Visual Neuroscience最新文献

The transient receptor potential channel TRPM1 is required for synaptic transmission between photoreceptors and the ON subtype of bipolar cells (ON-BPC), mediating depolarization in response to light. TRPM1 is present in the somas and postsynaptic dendritic tips of ON-BPCs. Monoclonal antibodies generated against full-length TRPM1 were found to have differential labeling patterns when used to immunostain the mouse retina, with some yielding reduced labeling of dendritic tips relative to the labeling of cell bodies. Epitope mapping revealed that those antibodies that poorly label the dendritic tips share a binding site (N2d) in the N-terminal arm near the transmembrane domain. A major splice variant of TRPM1 lacking exon 19 does not contain the N2d binding site, but quantitative immunoblotting revealed no enrichment of this variant in synaptsomes. One explanation of the differential labeling is masking of the N2d epitope by formation of a synapse-specific multiprotein complex. Identifying the binding partners that are specific for the fraction of TRPM1 present at the synapses is an ongoing challenge for understanding TRPM1 function.

Although historically, treatment of amblyopia has been recommended prior to closure of a critical window in visual development, the existence and duration of that critical window is currently unclear. Moreover, there is clear evidence, both from animal and human studies of deprivation amblyopia, that there are different critical windows for different visual functions and that monocular and binocular deprivation have different neural and behavioral consequences. In view of the spectrum of critical windows for different visual functions and for different types of amblyopia, combined with individual variability in these windows, treatment of amblyopia has been increasingly offered to older children and adults. Nevertheless, treatment beyond the age of 7 years tends to be, on average, less effective than in younger children, and the high degree of variability in treatment response suggests that age is only one of many factors determining treatment response. Newly emerging treatment modalities may hold promise for more effective treatment of amblyopia at older ages. Additional studies are needed to characterize amblyopia by using new and existing clinical tests, leading to improved clinical classification and better prediction of treatment response. Attention also needs to be directed toward characterizing and measuring the impact of amblyopia on the patients' functional vision and health-related quality of life.

There are many levels of disorder in amblyopic vision, from basic acuity and contrast sensitivity loss to abnormal binocular vision and global perception of motion and form. Amblyopia treatment via patching to restore acuity often leaves other aspects of vision deficient. The source for these additional deficits is unclear. Neural correlates of poor binocular function and acuity loss are found in V1 and V2. However, they are generally not sufficient to account for behaviorally measured vision loss. This review summarizes the known cortical correlates of visual deficits found in association with amblyopia, particularly those relevant to binocular vision and higher-order visual processing, in striate and extrastriate cortex. Recommendations for future research address open questions on the role of suppression and oculomotor abnormalities in amblyopic vision, and underexplored mechanisms such as top-down influences on information transmission in the amblyopic brain.

Unquestionably, the last six decades of research on various animal models have advanced our understanding of the mechanisms that underlie the many complex characteristics of amblyopia as well as provided promising new avenues for treatment. While animal models in general have served an important purpose, there nonetheless remain questions regarding the efficacy of particular models considering the differences across animal species, especially when the goal is to provide the foundations for human interventions. Our discussion of these issues culminated in three recommendations for future research to provide cohesion across animals models as well as a fourth recommendation for acceptance of a protocol for the minimum number of steps necessary for the translation of results obtained on particular animal models to human clinical trials. The three recommendations for future research arose from discussions of various issues including the specific results obtained from the use of different animal models, the degree of similarity to the human visual system, the ability to generate animal models of the different types of human amblyopia as well as the difficulty of scaling developmental timelines between different species.

Amblyopia is a developmental disorder that affects the spatial vision of one or both eyes in the absence of an obvious organic cause; it is associated with a history of abnormal visual experience during childhood. Subtypes have been defined based on the purported etiology, namely, strabismus (misaligned eyes) and/or anisometropia (unequal refractive error). Here we consider the usefulness of these subclassifications.

