of these cells responded with a biphasic pattern reflecting the bidirectional changes in load force as the object was first accelerated and then decelerated. One hundred sixty-eight of the 386 isolated neurons were tested with brief perturbations during the task. Of these, 147 (88%) responded to the perturbation with a significant change in activity. In most of the cells, the response to the perturbation was shorter than 100 ms with a mean latency of 44.1 +/- 16.3 (SD) ms. For each of the cell groups, the activity patterns triggered by the perturbations were consistent with the activity patterns generated during the grasping and lifting of the coated object. (+info)
Retinal input induces three firing patterns in neurons of the superficial superior colliculus of neonatal rats.
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By using an in vitro isolated brain stem preparation, we recorded extracellular responses to electrical stimulation of the optic tract (OT) from 71 neurons in the superficial superior colliculus (SC) of neonatal rats (P1-13). At postnatal day 1 (P1), all tested neurons (n = 10) already received excitatory input from the retina. Sixty-nine (97%) superficial SC neurons of neonatal rats showed three response patterns to OT stimulation, which depended on stimulus intensity. A weak stimulus evoked only one spike that was caused by activation of non-N-methyl-D-aspartate (NMDA) glutamate receptors. A moderate stimulus elicited a short train (<250 ms) of spikes, which was induced by activation of both NMDA and non-NMDA receptors. A strong stimulus gave rise to a long train (>300 ms) of spikes, which was associated with additional activation of L-type high-threshold calcium channels. The long train firing pattern could also be induced either by temporal summation of retinal inputs or by blocking gamma-aminobutyric acid-A receptors. Because retinal ganglion cells show synchronous bursting activity before eye opening at P14, the retinotectal inputs appear to be sufficient to activate L-type calcium channels in the absence of pattern vision. Therefore activation of L-type calcium channels is likely to be an important source for calcium influx into SC neurons in neonatal rats. (+info)
C-fiber depletion alters response properties of neurons in trigeminal nucleus principalis.
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The effects of C-fiber depletion induced by neonatal capsaicin treatment on the functional properties of vibrissa-sensitive low-threshold mechanoreceptive (LTM) neurons in the rat trigeminal nucleus principalis were examined in adult rats. Neonatal rats were injected either with capsaicin or its vehicle within 48 h of birth. The depletion of unmyelinated afferents was confirmed by the significant decrease in plasma extravasation of Evan's blue dye induced in the hindlimb skin of capsaicin-treated rats by cutaneous application of mustard oil and by the significant decrease of unmyelinated fibers in both the sciatic and infraorbital nerves. The mechanoreceptive field (RF) and response properties of 31 vibrissa-sensitive neurons in capsaicin-treated rats were compared with those of 32 vibrissa-sensitive neurons in control (untreated or vehicle-treated) rats. The use of electronically controlled mechanical stimuli allowed quantitative analysis of response properties of vibrissa-sensitive neurons; these included the number of center- and surround-RF vibrissae within the RF (i.e., those vibrissae which when stimulated elicited >/=1 and <1 action potential per stimulus, respectively), the response magnitude and latency, and the selectivity of responses to stimulation of vibrissae in different directions with emphasis on combining both the response magnitude and direction of vibrissal deflection in a vector analysis. Neonatal capsaicin treatment was associated with significant increases in the total number of vibrissae, in the number of center-RF vibrissae per neuronal RF, and in the percentage of vibrissa-sensitive neurons that also responded to stimulation of other types of orofacial tissues. Compared with control rats, capsaicin-treated rats showed significant increases in the response magnitude to stimulation of surround-RF vibrissae as well as in response latency variability to stimulation of both center- and surround-RF vibrissae. C-fiber depletion also significantly altered the directional selectivity of responses to stimulation of vibrissae. For neurons with multiple center-RF vibrissae, the proportion of center-RF vibrissae with net vector responses oriented toward the same quadrant was significantly less in capsaicin-treated compared with control rats. These changes in the functional properties of principalis vibrissa-sensitive neurons associated with marked depletion of C-fiber afferents are consistent with similarly induced alterations in LTM neurons studied at other levels of the rodent somatosensory system, and indeed may contribute to alterations previously described in the somatosensory cortex of adult rodents. Furthermore, these results provide additional support to the view that C fibers may have an important role in shaping the functional properties of LTM neurons in central somatosensory pathways. (+info)
Visuomotor processing as reflected in the directional discharge of premotor and primary motor cortex neurons.
