Biomedical subjects

V Perciavalle

Publications and source records attributed to V Perciavalle.

At least 19 recordsLinked to original sources

PubMed2001

Tiagabine treatment and DNA damage in rat astrocytes: an in vitro study by comet assay.

We studied in vitro the effects of Tiagabine on genomic DNA of cortical rat astrocytes. To evaluate DNA damage, we used a relatively simple technique called Single Cell Gel Electrophoresis or Comet assay. Tiagabine was dissolved in culture medium and added at concentration of 1, 10, 20 and 50 microg/ml on 12-day old cultured astrocytes. In presence of 1 and 10 microg/ml of Tiagabine, no DNA damage was observed after 48 h of treatment. A moderate DNA damage was instead observed for cells exposed to 20 microg/ml of antiepileptic drug. Finally, DNA fragmentation was more evident after treatment with 50 microg/ml of Tiagabine. We conclude that Tiagabine, at the usual recommended doses, does not appear to influence negatively the cortical rat astrocytes, inducing DNA fragmentation only at very high concentrations.

Animals↗

PubMed2001

Effects of Gabapentin and Topiramate in primary rat astrocyte cultures.

We studied in vitro the effects of anticonvulsant drugs Gabapentin and Topiramate on the production of reactive oxygen species and nitric oxide (NO), the activity of glutamine synthetase (GS), and cell viability in primary cultures of rat cortical astrocytes which are intimately involved in the normal functioning of neurons. We investigated the effects of these drugs at concentrations within the therapeutic range (1, 10 and 50 microg/ml). We observed that, in cultured astrocytes, Gabapentin induced a weak increase in the biosynthesis of NO, a mild decrease in GS activity and cell viability, and minor induction of a stress condition. Topiramate was observed to induce even greater stressor effects on these cells.

Acetates↗

PubMed2000

Biological effects of tiagabine on primary cortical astrocyte cultures of rat.

Biological effects of tiagabine, a new antiepileptic drug, were analyzed on cultures of rat's cortical astrocytes. Tiagabine was added to the cultures at concentrations of 1 and 10 microg/ml, correspondent to therapeutic range; cell viability (tetrazolium salt assay and lactic dehydrogenase release), maturation and differentiation (glutamine synthetase activity) and presence of stress conditions (reactive oxygen species formation, inducible nitric oxide synthetase expression and 70 kDa heath shock protein production) were tested. Our results indicate that the addition of Tiagabine to primary astrocytes not only did not change significantly the examined metabolic activities but also seems to exert a protective action against oxidative stress. Thus, our data reinforce the idea that Tiagabine may be considered an effective promising drug in the treatment of epilepsy.

Animals↗

PubMed2000

Sensory representation of passive movement kinematics by rat's spinocerebellar Purkinje cells.

In this paper we examined Purkinje cells' sensory representations of kinematic parameters of passive movements imposed to the forelimb of anesthetized rats. Simple spike Purkinje cell activity was recorded while the rat's ipsilateral forearm was moved passively along circular footpaths at two different speeds. We found that the activity of 35.33% (165/467) of the neurons was significantly modulated during movement cycles. A multivariate regression analysis indicated that movement direction was the predominant factor in determining Purkinje cell activity, whereas movement velocity (i.e. the combination of movement direction and speed) was represented to a much lesser degree. Based on this result, we might suggest that a cortical efferent copy is necessary to the cerebellum in order to elaborate a movement velocity signal.

Action Potentials↗

PubMed2000

Distribution of spinocerebellar Purkinje cell responses to passive forelimb movements in the rat.

