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Biomedical subjects

P Errico

Publications and source records attributed to P Errico.

At least 19 recordsLinked to original sources

MTBE ambient water quality criteria development: a public/private partnership.

A public/private partnership was established in 1997, under the administrative oversight of the American Petroleum Institute (API), to develop aquatic toxicity data sufficient to calculate ambient water quality criteria for methyl tertiary-butyl ether (MTBE), a gasoline oxygenate. The MTBE Water Quality Criteria Work Group consisted of representatives from private companies, trade associations, and USEPA. Funding was provided by the private entities, while aquatic biological/toxicological expertise was provided by industry and USEPA scientists. This public/private partnership constituted a nonadversarial, cost-effective, and efficient process for generating the toxicity data necessary for deriving freshwater and marine ambient water quality criteria. Existing aquatic toxicity data were evaluated for acceptability, consistent with USEPA guidance, and nineteen freshwater and marine tests were conducted by commercial laboratories as part of this effort to satisfy the federal criteria database requirements. Definitive test data were developed and reported under the oversight of industry study monitors and Good Laboratory Practice standards auditors, and with USEPA scientists participating in advisory and critical review roles. Calculated, preliminary freshwater criteria for acute (Criterion Maximum Concentration) and chronic (Criterion Continuous Concentration) exposure effect protection are 151 and 51 mg MTBE/L, respectively. Calculated, preliminary marine criteria for acute and chronic exposure effect protection are 53 and 18 mg MTBE/L, respectively. These criteria values may be used for surface water quality management purposes, and they indicate that ambient MTBE concentrations documented in U. S. surface waters to date do not constitute a risk to aquatic organisms.

Animals↗

Cerebellar nodulectomy impairs spatial memory of vestibular and optokinetic stimulation in rabbits.

Natural vestibular and optokinetic stimulation were used to investigate the possible role of the cerebellar nodulus in the regulation and modification of reflexive eye movements in rabbits. The nodulus and folium 9d of the uvula were destroyed by surgical aspiration. Before and after nodulectomy the vertical and horizontal vestibuloocular reflexes (VVOR, HVOR) were measured during sinusoidal vestibular stimulation about the longitudinal (roll) and vertical (yaw) axes. Although the gain of the HVOR (G(HVOR) = peak eye movement velocity/peak head velocity) was not affected by the nodulectomy, the gain of the VVOR (G(VVOR)) was reduced. The gains of the vertical and horizontal optokinetic reflexes (G(VOKR), G(HOKR)) were measured during monocular, sinusoidal optokinetic stimulation (OKS) about the longitudinal and vertical axes. Following nodulectomy, there was no reduction in G(VOKR) or G(HOKR). Long-term binocular OKS was used to generate optokinetic afternystagmus, OKAN II, that lasts for hours. After OKAN II was induced, rabbits were subjected to static pitch and roll, to determine how the plane and velocity of OKAN II is influenced by a changing vestibular environment. During static pitch, OKAN II slow phase remained aligned with earth-horizontal. This was true for normal and nodulectomized rabbits. During static roll, OKAN II remained aligned with earth-horizontal in normal rabbits. During static roll in nodulectomized rabbits, OKAN II slow phase developed a centripetal vertical drift. We examined the suppression and recovery of G(VVOR) following exposure to conflicting vertical OKS for 10-30 min. This vestibular-optokinetic conflict reduced G(VVOR) in both normal and nodulectomized rabbits. The time course of recovery of G(VVOR) after conflicting OKS was the same before and after nodulectomy. In normal rabbits, the head pitch angle, at which peak OKAN II velocity occurred, corresponded to the head pitch angle maintained during long-term OKS. If the head was maintained in a "pitched-up" or "pitched-down" orientation during long-term OKS, the subsequently measured OKAN II peak velocity occurred at the same orientation. This was not true for nodulectomized rabbits, who had OKAN II peak velocities at head pitch angles independent of those maintained during long-term OKS. We conclude that the nodulus participates in the regulation of compensatory reflexive movements. The nodulus also influences "remembered" head position in space derived from previous optokinetic and vestibular stimulation.

Animals↗

Role of cerebellar nodulus and uvula on the vestibular quick phase spatial constancy.

