The ipsilateral optic pathway to the dorsal lateral geniculate nucleus and superior colliculus in mice with prenatal or postnatal loss of one eye.

The projections, and more particularly the ipsilateral projections, from the retina to the dorsal lateral geniculate nucleus (dlGn) and the superior colliculus have been investigated in adult mice of the C57BL/6J strain after rearing in one of four different conditions: 1) after normal visual experience; 2) after unilateral enucleation at birth; 3) in mice with congenital unilateral anophthalmia (in which only one eye develops) 4) in mice with congenital unilateral microphthalmia (in which one eye is of reduced size while the other is normal). In neonatally enucleated and congenitally monocular mice there is an aberrant uncrossed pathway to regions of the dlGn and the superior colliculus which do not normally receive such a projection. This projection is limited in its distribution; in both the neonatally enucleated and the congenitally monocular animals the uncrossed projection does not reach the lateral and dorsal parts of the dlGn and it only innervates the rostral half of the superior colliculus. The density of the uncrossed pathway in these animals is highest in those regions in which the normal uncrossed pathway terminates. In microphthalmic mice the expansion of the uncrossed pathway is less marked than in monocular mice. In the superior colliculus the aberrant uncrossed projections innervate the stratum griseum superficiale where they are often found distributed in small patches. An intertectal crossing of retinal fibers is described from the contralateral superior colliculus to the deprived ipsilateral superior colliculus.

Thalamic afferents to the visual cortex in congenitally anophthalmic mice.

Retrograde cell labelling with horseradish peroxidase (HRP) has been used to study the thalamic afferents to the primary visual cortex (area 17) in mutant H1-ZRDCT-An ('eyeless') mice, in which the eyes are missing throughout development. Injections of HRP that were localised to a subregion of area 17, resulted in the labelling of a group of neurons in the ipsilateral dorsal lateral geniculate nucleus, showing the existence of a point-to-point connectivity. Many labelled cells were also found in other posterior thalamic nuclei especially in the lateral posterior nucleus which in normal animals contain very few or no labelled cells.

Experience-dependent maturation of the spatial and temporal characteristics of the cell receptive fields in the kitten visual cortex.

The development of contrast sensitivity to spatial and temporal frequencies was studied in the visual cortex of 6-week-old kittens reared from birth in three conditions: normal, dark-reared (DR) and dark-reared after 6 h of visual experience. Receptive fields of cells recorded in area 17 were quantitatively analysed using drifting sine-wave gratings. Compared to the low values obtained in the DR kittens, we observed after 6 h of visual experience: (1) an adult-like detection of higher spatial frequencies, (2) an increase of contrast sensitivity at low temporal frequencies; (3) a shift of the cell optimum towards 3 Hz, all values close to the normal ones. Unlike the spatial frequency selectivity, contrast sensitivity and detection of higher temporal frequencies continue to develop with age and visual experience.

Does neuronal expression of GDNF effectively protect dopaminergic neurons in a rat model of Parkinson's disease?

The transfer of the Glial cell line-derived neurotrophic factor (GDNF) gene to the central nervous system by a recombinant adenoviral vector (Ad) was studied. We constructed the adenovirus vector Ad-NSE-GDNF from which the E1, E3/E4 regions of Ad5 have been deleted and in which the GDNF gene was under the control of a neuron-specific enolase (NSE) promoter. The vector was injected into the striatum of a rat model of Parkinson's disease. We found that (i) the NSE promoter can restrict transgene expression in neurons; (ii) Ad-NSE-GDNF significantly protected dopaminergic (DA) neurons in the substantia nigra (SN) but did not reverse the impairments of amphetamine-induced rotational behavior in lesioned rats.

[Absence of ipsilateral retinal projections after very early prenatal destruction of one eye in mice]. / Absence de projections réiniennes ipsilatérales après destruction très précoce in utéro d'un aeil chez la souris.

Mice embryos underwent unilateral destruction of one eye, in utero between 13 (E 13) and 17 days (E 17) of gestation, or at birth. The extension of the retinal projections from the remaining eye was determined, after birth, using the technique of anterograde transport of HRP. The results show that enucleations performed between E 15 and birth (E 19) result in the formation of an augmented ipsilateral pathway, the terminal extent of which does not depend greatly upon the exact timing of enucleation. However, following enucleations at E 13, the projections from the remaining eye are only crossed, there being practically no projections to the ipsilateral side of the brain.

[Physiological and anatomical study of the retinogeniculate projections in the mouse]. / Etude physiologique et anatomique des projections rétinogéniculées chez la Souris.

