Search PubMedSearch

Biomedical subjects

L Maffei

Publications and source records attributed to L Maffei.

At least 37 records · Page 2Linked to original sources

Nerve growth factor (NGF) prevents the shift in ocular dominance distribution of visual cortical neurons in monocularly deprived rats.

The hypothesis that NGF could play a role in the plasticity of the developing mammalian visual cortex was tested in monocularly deprived (MD) rats. In particular, we have asked whether an exogenous supply of NGF could prevent the changes in ocular dominance distribution induced by monocular deprivation. Hooded rats were monocularly deprived for 1 month, starting at postnatal day 14 (P14), immediately before eye opening, by means of eyelid suture. In eight rats, only monocular deprivation was performed; in eight rats, monocular deprivation was combined with intraventricular injections of beta-NGF, and in three rats, with intraventricular injections of cytochrome C. Injections (2 microliters) were given every other day for a period of 1 month. Single neuron activity was recorded in the primary visual cortex of MD rats, MD rats treated with NGF, and MD rats treated with cytochrome C at the end of the deprivation period, and in normal rats of the same age. We found that monocular deprivation caused a striking change in the ocular dominance distribution of untreated MD rats, reducing binocular cells by a factor of two and increasing by a factor of eight the number of cells dominated by the nondeprived eye. In MD NGF-treated rats, the ocular dominance distribution was indistinguishable from the normal. Cytochrome C treatment was completely ineffective in preventing the ocular dominance shift induced by monocular deprivation. To test whether NGF affected cortical physiology or interfered with transmission of visual information, we evaluated in NGF-treated rats the spontaneous discharge and the orientation selectivity. We found these functional properties to be in the normal range. We conclude that NGF is effective in preventing the effects of monocular deprivation in the rat visual cortex and suggest that NGF is a crucial factor in the competitive processes leading to the stabilization of functional geniculocortical connections during the critical period.

Animals

Nerve growth factor prevents the amblyopic effects of monocular deprivation.

Monocular deprivation early in life causes dramatic changes in the functional organization of mammalian visual cortex and severe reduction in visual acuity and contrast sensitivity of the deprived eye. We tested whether or not these changes could be from competition between the afferents from the two eyes for a target-derived neurotrophic factor. Rats monocularly deprived during early postnatal development were treated with repetitive intraventricular injections or topical administration of nerve growth factor. The effects of monocular deprivation were then assessed electrophysiologically. In untreated animals visual acuity and contrast sensitivity of the deprived eye were strongly reduced, whereas in nerve growth factor-treated animals these parameters were normal.

Amblyopia

Different effects of intracranial and intraorbital section of the optic nerve on the functional responses of rat retinal ganglion cells.

A lesion to the optic nerve of adult mammals leads to the retrograde degeneration and finally to the death of injured retinal ganglion cells. In this study, we have evaluated the effects induced by different sites of axotomy on the functional changes occurring in the retinal ganglion cells after optic nerve section. We have investigated the functional properties of retinal ganglion cells of adult rats by recording the retinal responses to patterned stimuli (pattern electroretinogram) after unilateral section of the optic nerve at two different levels: intraorbital and intracranial. The results show that the site of lesion of the optic nerve affects the time of disappearance of the pattern electroretinogram. The pattern electroretinogram takes longer to be degraded after an intracranial section than an intraorbital section.

Animals

Expression of NGF receptor and NGF receptor mRNA in the developing and adult rat retina.

Nerve growth factor (NGF) has been recently found to rescue axotomized retinal ganglion cells (RGCs) of the adult rat from degeneration. Because the trophic effect of NGF involves a receptor-coupling event, the characterization and cellular localization of the NGF receptor (NGFR) in the retina are essential to understanding the possible specific action of NGF in this district of the central nervous system. We report here that the NGFR mRNA is expressed in fetal, neonatal, and adult rat retina. Using monoclonal antibody 192-IgG to immunoprecipitate and immunohistochemically identify NGFR, we also found that the NGFR from the retina has a molecular weight identical to that of the NGFR from PC12 cells. The NGFR is localized on RGCs and Müller cells. Finally, following ligation of the optic nerve, NGFR-immunopositive material was found to accumulate both distal and proximal to the site of ligation, suggesting that RGC axons anterogradely and retrogradely transport the NGFR. These data raise the possibility that NGF may play a specific role in rat RGCs.

