Biomedical subjects

F Tempia

Publications and source records attributed to F Tempia.

At least 19 recordsLinked to original sources

PubMed2006

Membrane excitability and fear conditioning in cerebellar Purkinje cell.

In a previous study it has been demonstrated that fear conditioning is associated with a long-lasting potentiation of parallel fiber to Purkinje cell synaptic transmission in vermal lobules V and VI. Since modifications of intrinsic membrane properties have been suggested to mediate some forms of memory processes, we investigated possible changes of Purkinje cell intrinsic properties following the same learning paradigm and in the same cerebellar region. By means of the patch clamp technique, Purkinje cell passive and active membrane properties were evaluated in slices prepared from rats 10 min or 24 h after fear conditioning and in slices from control naïve animals. None of the evaluated parameters (input resistance, inward rectification, maximal firing frequency and the first inter-spike interval, post-burst afterhyperpolarization, action potential threshold and amplitude, action potential afterhyperpolarization) was significantly different between the three studied groups also in those cells where parallel fiber-Purkinje cell synapse was potentiated. Our results show that fear learning does not affect the intrinsic membrane properties involved in Purkinje cell firing. Therefore, at the level of Purkinje cell the plastic change associated with fear conditioning is specifically restricted to synaptic efficacy.

Action Potentials↗

PubMed2001

Presynaptic modulation by group III metabotropic glutamate receptors (mGluRs) of the excitatory postsynaptic potential mediated by mGluR1 in rat cerebellar Purkinje cells.

Purkinje neurons were recorded from rat cerebellar slices. Parallel fibres stimulation elicited a fast excitatory postsynaptic potential (EPSP) mediated by ionotropic glutamate (iGluR) -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors followed by the inhibitory gamma-aminobutyric acidA (GABAA)-dependent postsynaptic potential. In the presence of antagonists for iGluRs and for GABAA receptors, brief tetanic activation evoked a slow metabotropic glutamate receptor (mGluR)-dependent EPSP (mGluR-EPSP). This mGluR-EPSP was blocked by the selective mGluR1 antagonists LY367385 and CPCCOEt, but not by the mGluR5 antagonist MPEP. Group II agonists affected neither iGluR-EPSP nor mGluR-EPSP. Conversely, L-AP4 and L-SOP, group III mGluR agonists, inhibited both iGluR- and mGluR-EPSPs. The depolarisations evoked by both AMPA and group I agonists were unaffected, indicating a presynaptic action of group III mGluRs. These data suggest that glutamate released by parallel fibres activates group III mGluR autoreceptors, depressing both iGluR- and mGluR1-mediated EPSPs.

Animals↗

PubMed2001

Postsynaptic currents in deep cerebellar nuclei.