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Premotor and primary motor cortical neuronal firing was studied in two monkeys during an instructed delay, pursuit tracking task. The task included a premovement "cue period," during which the target was presented at the periphery of the workspace and moved to the center of the workspace along one of eight directions at one of four constant speeds. The "track period" consisted of a visually guided, error-constrained arm movement during which the animal tracked the target as it moved from the central start box along a line to the opposite periphery of the workspace. Behaviorally, the animals tracked the required directions and speeds with highly constrained trajectories. The eye movements consisted of saccades to the target at the onset of the cue period, followed by smooth pursuit intermingled with saccades throughout the cue and track periods. Initially, an analysis of variance (ANOVA) was used to test for direction and period effects in the firing. Subsequently, a linear regression analysis was used to fit the average firing from the cue and track periods to a cosine model. Directional tuning as determined by a significant fit to the cosine model was a prominent feature of the discharge during both the cue and track periods. However, the directional tuning of the firing of a single cell was not always constant across the cue and track periods. Approximately one-half of the neurons had differences in their preferred directions (PDs) of >45 degrees between cue and track periods. The PD in the cue or track period was not dependent on the target speed. A second linear regression analysis based on calculation of the preferred direction in 20-ms bins (i.e., the PD trajectory) was used to examine on a finer time scale the temporal evolution of this change in directional tuning. The PD trajectories in the cue period were not straight but instead rotated over the workspace to align with the track period PD. Both clockwise and counterclockwise rotations occurred. The PD trajectories were relatively straight during most of the track period. The rotation and eventual convergence of the PD trajectories in the cue period to the preferred direction of the track period may reflect the transformation of visual information into motor commands. The widely dispersed PD trajectories in the cue period would allow targets to be detected over a wide spatial aperture. The convergence of the PD trajectories occurring at the cue-track transition may serve as a "Go" signal to move that was not explicitly supplied by the paradigm. Furthermore, the rotation and convergence of the PD trajectories may provide a mechanism for nonstandard mapping. Standard mapping refers to a sensorimotor transformation in which the stimulus is the object of the reach. Nonstandard mapping is the mapping of an arbitrary stimulus into an arbitrary movement. The shifts in the PD may allow relevant visual information from any direction to be transformed into an appropriate movement direction, providing a neural substrate for nonstandard stimulus-response mappings. (+info)
Binding partners for the myelin-associated glycoprotein of N2A neuroblastoma cells.
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The myelin-associated glycoprotein (MAG) has been proposed to be important for the integrity of myelinated axons. For a better understanding of the interactions involved in the binding of MAG to neuronal axons, we performed this study to identify the binding partners for MAG on neuronal cells. Experiments with glycosylation inhibitors revealed that sialylated N-glycans of glycoproteins represent the major binding sites for MAG on the neuroblastoma cell line N2A. From extracts of [3H]glucosamine-labelled N2A cells several glycoproteins with molecular weights between 20 and 230 kDa were affinity-precipitated using immobilised MAG. The interactions of these proteins with MAG were sialic acid-dependent and specific for MAG. (+info)
Long term lithium treatment suppresses p53 and Bax expression but increases Bcl-2 expression. A prominent role in neuroprotection against excitotoxicity.
