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Neural Regeneration Research Dec 2023Vision depends on accurate signal conduction from the retina to the brain through the optic nerve, an important part of the central nervous system that consists of...
Vision depends on accurate signal conduction from the retina to the brain through the optic nerve, an important part of the central nervous system that consists of bundles of axons originating from retinal ganglion cells. The mammalian optic nerve, an important part of the central nervous system, cannot regenerate once it is injured, leading to permanent vision loss. To date, there is no clinical treatment that can regenerate the optic nerve and restore vision. Our previous study found that the mobile zinc (Zn) level increased rapidly after optic nerve injury in the retina, specifically in the vesicles of the inner plexiform layer. Furthermore, chelating Zn significantly promoted axonal regeneration with a long-term effect. In this study, we conditionally knocked out zinc transporter 3 (ZnT3) in amacrine cells or retinal ganglion cells to construct two transgenic mouse lines (VGATZnT3 and VGLUT2ZnT3, respectively). We obtained direct evidence that the rapidly increased mobile Zn in response to injury was from amacrine cells. We also found that selective deletion of ZnT3 in amacrine cells promoted retinal ganglion cell survival and axonal regeneration after optic nerve crush injury, improved retinal ganglion cell function, and promoted vision recovery. Sequencing analysis of reginal ganglion cells revealed that inhibiting the release of presynaptic Zn affected the transcription of key genes related to the survival of retinal ganglion cells in postsynaptic neurons, regulated the synaptic connection between amacrine cells and retinal ganglion cells, and affected the fate of retinal ganglion cells. These results suggest that amacrine cells release Zn to trigger transcriptomic changes related to neuronal growth and survival in reginal ganglion cells, thereby influencing the synaptic plasticity of retinal networks. These results make the theory of zinc-dependent retinal ganglion cell death more accurate and complete and provide new insights into the complex interactions between retinal cell networks.
PubMed: 37449644
DOI: 10.4103/1673-5374.373660 -
Current Opinion in Neurobiology Dec 2018Dendrites are the conduits for receiving (and in some cases transmitting) neural signals; their ability to do these jobs is a direct result of their morphology.... (Review)
Review
Dendrites are the conduits for receiving (and in some cases transmitting) neural signals; their ability to do these jobs is a direct result of their morphology. Developmental patterning mechanisms are critical to ensuring concordance between dendritic form and function. This article reviews recent studies in vertebrate retina and brain that elucidate key strategies for dendrite functional maturation. Specific cellular and molecular signals control the initiation and elaboration of dendritic arbors, and facilitate integration of young neurons into particular circuits. In some cells, dendrite growth and remodeling continues into adulthood. Once formed, dendrites subdivide into compartments with distinct physiological properties that enable dendritic computations. Understanding these key stages of dendrite patterning will help reveal how circuit functional properties arise during development.
Topics: Amacrine Cells; Animals; Dendrites; Humans; Morphogenesis; Nerve Net; Neuronal Plasticity
PubMed: 30092409
DOI: 10.1016/j.conb.2018.07.007 -
Journal of Imaging Jan 2022The retina is the entrance of the visual system. Although based on common biophysical principles, the dynamics of retinal neurons are quite different from their cortical...
The retina is the entrance of the visual system. Although based on common biophysical principles, the dynamics of retinal neurons are quite different from their cortical counterparts, raising interesting problems for modellers. In this paper, I address some mathematically stated questions in this spirit, discussing, in particular: (1) How could lateral amacrine cell connectivity shape the spatio-temporal spike response of retinal ganglion cells? (2) How could spatio-temporal stimuli correlations and retinal network dynamics shape the spike train correlations at the output of the retina? These questions are addressed, first, introducing a mathematically tractable model of the layered retina, integrating amacrine cells' lateral connectivity and piecewise linear rectification, allowing for computing the retinal ganglion cells receptive field together with the voltage and spike correlations of retinal ganglion cells resulting from the amacrine cells networks. Then, I review some recent results showing how the concept of spatio-temporal Gibbs distributions and linear response theory can be used to characterize the collective spike response to a spatio-temporal stimulus of a set of retinal ganglion cells, coupled via effective interactions corresponding to the amacrine cells network. On these bases, I briefly discuss several potential consequences of these results at the cortical level.