Postsynaptic currents were studied by whole cell recordings in visually identified large neurons of the deep cerebellar nuclei (DCN) in slices of 4- to 11-day-old mice. Spontaneous postsynaptic currents were abolished by the GABA(A) receptor antagonist bicuculline and had a single-exponential decay with a mean time constant of 13.6 +/- 3.2 (SD) ms. Excitatory postsynaptic currents (EPSCs) were evoked in 48/56 neurons recorded. The addition of AMPA and N-methyl-D-aspartate (NMDA) receptor antagonists together completely abolished all synaptic responses. In 1 mM [Mg(2+)](o) and at a holding potential of -60 mV, the peak amplitude of the NMDA component of the EPSC (NMDA-EPSC) was 83.2 +/- 21.2% of the AMPA component (AMPA-EPSC). This indicates that in DCN neurons, at a physiological [Mg(2+)](o) and at the resting membrane potential, NMDA receptors contribute to the synaptic signal. AMPA-EPSCs had a linear current-voltage relationship with a reversal potential of +2.3 +/- 0.4 mV and a single-exponential decay with a voltage-dependent time constant that at -60 mV was 7.1 +/- 3.3 ms. In 10 microM glycine and 1 mM [Mg(2+)](o), the I-V relationship of NMDA-EPSCs had a reversal potential of -0.5 +/- 3.3 mV and a maximal inward current at -33.4 +/- 5.8 mV. The apparent dissociation constant (K(D)) of Mg(2+) for the NMDA receptor-channel at -60 mV, measured by varying [Mg(2+)](o), was 135.5 +/- 55.3 microM, and when measured by fitting the I-V curves with a theoretical function, it was 169.9 +/- 119.5 microM. Thus in the DCN, NMDA receptors have a sensitivity to Mg(2+) that corresponds to subunits that are weakly blocked by this ion (epsilon 3 and epsilon 4) of which the DCN express epsilon 4. NMDA-EPSCs had a double-exponential decay with voltage-dependent time constants that at -60 mV were 20.2 +/- 8.9 and 136.4 +/- 62.8 ms. At positive voltages, the time constants were slower and their contributions were about equal, while in the negative slope conductance region of the I-V curve, the faster time constant became predominant, conferring faster kinetics to the EPSC. The weak sensitivity to Mg(2+) of NMDA receptors, together with a relatively fast kinetics, provide DCN neurons with strong excitatory inputs in which fast dynamic signals are relatively well preserved.

Animals↗

PubMed2001

Characterization of the mGluR(1)-mediated electrical and calcium signaling in Purkinje cells of mouse cerebellar slices.

The metabotropic glutamate receptor 1 (mGluR(1)) plays a fundamental role in postnatal development and plasticity of ionotropic glutamate receptor-mediated synaptic excitation of cerebellar Purkinje cells. Synaptic activation of mGluR(1) by brief tetanic stimulation of parallel fibers evokes a slow excitatory postsynaptic current and an elevation of intracellular calcium concentration ([Ca2+](i)) in Purkinje cells. The mechanism underlying these responses has not been identified yet. Here we investigated the responses to synaptic and direct activation of mGluR(1) using whole cell patch-clamp recordings in combination with microfluorometric measurements of [Ca2+](i) in mouse Purkinje cells. Following pharmacological block of ionotropic glutamate receptors, two to six stimuli applied to parallel fibers at 100 Hz evoked a slow inward current that was associated with an elevation of [Ca2+](i). Both the inward current and the rise in [Ca2+](i) increased in size with increasing number of pulses albeit with no clear difference between the minimal number of pulses required to evoke these responses. Application of the mGluR(1) agonist (S)-3,5-dihydroxyphenylglycine (3,5-DHPG) by means of short-lasting (5-100 ms) pressure pulses delivered through an agonist-containing pipette positioned over the Purkinje cell dendrite, evoked responses resembling the synaptically induced inward current and elevation of [Ca2+](i). No increase in [Ca2+](i) was observed with inward currents of comparable amplitudes induced by the ionotropic glutamate receptor agonist AMPA. The 3,5-DHPG-induced inward current but not the associated increase in [Ca2+](i) was depressed when extracellular Na+ was replaced by choline, but, surprisingly, both responses were also depressed when bathing the tissue in a low calcium (0.125 mM) or calcium-free/EGTA solution. Thapsigargin (10 microM) and cyclopiazonic acid (30 microM), inhibitors of sarco-endoplasmic reticulum Ca2+-ATPase, had little effect on either the inward current or the elevation in [Ca2+](i) induced by 3,5-DHPG. Furthermore, the inward current induced by 3,5-DHPG was neither blocked by 1-[2-(4-methoxyphenyl)-2-[3-(4-methoxyphenyl)propoxy] ethyl-1H-imidazole, an inhibitor of store operated calcium influx, nor by nimodipine or omega-agatoxin, blockers of voltage-gated calcium channels. These electrophysiological and Ca2+-imaging experiments suggest that the mGluR(1)-mediated inward current, although mainly carried by Na+, involves influx of Ca2+ from the extracellular space.

