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Biomedical subjects

M A Pozo

Publications and source records attributed to M A Pozo.

At least 19 recordsLinked to original sources
PubMed2006

Evaluation of the effect of training using auditory stimulation on rhythmic movement in Parkinsonian patients--a combined motor and [18F]-FDG PET study.

INTRODUCTION: A programme of rehabilitation using auditory cues has previously been shown to decrease movement variability in the gait of Parkinsonian patients. OBJECTIVE AND METHODS: We studied the temporal variability of finger-tapping and gait in 9 patients with Parkinson's disease (PD) before and after they undertook a physical rehabilitation programme. Positron Emission Tomography (PET) using 2-deoxy-2[(18)F]fluoro-D-glucose (FDG) was performed in these subjects to look for changes in metabolic brain activity after completion of the rehabilitation program. RESULTS: The reduction of variability was seen not only in gait but also other repetitive movements such as finger tapping. Furthermore, here we show differences in resting regional cerebral glucose utilisation in these patients compared to healthy controls (significant hypometabolism-p < 0.001-for the PD group in the right parietal and temporal lobes, left temporal and frontal lobes and a hypermetabolism in the left cerebellum) and specific changes following the improvements in repetitive movement abilities (significant metabolic increment-p < 0.001-in the PD group in the right cerebellum and in the right parietal and temporal lobes). CONCLUSIONS: Although our study does not allow us to draw firm conclusions, it provides new information on the neural basis of auditory stimulation in PD. Our results extend those from previous studies to show improvement in the temporal variability of two types of rhythmic movements after participation by PD patients in a physical rehabilitation programme, along with changes in glucose uptake in several brain areas involved in sensorimotor processing.

Acoustic Stimulation↗
PubMed2003

Electrophysiological and morphological diversity of neurons from the rat subicular complex in vitro.

We combined whole-cell recordings with Neurobiotin labeling to examine the electrophysiological and morphological properties of neurons from the ventral subicular complex in vitro (including the subicular, presubicular, and parasubicular areas). No a priori morphological sampling criteria were used to select cells. Cells were classified as bursting (IB), regular-spiking (RS), and fast-spiking (FS) according to their firing patterns in response to depolarizing current pulses. A number of cells remained unclassified. We found 54% RS, 26% IB, 11% FS, and 9% unclassified cells out of a total of 131 neurons examined. We also found cells showing intrinsic membrane potential oscillations (MPO) (6%), which represented a subgroup of the unclassified cells. We analyzed several electrophysiological parameters and found that RS and IB cells can be subclassified into two separate subgroups. RS cells were subclassified as tonic and adapting, according to the degree of firing adaptation. Both responded with single spikes to orthodromic stimulation. IB cells were subclassified in two subgroups according to their capacity to fire more than one burst, and showed different responses to orthodromic stimulation. We observed that bursting in these two subgroups appeared to involve both Ca2+ and persistent Na+ components. Both IB and RS cells, as well as MPO neurons, were projecting cells. FS cells were morphologically identified as local circuit interneurons. We also analyzed the spatial distribution of these cell types from the vicinity of CA1 to the parasubicular areas. We conclude that, in contrast to the commonly accepted idea of the subicular complex as a bursting structure, there is a wide electrophysiological variability even within a given cellular group.

Action Potentials↗
PubMed2002

Excitatory and inhibitory control of epileptiform discharges in combined hippocampal/entorhinal cortical slices.

We examined whether epileptiform activity can be induced and prevented by mild reduction of GABA(A) receptor-mediated inhibition and non-NMDA receptor-mediated excitation, respectively, in different regions of combined hippocampal/entorhinal cortical slices from juvenile rats (P15-21). We used the receptor antagonists bicuculline (GABA(A)) and CNQX (non-NMDA) as tools to investigate the sensitivities of the CA1, the subiculum (SUB) and the medial entorhinal cortex (MEC) for generating epileptiform discharges upon extracellular stimulation. We found that low concentrations of bicuculline (<3.5 microM) were enough to induce epileptiform discharges in the three regions. These discharges were similar to those observed under high concentrations of bicuculline (>10 microM) and consisted of stereotyped population bursts, recorded both extra- and intracellularly. Interestingly, the CA1 and SUB were more susceptible to generate discharges compared to the MEC in the same slices. We also found that non-NMDA excitation was critical in controlling discharges, as they were blocked by CNQX in a concentration-dependent manner. The sensitivity of the CA1 region to CNQX was lower than that of the SUB and MEC. Based on these regional differences, we show that epileptiform activity can be pharmacologically isolated within the CA1 region in the hippocampal-entorhinal circuitry in vitro.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2002