Adrenal Gland Neoplasms

Transplant of embryonal nervous tissue preserves the responses of rat retinal ganglion cells after section of the optic nerve.

We have investigated the effectiveness of embryonal tectal tissue transplants in preserving the physiological activity of lesioned ganglion cells by recording the visual responses from the adult rat retina after section of the optic nerve, with or without transplants of embryonal nervous tissue on the stump. We have found that transplant of embryonal nervous tissue at the level of the optic nerve section has dramatic effects in preserving visual retinal responses to patterned stimuli for times as long as five months after surgery. By this time retinal responses to patterned stimuli have almost completely disappeared in control animals with optic nerve section alone.

Action Potentials

Monocular deprivation in split-chiasm kittens does not impair the development of visuo-motor behaviour.

Development of visual acuity is known to be impaired by early monocular deprivation. This may be due to lack of visual experience or to abnormal binocular competition. We report here the results of behavioural experiments on monocularly deprived kittens in which the optic chiasm had been split. In these kittens it has been found that visual acuity of the deprived eye is as good as the visual acuity of the non-deprived eye, namely 2-2.5 c/deg.

Animals

Pattern ERG in rats following section of the optic nerve.

The aim of this study is to investigate in the rat the properties of the pattern electroretinogram (ERG) and to assess whether it depends upon the functional integrity of ganglion cells. Flash and pattern ERG were recorded from urethane anaesthetized hooded rats. The pattern ERG was evoked by phase alternating gratings of various spatial frequencies and contrasts. In the first part of the study we determined how the amplitude of the main harmonic of the pattern ERG (2nd harmonic) varies as a function of stimulus parameters such as spatial and temporal frequency, contrast and mean luminance. In the second part of the study we investigated the effects of the retrograde degeneration of ganglion cells following optic nerve section on the amplitude of pattern ERG. We found that the section of the optic nerve leads to the progressive disappearance of the P-ERG which is almost complete 4 months after surgery. By this time only few axotomized ganglion cells are left. The flash ERG remained unaffected. Thus, the pattern electroretinogram seems to be a simple and sensitive tool to investigate the functional integrity of retinal ganglion cells in rats.

Animals

The visual acuity of the lynx.

Visual evoked potentials were recorded from the occipital scalp of two anaesthetized Lynx (Lynx europea) in response to alternating gratings of various spatial frequencies and contrasts. The visual acuity of the Lynx was found to be around 5-6 c/deg, i.e. very close to the visual acuity of the cat and by far inferior to human acuity.

Animals

Schwann cells promote the survival of rat retinal ganglion cells after optic nerve section.

Schwann cells (SCs) are known to play an important role for the regeneration of mammalian peripheral nerves. Their effect is likely due to the production of neuronotrophic and/or supportive factors. Here we study the effect of intraocular transplant of SCs on the survival of rat retinal ganglion cells (RGCs) after the intracranial section of the optic nerve. SCs were injected intraocularly in adult hooded rats. Surviving RGCs were retrogradely labeled with horseradish peroxidase applied to the proximal stump of the optic nerve. Results show that intraocular transplants of SCs promote the survival of a large number of RGCs for periods as long as 9 and 14 weeks after optic nerve section. In experimental retinae, surviving RGCs were 2- to 8-fold more numerous than in controls. This finding suggests that SCs are the source of factors that promote the survival of RGCs. Nerve growth factor is produced by SCs, and the intraocular injection of nerve growth factor has been previously shown to promote RGC survival. The rescuing effect of SCs on RGCs is greater than that obtained by intraocular injection of nerve growth factor. This greater effect may be due to the action of other neurotrophic factors produced by SCs or by transplanted SCs producing NGF in a sustained fashion.