Animals↗

PubMed2000

Atm-deficient mice Purkinje cells show age-dependent defects in calcium spike bursts and calcium currents.

Ataxia telangiectasia in humans results from homozygous loss-of-function mutations in ATM. Neurological deterioration is the major cause of death in ataxia telangiectasia patients: in the cerebellum, mainly Purkinje cells are affected. We have generated Atm-deficient mice which display neurological abnormalities by several tests of motor function consistent with an abnormality of cerebellar function, but without histological evidence of neuronal degeneration. Here we performed a more detailed morphological analysis and an electrophysiological study on Purkinje cells from Atm-deficient mice of different ages. We found no histological or immunohistochemical abnormalities. Electrophysiology revealed no abnormalities in resting membrane potential, input resistance or anomalous rectification. In contrast, there was a significant decrease in the duration of calcium and sodium firing. The calcium deficit became significant between six to eight and 12-20 weeks of age, and appeared to be progressive. By voltage-clamp recording, we found that the firing deficits were due to a significant decrease in calcium currents, while inactivating potassium currents seem unaffected. In other mutant mice, calcium current deficits have been shown to be related to cell death.Our experiments suggest that the electrophysiological defects displayed by Atm-deficient mice are early predegenerative lesions and may be a precursor of Purkinje cell degeneration displayed by ataxia telangiectasia patients.

Action Potentials↗

PubMed2000

Elevation of intradendritic sodium concentration mediated by synaptic activation of metabotropic glutamate receptors in cerebellar Purkinje cells.

Cerebellar Purkinje cells express both ionotropic glutamate receptors and metabotropic glutamate receptors. Brief tetanic stimulation of parallel fibers in rat and mouse cerebellar slices evokes a slow excitatory postsynaptic current in Purkinje cells that is mediated by the mGluR1 subtype of metabotropic glutamate receptors. The effector system underlying this mGluR1 EPSC has not yet been identified. In the present study, we recorded the mGluR1 EPSC using the whole-cell patch-clamp technique in combination with microfluorometric recordings of the intracellular sodium concentration ([Na+]i) by means of the fluorescent sodium indicator SBFI. The mGluR1 EPSC was induced by local parallel fibre stimulation in the presence of the ionotropic glutamate receptor antagonists NBQX and D-APV and the GABAA receptor antagonists bicuculline or picrotoxin. The mGluR1 EPSC was associated with an increase in [Na+]i that was restricted to a specific portion of the dendritic tree. The mGluR1 EPSC as well as the increase in [Na+]i were inhibited by the mGluR antagonist S-MCPG. In the presence of NBQX, D-APV, pictrotoxin and TTX, bath application of the selective mGluR agonist 3,5-DHPG induced an elevation in [Na+]i which extended over the whole dendritic field of the Purkinje cell. This finding demonstrates that the mGluR1-mediated postsynaptic current leads to a significant influx of sodium into the dendritic cytoplasm of Purkinje cells and thereby provides a novel intracellular signalling mechanism that might be involved in mGluR1-dependent synaptic plasticity at this synapse.

2-Amino-5-phosphonovalerate↗

PubMed1998

Postsynaptic current mediated by metabotropic glutamate receptors in cerebellar Purkinje cells.