The effect of different morphological sampling criteria on the fraction of bursting cells recorded in the rat subiculum in vitro.

In spite of the large variability of the fraction of bursting cells reported in the subiculum (from 54 to 100%), this structure has been considered as intrinsically bursting. Here, using visually assisted whole-cell recordings and Neurobiotin labeling in vitro, we correlated the electrophysiological firing modes of subicular cells (bursting, regular-spiking and fast-spiking) with their morphological characteristics (somatic size and shape). We then examined how different morphological sampling criteria for patching affect cell classification. We found a dramatic variability in the fraction of bursting cells, which ranged from 30 to 76% depending on the sampling criteria. We discuss the implications of these findings for the notion of the subiculum as an intrinsically bursting structure.

Action Potentials↗
PubMed2001

Semantic processing of open- and closed-class words: an event-related potentials study.

Previous research on open- and closed-class words has revealed the existence of several differences in the processing of these types of vocabulary. In this paper the processing of open- and closed-class words was compared by means of an early electrical brain response, recognition potential (RP), which indexes semantic processing and originates from basal extrastriate areas. The effects of word frequency on closed-class words were also investigated. For these purposes, open- and closed-class words, among other stimuli, were presented by means of the rapid stream stimulation procedure. Results showed that there were no significant differences when comparing the RP evoked by open- and closed-class words in the left hemisphere. However, in the right hemisphere this situation changed: the RP evoked by open- and closed-class words did differ. Moreover, there were no differences between the RP evoked by closed-class words and pseudowords. These patterns of results suggest that the semantic processing of closed-class words shares some aspects with the processing of open-class words, despite the existence of some differences. Thus, whereas the semantic processing of open-class words recruits brain areas of both hemispheres, the semantic processing of closed-class words is left-lateralized. A second purpose of this work is to study word-frequency effects on closed-class words. Our results show the insensitivity of closed-class words to word-frequency effects.

Adult↗
PubMed2001

Electrophysiological evidence of a semantic system commonly accessed by animals and tools categories.

Some theoretical perspectives propose a semantic system in which categories are represented in different brain regions. Others assume that distinctions are based rather on differences in the demands placed by different categories on shared processing systems. In this study semantic categorization processes were investigated using the recognition potential (RP), an event-related brain response that reflects semantic processing, peaks at around 250 ms after stimulus onset and originates in areas subserving perceptual-semantic analyses. Results indicate that the RP shows some degree of sensitivity to categorization processes, but that categories assumed to differ markedly in their processing demands share, to a large extent, a common neural generator. This provides support for the non-categorical view on the organization of the semantic system, though introducing subtle variations, and suggesting the existence of a semantic subsystem specializing in the processing of perceptual-semantic features regardless of the semantic category involved.

Adolescent↗
PubMed2001

Studying semantics in the brain: the rapid stream stimulation paradigm.

Event-related potentials (ERPs) provide information about the temporal course of cognitive processes in the brain. They have proved to be a valuable tool in order to explore semantic aspects of word processing. However, to date, research in this field has been mostly concerned with the study of post-lexical features by means of the N400-paradigm. We introduce here the rapid stream stimulation paradigm, in which stimuli reflecting different levels of linguistic information are presented to subjects at a high rate of stimulation. The present protocol shows in detail how this paradigm can be applied. The application of the rapid stream stimulation paradigm evokes the recognition potential (RP), an ERP component that peaks at around 260 ms after stimuli onset and seems to be reflecting lexical selection processes. Results of studies that revealed the sensibility of the RP to visual-semantic aspects and the location of its neural generators within basal extrastriate areas are reported. Although some research has been conducted with the rapid stream stimulation paradigm much remains still to be done. Some of the possibilities that this paradigm offers are further discussed.