We investigated the orientation of quick phases (QPs) of vestibularly-induced eye movements in rabbits in response to "off-vertical" sinusoidal vestibular stimulation. We also examined the possible role of the cerebellar nodulus and ventral uvula in controlling QP spatial orientation and modification. During "off-vertical" vestibular stimulation QPs remained aligned with the earth's horizontal plane, while the slow phases (SPs) were aligned with the plane of vestibular stimulation. This suggests that QPs are coded in gravito-inertial coordinates and SPs in head coordinates. When rabbits were oscillated in the light (20 degrees peak-to-peak; 0.2 Hz) about an "off-vertical" axis for 2 h, the QPs changed their trajectory, abandoning the earth's horizontal plane to approach the plane of the stimulus. By contrast, in the absence of conjunctive optokinetic stimulation, QPs remained fixed in the earth's horizontal plane even after 2 h of "off-vertical" stimulation. The conjunctive combination of optokinetic and vestibular stimulation caused QPs to change their plane of rotation. After lesion of the nodulus-uvula the ability of rabbits to reorient QPs during conjoint vestibular-optokinetic stimulation was maintained. We conclude that the space orientation and adaptation of QPs do not require cerebellar control.

Adaptation, Physiological↗

Optokinetic and vestibular stimulation determines the spatial orientation of negative optokinetic afternystagmus in the rabbit.

Prolonged binocular optokinetic stimulation (OKS) in the rabbit induces a high-velocity negative optokinetic afternystagmus (OKAN II) that persists for several hours. We have taken advantage of this uniform nystagmus to study how changes in static head orientation in the pitch plane might influence the orientation of the nystagmus. After horizontal OKS, the rotation axis of the OKAN II remained almost constant in space as it was kept aligned with the gravity vector when the head was pitched by as much as 80 degrees up and 35 degrees down. Moreover, during reorientation, slow-phase eye velocity decreased according to the head pitch angle. Thereafter, we analyzed the space orientation of OKAN II after optokinetic stimulation during which the head and/or the OKS were pitched upward and downward. The rotation axis of OKAN II did not remain aligned with an earth vertical axis nor a head vertical axis, but it tended to be aligned with that of the OKS respace. The slow-phase eye velocity of OKAN II was also affected by the head pitch angle during OKS, because maximal OKAN II velocity occurred at the same head pitch angle as that during optokinetic stimulation. We suggest that OKAN II is coded in gravity-centered rather than in head-centered coordinates, but that this coordinate system may be influenced by optokinetic and vestibular stimulation. Moreover, the velocity attenuation of OKAN II seems to depend on the mismatch between the space-centered nystagmus rotation axis orientation and that of the "remembered" head-centered optokinetic pathway activated by OKS.

Animals↗

Otolithic and extraocular muscle proprioceptive influences on the spatial organization of the vestibulo- and cervico-ocular quick phases.

The cervico-ocular reflex (COR) was studied alone or in combination with the vestibulo-ocular reflex (VOR) in the rabbit. Step stimulations of the body with respect to the fixed head induced small slow compensatory responses followed by large compensatory quick phases (QP). These responses remained aligned with the horizon at different head pitch angles. The QP reorientation in space was due to the gravity influence on the otolithic receptors. The vestibular induced QPs exhibit a similar pattern. Because of this reorientation, the reduction of the amplitude of the vestibular induced QPs, due to the addition of the COR, was maintained even at different static head positions. The electrolytic lesion of the ophthalmic branch of the trigeminal nerve deeply affected the space orientation of the COR. In particular, the cervically induced compensatory QPs of the eye ipsilateral to the lesion showed a remarkable variability of their trajectories and they lost space reorientation. These findings suggest that the coordinate system controlling the QPs is influenced by signals originating from both head position in space and eye position in the orbit.

Animals↗

Influence of the extraocular muscle proprioceptors on the orientation of the vestibulo-ocular reflex.

In the intact brain lamb, unilateral electrolytic lesion of the medial dorso-lateral portion of the semilunar ganglion containing the first order neurons of the eye muscle proprioception induced modifications of the horizontal and vertical vestibulo-ocular reflex (HVOR and VVOR) which consisted in marked alterations of the trajectories of the quick phases, while the slow phases were scarcely affected. Similar results were observed after section of the branches described by Winckler in the retrobulbar region along the extraocular muscle proprioceptive information travels. These findings extend those of previous investigations carried out in decorticate animals.

Animals↗

Influence of gravity on the orientation of vestibular induced quick phases.