A physiological and anatomical study of the dorsal lateral geniculate nucleus (dlGn) in pigmented C57BL/6 Mice is reported. Neurons responding to the ipsilateral eye are clustered in a region near the medial border of dlGn, and are surrounded by contralateral neurons. Electrode penetrations in this part of dlGn show the existence of contra/ipsi/contralateral projection lines. Practically only the contralateral field of vision is represented in each dlGn. Local HRP injections show evidence in the retina of a decussation line for contralateral retinogeniculate projections, the border of which follows the inner border of the region of ipsilateral projection. The mean diameter of ipsilateral retinogeniculate ganglion cells is larger than that of contralateral cells.

Effect of dark rearing on the volume of visual cortex (areas 17 and 18) and number of visual cortical cells in young kittens.

The surface area, total volume, and total number of neurons of areas 17 and 18 in one hemisphere of dark-reared (DR), dark-reared and light-exposed (DRL), and normally reared (NR) kittens were studied at the age of 6 weeks. The thickness of the visual cortex was lower by 13% and 11% (area 17) and by 17% and 16% (area 18) in DR and DRL groups, respectively, when compared with similar cortical areas in NR kittens. The surface area values of area 17 were nearly the same in DR and DRL kittens, both being, however, 37% smaller than in NR animals. The surface area of area 18 was significantly smaller than that of area 17 in each group, and was also lower in DR (by 27%) and DRL (by 21%) groups when compared with the NR group. As a consequence of dark rearing, the numerical density of cortical neurons in area 17 amounted to about double of the value observed in normally reared kittens and was also significantly higher in area 18. The numerical density of nerve cells of DRL kittens fell between the DR and NR groups. The total cortical volume of area 17 was similar in DR and DRL groups but it was by 46% (DR) and by 44% (DRL) smaller than in NR kittens. In each experimental group, the total volume of area 18 was significantly smaller than that of area 17. The cortical volume of area 18 was also smaller than in the NR group by 39% and 34% in DR and DRL groups, respectively. In DR and NR kittens, the total numbers of neurons in areas 17 (DR = 26.4 million, NR = 25.7 million) and 18 (DR = 8.5 million, NR = 9.0 million) were essentially similar. In the DRL groups a significantly smaller number of cortical neurons was found both in area 17 (21.5 million) and in area 18 (6.8 million). It is concluded that, in spite of considerable differences in the cortical thickness, surface area, numerical density, and total cortical volume, the absolute numbers of neurons in area 17 and 18 of visually deprived (DR) and NR kittens do not differ at 6 weeks of age. The main deficit in cortical organization following dark rearing, therefore, appears to be confined mainly to the neuropil, as a result of an underdevelopment of neuronal processes and of depressed synaptic organization.(ABSTRACT TRUNCATED AT 400 WORDS)

Temporal correlations in modulated evoked responses in the visual cortical cells of the cat.

We analysed evoked responses recorded from 97 cells in the visual cortex of 4 adult cats and 8 kittens, stimulated by a drifting sinusoidal grating. A Fourier analysis of the responses allowed us to select 30 cells showing a clear modulating response (relative modulation index greater than 1). The 162 records from these selected cells were scanned to detect precise temporal correlations in the form of replicating triplets and associated "ghost" doublets. Temporal correlations of this nature were observed in these cells. They are about 10 times more abundant in adult cats than in kittens, and mostly observed in infragranular cortical layer cells. The possible role of these precise temporal patterns in information processing in the brain is examined, as well as the relation between this type of temporal correlation with coherent oscillations and principal components waveforms.

Delivery of GDNF by an E1,E3/E4 deleted adenoviral vector and driven by a GFAP promoter prevents dopaminergic neuron degeneration in a rat model of Parkinson's disease.

A new adenoviral vector (Ad-GFAP-GDNF) (Ad=adenovirus, GFAP=glial fibrillary acidic protein, GDNF=glial cell line-derived neurotrophic factor) was constructed in which (i) the E1,E3/E4 regions of Ad5 were deleted and (ii) the GDNF transgene is driven by the GFAP promoter. We verified, in vitro, that the recombinant GDNF was expressed in primary cultures of astrocytes. In vivo, the Ad-GFAP-GDNF was injected into the striatum of rats 1 week before provoking striatal 6-OHDA lesion. After 1 month, the striatal GDNF levels were 37 pg/microg total protein. This quantity was at least 120-fold higher than in nontransduced striatum or after injection of the empty adenoviral vector. At 3 months after viral injection, GDNF expression decreased, whereas the viral DNA remained unchanged. Furthermore, around 70% of the dopaminergic (DA) neurons were protected from degeneration up to 3 months as compared to about 45% in the control groups. In addition, the amphetamine-induced rotational behavior was decreased. The results obtained in this study on DA neuron protection and rotational behavior are similar to those previously reported using vectors with viral promoters. In addition to these results, we established that a high level of GDNF was present in the striatum and that the period of GDNF expression was prolonged after injection of our adenoviral vector.