Brain↗
PubMed2001

Biochemical, electrophysiological and neurohormonal studies with B-20991, a selective 5-HT1A receptor agonist.

Different receptor subtypes mediate the effects produced by serotonin (5-HT) in mammals. Besides their proved anxiolytic action, agonists of the 5-HT1A receptor subtype show prospects as antidepressants or neuroprotective agents in case of ischemia. In order to better define the pharmacological profile and determine the selectivity for the 5-HT receptor type, the properties of the new 5-HT1A receptor agonist 2[[4-(o-methoxyphenyl)piperazin-1-yl]-methyl]-1.3-dioxoperhydroimidazo[1.5-a]pyridine (B-20991), an arylpiperazine derivative, have now been further studied. B-20991 was found to antagonize the forskolin-induced increase of cAMP synthesis in a HeLa cell line transfected with the human 5-HT1A in a process sensitive to the selective blocker N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-cyclohexanecarboxamide maleate (WAY 100635). Additionally, B-20991 showed a dose-dependent inhibition of the spontaneous on-going activity of serotonin (5-HT) neurons in the dorsal raphe nucleus in rats, an effect that was reversed by treatment with WAY 100635. This, together with the fact that the hypothermia induced by B-20991 in mice was also antagonized by WAY 100635, suggests that the new compound acts upon somatodendritic 5-HT1A receptors. Additional activation of 5-HT1A postsynaptic receptors was indicated by the increase of corticosterone plasma levels induced by B-20991 in the rat. These results demonstrate that B-20991 is a selective 5-HT1A receptor agonist acting both pre- and postsynaptically, which represents an useful pharmacological tool to study 5-HT1A-receptor-mediated effects.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2000

Responses of nerve fibres of the rat saphenous nerve neuroma to mechanical and chemical stimulation: an in vitro study.

The response of neuroma nerve endings to different stimuli was studied in a saphenous nerve neuroma preparation in vitro. Electrical activity was recorded from 141 single fibres dissected of saphenous nerve. One-third (27 %) displayed spontaneous activity. Based on their response to mechanical and chemical stimuli, neuroma nerve fibres were classified as mechanosensory fibres (47.5 %), mechanically insensitive chemosensory fibres (17.0 %), polymodal nociceptor fibres (28.4 %) and unresponsive fibres (7.1 %). Mechanosensory and polymodal neuroma endings responded to von Frey hair stimulation either with a few impulses (phasic units) or a sustained discharge (tonic units). Polymodal units were additionally activated by at least one of the following stimuli: acidic solutions; a combination of bradykinin, prostaglandin E2, serotonin, substance P and histamine (all at 1 microM) plus 7 mM KCl (inflammatory soup); 600 mM NaCl and capsaicin. Low pH solutions increased the firing discharge of polymodal endings proportionally to the proton concentration. The 'inflammatory soup' evoked a firing response characterized by the absence of tachyphylaxis, which appeared when its components were applied separately. Both stimuli sensitized polymodal fibres to mechanical stimulation. Hypertonic NaCl (600 mM) and capsaicin (3.3 mM) induced a prolonged discharge that outlasted the stimulus duration. Mechanically insensitive chemosensory neuroma fibres exhibited responses to chemical stimuli analogous to polymodal fibres. They became mechanically sensitive after chemical stimulation. These findings show that neuroma nerve endings in the rat saphenous nerve neuroma in vitro are functionally heterogeneous and exhibit properties reminiscent of those in intact mechanosensory, polymodal and 'silent' nociceptor sensory afferents, including their sensitization by algesic chemicals.

Animals↗
PubMed2000

Attentional set shifting modulates the target P3b response in the Wisconsin card sorting test.