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This study was undertaken to investigate the molecular mechanisms underlying the neuroprotective actions of lithium against glutamate excitotoxicity with a focus on the role of proapoptotic and antiapoptotic genes. Long term, but not acute, treatment of cultured cerebellar granule cells with LiCl induces a concentration-dependent decrease in mRNA and protein levels of proapoptotic p53 and Bax; conversely, mRNA and protein levels of cytoprotective Bcl-2 are remarkably increased. The ratios of Bcl-2/Bax protein levels increase by approximately 5-fold after lithium treatment for 5-7 days. Exposure of cerebellar granule cells to glutamate induces a rapid increase in p53 and Bax mRNA and protein levels with no apparent effect on Bcl-2 expression. Pretreatment with LiCl for 7 days prevents glutamate-induced increase in p53 and Bax expression and maintains Bcl-2 in an elevated state. Glutamate exposure also triggers the release of cytochrome c from the mitochondria into the cytosol. Lithium pretreatment blocks glutamate-induced cytochrome c release and cleavage of lamin B1, a nuclear substrate for caspase-3. These results strongly suggest that lithium-induced Bcl-2 up-regulation and p53 and Bax down-regulation play a prominent role in neuroprotection against excitotoxicity. Our results further suggest that lithium, in addition to its use in the treatment of bipolar depressive illness, may have an expanded use in the intervention of neurodegeneration. (+info)
A human beta-spectrin gene promoter directs high level expression in erythroid but not muscle or neural cells.
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beta-Spectrin is an erythrocyte membrane protein that is defective in many patients with abnormalities of red blood cell shape including hereditary spherocytosis and elliptocytosis. It is expressed not only in erythroid tissues but also in muscle and brain. We wished to determine the regulatory elements that determine the tissue-specific expression of the beta-spectrin gene. We mapped the 5'-end of the beta-spectrin erythroid cDNA and cloned the 5'-flanking genomic DNA containing the putative beta-spectrin gene promoter. Using transfection of promoter/reporter plasmids in human tissue culture cell lines, in vitro DNase I footprinting analyses, and gel mobility shift assays, a beta-spectrin gene erythroid promoter with two binding sites for GATA-1 and one site for CACCC-related proteins was identified. All three binding sites were required for full promoter activity; one of the GATA-1 motifs and the CACCC-binding motif were essential for activity. The beta-spectrin gene promoter was able to be transactivated in heterologous cells by forced expression of GATA-1. In transgenic mice, a reporter gene directed by the beta-spectrin promoter was expressed in erythroid tissues at all stages of development. Only weak expression of the reporter gene was detected in muscle and brain tissue, suggesting that additional regulatory elements are required for high level expression of the beta-spectrin gene in these tissues. (+info)
Identification of an integration center for cross-talk between protein kinase C and G protein modulation of N-type calcium channels.
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The modulation of presynaptic calcium channel activity by second messengers provides a fine tuning mechanism for neurotransmitter release. In neurons, the activation of certain G protein-coupled receptors reduces N-type channel activity by approximately 60%. In contrast, activation of protein kinase C (PKC) results in an approximately 50% increase in N-type channel activity, and subsequent G protein inhibition is antagonized. Here, we describe the molecular determinants that control the dual effects of PKC-dependent phosphorylation. The double substitution of two adjacent PKC consensus sites in the calcium channel domain I-II linker (Thr422, Ser425) to alanines abolished both PKC-dependent up-regulation and the PKC-G protein cross-talk. The single substitution of Ser425 to glutamic acid abolished PKC up-regulation but had no effect on G protein modulation. Replacement of Thr422 with glutamic acid eliminated PKC-dependent up-regulation and mimicked the effects of PKC phosphorylation on G protein inhibition. Our data suggest that Thr422 mediates the antagonistic effect of PKC on G protein modulation, while phosphorylation of either Thr422 or Ser425 are sufficient to increase N-type channel activity. Thus, Thr422 serves as a molecular switch by which PKC is able to simultaneously trigger the up-regulation of channel activity and antagonize G protein inhibition. (+info)