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Biomedical subjects

M Pirchio

Publications and source records attributed to M Pirchio.

At least 19 recordsLinked to original sources

Postnatal development of membrane properties and delta oscillations in thalamocortical neurons of the cat dorsal lateral geniculate nucleus.

The development of membrane properties, firing patterns, and delta oscillations in neurons of the cat dorsal lateral geniculate nucleus (dLGN) was investigated in vitro during the first 7 postnatal weeks. Compared with adult neurons, the resting membrane potential was more depolarized at postnatal days 1-9 (P1-P9), the input resistance was higher at P1-P7, and action potentials had a higher threshold and a smaller amplitude at P1-P3 and a longer duration at P1-P9. At P1-P3 trains longer than 200 msec were rarely observed, and trains with more than three action potentials were only present in 41% of the neurons, whereas at P1-P7 the normalized slope of the instantaneous frequencies at the first five interspike intervals was smaller than in the adult. A long-lasting (up to 6 sec) afterhyperpolarization followed a short train of action potentials in 88 and 30% of neurons at P1-P3 and P30-P32, respectively, but it was rarely observed in the adult. The low-threshold Ca2+ potential could evoke a burst of action potentials since P1. However, at P1-P7 the number of action potentials per burst was smaller (range, one to five), and at P1-P9 their maximum instantaneous frequency was lower (<190 Hz) than in the adult (range, six to eight, and 344 Hz, respectively). No delta oscillations were observed until P17, and their frequency (0.36 Hz) was lower than that in the adult (1.8 Hz). The percentage of neurons displaying delta oscillations and their frequency reached adult values by the end of the seventh postnatal week, i.e., well after the maturation of the membrane properties and firing patterns (second postnatal week). In conclusion, the maturation of the electrophysiological properties of thalamocortical neurons in the cat dLGN is completed later than the retinogeniculate axon segregation (Shatz CJ, 1983), and the immaturity of the oscillatory, and not of the burst-firing, activity is a limiting factor in the development of delta waves.

Action Potentials↗

Postnatal development of the T calcium current in cat thalamocortical cells.

The burst firing of thalamic cells in the adult cat is mainly controlled by a voltage-dependent membrane current that has recently been characterized as being similar to the low voltage-activated (i.e. low threshold), T-type, Ca2+ current originally described in sensory neurons. In those neurons so far studied, as well as in skeletal muscle, the low threshold Ca2+ current has been shown to decrease in amplitude or even disappear during embryogenesis or the first few weeks of postnatal life. We have now investigated the in vivo postnatal development of the low threshold Ca2+ current present in thalamocortical cells of the dorsal lateral geniculate nucleus of cats aged four to 100 days. The results show that the amplitude of the low threshold Ca2+ current triples from 0.5 nA in the first few days after birth to over 1.5 nA in the adult. However, this increase in amplitude is not accompanied by any change in its inactivation and activation properties, its latency to peak and the time dependence of inactivation removal. Because of these similarities during development and in adulthood it is likely that a major role of the low threshold Ca2+ current during neuronal development is the generation of oscillatory activities similar to those observed in adult thalamocortical cells.

Animals↗

Cl- - and K+-dependent inhibitory postsynaptic potentials evoked by interneurones of the rat lateral geniculate nucleus.

