Biomedical subjects

François Tremblay

Publications and source records attributed to François Tremblay.

At least 19 recordsLinked to original sources

PubMed2006

Corticomotor facilitation associated with observation, imagery and imitation of hand actions: a comparative study in young and old adults.

In the present report, we extent our previous findings (Clark et al. in Neuropsychologia 42:105-122, 2004) on corticomotor facilitation associated with covert (observation and imagery) and overt execution (action imitation) of hand actions to better delineate the selectivity of the effect in the context of an object-oriented action. A second aim was to examine whether the pattern of facilitation would be affected by age. Corticomotor facilitation was determined in two groups of participants (young n = 21, 24 +/- 2 years; old n = 19, 62 +/- 6 years) by monitoring changes in the amplitude and latency of motor evoked potentials (MEPs) elicited in hand muscles by transcranial magnetic stimulation. MEP responses were measured from both the first dorsal interosseous (FDI, task selective muscle) and the abductor digiti minimi (ADM) of the right hand while participants attended to four different video presentations. Each of four videos provided specific instructions for participants to either: (1) close their eyes and relax (REST), (2) observe the action attentively (OBS), (3) close their eyes and mentally simulate the action (IMAG), or (4) imitate the action (IMIT). The action depicted in the videos represented a male subject cutting a piece of material with scissors. In the young group, the pattern of results revealed selective facilitation in the FDI in conditions involving either covert (OBS and IMAG) or overt action execution (IMIT). In the ADM, only overt execution with action imitation was associated with significant MEP facilitation. In the old group, a similar pattern of results was observed, although the modulation was less selective than that seen in the young group. In fact, older individuals often exhibited concomitant facilitation in both the FDI and ADM during either covert (OBS and IMAG conditions) or overt action execution (IMIT condition). Taken together, these results further corroborate the notion that the corticomotor system is selectively active when actions are covertly executed through internal simulation triggered by observation or by motor imagery, as proposed by Jeannerod (Neuroimage 14:S103-S109, 2001). With aging, the ability to produce corticomotor facilitation in association with covert action execution appears to be largely preserved, although there seems to be a loss in selectivity. This lack of selectivity may, in turn, reflect age-related alterations in the function of the corticospinal system, which may impair the ability to individuate finger movements either in the covert or overt stage of action execution.

Adult↗

PubMed2006

Corticomotor excitability associated with unilateral knee dysfunction secondary to anterior cruciate ligament injury.

In the present report, we investigated changes in corticomotor excitability associated with unilateral knee dysfunction secondary to anterior cruciate ligament (ACL) injury. Ten participants, each with a previous history of unilateral ACL injury (median time post-injury 22 months) and eight healthy controls underwent transcranial magnetic stimulation (TMS) to assess excitability of the lower limb motor representation. Resting motor thresholds (RMTs) and stimulus response curves were measured at rest, while amplitude of motor evoked potentials and silent period duration were measured during active contraction. Correlations between these indices of excitability and three clinical measures of knee function were identified. Paired comparisons of indices by hemisphere revealed an asymmetry only in RMTs, which were significantly reduced on the side of injury in the ACL group. Correlations with clinical measures showed that the extent of quadriceps motor representation, as reflected by the steepness of SR curves, was strongly associated with quadriceps strength (r 2=0.71) on the injured side. The RMT asymmetry reported here in the context of ACL injury is consistent with other recent reports describing enhanced excitability of corticomotor projections targeting muscles adjacent to an immobilized or a painful joint. In such conditions, alterations in the quantity and quality of sensory feedback from the affected limb may underlie the rise in cortical excitability.

Adult↗

PubMed2006

Formal enantioselective synthesis of (+)-compactin.

[reaction: see text] The challenging structural features and important biological activity of (+)-compactin (1) explain the substantial synthetic interest that it has generated. We report a novel enantioselective approach to the advanced intermediate 2a, which constitutes a formal synthesis of (+)-1. The sequence utilizes MacMillan's organocatalytic Mukaiyama-Michael reaction, which stereoselectively adds the silyloxyfuran 6 to alpha,beta-unsaturated aldehyde 7. The chirality generated in this reaction guides the formation of the other three consecutive stereocenters found in 2a.