In rabbits and cats the orientation of the quick phases (QPs) of the vestibulo-ocular reflex (VOR) was studied varying the head position in space. At different head tilt positions, QPs induced by step vestibular stimulation disaligned with respect to the stimulus toward the orientation of the earth's horizontal axis. The rabbits' QPs were horizontal during yaw stimulation and remained horizontal in a range of head pitch of +/- 90 degrees (reorientation gain = 1). Therefore, the slow compensatory responses (CSPs) progressively disaligned compared with the QPs. QPs induced by roll stimulation also showed horizontal orientation, although these were rare in the upright position and occurred more frequently when the head was pitched. In cats only the yaw-induced QPs were coplanar with the stimulus, while QPs induced by pitching were mostly oblique. It followed that in either yawing or pitching, the QPs had their end point scattered within a horizontally elongated area of the visual field. When tilting cats in the frontal plane, the orientation of QP trajectories changed with respect to the stimulus so that the end point distribution tended to remain aligned toward the horizontal instead of being fixed in the orbit. The reorientation gain decreased from 1 to 0.5 by increasing the head tilt. On the basis of difference regarding eye implantation and motility it was suggested that the effect of gravity on the orientation of QPs could be aimed at maintaining the interocular axis aligned with the horizon in the rabbit and at orientating the visual scanning system in the horizontal plane in the cat.

Animals↗

Extraocular muscle proprioception and eye position.

In the lamb, acute unilateral section of the ophthalmic branch induced in the ipsilateral eye occasional oscillations of the resting position and misalignment of the horizontal vestibulo-ocular reflex (HVOR) with respect to the stimulus. Additional electrolytic lesion of the cells innervating the proprioceptors of the medial rectus muscle, or of the lateral rectus muscle in the contralateral semilunar ganglion, provoked a 4 degrees-7 degrees consensual eye deviation towards and away from the lesioned side, respectively. The optokinetic beating field was similarly deviated. Under these experimental conditions, HVOR showed enhanced gain and marked misalignment in both eyes. Therefore, the selective suppression of muscular proprioceptive input deviated both eyes towards the direction opposite to the muscle whose gangliar proprioceptive representation has been destroyed.

Animals↗

Origins of cerebellar mossy and climbing fibers immunoreactive for corticotropin-releasing factor in the rabbit.

Corticotropin-releasing factor (CRF) has been implicated by both anatomical and physiological techniques as a potential cerebellar transmitter or modulator. In the present experiment, with the aid of immunohistochemistry, we have described specific cerebellar afferent pathways in the rabbit in which CRF is located. CRF-immunoreactive climbing fibers were present in the molecular layer throughout the cerebellum, but especially in lobules 8-9a. All inferior olivary neurons were CRF-immunoreactive. In lobules 8-9a, CRF-immunoreactive mossy fibers were organized in sagittal bands. The highest density of CRF-immunoreactive mossy fiber terminals was observed in the granule cell layer of lobules 8-9a and the flocculus. No CRF-immunoreactive perikarya were located in rabbit cerebellum. The brainstem origin of CRF-immunoreactive mossy fiber terminals was suggested by numerous CRF-immunoreactive perikarya located in the medial, lateral and descending vestibular nuclei, nucleus prepositus hypoglossi, nucleus x, paramedian reticular nucleus, gigantocellular reticular nucleus, lateral reticular nucleus, and raphé nuclei. Using double label experiments, we investigated the specific CRF afferent projection to the flocculus and posterior vermis. Horseradish peroxidase (HRP) injections into the posterior vermis double labeled CRF-immunoreactive neurons in the caudal medial and descending vestibular nuclei and nucleus prepositus hypoglossi. HRP injections into the flocculus double labeled more CRF-immunoreactive neurons in the nucleus prepositus hypoglossi than in the vestibular nuclei. HRP injections into either the posterior vermis or flocculus double labeled CRF-immunoreactive neurons in the paramedian reticular nucleus, nucleus reticularis gigantocellularis, and raphé nuclei. These data suggest that CRF may play an important role in vestibularly related functions of the cerebellum.

Afferent Pathways↗

Cholinergic projection to the dorsal cap of the inferior olive of the rat, rabbit, and monkey.