We recorded Purkinje cell activity throughout the spinocerebellum of anaesthetized rats while imposing circular passive movements to the unrestrained forelimb. The aim was to understand the type of processing of sensory information occurring at the level of the cerebellar cortex, on the basis that precerebellar sensory neurons have been shown to represent whole limb movement parameters better than single joint movements. We observed that neurons representing sensory aspects of arm movements were scattered throughout the spinocerebellar cortex without a distinct segregation from those that did not respond, albeit the relative density of responsive and unresponsive neurons was quite variable and depended on the area of the cortex. Furthermore, Purkinje cells that responded significantly to the arm movement cycles all showed the same response pattern consisting of a firing rate increase during the downward extension of the arm. These results are discussed as suggesting a coordinate framework for the representation of proprioceptive information in the cerebellum congruent to that observed for encoding motor parameters.

Animals↗

PubMed2000

C-Fos expression in the basilar pontine nuclei and reticulotegmental nucleus of the rat following lateral cerebellar nucleus stimulation.

The present study was carried out with the aim to observe whether, in the rat, the electric activation of the projection form the cerebellar lateral nucleus (LN) to the basilar pontine nuclei (BPN) and to the reticulotegmental nucleus (RtTg) is capable to induce the c-Fos expression. In particular, we compared the effects of a continuous LN stimulation at low-frequency (tonic stimulation) with those induced by high frequency pulse trains (phasic stimulation). The observed results show that the stimulation of LN induces c-Fos expression in a significant fraction of neurons in the contralateral BPN and RtTg. It was also observed that phasic stimulation was slightly more capable in producing c-Fos expression with respect to the tonic stimulation. Furthermore, systemic injection of MK-801, a non-competitive antagonist of the NMDA receptor, reduced the LN-induced c-Fos expression in BPN and RtTg. In contrast, GYKI 52466, an AMPA/kainate receptor antagonist, did not change the LN driven induction of c-Fos in both BPN and RtTg.

Animals↗

PubMed1999

Cortical control of cerebellar dentato-rubral and dentato-olivary neurons.

The cortical input of 117 dentate nucleus neurons projecting either to the red nucleus (73 cells) or to the inferior olive (44 units) was studied electrophysiologically in rats. The majority of cells in both groups responded to electrical stimulation of discrete sites of the contralateral motor cortex. However, activation latencies from the same cortical focus were shorter for neurons projecting to the red nucleus than for olivary-projecting neurons. Principal components analysis pointed out significant differences between the two neuronal subgroups also in the temporal pattern of activity. These results suggest that a motor command might be transmitted through parallel independent channels to cerebellar neurons projecting to different regions of the brainstem.

Animals↗

PubMed1999

On the relation of rat's external cuneate activity to global parameters of forelimb posture.

Using anesthetized adult rats, we studied the relationships between the activity of cells belonging to the external cuneate nucleus (ECN) and passive forelimb positions. In essence, we sought to distinguish between a representation of limb position based on local limb parameters (individual joint angles, for example) or a representation based on more global parameters such as the length and the orientation of the limb axis. Using multivariate regression analyses we found that most neurons showed strong linear relationships with the length and the orientation of the limb axis. Relationships to individual joint angles were, instead, rather weak and in most cases not significant. This result implies an extensive integration of sensory information at the level of second order sensory neurons.

Animals↗

PubMed1998

Spinocerebellar Purkinje cells and rat forelimb postures: a direction-dependent activity.

On anesthetized adult rats, we examined the possibility that the discharges of spinocerebellar Purkinje cells (PCs) are modulated by passive limb positioning. The rat forelimb was passively placed in four different sagittal positions while the simple spike spontaneous activity of single PCs was recorded; recordings started 5 s after the reaching of the posture and the forelimb remained at each position for at least 30 s. Although the activity of the PCs did not reflect the forelimb position, it showed hysteresis that depended in a cosine fashion on the direction of the preceding movement. This implies that the directional sensitivity of spinocerebellar PCs is persistent, since the activity levels were almost constant throughout the recording time.

Action Potentials↗

PubMed1998

Spatial organization of proprioception in the cat spinocerebellum. Purkinje cell responses to passive foot rotation.