Cyclization↗

PubMed2006

Importance of K+-dependent Na+/Ca2+-exchanger 2, NCKX2, in motor learning and memory.

Plasma membrane Na+/Ca2+-exchangers play a predominant role in Ca2+ extrusion in brain. Neurons express several different Na+/Ca2+-exchangers belonging to both the K+-independent NCX family and the K+-dependent NCKX family. The unique contributions of each of these proteins to neuronal Ca2+ homeostasis and/or physiology remain largely unexplored. To address this question, we generated mice in which the gene encoding the abundant neuronal K+ -dependent Na+/Ca2+-exchanger protein, NCKX2, was knocked out. Analysis of these animals revealed a significant reduction in Ca2+ flux in cortical neurons, a profound loss of long term potentiation and an increase in long term depression at hippocampal Schaffer/CA1 synapses, and clear deficits in specific tests of motor learning and spatial working memory. Surprisingly, there was no obvious loss of photoreceptor function in cones, where expression of the NCKX2 protein had been reported previously. These data emphasize the critical and non-redundant role of NCKX2 in the local control of neuronal [Ca2+] that is essential for the development of synaptic plasticity associated with learning and memory.

Animals↗

PubMed2006

Semiquantitative optic nerve grading scheme for determining axonal loss in experimental optic neuropathy.

PURPOSE: To describe and evaluate a semiquantitative optic nerve grading scheme for assessing axonal loss in endothelin (ET)-1-induced chronic optic neuropathy. METHODS: Optic nerve cross-sections from both eyes of 39 Brown Norway rats unilaterally treated with various concentrations of ET-1 or physiological saline solution via a surgically implanted osmotic minipump were processed for light and transmission electron microscopy (TEM). The optic nerve damage grade, between 0 (no damage) and 10 (total damage), was based on the number of zones of approximately equal damage and the mean percentage of damage within each zone. Grading was performed under light microscopy by three observers and compared with axonal survival determined with TEM using two quantification methods: the sampling method, in which approximately 10% of the section was counted, and the full-count method, in which the whole section was counted (n = 12). Axonal survival was expressed as a ratio of axon counts in the experimental to control eye. Before these comparisons, the inter- and intraobserver agreement rates were determined in another group of 85 and 12 ET-1-treated animals, respectively. RESULTS: The interobserver kappa was 0.66 (95% confidence interval [CI]: 0.58-0.74) for all eyes and 0.55 (95% CI: 0.43-0.67) for the experimental eyes only. The intraobserver kappa was 0.80, 0.81, and 0.80 for all 24 eyes and 0.60, 0.64, and 0.71 for experimental eyes only. The correlation between damage grade in the experimental eye and axonal survival using the TEM sampling method (Spearman's rho = -0.677 for all animals and -0.827 for the subset of animals with full counts only) was lower than that with the full-count method (Spearman's rho = -0.926). When axonal survival was less than 0.7, the sampling method always underestimated the extent of damage. CONCLUSIONS: The grading scheme had good inter- and intraobserver agreement, and high correlation with the TEM methods. It is a practical and time-saving method, requiring less than 1 minute per nerve and is an alternative to sampling methods that can yield significant errors.

Animals↗

PubMed2005

Retinal ganglion cell activity from the multifocal electroretinogram in pig: optic nerve section, anaesthesia and intravitreal tetrodotoxin.