The inferior olive is divided into several subnuclei that receive specific sensory information. The caudal dorsal cap of the medial accessory subdivision of the inferior olive receives horizontal optokinetic information from the nucleus of the optic tract. The immediately subjacent beta-nucleus receives vertical vestibular information mediated by a GABAergic pathway originating from the ipsilateral descending and medial vestibular nuclei. None of the transmitters to the dorsal cap have been identified. Using choline acetyltransferase (ChAT) immunohistochemistry, we have identified a cholinergic pathway that terminates exclusively in the dorsal cap of rats and monkeys. No other division of the inferior olive received a significant cholinergic innervation. In the rabbit, immunostaining for ChAT reveals a weaker and more diffuse cholinergic innervation of both the dorsal cap and the subjacent beta-nucleus. In rats and rabbits we injected iontophoretically the orthograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L) into the medial and descending vestibular nuclei (MVN, DVN) as well as the nucleus prepositus hypoglossi (NPH) in order to trace the possible origin of the cholinergic projection. PHA-L injections into the NPH and medial aspect of the MVN labeled terminals within the contralateral dorsal cap. PHA-L injections in the central and lateral aspects of the MVN as well as the DVN labeled the ipsilateral beta-nucleus. Pressure injections of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) in the caudal dorsal cap of the rabbit inferior olive demonstrated a predominantly contralateral projection to the dorsal cap from the lateral aspect of the NPH. However, pressure injections of HRP into the caudal dorsal cap combined with ChAT immunohistochemistry in the rabbit demonstrated that most of the neurons of the NPH that projected to the dorsal cap were not cholinergic, and that most of the ChAT-positive neurons within the NPH occupied a more ventral location than the neurons within the NPH that were retrogradely labeled from the HRP injection into the contralateral dorsal cap. In the rat, we made lesions in the MVN, DVN and NPH by injection of ibotenic acid (0.3-0.5 microliter), in an attempt to deplete the dorsal cap of the inferior olive of its cholinergic input. Lesions confined to the NPH and medial aspect of the MVN of the rat caused a loss of ChAT staining in the contralateral dorsal cap. Lesions placed more laterally within the MVN or DVN failed to deplete ChAT-positive terminals in the contralateral or ipsilateral dorsal caps. The dorsal cap of the rat and monkey receives a discrete cholinergic projection.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Vestibular primary afferent projection to the cerebellum of the rabbit.

The vestibular primary afferent projection to the cerebellum of the rabbit was studied with retrograde and orthograde tracers. We injected individual lobules of the cerebellum with horseradish peroxidase (HRP) or wheat germ agglutinin-HRP (WGA-HRP). Following these injections the numbers of labeled and unlabeled cells in Scarpa's ganglion were counted. Approximately 64-89% of the cells in Scarpa's ganglion were labeled retrogradely following uvula-nodular injections. About 2% of the cells in the ipsilateral Scarpa's ganglion were labeled after injections of the flocculus. Virtually no cells were labeled following injections of the ventral paraflocculus. The vestibular primary afferent projection to the uvula-nodulus is so extensive that it must be part of a collateral system that also innervates the vestibular nuclei. This collateral projection pattern was confirmed by using fluorescent tracers injected into the uvula-nodulus and vestibular complex. Fluorogold was injected into the uvula-nodulus and peroxidase-rhodamine isothiocyanate was injected into the vestibular complex. More than 50% of the neurons in Scarpa's ganglion were double labeled by these subtotal injections. The dense vestibular primary afferent projection to the uvula-nodulus was confirmed by using the C fragment of tetanus toxin (TTC) injected into the labyrinth as an orthograde tracer. With the TTC technique, the vestibular primary afferent projection to the uvula-nodulus terminated exclusively in the ipsilateral granule cell layer of lobules 9d and 10. Much sparser vestibular primary afferent projections were found in the banks of major cerebellar sulci. A barely detectable projection was found to the flocculus and ventral paraflocculus.

Afferent Pathways↗

Gravity load related asymmetries in the sagittal vestibulo-collic reflex.

EMG recordings of the neck muscles (biventer cervicis, complexus, splenius, longus capitis) of decerebrate cats were obtained during pitch and roll stimulations (sinusoidal stimulation: 30 degrees p-p amplitude, 0.2 Hz frequency). Most of the EMG responses to pitch showed activation peaks leading the position stimuli by 56 degrees and inhibition peaks leading by 11 degrees. Conversely, in response to roll the activation peak led by 16 degrees and the inhibition peak by 10 degrees. The activation peaks of the pitch responses were, thus, more asymmetric and more leading than those of the roll responses. Consequently, the harmonic distortion coefficient was significantly higher in pitch than in roll. Moreover, when the vertical semicircular canals were activated in absence of otolithic modulation, the pitch and roll responses maintained the same difference in timing observed in the presence of otolithic coactivation. It appeared that the simultaneous stimulation of both anterior semicircular canals (pitch) induces a greater lead than that of combined anterior and posterior canals (roll). Thus the timing of neck muscle responses to vestibular stimulation depends on the pair of activated vertical semicircular canals.

Animals↗

Botulinum A toxin effects on rat jaw muscle spindles.

Botulinum A toxin (Botox) is used for the treatment of many muscular dystonias. However, the relief of the sustained and abnormal postures induced by Botox administration is not fully explained. In this work the possibility was considered that Botox can produce a block not only at the alpha motor endings, but also at the gamma motor endings, consequently reducing the spindle inflow to the alpha motoneurons, which have a great role in maintaining the tonic myotatic reflex. Jaw muscle spindle discharge was recorded before and after Botox injection in the deep masseter muscle. The drug consistently reduced the spindle afferent discharge. Such an effect is suggested to be direct on gamma endings as: i) muscle tension was not modified by Botox during the recording time; ii) saline administration never changed the spindle discharge. The Botox effect on muscle spindles suggests that the relief from dystonias could be due not only to a partial motor paralysis, but also to a decrease of the reflex muscular tone.