In rat cerebellar slices, repetitive parallel fiber stimulation evokes an inward, postsynaptic current in Purkinje cells with a fast component mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptors and a slower component mediated by metabotropic glutamate receptors (mGluR). The mGluR-mediated excitatory postsynaptic current (mGluR-EPSC) is evoked selectively by parallel fiber stimulation; climbing fiber stimulation is ineffective. The mGluR-EPSC is elicited most effectively with increasing frequencies of parallel fiber stimulation, from a threshold of 10 Hz to a maximum response at approximately 100 Hz. The amplitude of the mGluR-EPSC is a linear function of the number of stimulus pulses without any apparent saturation, even with >10 pulses. Thus mGluRs at the parallel fiber-Purkinje cell synapse can function as linear detectors of the number of spikes in a burst of activity in parallel fibers. The mGluR-EPSC is present from postnatal day 15 and persists into adulthood. It is inhibited by the generic mGluR antagonist (RS)-a-methyl-4-carboxyphenylglycine and by the group I mGluR antagonist (RS)-1-aminoindan-1,5-dicarboxylic acid at a concentration selective for mGluR1. Although the intracellular transduction pathway involves a G protein, the putative mediators of mGluR1 (phospholipase C and protein kinase C) are not directly involved, indicating that the mGluR-EPSC studied here is mediated by a different and still unidentified second-messenger pathway. Heparin, a nonselective antagonist of inositol-trisphosphate (IP3) receptors, has no significant effect on the mGluR-EPSC, suggesting that also IP3 might be not required for the response. Buffering intracellular Ca2+ with a high concentration of bis-(o-aminophenoxy)-N,N,N', N'-tetraacetic acid partially inhibits the mGluR-EPSC, indicating that Ca2+ is not directly responsible for the response but that resting Ca2+ levels exert a tonic potentiating effect on the mGluR-EPSC.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1997

A pacemaker current in dye-coupled hilar interneurons contributes to the generation of giant GABAergic potentials in developing hippocampus.

The establishment of synaptic connections and their refinement during development require neural activity. Increasing evidence suggests that spontaneous bursts of neural activity within an immature network are mediated by gamma-aminobutyric acid via a paradoxical excitatory action. Our data show that in the developing hippocampus such synchronous burst activity is generated in the hilar region by transiently coupled cells. These cells have been identified as neuronal elements because they fire action potentials and they are not positive for the glial fibrillary acidic protein staining. Oscillations in hilar cells are "paced" by a hyperpolarization-activated current, with properties of Ih. Coactivated interneurons synchronously release GABA, which via its excitatory action may serve a neurotrophic function during the refinement of hippocampal circuitry.

Aging↗

PubMed1997

Reciprocal trophic interactions between climbing fibres and Purkinje cells in the rat cerebellum.

In the adult cerebellum both the climbing fibre arbour and the Purkinje cell are very plastic and each element is able to exert a remarkable action on the other one. The adult phenotype of the Purkinje cell is strictly dependent on the presence of its climbing fibre arbour. When the climbing fibre is missing, the Purkinje cell undergoes a hyperspiny transformation and becomes hyperinnervated by the parallel fibres. However, this change is fully reversible. The climbing fibre-deprived Purkinje cell is able to elicit sprouting of nearby located intact climbing fibres and the new arbour is able to fully restore synaptic connections which appear normal both morphologically and functionally. Multiple climbing fibre innervation of a single Purkinje cell persists in the adult hypogranular cerebellum. The different fibres are distributed to separate dendritic regions, suggesting a local competition between the different arbours for their territory. It is postulated that in the intact rat, an activity dependent mechanism of the parallel fibre favours the predominance of one arbour with the elimination of its competitors. When the Purkinje cell is deleted, the climbing fibre arbour becomes heavily atrophic and reduced in size. The analysis of the pattern of this atrophy indicates that the climbing fibre arbour is made by two compartments: a proximal one, whose survival depends on the integrity of the inferior olive, and a distal one, which represents the true pre-synaptic site, which strictly depends on the target. The climbing fibre terminal arbour is able to extend its territory of innervation not only when adult intact climbing fibres are confronted with nearby denervated Purkinje cells, but also when an embryonic cerebellum is grafted onto the surface of an adult unlesioned cerebellum. In this case, collaterals of intact climbing fibre arbours elongate through the pial surface, enter the graft to innervate the Purkinje cells. This growth is likely under the influence of a tropic signal released by the embryonic Purkinje cells. This suggests that the sprouting observed in the adult rat following a subtotal inferior olive lesion is also triggered by a similar factor. The axonal elongation and the consequent synaptogenesis are likely guided by local cues. In this condition, the distribution of the new collateral reinnervation occurs within its projectional map. In addition, when the inferior cerebellar peduncle is sectioned at birth, the climbing fibres of the non-deafferented hemicerebellum emit collaterals which cross the midline and innervate cerebellar strips which are symmetrically positioned relative to the intact side. In the grafting experiments, both the migrated and non-migrated Purkinje cells show the typical electrophysiological properties of the mature cerebellum. These data show that the disappearance of neuronal elements is not a necessary prerequisite to allow new neurones to become fully morphologically and functionally integrated into an adult brain. The reciprocal trophic influence between the climbing fibres and the Purkinje cells shown in the present series of experiments are likely operative in the adult brain not only in pathological conditions and they could give a basic contribution to the synaptic plasticity underlying learned behaviour.