Non-invasive recordings of the retinal activity have an important role to play in the diagnosis of retinal pathologies. The detection of diseases that involve retinal ganglion cells (RGCs), such as optic atrophy and glaucoma, may be improved by isolating the RGC contribution from the multifocal electroretinogram (mfERG). In this study, mfERGs were performed on 20 pigs, 1-6 weeks following unilateral retrobulbar optic nerve section (ONS). The stimuli were 103 non-scaled high-contrast hexagons from which summed and individual mfERG responses were obtained in experimental and control fellow eyes under conditions of ketamine (n = 11) or isoflurane anaesthesia (n = 9). The effect of intravitreal injection of tetrodotoxin (TTX; n = 6) was also investigated. The summed mfERG responses showed a first positive peak (P1) with a short latency (21 ms) followed by two smaller peaks (P2 and P3) of longer latency (46 and 65 ms, respectively). While P2 and P3 amplitude were highly correlated with the time post-optic nerve section (ONS) (P2: r(2) = 0.669; P = 0.007; P3: r(2) = 0.651; P = 0.005), P1 was not (r(2) = 0.193; P = 0.38). P1 and P2 showed no implicit time variation as a function of retinal location, while P3 implicit time varied along the axis of the visual streak, generating a naso-temporal asymmetry. However, the P3 implicit time did not vary consistently with distance away from the optic nerve head. Intravitreal injections of TTX reduced P2 and P3 in the control eyes, consistent with the effect of ONS, and also induced a series of regular oscillations lasting up to 200 ms post stimulus. Under isoflurane anaesthesia, all components of the mfERG ifn experimental and control eyes were, at all time points post-ONS, of similar amplitude and without naso-temporal asymmetry, suggesting a reduced participation of RGCs under these anaesthesic conditions. These data clearly demonstrate that it is possible to isolate the RGC contribution from non-invasive multifocal electroretinography.

Anesthesia↗

PubMed2005

Tracer coupling of neurons in the rat retina inner nuclear layer labeled by Fluorogold.

A subpopulation of neurons in the inner nuclear layer (INL) of the rat retina were labeled 9-13 weeks after application of Fluorogold (FG) to the superior colliculus. Neurobiotin injection of FG-labeled cells in the INL of flatmounted living retina revealed that these cells consisted of both displaced ganglion cells and a subset of amacrine cells. Fluorogold-labeled amacrine cells in the INL showed tracer coupling to other presumptive amacrine cells in the INL, but there was no evidence of coupling to neurons in the ganglion cell layer (GCL). As the labeling of amacrine cells by FG may be due to gap junction coupling between ganglion and amacrine cells, these data add to the evidence that tracer coupling between these cells can be unidirectional. Some of the FG-labeled displaced ganglion cells in the INL injected with Neurobiotin also showed tracer coupling to neurons in the INL or GCL.

Amacrine Cells↗

PubMed2005

Postural stabilization from fingertip contact II. Relationships between age, tactile sensibility and magnitude of contact forces.

In the present report, we extend our previous observations on the effect of age on postural stabilization from fingertip contact (Exp Brain Res 157 (2004) 275) to examine the possible influence of sensory thresholds measured at the fingertip on the magnitude of contact forces. Participants (young, n=25, 19-32 years; old, n=35, 60-86 years) underwent psychophysical testing of the right index finger to determine thresholds for spatial acuity, pressure sensitivity and kinesthetic acuity. Spatial acuity was determined from the ability to detect gaps of different widths, while Semmes-Weinstein monofilaments were used for pressure sensitivity. Kinesthetic acuity was determined by asking participants to discriminate plates of different thicknesses using a thumb-index precision grip. These tests were selected on the basis that each reflected different sensory coding mechanisms (resolution of spatial stimuli, detection of mechanical forces and integration of multi-sensory inputs for hand conformation) and thus provided specific information about the integrity and function of mechanoreceptive afferents innervating the hand. After log transformation, thresholds were first examined to determine the influence of age (young and old) and gender (male, female) on tactile acuity. Sensory thresholds were then entered into multiple linear regression models to examine their ability to predict fingertip contact forces (normal and tangential) applied to a smooth surface when subjects stood with eyes closed on either a firm or a compliant support surface. As expected, age exerted a significant effect (p<0.01) on all three thresholds, but its impact was greater on spatial acuity than on pressure sensitivity or kinesthetic acuity. Gender had a marginal impact on pressure sensitivity thresholds only. The regression analyses revealed that tactile thresholds determined at the index fingertip accounted for a substantial proportion of the variance (up to 30%) seen in the contact forces deployed on the touch-plate, especially those exerted in the normal direction. The same analyses further revealed that much of the variance explained by the models arose from inter-individual differences in tactile spatial acuity and not from differences in pressure sensitivity or in kinesthetic acuity. Thus, of all three tests, the spatial acuity task was the most sensitive at detecting differences in hand sensibility both within and between age groups and, accordingly, was also better at predicting the magnitude of fingertip forces deployed for postural stabilization. Since spatial acuity is critically dependent upon innervation density, we conclude that the degree of functional innervation at the fingertip was likely an important factor in determining the capacity of older participants to use contact cues for stability purposes, forcing the most affected individuals to exert unusually high pressures in order to achieve stabilization in the presence of reduced tactile inputs arising from contact with the touched surface.

