RESUMO
How neurons detect the direction of motion is a prime example of neural computation: Motion vision is found in the visual systems of virtually all sighted animals, it is important for survival, and it requires interesting computations with well-defined linear and nonlinear processing steps-yet the whole process is of moderate complexity. The genetic methods available in the fruit fly Drosophila and the charting of a connectome of its visual system have led to rapid progress and unprecedented detail in our understanding of how neurons compute the direction of motion in this organism. The picture that emerged incorporates not only the identity, morphology, and synaptic connectivity of each neuron involved but also its neurotransmitters, its receptors, and their subcellular localization. Together with the neurons' membrane potential responses to visual stimulation, this information provides the basis for a biophysically realistic model of the circuit that computes the direction of visual motion.
Assuntos
Percepção de Movimento , Animais , Percepção de Movimento/fisiologia , Vias Visuais/fisiologia , Drosophila/fisiologia , Visão Ocular , Neurônios/fisiologia , Estimulação LuminosaRESUMO
Information processing relies on precise patterns of synapses between neurons. The cellular recognition mechanisms regulating this specificity are poorly understood. In the medulla of the Drosophila visual system, different neurons form synaptic connections in different layers. Here, we sought to identify candidate cell recognition molecules underlying this specificity. Using RNA sequencing (RNA-seq), we show that neurons with different synaptic specificities express unique combinations of mRNAs encoding hundreds of cell surface and secreted proteins. Using RNA-seq and protein tagging, we demonstrate that 21 paralogs of the Dpr family, a subclass of immunoglobulin (Ig)-domain containing proteins, are expressed in unique combinations in homologous neurons with different layer-specific synaptic connections. Dpr interacting proteins (DIPs), comprising nine paralogs of another subclass of Ig-containing proteins, are expressed in a complementary layer-specific fashion in a subset of synaptic partners. We propose that pairs of Dpr/DIP paralogs contribute to layer-specific patterns of synaptic connectivity.
Assuntos
Proteínas de Drosophila/metabolismo , Imunoglobulinas/metabolismo , Neurônios/metabolismo , Receptores Imunológicos/metabolismo , Sinapses , Animais , Drosophila , Citometria de Fluxo , Análise de Sequência de RNA , Visão OcularRESUMO
During the development of the vertebrate nervous systems, genetic programs assemble an immature circuit that is subsequently refined by neuronal activity evoked by external stimuli. However, prior to sensory experience, the intrinsic property of the developing nervous system also triggers correlated network-level neuronal activity, with retinal waves in the developing vertebrate retina being the best documented example. Spontaneous activity has also been found in the visual system of Drosophila Here, we compare the spontaneous activity of the developing visual system between mammalian and Drosophila and suggest that Drosophila is an emerging model for mechanistic and functional studies of correlated spontaneous activity.
Assuntos
Drosophila melanogaster/citologia , Drosophila melanogaster/crescimento & desenvolvimento , Retina/citologia , Retina/embriologia , Células Receptoras Sensoriais/fisiologia , Animais , Drosophila melanogaster/fisiologia , Olho/citologia , Olho/crescimento & desenvolvimento , Humanos , Modelos Animais , Retina/fisiologia , Células Receptoras Sensoriais/citologiaRESUMO
Cell-type-specific tools facilitate the identification and functional characterization of the distinct cell types that form the complexity of neuronal circuits. A large collection of existing genetic tools in Drosophila relies on enhancer activity to label different subsets of cells and has been extremely useful in analyzing functional circuits in adults. However, these enhancer-based GAL4 lines often do not reflect the expression of nearby gene(s) as they only represent a small portion of the full gene regulatory elements. While genetic intersectional techniques such as the split-GAL4 system further improve cell-type-specificity, it requires significant time and resources to screen through combinations of enhancer expression patterns. Here, we use existing developmental single-cell RNA sequencing (scRNAseq) datasets to select gene pairs for split-GAL4 and provide a highly efficient and predictive pipeline (scMarco) to generate cell-type-specific split-GAL4 lines at any time during development, based on the native gene regulatory elements. These gene-specific split-GAL4 lines can be generated from a large collection of coding intronic MiMIC/CRIMIC lines or by CRISPR knock-in. We use the developing Drosophila visual system as a model to demonstrate the high predictive power of scRNAseq-guided gene-specific split-GAL4 lines in targeting known cell types, annotating clusters in scRNAseq datasets as well as in identifying novel cell types. Lastly, the gene-specific split-GAL4 lines are broadly applicable to any other Drosophila tissue. Our work opens new avenues for generating cell-type-specific tools for the targeted manipulation of distinct cell types throughout development and represents a valuable resource for the Drosophila community.