Animals↗

PubMed1996

Fractional Ca2+ currents through somatic and dendritic glutamate receptor channels of rat hippocampal CA1 pyramidal neurones.

1. The Ca2+ permeability of non-NMDA and NMDA receptor channels was studied using a fluorometric flux measurement approach in somata and dendrites of CA1 pyramidal neurones in rat hippocampal slices. For this purpose, the Ca2+ fraction of the total cation current (named 'fractional Ca2+ current') was measured directly from the change in the Ca(2+)-sensitive fura-2 fluorescence at 380 nm excitation wavelength. 2. The fractional Ca2+ current through the somatic NMDA receptor channels was 10.69 +/- 2.13% (mean +/- S.D.) and that through dendritic receptor channels was 10.70 +/- 1.96%. The fractional Ca2+ current was not dependent on the extracellular Mg2+ concentration and its voltage dependence was in agreement with the Goldman-Hodgkin-Katz current equation. 3. AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate) or kainate applications produced small but significant Ca2+ entry. Fractional Ca2+ currents of 0.58 +/- 0.34% were measured for somatic AMPA applications, 0.68 +/- 0.20% for somatic kainate applications, 0.66 +/- 0.25% for dendritic AMPA applications and 0.61 +/- 0.16% for dendritic kainate applications. 4. The expression pattern of glutamate receptor subunits encoding messenger ribonucleic acids (mRNAs) was analysed with the single-cell reverse transcriptase-polymerase chain reaction (RT-PCR) approach applied to CA1 pyramidal neurones. The AMPA receptor subunits GluR-A, GluR-B and GluR-C, and the NMDA receptor subunits NR2A and NR2B were found to be abundantly expressed in all CA1 pyramidal neurones tested. 5. This study establishes the fractional Ca2+ current through somatic and dendritic NMDA and non-NMDA receptor channels in CA1 pyramidal neurones. The dendritic, presumably synaptic, NMDA receptor channels are highly Ca2+ permeable and have a fractional Ca2+ current closely resembling that of somatic extrasynaptic NMDA receptor channels. Both somatic and dendritic non-NMDA receptor channels are of the 'low Ca2+ permeable' type and have a fractional Ca2+ current that is about twenty times smaller than that of NMDA receptor channels.

Animals↗

PubMed1996

Fractional calcium current through neuronal AMPA-receptor channels with a low calcium permeability.