PubMed: 35049855
DOI: 10.3390/jimaging8010014 -
Journal of Anatomy Aug 2023The precise specification of cellular fate is thought to ensure the production of the correct number of neurons within a population. Programmed cell death may be an... (Review)
Review
The precise specification of cellular fate is thought to ensure the production of the correct number of neurons within a population. Programmed cell death may be an additional mechanism controlling cell number, believed to refine the proper ratio of pre- to post-synaptic neurons for a given species. Here, we consider the size of three different neuronal populations in the rod pathway of the mouse retina: rod photoreceptors, rod bipolar cells, and AII amacrine cells. Across a collection of 28 different strains of mice, large variation in the numbers of all three cell types is present. The variation in their numbers is not correlated, so that the ratio of rods to rod bipolar cells, as well as rod bipolar cells to AII amacrine cells, varies as well. Establishing connectivity between such variable pre- and post-synaptic populations relies upon plasticity that modulates process outgrowth and morphological differentiation, which we explore experimentally for both rod bipolar and AII amacrine cells in a mouse retina with elevated numbers of each cell type. While both rod bipolar dendritic and axonal arbors, along with AII lobular arbors, modulate their areal size in relation to local homotypic cell densities, the dendritic appendages of the AII amacrine cells do not. Rather, these processes exhibit a different form of plasticity, regulating the branching density of their overlapping arbors. Each form of plasticity should ensure uniformity in retinal coverage in the presence of the independent specification of afferent and target cell number.
Topics: Mice; Animals; Dendrites; Retina; Amacrine Cells; Axons
PubMed: 35292986
DOI: 10.1111/joa.13653 -
Molecular Therapy. Methods & Clinical... Sep 2023Ectopic induction of optogenetic actuators, such as channelrhodopsin, is a promising approach to restoring vision in the degenerating retina. However, the cell...
Ectopic induction of optogenetic actuators, such as channelrhodopsin, is a promising approach to restoring vision in the degenerating retina. However, the cell type-specific response of ectopic photoreception has not been well understood. There are limits to obtaining efficient gene expression in a specifically targeted cell population by a transgenic approach. In the present study, we established a murine model with high efficiency of gene induction to retinal ganglion cells (RGCs) and amacrine cells using an improved tetracycline transactivator-operator bipartite system (KENGE-tet system). To investigate the cell type-specific visual restorative effect, we expressed the channelrhodopsin gene into RGCs and amacrine cells using the KENGE-tet system. As a result, enhancement in the visual restorative effect was observed to RGCs and starburst amacrine cells. In conclusion, a photoresponse from amacrine cells may enhance the maintained response of RGCs and further increase or improve the visual restorative effect.
PubMed: 37324975
DOI: 10.1016/j.omtm.2023.05.011 -
Frontiers in Neuroanatomy 2022Although retinal organization is remarkably conserved, morphological anomalies can be found to different extents and varieties across animal species with each presenting...
Although retinal organization is remarkably conserved, morphological anomalies can be found to different extents and varieties across animal species with each presenting unique characteristics and patterns of displaced and misplaced neurons. One of the most widely used non-human primates in research, the common marmoset () could potentially also be of interest for visual research, but is unfortunately not well characterized in this regard. Therefore, the aim of our study was to provide a first time description of structural retinal layering including morphological differences and distinctive features in this species. Retinas from animals ( = 26) of both sexes and different ages were immunostained with cell specific antibodies to label a variety of bipolar, amacrine and ganglion cells. Misplaced ganglion cells with somata in the outermost part of the inner nuclear layer and rod bipolar cells with axon terminals projecting into the outer plexiform layer instead of the inner plexiform layer independent of age or sex of the animals were the most obvious findings, whereas misplaced amacrine cells and misplaced cone bipolar axon terminals occurred to a lesser extent. With this first time description of developmental retinal errors over a wide age range, we provide a basic characterization of the retinal system of the common marmosets, which can be taken into account for future studies in this and other animal species. The finding of misplaced ganglion cells and misplaced bipolar cell axon terminals was not reported before and displays an anatomic variation worthwhile for future analyzes of their physiological and functional impact.