1. Hyperpolarizing potentials evoked by electrical stimulation of the optic tract were studied in projection cells of the rat dorsal lateral geniculate nucleus (LGN) in vitro. In the same cells the effects of gamma-amino butyric acid (GABA), baclofen and acetylcholine (ACh) were also investigated. 2. In the majority of cells a short- (SHP) (34 ms) and a long-lasting (LHP) (240 ms) hyperpolarizing potential could be recorded in the presence and in the absence of a preceding EPSP. They were blocked by tetrodotoxin (1 microM) and were more sensitive than the monosynaptic EPSP to a low-Ca2+-high-Mg2+ solution. 3. The SHP was associated with a marked decrease (75%) in input resistance, was blocked by bicuculline (1-100 microM) and its reversal potential (-67 mV) was dependent on the extracellular Cl- concentration. 4. The LHP was associated with a smaller decrease (45%) in input resistance and its reversal potential (-76 mV) was dependent on the extracellular K+ concentration. It was increased by bicuculline (100% at 50 microM) and nipecotic acid (30% at 10 microM), blocked by Ba2+ (1 mM), and unaffected by eserine (1-10 microM), neostigmine (1-10 microM) or by recording with EGTA-filled electrodes. In the presence of bicuculline, a single LHP was able to evoke, as a rebound response, a low-threshold Ca2+ spike that was, however, not followed by another LHP (or any other long-lasting hyperpolarization). 5. Ionophoretic applications of GABA evoked in the same cell a Cl- -dependent hyperpolarization (reversal potential: -65 mV) and/or depolarization, both of which were associated with a marked decrease (91%) in input resistance and abolished by bicuculline. GABA was also able to evoke a bicuculline-insensitive, K+-dependent hyperpolarization that had a reversal potential of -75 mV and was associated with a smaller decrease (43%) in input resistance. 6. Baclofen, applied by ionophoresis, pressure ejection or in the perfusion medium (1-100 microM), produced a hyperpolarization that had a reversal potential of -79 mV and was associated with a decrease (45%) in input resistance. 7. In the majority of cells (thirty-seven out of forty) ACh evoked a slow depolarization and only in three cells a hyperpolarization which had a reversal potential of -80 mV.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗

The ventral and dorsal lateral geniculate nucleus of the rat: intracellular recordings in vitro.

1. The membrane properties and the electrotonic structure of neurones in the ventral and dorsal lateral geniculate nucleus (l.g.n.) of the rat were studied using an in vitro slice preparation. 2. Following electrophysiological characterization, horseradish peroxidase (HRP) was injected intrasomatically and the morphological features of impaled cells were characteristic of principal neurones of the rat ventral and dorsal l.g.n. 3. Neurones in the ventral l.g.n. had a higher input resistance but similar membrane time constants (tau o) and resting potentials than cells in the dorsal l.g.n. 4. Using a simple neuronal model, the electrotonic length (L) and the dendritic to somatic conductance ratio (rho) were calculated and found to be similar for cells in both divisions of the l.g.n. The mean value of L (0.7) and rho (1.5) suggest that both groups of neurones are electrotonically compact. 5. The width and after-hyperpolarization of directly evoked action potentials, but not their threshold or their amplitude, were different between cells of the ventral and dorsal l.g.n. 6. At potentials more negative than -55 mV, a slow rising and falling potential could be evoked in each neurone (n = 310) of the dorsal l.g.n. but only in three cells of the ventral l.g.n. (n = 94). The electrophysiological and pharmacological properties of this potential were identical with those of the low-threshold Ca2+-dependent potential observed in other thalamic nuclei. 7. These results indicate that some of the passive and active membrane properties of ventral and dorsal l.g.n. neurones are different. The implications of these findings for the control of the integrative capability and the response of l.g.n. neurones to visual stimulation are discussed.

Action Potentials↗

On the excitatory post-synaptic potential evoked by stimulation of the optic tract in the rat lateral geniculate nucleus.

1. The electrophysiological and pharmacological properties of the excitatory post-synaptic potentials (e.p.s.p.) evoked by electrical stimulation of the optic tract were studied in projection neurones of the ventral and dorsal lateral geniculate nucleus (l.g.n.) of the rat in vitro. 2. No difference was found in the rise time of e.p.s.p.s. recorded in the dorsal and ventral l.g.n. and in their threshold for action potentials. At membrane potentials more negative than -60 mV, e.p.s.p.s. in the dorsal l.g.n. were always followed by a Ca2+-dependent potential. Its amplitude could easily reach threshold for generating an action potential and thus evoke firing from an e.p.s.p. that was subthreshold at resting potential. No Ca2+ potential was observed to follow e.p.s.p.s. recorded in the ventral l.g.n. 3. At resting potential the excitability of dorsal and ventral cells was unaffected following an initial shock to the optic tract. However, in dorsal neurones, at potentials more negative than -60 mV, the presence of Ca2+ potentials evoked by the e.p.s.p.s. resulted in a period of decreased excitability. 4. Using intrasomatic injection of Cs+ the reversal potential (E) of the e.p.s.p. and of the depolarization produced by glutamate could be measured in the same l.g.n. neurone. They were: Eepsp, -0.9 mV; and Eglut, -3.9 mV. 5. gamma-D-glutamylglycine (DGG), an excitatory amino acid antagonist, reversibly inhibited the e.p.s.p. and depolarization produced by quisqualate and glutamate by a competitive action. The concentration of DGG that produced 50% inhibition (IC50) was 2.7 mM. 6. D-2-amino-5-phosphonovalerate (APV), the potent and selective N-methyl-D-aspartate (NMDA) antagonist, had no effect on the e.p.s.p. both in the presence and absence of Mg2+. The isomers of 2-amino-4-phosphonobutyrate (APB) were inactive or had a non-specific action on the e.p.s.p. 7. No difference could be detected in either the reversal potential or the action of the antagonists between neurones of the dorsal and the ventral l.g.n. 8. These results suggest that Ca2+-dependent potentials play an important role in modulating synaptic efficacy in principal neurones of the dorsal l.g.n. The quisqualate/kainate nature of the optic nerve receptors and the similarity of Eepsp and Eglut constitute strong support in favour of a glutamate-like substance as the transmitter of the optic nerve.