Animals

Correlation in the discharges of neighboring rat retinal ganglion cells during prenatal life.

The spontaneous discharges of neighboring retinal ganglion cells were recorded simultaneously in anesthetized prenatal rats between embryonic days 18 and 21. We report here that in the majority of cases the firings of neighboring retinal ganglion cells are strongly correlated during prenatal life. Correlation in the discharges of neighboring cells during development has long been suggested as a way to consolidate synaptic connections with a target cell onto which they converge, a model first proposed by Hebb. Correlation in the activities of neighboring neurons in the retina could be the basis of developmental processes such as refinement of retinotopic maps in the brain and segregation of the inputs from the two eyes.

Animals

Response properties in the dorsal lateral geniculate nucleus of the adult cat after interruption of prenatal binocular interactions.

1. Single-cell recordings were made in the magnocellular layer of the dorsal lateral genicule nucleus (dLGN) of five adult cats in which prenatal binocular interactions were interrupted by monocular enucleation at known gestational ages. Three cats (early enucleates) had one eye removed on either embryonic day 44.48, or 49, before retinogeniculate inputs are segregated into uniocular layers. Two other (late enucleates) underwent this procedure on embryonic days 55 and 58, when segregation is well advanced. Responses were compared with those obtained from recordings in the A and A1 layers of the dLGN of seven normal adult cats. 2. Cells were classified as ON or OFF by the use of spots of light and as X or Y based on a test of linearity of spatial summation with the use of counterphased sinusoidal gratings. Receptive-field size and spatial resolution were also obtained. 3. The dLGN of prenatally enucleated cats contains a dorsal magnocellular layer and a ventral parvocellular layer. In early enucleates, only an occasional hint of a cell-sparse interlaminar zone was apparent, located between the magnocellular and parvocellular layers. In late enucleates, a prominent cell-sparse band was observed contralateral to the remaining eye, in a region that would most likely correspond to layer A1 in the normal dLGN. No such cell-sparse band was seen ipsilateral to the remaining eye in late enucleates. 4. Eighty-six X cells and 22 Y cells were studied in the enucleates. Both cell types were found at all depths of the magnocellular layer. All but a few neurons had concentric ON-center or OFF-center receptive fields that were normal in size. The topography of receptive fields also appeared normal. In addition, spatial resolution of X and Y cells was similar in experimental and control animals. 5. In early enucleates there was a higher percentage of X cells and a lower percentage of Y cells than normal. The change in X-to-Y ratio was shown to be because of both a gain in cells with X properties and a loss of cells with Y properties. The distribution of dLGN somal sizes in the early enucleates was comparable with controls, so the change in X-to-Y ratio most likely did not result from an electrode sampling bias. It was suggested that the X-to-Y ratio difference could stem from the abnormalities in retinogeniculate terminal arbors that have been shown to follow early eye removal.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Effect of NGF on the survival of rat retinal ganglion cells following optic nerve section.

The ability of NGF (2.5S subunit) to support the survival of adult rat retinal ganglion cells (RGCs) and optic nerve fibers after intracranial section of the optic nerve was investigated. NGF was injected intraocularly at a dose of 3 micrograms/injection every 2.3 d from the day of axotomy to analysis. Control animals received cytochrome c injections. The survival of RGCs was analyzed in whole-mounted retinas after either cresyl violet staining or labeling with HRP applied to the proximal stump of the optic nerve. Survival times were 5 and 7 weeks. Diameter distribution and number of myelinated optic nerve fibers were assessed in ultrathin cross sections of the optic nerve. We found that RGCs surviving axotomy were much more numerous following NGF treatment compared with controls. Large-size cells were, in particular, preserved by NGF treatment. The quantitative ultrastructural studies indicated that the number of myelinated optic nerve fibers at 5 and 7 weeks postaxotomy was significantly greater in the NGF group with respect to the cytochrome c group. In agreement with the results obtained at the level of the RGCs, large-diameter axons were, in particular, preserved. We conclude that NGF injected intraocularly is effective in promoting the survival of RGCs and optic nerve fibers at least for a period as long as 7 weeks after intracranial section of the optic nerve.