The Ca(2+)-permeation properties of AMPA-receptor (AMPA-R) channels in Purkinje neurons in rat cerebellar slices were studied using a combination of whole-cell patch-clamp recordings, Fura-2 fluorometry, and single-cell reverse-transcription (RT)-PCR. Several lines of evidence indicate that Purkinje neurons, at both early and late stages of postnatal development, express exclusively AMPA-R channels with a low Ca2+ permeability. First, no Ca2+ signal was detected during application of either AMPA or kainate to Purkinje neurons loaded with the Ca2+ indicator Fura-2 AM. In contrast, kainate application induced large Ca2+ transients in Bergmann glia cells. Second, in ion substitution experiments, when Ca2+ is the only extracellular permeant cation, the reversal potential corresponds to that expected for AMPA-R channels with a low permeability for Ca2+. Third, using a fluorometric flux-measurement approach (Schneggenburger et al., 1993a), we found that the Ca2+ fraction of the total cation current through AMPA-R channels is approximately 0.6%. This value is approximately sixfold lower than that found for recombinant AMPA-R lacking the AMPA-R subunit GluR2. Furthermore, single-cell RT-PCR experiments revealed the presence of the AMPA-R subunits GluR1, GluR2, and GluR3 in Purkinje neurons in cerebellar slices at developmental stages corresponding to those studied electrophysiologically. The expression of GluR2 in all cells tested (n = 14) is consistent with the subunit composition predicted from studies of recombinant AMPA-R channels with a low permeability for Ca2+ (Burnashev et al., 1992b). In conclusion, this study establishes that cerebellar Purkinje neurons at all postnatal developmental stages possess AMPA-R channels with a low permeability for Ca2+.

Animals↗

PubMed1996

Postsynaptic currents and short-term synaptic plasticity in Purkinje cells grafted onto an uninjured adult cerebellar cortex.

It has been shown recently that embryonic Purkinje cells grafted extraparenchymally into an intact cerebellum, in the absence of any sign of damage, are able to migrate into the host molecular layer where they receive a climbing fibre innervation. Using the same technique, we investigated the development of the electrophysiological properties of the synapses between the grafted cells and their main afferents. Purkinje cells either in the graft or having migrated into the molecular layer of the host were recorded using the whole-cell patch-clamp method in acutely prepared slices 17-112 days after grafting. Spontaneous postsynaptic currents with a single-exponential decay and mediated by GABAA receptors were very similar to those described in normal Purkinje cells. Excitatory postsynaptic currents (EPSCs) evoked by climbing fibre and by parallel fibre stimulation were blocked by an alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)/kainate antagonist, and displayed the linear current-voltage relation typical of postnatal Purkinje cells. The attainment of normal functional properties by the adult axons at the newly formed synaptic sites was shown by the expression of short-term facilitation of parallel fibre EPSCs and of short-term depression of climbing fibre EPSCs. The grafted Purkinje cells showed climbing fibre polyinnervation 17-20 days after grafting which evolved to monoinnervation at 23-45 days, confirming the completion of the developmental programme up to maturation. Our experiments support the view that the adult intact brain is able to accept and integrate an additional number of neurons which show fully mature electrophysiological properties which are electrophysiologically indistinguishable from those of the host neurons.

Animals↗

PubMed1995

Influence of eye motion on adaptive modifications of the vestibulo-ocular reflex in the rat.

While sustained retinal slip is assumed to be the basic conditioning stimulus in adaptive modifications of the vestibulo-ocular reflex (VOR) gain, several observations suggest that eye motion-related signals might also be involved. We oscillated pigmented rats over periods of 20 min around the vertical axis, at 0.3 Hz and 20 degrees/s peak velocity, in different retinal slip and/or eye motion conditions in order to modify their VOR gain. The positions of both eyes were recorded by means of a phase-detection coil system with the head restrained. The main findings came from the comparison of two basic conditions--including their respective controls--in which one or both eyes were reversibly immobilised by threads sutured to the eyes. In the first condition the animals were rotated in the light with one eye immobilised and the other eye free to move but covered. Rotation in the light in this open-loop condition immediately elicited high-gain compensatory eye movements of the non-impeded, covered eye. At the end of this training procedure, the VOR gain increased by 43.2%. In the second condition, both eyes were immobilised and one eye was covered. The result was an increase in the VOR gain of 26.3%. These two conditions were similar as to the visuo-vestibular drive during the exposure, but different as to the resulting--and allowed--eye motion, showing that the condition where the larger eye movements occurred yielded the larger VOR gain change. Our data support the idea proposed by Collewijn and Grootendorst (1979, p. 779) and Collewijn (1981, p. 146) that "[retinal] slip and eye movements seem to be relevant signals for the adaptation of the rabbit's visuo-vestibular oculomotor reflexes".(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗

PubMed1994

Calcium requirement of long-term depression and rebound potentiation in cerebellar Purkinje neurons.