This study examines the spinocerebellar locations of Purkinje cells that responded to passive foot rotations at the ankle joint in anaesthetized cats. Using a novel approach for mapping the locations of recorded cells from several animals onto an unfolded two-dimensional representation of the cortex, we found that cells distributed throughout the anterior-posterior extent of the spinocerebellar cortex, except in the most medial parts corresponding to zones a and b, were responsive to ankle joint rotation. The cell distributions revealed a clustering according to their response amplitudes, which showed evidence for both parasagittal and transverse banding.

Animals↗

PubMed1996

Effects of the retrorubral field stimulation on the excitability of the rat hippocampus in vivo.

We studied in vivo the influences exerted by the retrorubral field (RRF) on the on commissural-evoked CA1 pyramidal cell excitability in the rat hippocampal formation (HF). The stimulation of RRF before the activation of the contralateral CA3 area evoked in all the studied rats a reduction in amplitude of the evoked population spike in the CA1 pyramidal cell body layer of both the dorsal and the ventral HF. No significant differences in the intensity of the inhibitory effect were observed between dorsal and ventral parts of the HF. The stimulation of the ipsilateral RRF reduced the amplitude of the evoked population spike in a higher degree with respect to the contralateral side. Since these side-to-side differences were significant, it can be concluded that the RRF-induced inhibitory effect is stronger on the ipsilateral CA1 pyramidal cells. The inhibitory effect appears within 0.1 s of stimulating the RRF, reaches its maximal effect around 0.4-0.5 s following the conditioning train and returned to its control size after 5 s.

Animals↗

PubMed1996

c-fos expression in the accessory oculomotor nuclei following neocerebellar stimulation.

The present study was carried out to determine whether, in the rat, the electric activation of the projection from the cerebellar lateral nucleus (LN) to the accessory oculomotor nuclei (AON; nucleus of posterior commissure, nucleus of Darkschewitsch, interstitial nucleus of Cajal) is capable of inducing c-fos expression. In particular, we compared the effects of a continuous LN stimulation at low-frequency (tonic stimulation) with those induced by high frequency pulse trains (phasic stimulation). The observed results show that the stimulation of LN induces c-fos expression in a significant proportion of neurones in the contralateral AON. Phasic stimulation was slightly more effective than tonic stimulation in producing c-fos expression.

Analysis of Variance↗

PubMed1996

The projections of the retrorubral field A8 to the hippocampal formation in the rat.

The dopaminergic neurons in the midbrain of the rat are located in three groups: the ventral tegmental area (VTA-A10), substantia nigra (SN-A9), and retrorubral field (RRF-A8). We have recently examined the organization of the projections from the VTA and the SN to the hippocampal formation (HF) in the rat. In the present study we characterize the projections of the RRF to the HF by using anterograde tracing, retrograde tracers, and tyrosine hydroxylase (TH) immunohistochemistry. Following iontophoretical injections of Phaseolous vulgaris leucoagglutinin (PHA-L) into the RRF, anterograde labeling was observed primarily in the ipsilateral subiculum and adjacent CA1 cell field. Sparse labeling was also observed in the CA3 cell field and dentate gyrus. The distribution of RRF neurons projecting to the HF was examined by injecting retrograde fluorescent tracers (fluorogold, fast blue, and nuclear yellow) into several hippocampal areas. The retrograde tracer findings indicate that the medial aspects of the RRF project to the subiculum and adjacent CA1 cell field of both the septal and temporal HF. In order to evaluate the percentage of dopaminergic cells of the RRF projecting to the HF, the retrograde neuronal tracer fluorogold was used in combination with TH immunohistochemistry. The quantitative evaluation of retrograde labeled and TH-immunoreactive (IR) cells showed that RRF projections to the HF are partially (10-18%) dopaminergic. The findings suggest that the general pattern of distribution and organization of the RRF-A8 projections to the HF is similar to that observed in our previous studies examining hippocampal afferents from the VTA and SN. The data also suggest a crude topographical organization of RRF afferents to the HF and a more prominent input to the temporal than to the septal HF.

Amidines↗

PubMed1996

Influences exerted by the frontal eye field on accessory oculomotor nuclei neurons of the rat.

