Strain differences of the effect of enucleation and anophthalmia on the size and growth of sensory cortices in mice (original) (raw)

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

European Journal of Neuroscience, 2007

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.

Subcortical auditory input to the primary visual cortex in anophthalmic mice

Neuroscience Letters, 2008

Anatomical and imaging studies show ample evidence for auditory activation of the visual cortex following early onset of blindness in both humans and animal models. Anatomical studies in animal models of early blindness clearly show intermodal pathways through which auditory information can reach the primary visual cortex. There is clear evidence for intermodal corticocortical pathways linking auditory and visual cortex and also novel connections between the inferior colliculus and the visual thalamus. A recent publication [L.K. Laemle, N.L. Strominger, D.O. Carpenter, Cross-modal innervation of primary visual cortex by auditory fibers in congenitally anophthalmic mice, Neurosci. Lett. 396 (2006) 108-112] suggested the presence of a direct reciprocal connection between the inferior colliculus and the primary visual cortex (V1) in congenitally anophthalmic ZRDCT/An mice. This implies that this mutant mouse would be the only known vertebrate having a direct tectal connection with a primary sensory cortex. The presence of this peculiar pathway was reinvestigated in the ZRDCT/An mouse with highly sensitive neuronal tracers. We found the connections normally described in the ZRDCT/An mouse between: (i) the inferior colliculus and the dorsal lateral geniculate nucleus, (ii) V1 and the superior colliculus, (iii) the lateral posterior nucleus and V1 and between (iv) the inferior colliculus and the medial geniculate nucleus. We also show unambiguously that the auditory subcortical structures do not connect the primary visual cortex in the anophthalmic mouse. In particular, we find no evidence of a direct projection from the auditory mesencephalon to the cortex in this animal model of blindness.

Cross-modal innervation of primary visual cortex by auditory fibers in congenitally anophthalmic mice

Neuroscience Letters, 2006

Auditory-visual cross-modal innervation was examined in control (sighted, ZRDCT-N) and congenitally anophthalmic (eyeless, ZRDCT-AN) mice using electrophysiological recording and pathway tracing with carbocyanine dyes. Electrophysiological data demonstrate that the primary visual cortex of congenitally eyeless, blind, mice receives auditory stimuli. Neuroanatomical data demonstrate a direct connection between the inferior colliculus (IC) and visual cortex. Our experiments provide new information about how the brain adapts to the loss of sight.

Structural brain plasticity induced by early blindness

European Journal of Neuroscience, 2020

It is well established that early blindness results in behavioral adaptations. While the functional effects of visual deprivation have been well researched, anatomical studies are scarce. The aim of this study was to investigate whole brain structural plasticity in a mouse model of congenital blindness. Volumetric analyses were conducted on high-resolution MRI images and histological sections from the same brains. These morphometric measurements were compared between anophthalmic and sighted ZRDBA mice obtained by breeding ZRDCT and DBA mice. Results from MRI analyses using the Multiple Automatically Generated Templates method showed smaller volume for the primary visual cortex and superior colliculi in anophthalmic compared with sighted mice. Deformation-based morphometry revealed smaller volumes within the dorsal lateral geniculate nuclei and the lateral secondary visual cortex and larger volumes within olfactory areas, piriform cortex, orbital areas, and the amygdala, in anophthalmic compared with sighted mice. Histological analyses revealed a larger volume for the amygdala and smaller volume for the superior colliculi, primary visual cortex, and medial secondary visual cortex, in anophthalmic compared with sighted mice. The absence of superficial visual layers of the superior colliculus and the thinner cortical layer IV of the primary and secondary visual cortices may explain the smaller volume of these areas, although this was observed in a limited sample. The present study provides evidence for large-scale brain plasticity in a mouse model of congenital blindness. In addition, the congruence of MRI and histological findings support the use of MRI to investigate structural brain plasticity in the mouse.

Thalamic afferents to the visual cortex in congenitally anophthalamic mice

Neuroscience Letters, 1979

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-ZRDC'r-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, sh~ ring the existence of a point~t~p(>int 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.

Anatomical changes in the primary visual cortex of the congenitally blind Crx−/− mouse

Neuroscience, 2010

Mutations in the human cone-rod homeobox (Crx) gene are associated with retinal dystrophies such as Leber Congenital Amaurosis (LCA), characterized by complete or near complete absence of vision from birth. The photoreceptors of Crx؊/؊ mice lack outer segments, and therefore cannot capture light signals through rods and cones, thus resulting in a lack of normal retinal ganglion cell activity from birth. Using specific antibodies to subsets of neurons and markers of activity, we examined the impact of this absence of sensory input on the development of the primary visual cortex (V1) in early postnatal Crx؊/؊ mice, before wiring of the visual system is complete, and in adulthood. We revealed that Crx؊/؊ mice did not exhibit gross anatomical differences in V1; however, they exhibited significantly fewer calcium-binding protein (parvalbumin and calbindin-D28k) expressing interneurons, as well as reduced nonphosphorylated neurofilament expression in V1. These results reveal that the Crx mutation and lack of light stimulation through the photoreceptor pathway regulate the development and phenotype of different neuronal populations in V1 but not its general morphology. We conclude, therefore, that photoreceptor-mediated visual input during development is crucial for the normal postnatal development and maturation of subsets of cortical neurons.

The development of corticocollicular projections in anophthalmic mice

Developmental Brain Research, 1999

To determine the role of retinal axons in the development of the corticocollicular projection in mice, the lipophilic fluorescent dye, Ž . DiI, was used to compare the development of the cortical projections in phenotypically normal C57BLr6J mice to that of anophthalmic 129SVrCPor J mice. Cortical axons in anophthalmic mice found their targets and established a laminar specificity similar to those of cortical axons in normal mice despite the absence of the retinal projection. Cortical axons in normal mice reached the superior colliculus before those in anophthalmic mice and also had a faster rate of growth within the colliculus. Unlike cortical axons in normal mice in early postnatal ages, those in anophthalmic mice formed a disperse bundle in the stratum opticum. Axons labeled by focal applications of DiI into area 17 terminated in a larger and more medial area in anophthalmic mice than in normal mice. Thus, retinal axons are not essential for cortical axons to reach the superior colliculus, but they may have a role in organizing the growth of later-arriving cortical axons. Furthermore, cortical axons can terminate in the superior colliculus with a coarse topography when retinal axons are absent, but they cannot form a topographically refined projection. q

Auditory responses in the visual cortex of neonatally enucleated rats

Neuroscience, 2007

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.