Adult↗

PubMed2005

Weight discrimination after anterior cruciate ligament injury: a pilot study.

OBJECTIVE: To determine whether the ability to discriminate weights remained accurate after anterior cruciate ligament (ACL) injury. DESIGN: Descriptive case series. SETTING: Outpatient physical therapy. PARTICIPANTS: Convenience sample of 10 participants with unilateral ACL injuries (age, 27.1+/-8.2 y) and 8 healthy controls (age, 22.6+/-2.8 y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Weber fractions, expressed as percentage differences from the standard weight (3.00 kg) that could be reliably detected (75% correct level), were derived from each leg to provide an index of proprioceptive acuity for weight discrimination. Subjective ratings of knee function (Activities of Daily Living Scale of the Knee Outcome Survey) and measurements of quadriceps strength (peak isometric torque). RESULTS: The ACL group exhibited a reduced acuity to detect differences in weight on the injured, as compared with the uninjured, side as reflected in the increase in Weber fractions (mean, 6.7%+/-2.3% vs 4.8%+/-1.1%, respectively; P = .043). No such difference in acuity between legs was detected in healthy controls (mean right and left, 5.4%+/-1.4% vs 5.7%+/-1.3%, respectively, P = .99). CONCLUSIONS: Proprioceptive acuity for weight discrimination was significantly reduced after an ACL injury, possibly reflecting deficits in the ability to properly calibrate force signals generated while muscles are actively contracting, as a result of a loss in ligamentous sensory innervation.

Activities of Daily Living↗

PubMed2004

Postural stabilization from fingertip contact: I. Variations in sway attenuation, perceived stability and contact forces with aging.

In this study, we compared the ability of young (n=10, 19-32 years) and older subjects (n=35, 60-86 years) to use fingertip contact as a balance aid during quiet stance under various conditions to determine whether aging would influence contact strategies. Experimental trials (duration, 60 s) included two visual conditions (vision; no vision), three fingertip contact conditions (no touch; smooth touch; rough touch) and two support surface conditions (firm; foam). In trials with contact, participants were required to maintain a light contact with their right index fingertip on an instrumented touch-plate. Subjects were not constrained to exert minimal contact force, although they were aware that the touch-plate was not designed for physical support. From displacements of the centre of foot pressure (COP), mean sway amplitude (MSA) was computed in the anterior-posterior (COP(AP)) and medio-lateral (COP(ML)) directions. Subjective estimates of stability were also obtained by asking participants to rate perceived stability on a visual analog scale in each condition. Mean normal force (FN) and mean resultant tangential force (F(TAN)) were computed from contact force data applied on the touch plate. In both age groups, touch conditions had a substantial effect on MSA in the AP direction under both support surface conditions, with reductions averaging between 40-55% when touch was allowed. Reductions in the ML direction, though less important (8-12% on average), were nevertheless highly significant, especially in the older subjects when standing on the foam. In the two groups, vision and texture had only marginal impact on MSA computed on both support surfaces. Contrasting with sway measurements, stability ratings were highly influenced by visual conditions in both age groups. Only in conditions of deficient support (foam surface) and absent vision did the perceived effect of touch exceed that of vision. Age had a major impact, however, on contact forces deployed during trials with touch. While individuals in the young group typically produced forces of <1 N (mean FN, 0.32+/-0.15 N) to achieve postural stabilization, older subjects tended to use higher, though not too excessive, contact forces (mean FN, 1.21+/-0.75 N) under the same conditions. From these findings, we conclude that the ability to use contact cues from the fingertip as a source of sensory information to improve postural stability is largely preserved in healthy older adults. The increase in contact force deployed by older individuals to achieve postural stabilization is interpreted as a compensatory strategy to help overcome age-related loss in tactile sensation, an issue that will be further addressed in a companion paper.