For years the Wisconsin card sorting test (WCST) has been used as a test of frontal lobe function. Recent event-related potential (ERP) research has shown large differences in the amplitude of P3b responses evoked by early and late trials within each WCST series ([8]: Barceló F., Sanz M., Molina V., Rubia FJ. The Wisconsin Card Sorting Test and the assessment of frontal function: A validation study with event-related potentials. Neuropsychologia 1997;35:399-408). In this study, 16 normal subjects performed a WCST adaptation to investigate the role of attentional set shifting in these WCST P3b effects. Two control tasks were designed to examine whether early-late WCST P3b changes reflect category selection (attention) or category storage (memory) operations. Results suggest both a sharp P3b attenuation during shift WCST trials, followed by a gradual P3b build-up during post-shift trials. This P3b modulation could not be attributed to selection or storage of simple sensory stimulus dimensions, nor was it observed when the new rule was externally prompted by the first card in the WCST series. Instead, WCST P3b changes seem related to the endogenously generated shift in the perceptual rule used to sort the cards (i.e., the shift in set). The gradual build-up in P3b amplitude paralleled a progressive improvement in sorting efficiency over several post-shift WCST trials. A model based on formal theories of visual attention and attentional set shifting is proposed to account for these effects. The model offers firm grounds for prediction and bridges the gap between related clinical and experimental evidence.

Adult↗
PubMed1997

Reduction of sensory responses to passive movements of inflamed knee joints by hylan, a hyaluronan derivative.

Hyaluronan (sodium hyaluronate) is a glycosaminoglycan that is present in all joint tissues. Painful arthritic joints have been characterized by hyaluronan of reduced elastoviscosity. The purpose of this investigation was to determine whether hyaluronan has an influence on joint nociceptor sensitivity and whether restoration of elastoviscosity would decrease nerve responses from nociceptive afferent fibers in arthritic joints. Nerve impulse activity was recorded from nociceptive afferent fibers of the medial articular nerve in anesthetized cats. An acute experimental arthritis was produced by intra-articular injection of kaolin and carrageenan. This caused, within 3 h, the development of ongoing nerve activity and enhancement of nerve impulse responses to passive movements in the normal range of the joint. Intra-articular injection of an elastoviscous solution of hylan, a hyaluronan derivative, significantly reduced both the ongoing activity and the movement-evoked responses in 1-2 h. This effect was not obtained when a nonelastoviscous solution of hylan was injected into the inflamed joint. The results indicate that intra-articularly injected elastoviscous solutions of hylan reduced nociceptive activity in inflamed joints through an elastoviscous, rheological effect on nociceptive afferent fibers through the intercellular matrix in which these fibers are embedded.

Afferent Pathways↗
PubMed1995

CO2 stimulation of the cornea: a comparison between human sensation and nerve activity in polymodal nociceptive afferents of the cat.

Excitation of nociceptors by low pH has been proposed as a cause of pain following tissue injury. Here we have studied the effect of pH reductions caused by application of CO2 pulses to the cornea on the activity of corneal afferent nerves of the cat and on the magnitude of pain sensations in humans. Single-unit activity was recorded from corneal afferent fibres in anaesthetized cats. The corneal receptive field of A-delta or C polymodal nociceptive units was exposed for 30 s to a gas mixture with different concentrations of CO2 in air (0, 35, 50, 65, 80 and 98.5%). Responses to CO2 were evoked at a mean threshold concentration of 40 +/- 3% CO2. They consisted of a discharge of impulses that decayed gradually to a tonic level. In 15% of the units the initial burst was absent. The CO2 concentration and firing frequency data could be fitted to a power function with an exponent of 1.12. Pulses of CO2 were also applied to the cornea of 16 human volunteers. Sensations experienced were measured by means of a visual analogue scale and a verbal descriptor scale. Flow was adjusted below the mechanical stimulation threshold (2.8 +/- 0.5 mg). When mixtures containing 10-90% CO2 in 5% steps were applied as 3 s pulses, threshold sensation, described as a mild stinging pain, was evoked at 33.5 +/- 4.0% CO2. This sensation became overtly painful with higher CO2 concentrations (47.5 +/- 3.6% CO2). For the same subject the sensory threshold was remarkably constant, though it changed with longer exposure times. The relationship between CO2 concentration and magnitude of pain could be adjusted to a power function with a power exponent of 1.12. Curves of CO2 concentration versus neural discharges in the cat and versus psychophysical sensation in humans were very similar. These results show that corneal polymodal nociceptors respond to protons, and encode changes in CO2 concentration presumably reflecting pH changes. The same stimulus evokes corneal pain sensations in humans, thus opening the possibility of using CO2 as an effective stimulus for corneal aesthesiometry.

