Biomedical subjects

A Casabona

Publications and source records attributed to A Casabona.

At least 19 recordsLinked to original sources

PubMed2001

Neuromuscular junction disassembly and muscle fatigue in mice lacking neurotrophin-4.

Neurotrophin-4 (NT-4) is produced by slow muscle fibers in an activity-dependent manner and promotes growth and remodeling of adult motorneuron innervation. However, both muscle fibers and motor neurons express NT-4 receptors, suggesting bidirectional NT-4 signaling at the neuromuscular junction. Mice lacking NT-4 displayed enlarged and fragmented neuromuscular junctions with disassembled postsynaptic acetylcholine receptor (AChR) clusters, reduced AChR binding, and acetylcholinesterase activity. Electromyographic responses, posttetanic potentiation, and action potential amplitude were also significantly reduced in muscle fibers from NT-4 knock-out mice. Slow-twitch soleus muscles from these mice fatigued twice as rapidly as those from wild-type mice during repeated tetanic stimulation. Thus, muscle-derived NT-4 is required for maintenance of postsynaptic AChR regions, normal muscular electrophysiological responses, and resistance to muscle fatigue. This neurotrophin may therefore be a key component of an activity-dependent feedback mechanism regulating maintenance of neuromuscular connections and muscular performance.

Acetylcholinesterase↗

PubMed2000

Involvement of the noradrenergic system in modulating the blink reflex in humans.

Several researches have shown that the spinal reflex transmission in animals, as well as humans, was inhibited by alpha(2)-agonists, due to a disfacilitation of tonic noradrenergic control on motoneuronal output. To understand better the mechanisms regulating certain aspects of motor activity, here we reinvestigated the possible role of noradrenergic systems in modulating reflex activity of the brainstem in humans. To this aim, blink reflex responses (R1 and R2) evoked by electrical stimulation of the supraorbital nerve were electromyographically recorded in healthy volunteers. Both R1 and R2 areas were measured at 10-min intervals before and after i.v. injection of alpha(2)-agonist clonidine (0.5 microg/kg). The substance induced consistent depression of R1, which reached its maximum 40 min after drug administration (-43% of the control values). Ipsilateral R2 area resulted little affected by clonidine (-15% at 50 min), whereas no effects were observed in contralateral R2. Blood pressure values were never altered by drug injections. These results, taken together with previous observations, support the hypothesis that alpha(2)-agonist substances may cause a transient inactivation of noradrenergic neurons, thus releasing neurons involved in the circuitry of the blink reflex from a facilitatory drive. Since clonidine differentially modulated blink reflex responses, it is likely to assume that such a disfacilitation concerns mostly pontine units mediating the R1. However, the complexity of clonidine's effects at multiple pre- and postsynaptic sites does not allow us to exclude that other systems are involved in the alpha(2)-mediated control of facial motoneurons.

Adult↗

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↗

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

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

Muscle-derived neurotrophin-4 as an activity-dependent trophic signal for adult motor neurons.

The production of neurotrophin-4 (NT-4) in rat skeletal muscle was found to depend on muscle activity. The amounts of NT-4 messenger RNA present decreased after blockade of neuromuscular transmission with alpha-bungarotoxin and increased during postnatal development and after electrical stimulation in a dose-dependent manner. NT-4 immunoreactivity was detected in slow, type I muscle fibers. Intramuscular administration of NT-4 induced sprouting of intact adult motor nerves. Thus, muscle-derived NT-4 acted as an activity-dependent neurotrophic signal for growth and remodeling of adult motor neuron innervation. NT-4 may thus be partly responsible for the effects of exercise and electrical stimulation on neuromuscular performance.

Animals↗

PubMed1994

The learning of novel finger movement sequences.