Cerebellar Purkinje neurons (PNs) receive two main excitatory inputs, from climbing fibers and parallel fibers, and inhibitory inputs, from GABAergic interneurons. The synapses formed by parallel fibers and by inhibitory interneurons on PNs are able to undergo long-lasting changes in efficacy. Thus, the excitatory parallel fiber-PN synapse undergoes long-term depression when it is activated in conjunction with climbing fibers. Synaptic inhibition can be potentiated by climbing fiber activity by a mechanism named rebound potentiation, resulting in a more powerful inhibitory effect of GABAergic interneurons. The induction of both long-term depression and rebound potentiation requires a transient elevation of the cytoplasmic calcium concentration ([Ca2+]i). The [Ca2+]i-transient is caused by Ca2+ entry through voltage-gated Ca2+ channels and, possibly, by release of Ca2+ from IP3- and ryanodine-sensitive stores. Direct Ca2+ entry through synaptic AMPA receptor channels seems not to contribute significantly to the Ca2+ signal mediating the induction of both long-term depression and rebound potentiation.

Animals↗

PubMed1994

Vergence compensation during binocularly- and monocularly-evoked horizontal optokinetic nystagmus in the pigmented rat.

During horizontal optokinetic nystagmus evoked by binocular stimulation in the rat, the slow phases are well-conjugate. The fast phases in the adducting eye are on average about 2 deg greater in amplitude than those of the abducting eye. This causes a transient convergence which is compensated for by a divergent drift within the 100 msec following the fast phase. The amplitudes of these convergence-divergence components fluctuates somewhat from one fast phase to another and their relative amplitudes may differ. As a consequence differences in vergence between successive slow phases may occur. Such differences are usually of small amplitude, but may be as large as 5 deg. When optokinetic nystagmus is evoked by monocular stimulation, the slow phase velocities are different in the two eyes, giving a disjunctive component which is compensated for by a difference in the relative amplitudes and velocities of the fast phases in the two eyes. However, the divergent drift immediately following the fast phases is very similar whatever form of stimulation is employed. It is suggested that during monocularly-evoked optokinetic nystagmus the oculomotor system compensates for the disjunctive component arising during the slow phases by giving a different balance to the pulses of innervation of two eyes, resulting in fast phases of different amplitude.

Animals↗

PubMed1993

Glutamate- and AMPA-mediated calcium influx through glutamate receptor channels in medial septal neurons.

The Ca(2+)-fraction of the ion current flowing through glutamate receptor channels activated either by glutamate or by AMPA was determined in forebrain neurons of the rat medial septum. By combining whole-cell patch-clamp and fura-2 fluorometric measurements we found that, at negative membrane potentials and at an extracellular free Ca(2+)-concentration of 1.6 mM, the Ca(2+)-fraction of the current activated by glutamate is 5.7%. A pharmacological analysis of responses produced by ionophoretically-released glutamate demonstrated a large contribution of NMDA-receptors but a small contribution of AMPA/kainate receptors to these responses. Interestingly, also AMPA-mediated currents were associated with significant changes in Ca(2+)-sensitive fluorescence. The fractional Ca2+ current of AMPA-induced responses was 1.2 +/- 0.4% (n = 5).

Animals↗

PubMed1991

Adaptation and habituation of the vestibulo-ocular reflex in intact and inferior olive-lesioned rats.