Adult↗

PubMed2004

Differential modulation of corticospinal excitability during observation, mental imagery and imitation of hand actions.

In this study, we attempted to better delineate the changes in corticospinal excitability that accompany perceptual to motor transformations when people are asked to observe, image or imitate actions. Motor evoked potentials (MEP) from transcranial magnetic stimulation were recorded in the first dorsal interosseous (FDI) muscle of the dominant hand (15 right, 4 left) in five different conditions: (1) passive observation; (2) observation to imitate; (3) imagery; (4) imitation; and (5) counting backwards mentally. MEPs were also recorded at rest at the beginning and at the end of the session to establish baseline (BL) values. For the observation conditions, participants (n=19, 18-38 years) watched video sequences (5s) of hand actions performed by a model with the right arm (passive observation: scissors; observation to imitate: OK sign). Active imitation produced the greatest MEP facilitation compared to baseline, followed by the two observation conditions and the imagery conditions, which all produced similar levels of facilitation (post hoc comparisons). Mental counting produced some facilitation, but this effect was inconsistent. Baseline MEPs remained stable at the end of the session. A further comparison between right-handers (n=15) and left-handers (n=4) revealed no difference in the pattern of modulation across conditions. The similarity found between observation and imagery of hand actions in terms of corticospinal facilitation is interpreted in the light of the motor-simulation theory of Jeannerod [Neuroimage 14 (2001)], which proposes that perceiving actions involves neural simulation of the same action by the observer, thereby explaining the parallel between actions observed and actions imaged at the representational level.

Adolescent↗

PubMed2004

Model of endothelin-1-induced chronic optic neuropathy in rat.

PURPOSE: To describe a model of chronic endothelin (ET)-1 administration to the optic nerve and evaluate its effect on retinal ganglion cell (RGC) and axon survival in rat. METHODS: Osmotic minipumps were surgically implanted in one eye of 113 Brown Norway rats to deliver 0.05, 0.10, 0.20, or 0.40 microg ET-1 per day (3.3, 6.7, 13.4, and 26.8 microM, respectively), or balanced salt solution (BSS) to the immediate retrobulbar optic nerve; the fellow untreated eye served as the control. Before pump implantation, RGCs were retrogradely labeled with fluorochrome. Animals were killed at 21, 42, or 84 days. RGC survival was expressed as the ratio of RGC counts in experimental versus control eyes in wholemounted retinas, whereas axon survival was expressed similarly from electron micrographs of the optic nerves. Serial optic disc changes were evaluated using scanning laser tomography. The effect of ET-1 (3 microL topical application of 10(-5) M) on blood flow in the surgically exposed optic nerve was measured using laser Doppler flowmetry in a separate group of five animals. RESULTS: ET-1 led to a mean reduction in optic nerve blood flow of 68%. There were no significant differences in RGC survival among the four ET-1 doses used in this study. Pooled across all ET-1 doses, RGC survival decreased incrementally at 21, 42, and 84 days (P < 0.001; mean +/- SD, 0.77 +/- 0.25, 0.60 +/- 0.27, and 0.50 +/- 0.26, respectively) and was statistically significantly lower at each time point than in the BSS-treated animals. The axon survival data also showed a similar time-dependent loss. Only one of 21 animals showed significantly increased disc cupping, and there was no relationship between RGC survival and change in cupping. CONCLUSIONS. Chronic administration of ET-1 to the rat optic nerve results in a time-dependent loss of RGCs and their axons without apparent change in optic disc topography.

Animals↗

PubMed2003

Sphingosine 1-phosphate effect on endothelial cell PAF synthesis: role in cellular migration.