1. Experienced typists typed phrases containing words in which one isolated letter was typed with one hand, while the remaining letters were typed with the contralateral hand. 2. The translational and rotational motion of the fingers and wrist of the right hand were obtained optoelectronically from the location of reflective markers placed on the fingers. 3. Midway through the experiment, the key corresponding to the isolated letter was physically switched with another key on the keyboard, and subjects typed the letter in its new location (for 140 trials). The letter "n," typed with the right index finger, was either switched with letters normally typed with the same finger (u), with a different finger but same hand (o), with the same finger of the left hand (v), or with a different finger of the left hand (w). 4. When the words were typed normally, the interkey intervals were relatively short, and the onset of movement of the right hand began before the preceding keypress with the left hand. Thus the movement of the two hands overlapped. Furthermore, the movement to the isolated key was highly stereotypical, with little trial-to-trial variability. 5. After the transposition of keys, there were prolongations in the interkey intervals, with the largest delay occurring directly before the typing of the transposed key. Switches between homologous fingers (involving mirror movements) delayed the onset of keypresses to a lesser extent than did other switches. With practice, these delays were reduced but never reached the control level. 6. After the keyswitch, the onset of movement to the isolated key did not occur on average until after the last keypress with the contralateral hand, except when the switch involved the use of homologous fingers. In the latter case, overlapping movement of the two hands was maintained. Thus the learning of a series of discrete movements does not necessarily require that each movement segment be performed sequentially. 7. After the transposition of keys, the movement pattern and time course to a given key were similar to the movement patterns for that key observed during control trials in all conditions. Thus the learning of a series of movements may involve the use of previously learned movements under new conditions. 8. The results suggest that typing movements may be organized at several levels, including the individual keystroke and word level.

Adult↗

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↗

PubMed1992

Effects of TRH-T on spinal motoneurones in man.

The effect of thyrotropin-releasing hormone tartrate (TRH-T) on the decrease in H Max/M Max ratio, an index of the spinal motoneurone pool, induced by haloperidol, was studied in 15 healthy volunteers. In all subjects, the H response was examined by an electromyographic apparatus. The values were expressed as H Max/M Max ratio, that gives an index of excitability of the spinal motoneurone pool. It was found that the mean H Max/M Max ratio value significantly decreased after haloperidol administration, but this effect was completely reversed by the injection of TRH-T. This finding suggests that the peptide may modulate motoneurone functions.

Adult↗

PubMed1990

Differences in H-reflex between athletes trained for explosive contractions and non-trained subjects.

The efficacy of type Ia synapse on alpha-motoneurons of soleus and lateral gastrocnemius muscles has been investigated, using the H-reflex technique, in athletes engaged in sports requiring very rapid and intense contractions (sprinters and volley-ball players) as well as in non-trained subjects. It has been observed, in both muscles, that the ratio between the mean value of the maximal reflex response (Hmax) and the mean value of the maximal direct response (Mmax) elicited upon electrical stimulation of the tibial nerve is significantly smaller in athletes trained for explosive-type movements than in non-trained subjects. This difference in the Hmax: Mmax ratio was dependent on a smaller amplitude of Hmax and not on a greater amplitude of Mmax. No significant differences were observed between sprinters and volley-ball players. In both trained and non-trained subjects, soleus and lateral gastrocnemius muscles displayed significant differences in Hmax: Mmax ratio and Mmax amplitude but not in Hmax amplitude. Since the H-response is considered to be due mainly to activation of the smallest motoneurons in the motoneuronal pools, the difference in Hmax amplitude and Hmax: Mmax ratio between athletes and non-trained subjects could have been dependent on a lower incidence of these motoneurons in the athletes. This is in accord with the mechanical needs of muscles during explosive-type power training. Although this difference may have been wholly determined genetically, the possibility is discussed as to whether the lower incidence in sprinters and volley-ball players of small motoneurons could have been related to a training-induced transformation of small and slow motoneurons into large and fast ones.

Adult↗

PubMed1990

[Modification of the blink reflex in hemidystonia].

With the aim of evaluating the excitability of the brain stem reflex centers, we studied the side-to-side differences in the EMG activity of the early and late components of the blink reflex, in subjects with unilateral dystonia without demonstrable brain lesions. We observed that both early and late responses of direct blink reflex were significantly higher in the affected side than in the contralateral one.

Blinking↗

PubMed1990

[Adaptation of motor nerve fibers to physical activity].

The effects induced by training on the H-reflex of soleus and lateral gastrocnemius muscles have been studied on 19 adult male volunteers; out of these, 10 were non-trained subjects and the remaining 9 were top level athletes engaged in sports requiring very rapid and intense contractions (sprinters and volley-ball players). It has been observed that the latency of the M response is significantly higher in the athletes than in the non-trained subjects. Instead, no significant differences were observed between these two groups, concerning the latency of H response. The increase of M response latency is likely due to a decrease of nerve conduction velocity in the terminal part of motor fibers. The possibility that this conduction speed decrease could be dependent on sprouting and/or terminal branching growth of the motor nerve ending is discussed.

Adolescent↗