Gilles Bronchti

Altered Sensory Processing in the Somatosensory Cortex of the Mouse Mutant Barrelless

Mice homozygous for the barrelless (brl) mutation, mapped here to chromosome 11, lack barrel-shaped arrays of cell clusters termed “barrels” in the primary somatosensory cortex. Deoxyglucose uptake demonstrated that the topology of the cortical whisker representation is nevertheless preserved. Anterograde tracers revealed a lack of spatial segregation of thalamic afferents into individual barrel territories, and single-cell recordings demonstrated a lack of temporal discrimination of center from surround information. Thus, structural segregation of thalamic inputs is not essential to generate topological order in the somatosensory cortex, but it is required for discrete spatiotemporal relay of sensory information to the cortex.

Resveratrol, a red wine polyphenol, protects dopaminergic neurons in MPTP-treated mice

Phytoestrogens, and particularly resveratrol, a red wine polyphenol, are currently under study for their therapeutic antioxidant properties. Administration of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to C57BL/6 mice targets nigrostriatal dopaminergic neurons, leading to cell death and striatal dopamine (DA) depletion. The aim of the present study was to analyze the protective effect of a diet rich in resveratrol against MPTP-induced neuronal death. Male mice were kept on a phytoestrogen-free diet, supplemented or not with 50 or 100 mg/kg/day of resveratrol for 1 or 2 weeks, after which MPTP was injected intraperitoneally. We observed that daily administration of resveratrol prevented MPTP-induced depletion of striatal DA, and maintained striatal tyrosine hydroxylase (TH) protein levels. Our results also demonstrated that mice treated with resveratrol prior to MPTP administration showed more abundant TH-immunopositive neurons than mice given only MPTP, indicating that resveratrol protects nigral neurons from MPTP insults. Altogether, these data revealed that resveratrol can counteract the toxic effects of the neurotoxin MPTP and, as such, it may be regarded as a powerful molecule for complementary neuroprotective therapy.

Invasion of visual cortex by the auditory system in the naturally blind mole rat

PREVIOUSLY we have shown that the dorsal lateral geniculate body (LGB), which is strictly visual in sighted mammals, receives a strong auditory input in the naturally blind mole rat (Spalax ehrenbergi). Here we show with the 2-deoxyglucose technique and with single-unit recordings that in this species the initially non-degenerated visual cortex, as defined by its connection with LGB, is also activated by the auditory modality. These findings suggest that cross-modal compensation may occur as a natural consequence of the degeneration of a sense organ.

Auditory activation of ‘visual’ cortical areas in the blind mole rat (Spalax ehrenbergi)

The mole rat (Spalax ehrenbergi) is a subterranean rodent whose adaptations to its fossorial life include an extremely reduced peripheral visual system and an auditory system suited for the perception of vibratory stimuli. We have previously shown that in this blind rodent the dorsal lateral geniculate nucleus, the primary visual thalamic nucleus of sighted mammals, is activated by auditory stimuli. In this report we focus on the manifestation of this cross‐modal compensation at the cortical level. Cyto‐ and myeloarchitectural analyses of the occipital area showed that despite the almost total blindness of the mole rat this area has retained the organization of a typical mammalian primary visual cortex. Application of the metabolic marker 2‐deoxyglucose and electrophysiological recording of evoked field potentials and single‐unit activity disclosed that a considerable part of this area is activated by auditory stimuli. Previous neuronal tracing studies had revealed the origin of the bulk of this auditory input to be the dorsal lateral geniculate nucleus which itself receives auditory input from the inferior colliculus.

Retinal projections in the blind mole rat: a WGA-HRP tracing study of a natural degeneration.

The mole rat Spalax ehrenbergi is a fossorial rodent. Although its peripheral visual system--eye and optic nerve--is highly degenerated, it shows some sensitivity to light. However, in the usual sense, it is essentially blind. An auditory take-over of the visual lateral geniculate nucleus and at least part of the visual cortices was recently demonstrated. In order to visualize the retinal projections during ontogeny, we used an anterograde tracing technique, with monocular injection of wheat germ agglutinin-labeled horseradish peroxidase (WGA-HRP). In the newborn mole rat the retina projects to most of its normal targets as compared with seeing rodents, with bilateral projections to the suprachiasmatic nuclei, the dorsal and ventral lateral geniculate nuclei, the lateroposterior nuclei, the optic tract nuclei and the superior colliculi. During the course of ontogeny, the retinohypothalamic connection is stabilized but the main optic tract undergoes progressive degeneration. In adults, only a few retinal fibers enter the contralateral ventral lateral geniculate nucleus, the lateroposterior nucleus, the optic tract nucleus and the superior colliculus. No retinal fibers could be detected in the dorsal lateral geniculate nucleus. Thus, the retinofugal projections in the adult mole rat could explain its reduced sensitivity to light, whereas the complete degeneration of the retino-dorsal lateral geniculate nucleus projection could underlie the invasion of auditory input into this normally visual center.

Audition differently activates the visual system in neonatally enucleated mice compared with anophthalmic mutants.

