Biomedical subjects

C Gargini

Publications and source records attributed to C Gargini.

14 recordsLinked to original sources

PubMed1999

Electrical activity regulates dendritic reorganization in ganglion cells after neonatal retinal lesion in the cat.

During the first month of postnatal life, the dendritic arborizations of cat retinal ganglion cells continue to develop and undergo a substantial remodeling. Mechanical and pharmacological interferences with the normal development induce, during this period of time, substantial modifications in ganglion cell morphology. Specifically, the degeneration of those neurons whose axons were severed by a neonatal retinal lesion leads to a zone depleted of ganglion cells. Neurons at the border of the depleted area develop an abnormal elongation of the dendritic trees toward the empty space. In the present paper, we report data showing that this dendritic reorganization can be prevented by blocking the electrical activity with repeated tetrodotoxin injections into the eye during the whole critical period. Our analysis was performed on neurons filled with horseradish peroxidase.

Animals↗

PubMed1999

Analysis of pharmacologically isolated components of the ERG.

An harmonic analysis was applied to the electroretinogram (ERG) measured in intact cat eyes in control conditions and after pharmacological isolation of the components attributed to photoreceptors (PIII) and bipolar neurons (PII). The frequency response curves obtained in various conditions showed that the bandwidth of the PII component extends over a range of stimulus frequencies higher than the bandwidth of PIII. The enhancement of the PII response to stimuli of high temporal frequency suggests the presence of a frequency dependent gain control located either pre- and/or post-synaptically in the transmission line between the phototransductive cascade and bipolar neurons. A possible role of these processes is to enhance relevant visual information whilst selectively attenuating low frequency signals originating in the transductive cascade.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1999

Effects of blocking the hyperpolarization-activated current (Ih) on the cat electroretinogram.

The temporal properties of the electroretinogram (ERG) recorded from cat eyes were analyzed in the presence of either Cs+ or zatebradine which are known to inhibit the hyperpolarization activated current (Ih) in retinal rods. Both Cs+ and zatebradine reduce the ERG response to high-frequency sinusoidal stimuli of high mean luminance and contrast. Conversely, blockade of Ih has no effect on the frequency response characteristics of the isolated receptor component (PIII). These observations support the idea that Ih plays an important role in the transfer of signals from photoreceptors to second order neurons by suppressing the slow components originated in the phototransductive cascade. The result of this operation is an enhancement of the light response in a range of temporal frequencies relevant to vision.

Animals↗

PubMed1999

Mechanisms of photoreceptor death and survival in mammalian retina.

The mammalian retina, like the rest of the central nervous system, is highly stable and can maintain its structure and function for the full life of the individual, in humans for many decades. Photoreceptor dystrophies are instances of retinal instability. Many are precipitated by genetic mutations and scores of photoreceptor-lethal mutations have now been identified at the codon level. This review explores the factors which make the photoreceptor more vulnerable to small mutations of its proteins than any other cell of the body, and more vulnerable to environmental factors than any other retinal neurone. These factors include the highly specialised structure and function of the photoreceptors, their high appetite for energy, their self-protective mechanisms and the architecture of their energy supply from the choroidal circulation. Particularly important are the properties of the choroidal circulation, especially its fast flow of near-arterial blood and its inability to autoregulate. Mechanisms which make the retina stable and unstable are then reviewed in three different models of retinal degeneration, retinal detachment, photoreceptor dystrophy and light damage. A two stage model of the genesis of photoreceptor dystrophies is proposed, comprising an initial "depletion" stage caused by genetic or environmental insult and a second "late" stage during which oxygen toxicity damages and eventually destroys any photoreceptors which survive the initial depletion. It is a feature of the model that the second "late" stage of retinal dystrophies is driven by oxygen toxicity. The implications of these ideas for therapy of retinal dystrophies are discussed.

Age Factors↗

PubMed1999

The impact of basic fibroblast growth factor on photoreceptor function and morphology.