Adult↗
PubMed1993

Response of sensory units with unmyelinated fibres to mechanical, thermal and chemical stimulation of the cat's cornea.

1. In the cat anaesthetized with sodium pentobarbitone, electrical activity was recorded from single unmyelinated sensory fibres innervating the cornea. 2. Based on their response to mechanical (calibrated aesthesiometer), chemical (10 mM acetic acid or 616 mM NaCl) and thermal (cooling from 35 to 5 degrees C; heating to 51 degrees C) stimuli, corneal unmyelinated fibres were classified as polymodal (71%) or 'cold' nociceptors (29%). 3. Polymodal units responded to mechanical indentation of the cornea and developed fatigue after repeated stimulation. They were excited by temperatures over 37 degrees C and exhibited sensitization to repeated heating. 4. Corneal polymodal units were also activated by topical application of 10 mM acetic acid and hypertonic NaCl (616 mM). Capsaicin (0.33 mM) elicited a discharge of impulses that was followed by inactivation to mechanical, chemical and thermal stimuli. 5. 'Cold' nociceptors had small receptive fields, preferentially located at the periphery of the cornea. They were excited by small temperature decreases of the corneal surface in a range between 30 and 8 degrees C, but were not responsive to noxious heat. 6. 'Cold' nociceptors encoded temperature changes between 35 and 23 degrees C. The discharge was proportional to the velocity of the temperature drop; sustained temperatures were not signalled by changes in static frequency values. 'Cold' nociceptive fibres responded to hypertonic NaCl (616 mM) and weakly to 10 mM acetic acid. Capsaicin (0.33 mM) first excited and then inactivated 'cold' nociceptors. 7. Thermoreceptive fibres were found in the episclera. They fired in bursts and responded to small temperature decreases, but were insensitive to irritant chemical and capsaicin.

Acetates↗
PubMed1993

Neurons in the rat spinal trigeminal complex driven by corneal nociceptors: receptive-field properties and effects of noxious stimulation of the cornea.

1. A survey of the receptive-field properties of neurons in the spinal trigeminal complex driven by stimulation of corneal afferents has been carried out. The afferent inputs to these neurons from the cornea and from the adjacent skin were studied as well as changes in the excitability of the cells and in the size of their receptive fields after thermal noxious stimulation of the cornea. 2. Single-unit electrophysiological recordings were made in pentobarbitone anesthetized rats from 54 neurons all of which were activated by mechanical stimulation of the ipsilateral cornea. Seventeen of these neurons were activated only by corneal stimulation and the other 37 had an additional cutaneous receptive field in the periorbital skin. Of the 37 neurons with a cutaneous receptive field, 29 were activated exclusively by noxious stimulation of the skin (Class 3) and the remaining 8 were driven by both innocuous and noxious cutaneous stimuli (Class 2). 3. All of the neurons were located in the ventro-lateral area of a region of the spinal trigeminal complex between +0.5 mm and -1.0 mm from the obex. This area corresponds to the most caudal part of subnucleus interpolaris, the transition zone between interpolaris and caudalis and the rostral half of subnucleus caudalis. Most neurons were located in the superficial layers of this part of the spinal trigeminal complex. No differences were observed between the locations of the recording sites of neurons with an exclusive corneal input and those with a corneal and a cutaneous receptive field.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗
PubMed1992

Blockade by calcium antagonists of chemical excitation and sensitization of polymodal nociceptors in the cat's cornea.