The occipital cortex, normally visual, can be activated by auditory or somatosensory tasks in the blind. This cross‐modal compensation appears after early or late onset of blindness with differences in activation between early and late blind. This could support the hypothesis of a reorganization of sensory pathways in the early blind that does not occur in later onset blindness. Using immunohistochemistry of the c‐Fos protein following a white noise stimulus and injections of the anterograde tracer dextran‐biotin in the inferior colliculus, we studied how the occurrence of blindness influences cross‐modal compensation in the mutant anophthalmic mouse strain and in C57BL/6 mice enucleated at birth. We observed, in mutant mice, immunolabeled nuclei in the visual thalamus – the dorsal lateral geniculate nucleus – in the primary visual area (V1) and a few labeled nuclei in the secondary visual area (V2). In enucleated mice, we observed auditory activity mainly in V2 but also sparsely in V1. No labeled cells could be found in the visual thalamus. Tracing studies confirmed the difference between anophthalmic and birth‐enucleated mice: whereas the first group showed inferior colliculus projections entering both the dorsal lateral geniculate and the latero‐posterior nuclei, in the second, auditory fibers were found only within the latero‐posterior thalamic nucleus. None was found in controls with intact eyes. We suggest that the prenatal period of spontaneous retinal activity shapes the differences of the sensory reorganization in mice.

Barrelfield expansion after neonatal eye removal in mice.

We investigated the effect of neonatal eye removal on the tangential extent of the barrelfield in mice. Areas were measured in drawings made from tangentially cut Nisslstained sections of somatosensory cortex. We compared areas of 29 barrels, corresponding to 29 mystacial vibrissae, between adult mice enucleated at birth (n = 13) and their intact littermates (n = 13). Multivariate analysis of variance showed that the barrelfield was larger in enucleated mice. This expansion was mainly due to the increase in areal extent of the barrels corresponding to the dorsalmost row of vibrissae, and of a set of barrels corresponding to rostral vibrissae near the nose and mouth. Evidently, early enucleation has a significant cross-modal effect on the somatosensory cortex.

Auditory responses in the visual cortex of neonatally enucleated rats.

A number of studies on humans and animals have demonstrated better auditory abilities in blind with respect to sighted subjects and have tried to define the mechanisms through which this compensation occurs. The aim of the present study, therefore, was to examine the participation of primary visual cortex (V1) to auditory processing in early enucleated rats. Here we show, using gaussian noise bursts, that about a third of the cells in V1 responded to auditory stimulation in blind rats and most of these (78%) had ON-type responses and low spontaneous activity. Moreover, they were distributed throughout visual cortex without any apparent tonotopic organization. Optimal frequencies determined using pure tones were rather high but comparable to those found in auditory cortex of blind and sighted rats. On the other hand, sensory thresholds determined at these frequencies were higher and bandwidths were wider in V1 of the blind animals. Blind and sighted rats were also stimulated for 60 min with gaussian noise, their brains removed and processed for c-Fos immunohistochemistry. Results revealed that c-Fos positive cells were not only present in auditory cortex of both groups of rats but there was a 10-fold increase in labeled cells in V1 and a fivefold increase in secondary visual cortex (V2) of early enucleated rats in comparisons to sighted ones. Also, the pattern of distribution of these labeled cells across layers suggests that the recruitment of V1 could originate at least in part through inputs arising from the thalamus. The ensemble of results appears to indicate that cross-modal compensation leading to improved performance in the blind depends on cell recruitment in V1 but probably also plastic changes in lower- and higher-order visual structures and possibly in the auditory system.

Environmental enrichment enhances auditory takeover of the occipital cortex in anophthalmic mice

Enrichment of the environment is an effective means of enhancing neuronal development and plasticity but its effect on the cross‐modal compensation resulting from sensory deprivation has never been investigated. The present study used c‐Fos immunohistochemistry and dextran–biotin neuronal tracing to examine the reorganization of sensory modalities in the brain of anophthalmic mutant mice (ZRDCT/An) raised in either enriched or standard environments. Auditory stimulation was found to elicit strong neuronal activation in thalamic and cortical structures that are normally visual. An important finding was that the latter auditory‐evoked cortical activity was considerably enhanced in blind mice raised in the enriched environment. The axonal tracing study demonstrated auditory inputs from the inferior colliculus to the visual thalamus. This animal model will be useful for understanding neuronal mechanisms underlying some cross‐modal sensory phenomena observed in blind or deaf humans.

Cortical and subcortical projections to primary visual cortex in anophthalmic, enucleated and sighted mice

The purpose of this study was to identify and compare the afferent projections to the primary visual cortex in intact and enucleated C57BL/6 mice and in ZRDCT/An anophthalmic mice. Early loss of sensory‐driven activity in blind subjects can lead to activations of the primary visual cortex by haptic or auditory stimuli. This intermodal activation following the onset of blindness is believed to arise through either unmasking of already present cortical connections, sprouting of novel cortical connections or enhancement of intermodal cortical connections. Studies in humans have similarly demonstrated heteromodal activation of visual cortex following relatively short periods of blindfolding. This suggests that the primary visual cortex in normal sighted subjects receives afferents, either from multisensory association cortices or from primary sensory cortices dedicated to other modalities. Here cortical afferents to the primary visual cortex were investigated to determine whether the visual cortex receives sensory input from other modalities, and whether differences exist in the quantity and/or the structure of projections found in sighted, enucleated and anophthalmic mice. This study demonstrates extensive direct connections between the primary visual cortex and auditory and somatosensory areas, as well as with motor and association cortices in all three animal groups. This suggests that information from different sensory modalities can be integrated at early cortical stages and that visual cortex activations following visual deprivations can partly be explained by already present intermodal corticocortical connections.