PURPOSE: To assess the impact of basic fibroblast growth factor (bFGF) on photoreceptor function and morphology. METHODS: Impact was assessed in two models. In one, the endogenous expression of bFGF in photoreceptors was raised by sectioning one optic nerve of rats 3 to 4 weeks before study. In the other, bFGF was injected into the vitreous chamber in rats and cats. Retinal function was assessed from the electroretinogram (ERG), and retinal morphology was studied using DNA dyes, immunolabeling, and in situ hybridization. RESULTS: In both models of bFGF upregulation, the ERG b-wave was suppressed over a wide stimulus range and in light- and dark-adapted conditions. The a-wave was not suppressed by either procedure and at the brightest intensities was enhanced by both procedures. In nerve-sectioned eyes, outer retina appeared normal histologically, but levels of bFGF protein in the inner and outer nuclear layers were raised, whereas bFGF mRNA levels remained unchanged. In both models, levels of synaptophysin in the outer plexiform layer and of cytochrome oxidase in inner segments were raised in association with increases in bFGF protein levels. CONCLUSIONS: bFGF increased the ability of photoreceptors to respond to light but attenuated the transmission of this response to inner retinal cells, presumably by blocking the photoreceptor-bipolar synapse. If the expression of bFGF protein is upregulated in human photoreceptor dystrophies, it may contribute a reversible component to the loss of vision. The relationship between these actions of bFGF and its ability to protect photoreceptors from stress remains to be established.

Animals↗

PubMed1999

Temporal fidelity in the visual system.

The temporal properties of the visual system have been analyzed by recording the ERG and its isolated components in response to light stimuli whose luminance was varied sinusoidally. The performance of the visual system to periodic light stimuli was tested in human subjects psychophysically. The comparison of the results in control conditions and after administration of drugs that specifically block the hyperpolarization activated current (Ih) suggest that the inner rectifying properties of the inner segment membrane of rods is involved in a process of temporal differentiation of the visual signals whereby high frequency components of the response especially relevant for the visual performance are enhanced. It is proposed that the temporal fidelity of the visual system is the results of an elaboration starting at early level of the signal generated by the phototransductive cascade.

Animals↗

PubMed1998

Somatostatin enhances neurite outgrowth in PC12 cells.

The rat pheochromocytoma cell line PC12 forms neurites in response to nerve growth factor (NGF), and it was also reported to extend processes in the presence of somatostatin (somatotropin release-inhibiting factor, SRIF), a neuroactive peptide that seems to act as a morphogenetic factor in the developing nervous system. In the present study, we re-evaluated the effects of SRIF on PC12 cell differentiation. Our results indicate that SRIF alone is ineffective in promoting neurite outgrowth. Instead, SRIF or its analogue, octreotide (a SRIF agonist on the receptor subtypes 2, 3 and 5), potentiates neurite extension induced by NGF. These results suggest that SRIF enhances neurite formation in PC12 cells without directly promoting neurite outgrowth. SRIF potentiation of NGF-induced neurite outgrowth persists at least in part in the presence of pertussis toxin (PTX), suggesting the involvement of PTX-insensitive G-proteins. In addition, protein kinase-dependent pathways are likely to mediate SRIF effects on NGF-induced differentiation.

Animals↗

PubMed1998

Evidence that the influence of ganglion cell axons on astrocyte morphology is mediated by action spike activity during development.

In many mammal retinas, the morphology of astrocytes is strongly influenced by nearby axons of ganglion cells. Astrocyte processes stretch along the axons, fine extensions of the processes contact node-like specialisation of the axon membrane and the morphology of the adult astrocyte is strongly determined by this relationship. The mechanism which attracts astrocyte processes to contact specific regions of the axon membrane is not known however. This study presents evidence that in the neonatal cat blocking the impulse activity of ganglion cells with the Na+-channel blocker tetrodotoxin (TTX) leads to a loss of the axon-related morphology of astrocytes. The morphological change induced in astrocytes by TTX was greater in younger animals and could not be detected in the adult. Conversely, if the TTX block was maintained for 4 postnatal weeks the changes induced in astrocytes persisted at least to 13 weeks. The TTX-induced loss of axon-related morphology in astrocytes suggests that the signal by which axons attract astrocyte processes to contact the axonal membrane in ways which modify astrocyte morphology is released by action spike activity during development.

Action Potentials↗

PubMed1998

Blockade of glutamate-mediated activity in the developing retina perturbs the functional segregation of ON and OFF pathways.

