Local cell proliferation upon enucleation in Direct Retinal Brain Targets in the Visual system of the Adult Mouse

2015

Front. Syst. Neurosci.

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The groundbreaking work of Hubel and Wiesel in the 1960’s on ocular dominance plasticity instigated many studies of the visual system of mammals, enriching our understanding of how the development of its structure and function depends on high quality visual input through both eyes. These studies have mainly employed lid suturing, dark rearing and eye patching applied to different species to reduce or impair visual input, and have created extensive knowledge on binocular vision. However, not all aspects and types of plasticity in the visual cortex have been covered in full detail. In that regard, a more drastic deprivation method like enucleation, leading to complete vision loss appears useful as it has more widespread effects on the afferent visual pathway and even on non-visual brain regions. One-eyed vision due to monocular enucleation (ME) profoundly affects the contralateral retinorecipient subcortical and cortical structures thereby creating a powerful means to investigate cortical plasticity phenomena in which binocular competition has no vote.In this review, we will present current knowledge about the specific application of ME as an experimental tool to study visual and cross-modal brain plasticity and compare early postnatal stages up into adulthood. The structural and physiological consequences of this type of extensive sensory loss as documented and studied in several animal species and human patients will be discussed. We will summarize how ME studies have been instrumental to our current understanding of the differentiation of sensory systems and how the structure and function of cortical circuits in mammals are shaped in response to such an extensive alteration in experience. In conclusion, we will highlight future perspectives and the clinical relevance of adding ME to the list of more longstanding deprivation models in visual system research.

Section: Monocular Enucleation As a Brain Plasticity Modelmentioning

confidence: 99%

Visual system plasticity in mammals: the story of monocular enucleation-induced vision loss

Nys

Scheyltjens

2015

Front. Syst. Neurosci.

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“…Through its involvement in actin metabolism, the peptide is implicated in processes like motility, synaptogenesis and growth of neuronal processes (Carpintero et al 1999;Gomez-Marquez and Anadon 2002;Van Kesteren et al 2006;Vartiainen et al 1996;Yang et al 2008), as well as in glial activation that occurs after brain damage (Cuyvers et al 2010;Dong et al 2005;Kim et al 2006;Vartiainen et al 1996). Indeed, actin polymerization is a crucial event for cellular motility, axonal path finding and synaptogenesis.…”

Section: Discussionmentioning

confidence: 98%

“…Likewise, Yoshida et al (2002) found an up-regulation in the kidney in an ischemiareperfusion model. We recently also reported an up-regulation of Tb4-immunoreactive microglia in all direct retinal target structures of the brain, including the superficial layers of the superior colliculus (SC), after monocular enucleation in the adult mouse (Cuyvers et al 2010).…”

Section: Introductionmentioning

confidence: 97%

Striking neuronal thymosin beta 4 expression in the deep layers of the mouse superior colliculus after monocular deprivation

Paulussen

2011

Brain Struct Funct

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Thymosin beta 4 (Tβ4), a small acidic peptide isolated originally from calf thymus, is recognized as a regulator of actin polymerization. It is widely distributed in the brain, in neurons as well as in microglia, and it has been implicated in lesion-induced neuroplasticity. In the present study, we quantitatively analyzed the immunocytochemical expression pattern of Tβ4 in the superior colliculus (SC) of the adult mouse following monocular enucleation. Immunocytochemistry revealed a remarkable neuronal profile in the SC of 2, 5 and 7-week enucleated animals. We investigated the morphology, number and layer-specific localization of these immunoreactive neurons. Neuronal Tβ4-immunoreactive cell bodies were only sparsely found in the deep layers of the SC of control mice and showed only few and short immunoreactive branches, whereas their number increased significantly with post-enucleation survival time, as well as the total extent of the neuritic tree and its degree of branching. Occasionally, some Tβ4-immunoreactive neurons were also detected in the periaqueductal gray. As a regulator of actin metabolism, Tβ4 may influence the remodeling of these collicular neuronal processes, possibly in the context of a re-alignment of the sensory and motor maps in the deep SC as a consequence of the visual deprivation paradigm.

“…Reactive oxygen species, which function as messenger molecules to mediate structural remodeling, were also detected in subcortical structures of the adult rat visual system 14 . Furthermore, microglial and astroglial activation across different subcortical visual target structures in the mouse occur in a specific post-enucleation time frame of one week 15 . Together, optic deafferentation results in different subcortical responses at the glial, structural and molecular level.…”

Section: Introductionmentioning

confidence: 99%

A Highly Reproducible and Straightforward Method to Perform <em>In Vivo</em> Ocular Enucleation in the Mouse after Eye Opening

Aerts

Nys

2014

JoVE

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Enucleation or the surgical removal of an eye can generally be considered as a model for nerve deafferentation. It provides a valuable tool to study the different aspects of visual, cross-modal and developmental plasticity along the mammalian visual system [1][2][3][4] .Here, we demonstrate an elegant and straightforward technique for the removal of one or both eyes in the mouse, which is validated in mice of 20 days old up to adults. Briefly, a disinfected curved forceps is used to clamp the optic nerve behind the eye. Subsequently, circular movements are performed to constrict the optic nerve and remove the eyeball. The advantages of this technique are high reproducibility, minimal to no bleeding, rapid post-operative recovery and a very low learning threshold for the experimenter. Hence, a large amount of animals can be manipulated and processed with minimal amount of effort. The nature of the technique may induce slight damage to the retina during the procedure. This side effect makes this method less suitable as compared to Mahajan et al. (2011) 5 if the goal is to collect and analyze retinal tissue. Also, our method is limited to post-eye opening ages (mouse: P10 -13 onwards) since the eyeball needs to be displaced from the socket without removing the eyelids. The in vivo enucleation technique described in this manuscript has recently been successfully applied with minor modifications in rats and appears useful to study the afferent visual pathway of rodents in general.