Animals

Spontaneous impulse activity of rat retinal ganglion cells in prenatal life.

The existence of spontaneous neural activity in mammalian retinal ganglion cells during prenatal life has long been suspected. This activity could play a key role in the refinement of retinal projections during development. Recordings in vivo from the retinas of rat fetuses between embryonic day 17 and 21 found action potentials in spontaneously active ganglion cells at all the ages studied.

Action Potentials

The axon initial segment as a possible determinant of retinal ganglion cell dendritic geometry.

In wholemounted retinae of cat, rat and monkey, in which ganglion cells were retrogradely labelled with horseradish peroxidase, a quantitative analysis of the direction of the axon initial segment with respect to the optic disc and of the relationship between the axon initial segment and the direction and distribution of primary dendrites was performed on the class of largest ganglion cells. The results show the following. (1) In all 3 species, the majority of primary dendrites of ganglion cells are directed away from the axon initial segment. (2) Primary dendrites arise with a greater frequency from the region of the cell body opposite to the axon initial segment than close to it. (3) In cat the direction of the axon initial segments show less variance in their initial direction with respect to the optic disc than in rat or monkey. In adult cats the nucleus of alpha-ganglion cells occupies a central position. In the kitten the position of the nucleus is eccentric and lies in a part of the cell body opposite to the axon initial segment. The nucleus moves to a central position over the next 3 weeks. The position of the axon initial segment is discussed as a possible determinant of ganglion cell dendritic geometry.

Animals

Dendritic competition: competition for what?

A lesion to the retina of a newborn rat results in the retrograde degeneration of ganglion cells in a sector of retina peripheral to the lesion. The dendritic tree of ganglion cells bordering the region depleted of ganglion cells have their dendrites preferentially directed into this area. We have examined the factors which play a role in this rearrangement of the dendritic tree. The results show that the lesion in neonates selects for or produces a population of cells with the axon directed away from the depleted area and primary dendrites directed towards the depleted area. The abnormal dendritic bias cannot be accounted for solely on the basis of a decrease in contact inhibition since a reduction in the density of all ganglion cells by 30% prior to making the retinal lesion does not attenuate the abnormal dendritic bias into the depleted area. The abnormal dendritic bias is present in animals operated on up to 15 days of age postnatally but not in more mature animals. The abnormal dendritic bias develops prior to the formation of a large number of synapses in the inner nuclear layer. Our results cannot be easily accounted for by competition for synaptic contacts or a loss of contact inhibition as previously suggested. We propose that chemotropic factors produced within the area depleted of ganglion cells induce the abnormal dendritic bias and the number of synaptic contacts may limit the size of the dendritic field.

Aging

The organization of receptive fields in area 18 neurones of the cat varies with the spatio-temporal characteristics of the visual stimulus.

The spatial frequency tuning curves of neurones of area 18 depend upon the velocity of the visual stimulus. The higher the velocity the lower the spatial frequencies to which the cell is tuned. Since in area 17 the size of the cell receptive field is inversely related with the optimal spatial frequency to which the cell responds, we have investigated whether the shift of the optimal spatial frequency with the velocity corresponds to a "change" in the receptive field size. We recorded extracellularly from neurones in area 18; for each cell we selected two gratings, one of high spatial frequency drifting at low velocity and another of low spatial frequency drifting at high velocity to which the cell gave comparable responses. The results show that the masking of the cells receptive field which abolishes the response to the high frequency low velocity grating does not prevent the cell from responding to the low frequency high velocity grating. We conclude that the size of the receptive field of neurones in area 18 depends upon the characteristics (spatial frequency and velocity) of the visual stimulus.

Animals