Animals↗

Optokinetically evoked expression of corticotropin-releasing factor in inferior olivary neurons of rabbits.

We investigated the influence of both binocular and monocular optokinetic stimulation on the expression of corticotropin-releasing factor (CRF), a neuropeptide, in inferior olivary neurons. Rabbits were placed at the center of a cylindrical optokinetic drum that rotated at a constant velocity of 5 degrees/sec, stimulating one eye in the posterior-->anterior direction and the other eye in the anterior-->posterior direction. After 48 hr of optokinetic stimulation, rabbits were killed and the brains were prepared for immunohistochemistry. An antiserum to rat/human CRF was used to label brain-stem sections of optokinetically stimulated rabbits. The density of CRF-specific reaction product within individual olivary neurons was analyzed with a computer-based densitometer. Binocular optokinetic stimulation for 48 hr caused a 20-70% increase in the optical density of "stimulated" dorsal cap neurons, measured relative to the optical density of control ("unstimulated") olivary neurons in the same histological section. This elevated expression of CRF lasted approximately 48 hr. When a delay of 18 hr was interposed between optokinetic stimulation and death of the rabbit, during which the rabbits were deprived of pattern vision, then both dorsal caps were densely labeled. Monocular optokinetic stimulation for 48 hr in the anterior-->posterior direction caused no change in CRF expression in either dorsal cap if the rabbit was immediately killed. However, following monocular anterior-->posterior stimulation, the dorsal cap contralateral to the "null-stimulated" eye was densely labeled if the rabbit was deprived of pattern vision for 18 hr prior to death. We infer that stopping prolonged "null stimulation" causes a rebound in activity in the stimulated dorsal cap. This "rebound" must have its origin at the level of the dorsal cap or more peripherally in the optokinetic pathway.

Animals↗

Asymmetries in ocular and cervical responses to sagittal vestibular stimulations.

In rabbits and cats vestibulo-ocular reflex (VOR) and vestibulo-ocular reflex (VCR) were tested in frontal and sagittal planes. The VOR evoked by pitching the animals in side down position showed asymmetric responses with peak eye velocity higher in upward direction than in downward one. This asymmetry was abolished when pitching the animal in upright position. This indicate that the otolithic coactivation, occurring in upright position, symmetrizes canal-induced vertical responses. Vestibulo-ocular reflex evoked by rolling the animals was also symmetric, no matter the animal position was. The electromyographic response of neck muscles to sagittal VCR showed an asymmetric behaviour as far as the timing of extensor and flexor activation was concerning. In fact, the increase of extensor muscle activity was steeper than the decrease and the activation peak was more leading than the inhibition peak. The flexor muscles showed an opposite behaviour. This flexion-extension asymmetry was present either with or without otolithic coactivation. On the contrary, the EMG responses to frontal VCR were much more symmetric. It can be suggested that the upward preponderance is present in the sagittal vestibular circuitry to enhance the upward VCR against a gravity load which opposes head stability during downward head displacements. On the contrary, at level of the eye, in which the gravity does not oppose the responses, the canal-induced vertical asymmetry is cancelled by the otolithic coactivation.

Animals↗

Role of NMDA receptors in the compensation of ocular nystagmus induced by hemilabyrinthectomy in the guinea pig.

The possibility that N-methyl-D-aspartate (NMDA) receptor activation plays a role in inducing the vestibular compensation following hemilabyrinthectomy (HL) in guinea pigs, was verified by means of continuous intraventricular osmotic pumping of DL-2-Amino-5-phosphono-valeric acid (APV). Our results show that high doses (40 and 20 mM) of APV decrease both the combined OKR and VOR and the nystagmus following HL. Low doses of APV (2.5 mM), affect the time course of the ocular compensation by maintaining a higher level of nystagmus beat frequency and by delaying the nystagmus disappearance. On the contrary, the compensation time course is not affected by administering APV later on in the compensation period. Therefore, it appears that NMDA receptors are activated during the precocious phase of vestibular compensation, when a large vestibular imbalance is present. This finding is explained by the development of NMDA receptor hypersensitivity, in the functionally inactivated commissural system or by the occurrence of NMDA-mediated long-term potentiation.

2-Amino-5-phosphonovalerate↗