PubMed: 36204677
DOI: 10.3389/fnana.2022.1000693 -
Neurotherapeutics : the Journal of the... Apr 2016Optogenetic techniques are a powerful tool for determining the role of individual functional components within complex neural circuits. By genetically targeting specific... (Review)
Review
Optogenetic techniques are a powerful tool for determining the role of individual functional components within complex neural circuits. By genetically targeting specific cell types, neural mechanisms can be actively manipulated to gain a better understanding of their origin and function, both in health and disease. The potential of optogenetics is not limited to answering biological questions, as it is also a promising therapeutic approach for neurological diseases. An important prerequisite for this approach is to have an identified target with a uniquely defined role within a given neural circuit. Here, we examine the retinal neurovascular unit, a circuit that incorporates neurons and vascular cells to control blood flow in the retina. We highlight the role of a specific cell type, the cholinergic amacrine cell, in modulating vascular cells, and demonstrate how this can be targeted and controlled with optogenetics. A better understanding of these mechanisms will not only extend our understanding of neurovascular interactions in the brain, but ultimately may also provide new targets to treat vision loss in a variety of retinal diseases.
Topics: Animals; Humans; Nervous System Diseases; Neural Pathways; Optogenetics
PubMed: 26758692
DOI: 10.1007/s13311-015-0419-x -
The Journal of Physiology Aug 2017Visual processing starts in the retina. Within only two synaptic layers, a large number of parallel information channels emerge, each encoding a highly processed feature... (Review)
Review
Visual processing starts in the retina. Within only two synaptic layers, a large number of parallel information channels emerge, each encoding a highly processed feature like edges or the direction of motion. Much of this functional diversity arises in the inner plexiform layer, where inhibitory amacrine cells modulate the excitatory signal of bipolar and ganglion cells. Studies investigating individual amacrine cell circuits like the starburst or A17 circuit have demonstrated that single types can possess specific morphological and functional adaptations to convey a particular function in one or a small number of inner retinal circuits. However, the interconnected and often stereotypical network formed by different types of amacrine cells across the inner plexiform layer prompts that they should be also involved in more general computations. In line with this notion, different recent studies systematically analysing inner retinal signalling at a population level provide evidence that general functions of the ensemble of amacrine cells across types are critical for establishing universal principles of retinal computation like parallel processing or motion anticipation. Combining recent advances in the development of indicators for imaging inhibition with large-scale morphological and genetic classifications will help to further our understanding of how single amacrine cell circuits act together to help decompose the visual scene into parallel information channels. In this review, we aim to summarise the current state-of-the-art in our understanding of how general features of amacrine cell inhibition lead to general features of computation.
Topics: Amacrine Cells; Animals; Pattern Recognition, Visual
PubMed: 28332227
DOI: 10.1113/JP273648 -
Vision Research Apr 2023By analyzing light-evoked spike responses, cation currents (ΔI) and chloride currents (ΔI) of over 100 morphologically-identified retinal ganglion cells (GCs) in...
By analyzing light-evoked spike responses, cation currents (ΔI) and chloride currents (ΔI) of over 100 morphologically-identified retinal ganglion cells (GCs) in dark-adapted mouse retina, we found there are at least 14 functionally- and morphologically-distinct types of RGCs. These cells can be divided into 5 groups based on their patterns of spike response to whole field light steps (SRWFLS), a GC identification scheme commonly used in studies with extracellular recording techniques. We also found that all GCs in the mouse retina express strychnine-sensitive glycine receptors, and receive light-elicited chloride current (ΔI) accompanied by a conductance increase from narrow-field, glycinergic amacrine cells. As the dark membrane potential of RGC are near the chloride-equilibrium potential, mouse GCs' spike responses are mediated primarily by bipolar cells inputs, and modulated by "shunting inhibition" from narrow-field amacrine cells. Analysis of strychnine actions on light-evoked cation current ΔI (bipolar cell inputs) in GCs suggests that narrow-field amacrine cells modulate GCs by sending ON-OFF crossover feedback signals to presynaptic bipolar cell axon terminals via sign-inverting glycinergic synapses, and the feedback signals are synergistic to the bipolar cell light responses. Therefore narrow-field amacrine cells enhance light-evoked bipolar cell inputs to GCs by presynaptic "synergistic addition", besides the abovementioned postsynaptic "shunting inhibition" in GCs.
Topics: Animals; Mice; Retinal Ganglion Cells; Amacrine Cells; Retina; Strychnine; Chlorides; Cations
PubMed: 36758452
DOI: 10.1016/j.visres.2023.108187 -
Frontiers in Neuroanatomy 2022
PubMed: 36726780
DOI: 10.3389/fnana.2022.1099583