Sphingosine 1-phosphate (S1P) and vascular endothelial growth factor (VEGF) are two inflammatory mediators capable of promoting endothelial cell (EC) migration and angiogenesis. As VEGF inflammatory effect is mediated by the synthesis of endothelial platelet-activating factor (PAF) which is also contributing to VEGF chemotactic activity, we wanted to assess if S1P can trigger PAF synthesis in EC and if S1P-induced migration is PAF-dependent. Treatment of bovine aortic EC (BAEC) with S1P (10(-10)-10(-6) M) increased dose- and time-dependently the synthesis of PAF by up to 3.3-fold above the basal level, with a maximal amount of PAF detected at 20 min post-stimulation. This biological response was attenuated by inhibiting p38 mitogen-activated protein kinase (MAPK), cytosolic or secreted phospholipase A(2) (cPLA(2), sPLA(2)) activity, suggesting that p38 MAPK activation by S1P promotes the conversion of membrane phospholipids into PAF through the combined activation of cPLA(2) and sPLA(2). Interestingly, pretreatment of BAEC with extracellular PAF receptor antagonists (BN52021, 10(-5) M and CV3988, 10(-6) M) reduced by up to 42% the cellular migration induced by S1P (10(-6) M). These data demonstrate the capacity of S1P to induce PAF synthesis, which contributes in part to S1P chemotactic activity.

Animals↗

PubMed2003

HPMPC therapy of MCMV-induced retinal disease in the SCID mouse measured by electroretinography, a non-invasive technique.

The purpose of these studies was to investigate the use of non-invasive electroretinography for the evaluation of retinal disease and its treatment in an ocular murine cytomegalovirus (MCMV) disease model. While under anesthesia, 10(2.6)plaque forming units (pfu) of salivary gland passaged, Smith strain MCMV was injected in the anterior chamber of 6- to 8-week-old severe combined immunodeficiency (SCID) mice. At various times post-inoculation, bright-flash scotopic electroretinogram, viral titer, and histology were obtained from the injected eye. Antiviral therapy was tested using 0.1 and 5mg/kg/day subcutaneous injections of HPMPC (Cidofovir) once daily for 5 consecutive days. In infected animals, the a- and b-waves of the electroretinographic (ERG) signal were significantly reduced as of 10 days post-inoculation when compared to control animals. Therapy with HPMPC 0.1mg/kg/day subcutaneously (s.c.) once daily for 5 consecutive days was able to delay the decrease in ERG wave amplitude and inhibit viral replication, whereas 5mg/kg/day s.c. significantly protected the ERG, completely inhibited viral replication, and maintained ocular viral titer below the limit of detection for up to 17 days post-infection. The reduction of ERG activity during progression of retinal disease correlated well with reduction of disease pathology. ERG recording represents a valuable non-invasive technique to measure the progression of the retinal disease induced by MCMV and the efficacy of antiviral treatment in the ocular MCMV disease model.

Animals↗

PubMed2003

Alteration of electroretinographic recordings when performed under sedation or halogenate anesthesia in a pediatric population.

Fran The effects of sedation and of halogenate anesthesia on electroretinographic recordings were investigated by reviewing the hospital charts of 27 patients who were eventually diagnosed free of retinal disease. The same ERG protocol was performed in conscious (n=9), sedated (chloral hydrate or pentobarbital sodium, n=9) and anesthetized (halothane or isoflurane, in combination with N2O, n=9) young patients. Sedation decreased the a- and b-wave amplitude of the scotopic bright-flash response, without affecting implicit times. ERG recordings performed in photopic conditions showed minimal disturbances. Anesthesia spared the a-wave of the scotopic bright-flash response but decreased more severely the b-wave. In addition, anesthesia reduced the amplitude and prolonged the implicit time of the photopic responses, affecting predominantly the ionotropic glutamate dependent OFF components (peak of b-wave, 0P4 and 0P5). The normal retinal physiology is affected by sedation and anesthesia through different mechanisms that still remain to be fully elucidated. These alterations in electroretinographic recordings must be considered when evaluating ERGs obtained under similar sedation/anesthetized conditions.

Anesthetics, Inhalation↗

PubMed2003

Tactile spatial acuity in elderly persons: assessment with grating domes and relationship with manual dexterity.