2-Amino-5-phosphonovalerate↗

Pattern reversal evoked potentials in infantile spasms.

Visual evoked potentials in response to sinusoidal gratings of various spatial frequencies, alternating in contrast at 8 Hz were recorded from infants affected by an idiopathic form of infantile spasms (West syndrome). In two infants in whom the spasms began at 3 and 5 months of age, respectively, the VEP's were found to be depressed in amplitude at and around a spatial frequency of 3 and 5 c/deg, respectively. This midfrequency depression, which has never been reported in the literature for normal infants, suggests that infantile spasms in idiopathic patients may interfere at least temporarily with the development of visual function.

Evoked Potentials, Visual↗

Development of retinal acuity in infants evaluated with pattern electroretinogram.

The electroretinographic (ERG) response to patterns of constant mean luminance (sinusoidal gratings reversed in contrast at 12 rev/s) has been recorded in infants 7 weeks to 6 months old. At each age the amplitude of the ERG for relatively fine gratings decreases with increasing spatial frequency and vanishes for a spatial frequency that can be defined as ERG acuity. It has been found that ERG acuity increases progressively with age. The acuity evaluated from cortical evoked potentials (VEP) recorded simultaneously with the ERG increases with age in parallel with ERG acuity. These findings are in agreement with data reported in the literature for the cat, indicating a parallel postnatal development of acuity at a retinal and cortical level.

Electroretinography↗

Visual acuity in the young infant is highest in a small retinal area.

Visual potentials (VEP) evoked by alternating gratings were recorded daily in one infant between 10 and 13 weeks of age and at 20 weeks of age. The VEP amplitude was measured for a stimulus field of increasing area at low and high spatial frequencies. At low spatial frequencies the VEP amplitude increases with increasing stimulus area, while at high spatial frequencies (near visual acuity) the VEP amplitude remains constant for stimulus field sizes beyond 2 deg. These findings parallel those obtained in the adult, and indicate that visual acuity of the infant is not uniform across the retina but is highest in a small region, as in the adult.

Adult↗

Development of retinal and cortical responses to pattern reversal in infants: a selective review.

Infant contrast sensitivity and visual acuity evaluated by recording steady-state visual evoked potentials (VEP) in response to sinusoidal gratings improve considerably during the first 6 months of life. Qualitatively similar findings are obtained in kittens 3-12 weeks old. In infants, the improvement in VEP acuity with age parallels the increase in retinal acuity estimated from electroretinographic (ERG) steady-state responses to sinusoidal gratings. Spatial frequency selective mechanisms with bandwidth substantially narrower than the overall contrast sensitivity function seem to be present in the visual system of very young infants. These findings are compared with data reported in the literature about the development of the cat and monkey visual system.

Animals↗

EMG changes in chronically dialyzed uraemic subjects undergoing d, 1-Carnitine treatment.