The gain of the vestibulo-ocular reflex (VOR) of intact pigmented rats was adaptively modified by training protocols that created a visual-vestibular conflict. For training, head restrained animals were oscillated on a turntable in front of an optokinetic pattern projected onto a cylindrical wall. The optokinetic pattern either moved the same amplitude with the animal ("in-phase": 0.05 Hz +/- 20 degrees/s) or opposite in direction ("out-of-phase": turntable and pattern 0.05 Hz +/- 10 degrees/s each). VOR responses were tested in darkness before and after each 8 min training period for a duration of 40 min. During "out-of-phase" training the gain of compensatory eye movements measured in light was close to 2 from the beginning on and the VOR tested in darkness increased in gain progressively from 0.48 (+/- 0.12) to 0.9 (+/- 0.3; P less than 0.05) in 5 out of 7 rats. Two rats did not adapt their VOR gain. Phase values decreased slightly by about 10 degrees. During "in-phase" stimulation compensatory eye movements were almost completely suppressed (gain close to 0) from the beginning on and the VOR tested in darkness decreased gradually in gain from 0.62 (+/- 0.17) to 0.13 (+/- 0.1; P less than 0.001) in all 6 trained rats. Phase values decreased in parallel from 151 degrees to 119 degrees (P less than 0.01). The effectiveness of the "in-phase" training paradigm in the absence of compensatory eye movements indicates that retinal image slip is the relevant signal for adaptation. In seven rats with histologically verified almost complete inferior olive (IO) lesions (chemically induced at least 45 days prior to training), "out-of-phase" and "in-phase" stimulation evoked compensatory eye movements with gains comparable to those in intact rats. VOR parameters measured in darkness were altered with respect to those of control rats. Gain differed extremely between individuals and phase lag re acceleration was in all IO-lesioned rats larger than in intact rats. The time constant of the VOR in response to table velocity steps was significantly longer (17 s +/- 4) than in intact rats (11 s +/- 3). Training did not alter the gain of the VOR in 5 out of 7 IO-lesioned rats. One rat increased its gain during "out-of-phase" training in the first, but not during a second training session (and not during "in-phase" training) and another rat decreased its gain during "in-phase" training (but not during "out-of-phase" training).(ABSTRACT TRUNCATED AT 400 WORDS)

Adaptation, Physiological↗

PubMed1989

Effects of ethanol and imidazobenzodiazepine Ro 15-4513 on spontaneous saccades of the pigmented rat.

The present study was aimed at investigating the alterations of the spontaneous saccadic eye movements of pigmented rats following ethanol administration. In addition we have studied the efficacy of the imidazobenzodiazepine Ro 15-4513 in reversing the effects of alcohol on saccades. The horizontal component of spontaneous eye movements was recorded by means of the magnetic field search coil technique on 11 head-restrained, pigmented rats. After the intraperitoneal injection of ethanol (1 g/kg) spontaneous saccades showed: i) a backward post-saccadic drift, with an exponential-like time course (time constant 100-150 ms); ii) a remarkable reduction of mean saccadic amplitude, up to 37% of control; iii) a significant decrease of peak velocity, which was reduced to about 80% of control. All these effects appeared and developed within a few minutes after the administration and were still present one hour later. When Ro 15-4513 (5 mg/kg) was injected i.p., 15 min after ethanol, the post-saccadic drift amplitude was immediately reduced and the drift was completely abolished within about 30 min. Mean saccadic amplitude returned to control values within a few minutes and was then steadily maintained for the following period examined (30 min). On the contrary, peak velocity showed only a slight tendency to recover which never was significant. When the same dose of Ro 15-4513 was injected alone there was no post-saccadic drift. However, mean saccadic amplitude increased, almost immediately, up to 160% of control. Its value showed a slight constant decrease in the following 30 min. Peak velocity was only slightly increased (up to 106% of control), but never was significantly different from control. Our results show that ethanol induces a remarkable impairment in the performance of spontaneous saccades. The imidazobenzodiazepine Ro 15-4513 is able to reverse completely only some of the alcohol-induced alterations, i.e. the post-saccadic drift and the reduction of saccadic amplitude, while it fails to counter efficiently the reduction of peak velocity. Ro 15-4513 exerts an intrinsic action, which is opposite to that of ethanol, on some of the saccadic parameters we have examined.

Animals↗