In this study, we sought to better define the limit of spatial resolution at the fingertips of elderly participants (n = 30, age 60-95 years) using an extended set of JVP grating domes, incorporating four new grating dimensions (2.5-, 3.5-, 4.0- and 4.5-mm width). A secondary aim was to examine whether deficits in tactile acuity could be related to hand dysfunction in older adults. Spatial resolution thresholds were determined by the finest grating whose orientation (dominant index finger) could be reported reliably. Manual dexterity was assessed with the Grooved Pegboard Test (GPT). The extended set of domes improved threshold measurements in a majority of participants (21/30). Still, accurate threshold estimates could not be obtained in one third of the participants, mostly in the older age group (8/9, 74-95 years). Grating resolution thresholds at the index finger were strongly correlated (r = 0.66, p<0.01) with dexterity scores derived from the GPT. From these results, we conclude that the 2.5- and 3.5-mm grating domes are suitable additions when assessing spatial acuity at the fingertips of older subjects between 60 and 70 years of age (mean threshold, 2.7+/-0.6 mm). For the older ones, the 4.0- and 4.5-mm domes can improve threshold measurements but interpretation of values can be complicated by the presence of undiagnosed pathologies (e.g., diffuse polyneuropathy) as people advance in age. The strong relationship between grating resolution thresholds and dexterity scores indicates that an impaired spatial acuity at the fingertips may translate into great difficulties in tasks requiring fine manipulations. These findings have important implications for the assessment of hand function in older adults.

Aged↗

PubMed2002

Central neural mechanisms contributing to the perception of tactile roughness.

This paper summarizes recent work showing that tactile roughness appreciation increases in a nearly linear fashion as tactile element spacing or spatial period (SP, distance centre-to-centre between raised dots in these experiments) is increased from 1.5 to 8.5 mm. Although a previous study had reported a U-shaped psychophysical function peaking at a nominal SP of 3.2 mm, differences in the surfaces (including changing SP in only one dimension as compared with two and higher dot heights that minimized contact with the smooth floor) likely contributed to the difference in the results. Roughness estimates were also unaffected by a 2-fold change in scanning speed (50 vs. 95 mm/s). Parallel recordings from neurones in primary somatosensory cortex (SI) during a texture discrimination task indicate that the discharge frequency of many SI cells shows a monotonic relation with SP (up to 5 mm tested). For some cells, the texture signals were ambiguous because discharge frequency co-varied with both texture and the scanning speed, as has also been reported for the peripheral mechanoreceptors that are activated by textured surfaces. Yet other SI cells showed a speed-invariant response to surface texture, consistent with perceptual constancy for roughness over a range of scanning speeds. We suggest that such a discharge pattern could be based on a simple intensive, or mean rate, code: an invariant central representation of surface texture could be obtained by subtracting a speed-varying signal from the ambiguous signals that co-vary with roughness and speed.

Animals↗

PubMed2002

Localization of adenylyl cyclase proteins in the rodent retina.

The isoforms of adenylyl cyclase that mediate cyclic AMP signaling pathways in the retina are, for the most part, unknown. Therefore, the protein expression patterns of adenylyl cyclase isoforms in the rodent retina were characterized immunocytochemically using antibodies directed against Ca(2+)-stimulated (AC1, AC3 and AC8), Ca(2+)-inhibited (AC9) and Ca(2+)-insensitive (AC2, AC4, AC7) isoforms of adenylyl cyclase. The ganglion cell layer and the inner nuclear layer (INL) were immunoreactive for both Ca(2+)-sensitive (AC1, AC3) and Ca(2+)-insensitive (AC2, AC4) isoforms of adenylyl cyclase. Antibodies against isoforms from all three classes of adenylyl cyclase labeled the inner plexiform layer. In the outer retina, antibodies against Ca(2+)-insensitive isoforms labeled photoreceptors and the outer plexiform layer (OPL). Radial elements in the ONL and INL were AC4-immunoreactive and the nerve fibre layer and optic nerve were AC2-, AC4- and AC9-immunoreactive. Antibodies against AC7 did not label rodent neural retina. These data indicate that there is a heterogeneous distribution of adenylyl cyclase isoforms throughout the rodent retina. Nonetheless, there is a general indication of a greater expression of Ca(2+)-insensitive adenylyl cyclase isoforms in the outer retina, particularly within photoreceptors.

Adenylyl Cyclases↗