The dendrites of ganglion cells initially ramify throughout the inner plexiform layer of the developing retina before becoming stratified into ON or OFF sublaminae. This ontogenetic event is thought to depend on glutamate-mediated afferent activity, because treating the developing retina with the glutamate analog 2-amino-4-phosphonobutyrate (APB), which hyperpolarizes ON cone bipolar cells and rod bipolar cells, thereby preventing their release of glutamate, effectively arrests the dendritic stratification process. To assess the functional consequences of this manipulation, extracellular recordings were made from single cells in the A laminae of the dorsal lateral geniculate nucleus and from the optic tract in mature cats that had received intraocular injections of APB during the first postnatal month. Such recordings revealed that stimulation of the APB-treated eye evoked both ON as well as OFF discharges in 37% of the cells tested. (As expected, when the normal eye was activated, virtually all cells yielded only ON or OFF responses.) The proportion of ON-OFF cells found here corresponds closely to the incidence of multistratified dendrites observed previously in anatomical studies of APB-treated cat retinas. This suggests that the ganglion cells with multistratified dendrites receive functional inputs from ON as well as OFF cone bipolar cells. This interpretation is further supported by the finding that the proportion of ON-OFF cells was very similar in the geniculate layer innervated by the treated eye and in the optic tract. The cells activated by the APB-treated eye were also found not to show response suppression when flashing stimuli of increasing size were used. This suggests that exposing the developing retina to APB perturbs the neural circuitry mediating the antagonistic center-surround organization found in normal receptive fields. The functional changes evident after treating the developing retina with APB suggest that it should now be feasible to assess how the segregation of ON and OFF retinal pathways relates to organizational features at higher levels of the visual system, such as orientation selectivity in cortical cells.

Aminobutyrates↗

PubMed1997

The energetic cost of photoreception in retinal rods of mammals.

The effects of temperature on rod sensitivity and adaptation are analysed in the general context of the energy requirements of photoreception. The dependence of adaptation on the [Na]i turn-over appears to be critical in mammalian rods where the metabolic load is particularly heavy because of both temperature conditions and large Na+ influx. Estimates of the energy dissipated by rods in darkness and during bright illumination show that the metabolic load is reasonably well distributed. From this analysis it also results that most of the energy, which a rod dissipates in both darkness and light, is needed to keep [Na]i and [Ca]i low.

Adaptation, Physiological↗

PubMed1997

Interocular interactions in esotropia.

In cats the unilateral convergent strabismus surgically induced in the early postnatal life causes monocular spatial vision deficits and loss of binocular activation of the primary visual cortex. It is assumed that the asynchrony of inputs from the two eyes, by disrupting binocular convergence, leads to unbalanced binocular interactions that favour the non-deviated eye. The competitive advantage of this eye reduces both the excitatory drive to the cortex and the behavioural visual capabilities of the strabismic eye that exhibits the loss of the nasal portion of the visual field. Our experimental evidence indicate that the esotropic input, released by interocular influences by the chiasm section, recovers at least as much effectiveness to achieve orienting reactions in the previously neglected nasal field. In addition we found that the excitatory drive of the ipsilateral strabismic input, which is the one mostly impaired in esotropic animals, is fully preserved when the interocular interactions are impeded at birth and it is greatly improved in the esotropic cats with section of the optic chiasm performed in adulthood. All together these results suggest that functional impairment of the esotropic input prior of chiasmotomy does not reflect developmental changes of the visual afferents yet the active inhibition exerted by interocular mechanisms.

Animals↗

PubMed1996

Visual field defects in esotropic cats: a developmental consequence of the squint.

In nine adult cats with surgically induced esotropia (squint-angle ranging between 8 degrees and 32 degrees), the extent of binocular and monocular visual fields was behaviourally assessed by the food-perimetry method. Results indicate that: (1) The extention of both the nasal and the temporal hemifield of the esotropic eye is narrowed. (2) Field losses are largest in the cats with severe esotropia (> 15 degrees); yet the relationship between rate of impairment scored in each animal and individual angles of squint is not linear. (3) In the cats with severe esotropia, the visual field of the non-deviated eye is also narrowed. (4) We suggest that field deficits reflect a stop in the developmental expansion of the immature visual field as a consequence of ocular misalignment.

Animals↗

PubMed1995

Recovery of the nasal field loss in esotropic cats after section of the optic chiasm.

It is assumed that in esotropic cats the behavioural suppression of the nasal field reflects inhibition of the input conveyed through the temporal retinal afferents of the strabismic eye. We hypothesized that inhibition underlying the field defect might be actively operated by interocular competitive mechanisms. If so, effectiveness of the strabismic eye input might be restored and loss of the corresponding visual field might be recovered by interrupting the direct interactions between the eyes with the section of the optic chiasm. Results obtained in eight esotropic split-chiasm cats confirm the hypothesis and suggest that suppressive mechanisms of binocular rivarly are involved in the behavioral loss of the esotropic nasal field.

Animals↗

PubMed1990

Stretch-activated cation channels with large unitary conductance in leech central neurons.

Stretch-activated cation channels were identified in the soma membrane of leech central neurons. These channels were almost silent under normal experimental conditions and were distinctly activated by application of negative pressure to the patch pipette. The channels exhibited a preferential selectivity for K+ and a slope conductance of about 200 pS, in symmetrical K+ solution. In cell-attached patches these cation channels were activated by cell swelling.

Animals↗