The shift in ocular dominance (OD) of binocular neurons induced by monocular deprivation is the canonical model of synaptic plasticity confined to a postnatal critical period. Developmental constraints on this plasticity not only lend stability to the mature visual cortical circuitry but also impede the ability to recover from amblyopia beyond an early window. Advances with mouse models utilizing the power of molecular, genetic, and imaging tools are beginning to unravel the circuit, cellular, and molecular mechanisms controlling the onset and closure of the critical periods of plasticity in the primary visual cortex (V1). Emerging evidence suggests that mechanisms enabling plasticity in juveniles are not simply lost with age but rather that plasticity is actively constrained by the developmental up-regulation of molecular 'brakes'. Lifting these brakes enhances plasticity in the adult visual cortex, and can be harnessed to promote recovery from amblyopia. The reactivation of plasticity by experimental manipulations has revised the idea that robust OD plasticity is limited to early postnatal development. Here, we discuss recent insights into the neurobiology of the initiation and termination of critical periods and how our increasingly mechanistic understanding of these processes can be leveraged toward improved clinical treatment of adult amblyopia.

The orderly spacing of retinal neurons is commonly regarded as a characteristic feature of retinal nerve cell populations. Exemplars of this property include the horizontal cells and the cholinergic amacrine cells, where individual cells minimize the proximity to like-type neighbors, yielding regularity in the patterning of their somata. Recently, two types of retinal bipolar cells in the mouse retina were shown to exhibit an order in their somal patterning no different from density-matched simulations constrained by soma size but being otherwise randomly distributed. The present study has now extended this finding to a type of retinal amacrine cell, the AII amacrine cell. Voronoi domain analysis revealed the patterning in the population of AII amacrine somata to be no different from density-matched and soma-size-constrained random simulations, while analysis of the density recovery profile showed AII amacrine cells to exhibit a minimal intercellular spacing identical to that for those random simulations: AII amacrine somata were positioned side-by-side as often as chance would predict. Regularity indexes and packing factors (PF) were far lower than those achieved by either the horizontal cells or cholinergic amacrine cells, with PFs also being comparable to those derived from the constrained random simulations. These results extend recent findings that call into question the widespread assumption that all types of retinal neurons are assembled as regular somal arrays, and have implications for the way in which AII amacrine cells must distribute their processes to ensure a uniform coverage of the retinal surface.

A unique class of intrinsically photosensitive retinal ganglion cells in mammalian retinae has been recently discovered and characterized. These neurons can generate visual signals in the absence of inputs from rods and cones, the conventional photoreceptors in the visual system. These light sensitive ganglion cells (mRGCs) express the non-rod, non-cone photopigment melanopsin and play well documented roles in modulating pupil responses to light, photoentrainment of circadian rhythms, mood, sleep and other adaptive light functions. While most research efforts in mammals have focused on mRGCs in retina, recent studies reveal that melanopsin is expressed in non-retinal tissues. For example, light-evoked melanopsin activation in extra retinal tissue regulates pupil constriction in the iris and vasodilation in the vasculature of the heart and tail. As another example of nonretinal melanopsin expression we report here the previously unrecognized localization of this photopigment in nerve fibers within the cornea. Surprisingly, we were unable to detect light responses in the melanopsin-expressing corneal fibers in spite of our histological evidence based on genetically driven markers and antibody staining. We tested further for melanopsin localization in cell bodies of the trigeminal ganglia (TG), the principal nuclei of the peripheral nervous system that project sensory fibers to the cornea, and found expression of melanopsin mRNA in a subset of TG neurons. However, neither electrophysiological recordings nor calcium imaging revealed any light responsiveness in the melanopsin positive TG neurons. Given that we found no light-evoked activation of melanopsin-expressing fibers in cornea or in cell bodies in the TG, we propose that melanopsin protein might serve other sensory functions in the cornea. One justification for this idea is that melanopsin expressed in Drosophila photoreceptors can serve as a temperature sensor.