1. The possibility that a modified Ca2+ channel mediates chemical and thermal excitation of nociceptors was examined in single polymodal nociceptive fibres of the cat's cornea. 2. Ca2+ channel blockers cadmium (2.5 mM) and diltiazem (1 mM), and high external [Ca2+] (40 mM), markedly reduced nociceptive responses to topical acidic solutions (pH 4.5). 3. Decreasing the pH to 6.5 did not cause excitation, but reduced the subsequent response to pH 4.5 buffer. 4. Diltiazem (1 mM), applied after repeated stimulation with stepped heating pulses (35 to 47-49 degrees C in 2 degrees C steps) decreased the impulse responses elicited by heat. The decrease in threshold to thermal stimulation produced by repeated heating was blocked by diltiazem. 5. Mechanical threshold and mechanical responsiveness of corneal polymodal nociceptors was not modified by Ca2+ antagonists or by a high-Ca2+ solution. 6. These results offer indirect evidence that proton-activated Ca2+ channels mediate stimulation of nociceptors by acidic solutions. The same type of ionic channel appears to be involved in the response of nociceptors to heat and in sensitization, but not in their responsiveness to mechanical stimulation. The blockade of nociceptive responses by Ca2+ antagonists opens the possibility of using Ca2+ blockers as selective analgesic drugs.

Animals↗
PubMed1991

Excitation by irritant chemical substances of sensory afferent units in the cat's cornea.

1. Single-unit electrical activity was recorded from thin myelinated sensory nerve fibres innervating the cornea of deeply anaesthetized cats. 2. Based on their responses to mechanical (calibrated von Frey hairs), chemical (10 mM-acetic acid and/or 616 mM-NaCl) and thermal (ice-cold or heat up to 51 degrees C) stimuli, corneal A delta fibres were classified as polymodal nociceptors (63%), high-threshold mechanoceptors (22%) and mechano-heat nociceptors (15%). Thin myelinated fibres responding only to cold were found in the limbus of the eye. 3. Application of 10 mM-acetic acid on the corneal surface for 30 s evoked in polymodal fibres a brisk discharge of impulses often followed by a low-frequency impulse activity. NaCl (616 mM) produced a more gradual and sustained firing response. 4. The responses of polymodal fibres to acid were proportional to extracellular pH values (pH range: 4.5-6.0). After sensitization to repeated heating, most mechano-heat units developed a sensitivity to acidic stimulation. 5. Topical 0.33 mM-capsaicin excited polymodal nociceptors of the cornea; 5 min after capsaicin about 15% of these fibres were inactivated to all subsequent stimuli. In the rest of the fibres, chemical and thermal sensitivity disappeared after 0.33-3.3 mM-capsaicin, but mechanosensitivity was preserved. 6. Corneal mechanoceptors and limbal cold receptors were not affected by capsaicin (up to 33 mM). 7. These experiments demonstrate that the cornea of the cat is innervated by polymodal as well as mechanoceptive A delta nociceptors. In polymodal nociceptive fibres, mechanical and chemical sensitivities appear to be subserved by separate transduction mechanisms.

Acetates↗
PubMed1990

Effects of capsaicin on corneal wound healing.

This study examined whether the depletion of neuropeptides from sensory nerve terminals induced by capsaicin modifies the healing rate of experimental corneal wounds in adult rabbits. Capsaicin (33 or 3.3 mM solutions) was administered topically and/or by a single retrobulbar injection to one eye while the fellow eye, treated with the vehicle, served as a control. After 1-3 weeks of treatment, an epithelial wound was made in the center of the cornea of both eyes with n-heptanol. Migration rates of epithelial cells surrounding the wound and estimated wound closure times were calculated by measuring the reduction in wound size. Combined treatment with 33 mM retrobulbar and 3.3 mM topical capsaicin for 3 weeks induced a significant delay in epithelial migration rates and in wound closure times (P less than 0.05). Topical or retrobulbar capsaicin alone for 3 weeks and combined treatment lasting only 1 week were not sufficient to modify wound healing times. The substance P antagonist, spantide (3 mM), applied topically for 1-3 weeks before or immediately after corneal wounding was also ineffective in changing wound closure rates. These findings suggest that the delayed wound healing observed after prolonged treatment with capsaicin could be due to a sustained depletion of neuropeptides from corneal sensory endings, supporting the hypothesis that trophic effects of sensory nerves on corneal epithelium are, at least in part, mediated by neuropeptides contained in peripheral nerve terminals.

Administration, Topical↗