The medial agranular cortex (AGm), considered the rat's analogous to the frontal eye fields of the monkey, sends a conspicuous projection towards the accessory oculomotor nuclei (AON), i.e. the nucleus of posterior commissure (NPC), the nucleus of Darkschewitsch (NDK) and the interstitial nucleus of Cajal (INC). The nature of the synaptic influences exerted by AGm on the AON neurons and the receptor(s) which mediates these cortical-evoked effects were studied in adult rats. Electrical stimulation of a single site within the AGm elicited changes in firing rate of a significant fraction of cells belonging to the ipsilateral accessory oculomotor nuclei (50% in INC, 52.3% in NDK and 52% in NPC). In the 82.9% of cases, the responses were excitations, most of which having latencies and response characteristics compatible with a monosynaptic linkage. The remaining 17.1% of cases were inhibitions with latencies ranging between 4 and 11 ms. Extracellular field potential recordings within the accessory oculomotor nuclei were interpreted as arising from impulses propagating along excitatory axons projecting in a bundle from the cortex. Effects of exogenously applied excitatory amino acid N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovaleric acid (2APV) and of selective non-NMDA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) were examined on synaptic excitation. Monosynaptic excitations induced by the cortical stimulation were abolished by microiontophoretic application of 2APV and not of DNQX. This finding indicates that cortical inputs activate specifically NMDA receptors of AON neurons.

2-Amino-5-phosphonovalerate↗

PubMed1995

Correlated activity in the spinocerebellum is related to spinal timing generators.

Encoding of information by neuronal populations implies a correlation of neural activity across cells. Therefore recent evidence for correlated activity in different parts of the nervous system has been interpreted as a possible mechanism for functional coupling or coordinated information processing. We compared the activity in the mossy fiber projection, the dorsal spinocerebellar tract (DSCT) with the responses of Purkinje cells in the spinocerebellum for evidence of correlated activity. A principal component analysis of post-stimulus spike activity revealed temporal patterns of correlated Purkinje cell activity in all parts of the spinocerebellum evoked by rapid, small amplitude passive joint rotations in anesthetized cats. The same basic temporal patterns were induced in DSCT neurons by joint rotations and also by direct nerve stimulation, showing that the patterning resulted from centrally generated rather than peripheral timing. The evidence implies that spinal timing generators, activated by mechanical stimulation of the ipsilateral hindlimb, transmit temporally correlated activity to the cerebellum via spinocerebellar pathways resulting in a coherent modulation of activity in diverse areas of the cerebellar cortex thereby providing the basis for a functional coupling.

Animals↗

PubMed1994

Projections from the cerebral cortex to the accessory oculomotor nuclei of the rat: a neuroanatomical and immunohistochemical study.

The projections from the cerebral cortex to the accessory oculomotor nuclei, i.e. the nucleus of posterior commissure (NPC), the nucleus of Darkschewitsch (NDK) and the interstitial nucleus of Cajal (INC) and the putative neurotransmitters subserving this pathway have been studied in adult rats. Retrograde labeling with Fluoro-Gold showed that only the more medial part of the agranular cortex, which is considered the rat's analogous to the frontal eye fields of the monkey, sends axon to the ipsilateral accessory oculomotor nuclei. The retrogradely-labeled cells were located primarily in the fifth layer of this cortical region. Following an injection of horseradish peroxidase conjugated with wheat germ agglutinin in this cortical area, we observed corticofugal labeled fibers reaching the accessory oculomotor nuclei and terminating as a fine dust-like terminal labeling in the NDK, in the dorso-lateral division of the INC and in the NPC, as well as in the medial oculomotor accessory nucleus, the red nucleus, the superior colliculus and, even though to a lesser extent, in the mesencephalic reticular formation and the central gray. With regard to the immunohistochemical approach, we observed that all the cells retrogradely labeled from the accessory oculomotor area were also stained by using glutamate or aspartate antisera.