The deficiency of muscle Carnitine secondary to chronic dialysis frequently induces lipid storage in striated muscles associated with progressive myocardial involvement. Serial EMG recordings disclose the presence of several motor unit potential families in tibialis anterior muscle related to damage of peripheral nervous fibres and muscular districts due to the storage of lipid vacuoles. The administration of d,1-Carnitine to twenty chronically dialyzed uraemic patients significantly improved distal latency of the M response of the external peroneal nerve at the EDB muscle and the MUP properties suggesting a Carnitine-dependent amelioration of fatty acid oxidative processes both in muscle and Schwann cells. The main side effects following d,1-Carnitine oral administration (3 g/daily) is a myasthenia-like symptom complex that is promptly reversed on drug interruption.

Action Potentials↗

Checkerboard reversal pattern and flash VEPs in dialysed and non-dialysed subjects.

In forty-three patients suffering from chronic renal failure (CRF; 32 non-dialysed, 11 dialysed) the flash VEP and the pattern VEP to different spatial (7.5', 15', 30', 60' checks) and temporal (2, 10, 20, 40 Hz) frequencies were investigated. Abnormally delayed flash VEPs were obtained in 53.6% of the cases; transient pattern VEPs had a delayed major positive deflection in 46% of the tested eyes and altered steady-state response in 58% with a total of 65% abnormal responses. Chronically dialysed subjects showed higher levels of altered VEPs for both the techniques. The shorter latencies normally observed with coarser checks in healthy people were maintained in CRF patients, resulting in an abnormal prolongation of the shift between high and low spatial frequencies. Higher statistical correlations linked the pattern VEP with blood urea nitrogen (P less than 0.001) and other renal chemistry than the flash VEP. These and other features could be ascribed to a specific involvement of a maculo-calcarine channel devoted to 'detailed' vision and suggest the usefulness of this method to provide a tool for the early detection of an encephalopathic uraemia.

Adult↗

The ERG in response to alternating gratings in patients with diseases of the peripheral visual pathway.

Electroretinogram (ERG) responses to alternating gratings have been recorded in patients with temporary occlusion of the retinal artery, retrobulbar optic neuritis, and other ganglion cell diseases. The ERG responses to alternating gratings were absent in first case and dramatically depressed in the others, whereas the ERG responses to light flashes or to homogeneous flickering light were normal. These findings corroborate recent evidence from studies on the cat, showing that the ERG in response to alternating gratings is correlated with ganglion cell activity.

Animals↗

Scotopic contrast sensitivity in infants evaluated by evoked potentials.

The contrast sensitivity function of infants 2 1/2 to 6 months old has been obtained at mean luminances of 6 and 0.06 cd/m2 by recording visual evoked potentials in response to simusoidal gratings of various spatial frequencies alternating in phase at 8 Hz. The scotopic contrast sensitivity develops earlier than the photopic contrast sensitivity, reaching values very close to those of the adult between 4 and 5 months of age. This suggests that mechanisms responsible for adaptive changes of receptive field organization from night to day vision are not yet mature at this age.

Adult↗

Foveal versus peripheral retinal responses: a new analysis for early diagnosis of multiple sclerosis.

Visual potentials evoked by brief flashes (VEPs) were recorded in 85 patients with MS, 30 healthy controls and 25 neurological patients without demyelinating diseases. In a group of 44 patients, diffuse field stimulation was used, resutling in 15 altered responses (34%). In a second group of 41 patients with superimposable characteristics including age, sex, diagnosis of MS (definite, probable and possible) and score on the Rose's scale, the separate responses of central and peripheral retina were analysed. A total of 30 abnormal VEPs were recognized (73%) with the following distribution: 16 foveal VEPs (78%), 4 peripheral responses (13%) and 26 centreperiphery latency differences (CPLD, 60%). Twenty subjects of Group A with normal or slightly altered full field VEPs were retested with both stimulating methods with the following result: 3 altered full field VEPs (15%) and 15 abnormal CPLD (75%). With diffuse field stimulation, the correlation between the VEP scores and the results of other examinations (visual, pyramidal, etc.) were insignficant; on the contrary, the CPLD was clearly correlated with the involvement of the visual and other systems in the fluctuating clinical course of MS.

Adolescent↗

A perceptual phenomenon and its neurophysiological correlate.

A square-wave grating from which the fundamental harmonic has been subtracted (missing fundamental grating) when viewed from a suitable distance appears similar to another grating of periodicity three times higher. The neurons of the visual cortex of the cat, in a given range of spatial frequencies characteristic of each cell, give similar responses to the two gratings.

Animals↗