Animals↗

PubMed1994

Non-N-methyl-D-aspartate receptors mediate neocerebellar excitation at accessory oculomotor nuclei synapses of the rat.

The nature of the receptor which mediates cerebellar-evoked monosynaptic excitations recorded from the accessory oculomotor nuclei (AON), i.e. the nucleus of posterior commissure, the nucleus of Darkschewitsch and the interstitial nucleus of Cajal, was studied in adult rats. Effects of exogenously applied excitatory amino acid (EAA) agonists N-methyl-D-aspartate (NMDA) and quisqualate (QUIS) and of selective NMDA receptor antagonist 2-amino-5-phosphonovaleric acid (2APV) and non-NMDA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) were examined on both amino acid induced and synaptic excitation. Microiontophoretic application of NMDA and QUIS in the AON of the rat increases the neuronal discharge in a dose-dependent manner. These findings suggest that in the rat cells belonging to AON bear both NMDA and non-NMDA receptors. This result was confirmed by the fact that applications of 2APV selectively antagonized NMDA-induced responses without affecting those to QUIS, while DNQX blocked specifically the excitatory responses to QUIS and did not affect NMDA-mediated excitations. We did not observe any difference, between rats anesthetized with urethane and those anesthetized with halothane, with respect to capability of EAA agonists NMDA and QUIS to increase the AON cells activity and of EAA receptor antagonists 2APV and DNQX to abolish the NMDA-induced and the QUIS-induced effects, respectively. In addition, monosynaptic excitations induced by the stimulation of cerebellar lateral nucleus were abolished by microiontophoretic application of DNQX, but not of 2APV. This finding indicates that neocerebellar inputs activate specifically non-NMDA receptors of AON neurons.

Action Potentials↗

PubMed1993

Cerebellar influences on accessory oculomotor nuclei of the rat: a neuroanatomical, immunohistochemical, and electrophysiological study.

With the aim to evaluate a possible neocerebellar control on eye movements, the projections from the cerebellar lateral nucleus (LN) to the accessory oculomotor nuclei (i.e., the nucleus of posterior commissure, the nucleus of Darkschewitsch, and the interstitial nucleus of Cajal), the putative neurotransmitters subserving this pathway, and the nature of the synaptic influences exerted by these projections were studied in adult rats. We used the orthograde transport of horseradish peroxidase conjugated with wheat germ agglutinin (WGA-HRP) to identify the mesencephalic areas where cerebellofugal fibers terminate, and retrograde labeling with the fluorescent dye fluoro-gold to estimate the incidence of cerebellar neurons projecting to the accessory oculomotor nuclei. Orthograde labeling showed that only a small contingent of cerebellofugal fibers reaches the contralateral accessory oculomotor nuclei. The retrogradely labeled cells were located primarily in the small-celled part of LN. By immunohistochemistry, we observed that all the cells retrogradely labeled from the accessory oculomotor area were also stained by using glutamate or aspartate antisera, but none of them were double-stained with a GABA antiserum. Electrical stimulation of the contralateral LN elicited changes in firing rate of a significant fraction of cells belonging to the accessory oculomotor nuclei (36.4% in the nucleus of posterior commissure, 47.1% in the nucleus of Darkschewitsch, and 44.6% in the interstitial nucleus of Cajal). In 57.8% of the cases, the responses were excitations, most of which had latencies and response characteristics compatible with a monosynaptic linkage. The remaining 42.2% of the cases were inhibitions with latencies ranging between 5 and 22 ms. Extracellular field potential recordings within the contralateral accessory oculomotor nuclei were interpreted as arising from impulses propagating along excitatory axons projecting in a bundle from the cerebellum. Stimulation of LN area in rats following intranuclear injection of kainic acid was not capable of evoking short latency excitations, so these responses can be considered to depend on the activation of LN efferents. The LN projection on accessory oculomotor nuclei could be part of the final precise control exerted by the neocerebellum on those brain structures concerned with movements of the eyes.

Animals↗