Assuntos
Proteínas de Drosophila , Fatores de Transcrição , Animais , Fatores de Transcrição/metabolismo , Drosophila/genética , Drosophila/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Técnicas Genéticas , Análise de Sequência de RNA , Drosophila melanogaster/metabolismoRESUMO
The superior colliculus (SC) is a prominent and conserved visual center in all vertebrates. In mice, the most superficial lamina of the SC is enriched with neurons that are selective for the moving direction of visual stimuli. Here, we study how these direction selective neurons respond to complex motion patterns known as plaids, using two-photon calcium imaging in awake male and female mice. The plaid pattern consists of two superimposed sinusoidal gratings moving in different directions, giving an apparent pattern direction that lies between the directions of the two component gratings. Most direction selective neurons in the mouse SC respond robustly to the plaids and show a high selectivity for the moving direction of the plaid pattern but not of its components. Pattern motion selectivity is seen in both excitatory and inhibitory SC neurons and is especially prevalent in response to plaids with large cross angles between the two component gratings. However, retinal inputs to the SC are ambiguous in their selectivity to pattern versus component motion. Modeling suggests that pattern motion selectivity in the SC can arise from a nonlinear transformation of converging retinal inputs. In contrast, the prevalence of pattern motion selective neurons is not seen in the primary visual cortex (V1). These results demonstrate an interesting difference between the SC and V1 in motion processing and reveal the SC as an important site for encoding pattern motion.
Assuntos
Camundongos Endogâmicos C57BL , Percepção de Movimento , Estimulação Luminosa , Retina , Colículos Superiores , Vias Visuais , Animais , Colículos Superiores/fisiologia , Percepção de Movimento/fisiologia , Camundongos , Masculino , Feminino , Retina/fisiologia , Estimulação Luminosa/métodos , Vias Visuais/fisiologia , Neurônios/fisiologia , Reconhecimento Visual de Modelos/fisiologiaRESUMO
Images projected onto the retina of an animal eye are rarely still. Instead, they usually contain motion signals originating either from moving objects or from retinal slip caused by self-motion. Accordingly, motion signals tell the animal in which direction a predator, prey, or the animal itself is moving. At the neural level, visual motion detection has been proposed to extract directional information by a delay-and-compare mechanism, representing a classic example of neural computation. Neurons responding selectively to motion in one but not in the other direction have been identified in many systems, most prominently in the mammalian retina and the fly optic lobe. Technological advances have now allowed researchers to characterize these neurons' upstream circuits in exquisite detail. Focusing on these upstream circuits, we review and compare recent progress in understanding the mechanisms that generate direction selectivity in the early visual system of mammals and flies.
Assuntos
Percepção de Movimento/fisiologia , Neurônios/fisiologia , Retina/fisiologia , Vias Visuais/fisiologia , Animais , Humanos , Movimento (Física)RESUMO
Genetic diseases affecting the retina can result in partial or complete loss of visual function. Leber's congenital amaurosis (LCA) is a rare blinding disease, usually inherited in an autosomally recessive manner, with no cure. Retinal gene therapy has been shown to improve vision in LCA patients caused by mutations in the RPE65 gene (LCA2). However, little is known about how activity in central visual pathways is affected by the disease or by subsequent gene therapy. Functional MRI (fMRI) was used to assess retinal signal transmission in cortical and subcortical visual structures before and 1 year after retinal intervention. The fMRI paradigm consisted of 15-s blocks of flickering (8 Hz) black and white checkerboards interleaved with 15 s of blank (black) screen. Visual activation in the brain was assessed using the general linear model, with multiple comparisons corrected using the false discovery rate method. Response to visual stimulation through untreated eyes of LCA2 patients showed heightened fMRI responses in the superior colliculus and diminished activities in the lateral geniculate nucleus (LGN) compared to controls, indicating a shift in the patients' visual processing towards the retinotectal pathway. Following gene therapy, stimuli presented to the treated eye elicited significantly stronger fMRI responses in the LGN and primary visual cortex, indicating some re-engagement of the geniculostriate pathway (GS) pathway. Across patients, the post-treatment LGN fMRI responses correlated significantly with performance on a clinical test measuring light sensitivity. Our results demonstrate that the low vision observed in LCA2 patients involves a shift in visual processing toward the retinotectal pathway, and that gene therapy partially reinstates visual transmission through the GS pathway. This selective boosting of retinal output through the GS pathway and its correlation to improved visual performance, following several years of degenerative retinal disease, is striking. However, while retinal gene therapy and other ocular interventions have given hope to RPE65 patients, it may take years before development of therapies tailored to treat the diseases in other low vision patients are available. Our demonstration of a shift toward the retinotectal pathway in these patients may spur the development of new tools and rehabilitation strategies to help maximize the use of residual visual abilities and augment experience-dependent plasticity.
Assuntos
Terapia Genética , Amaurose Congênita de Leber , Imageamento por Ressonância Magnética , Vias Visuais , Humanos , Terapia Genética/métodos , Vias Visuais/fisiopatologia , Vias Visuais/diagnóstico por imagem , Adulto , Masculino , Feminino , Amaurose Congênita de Leber/genética , Amaurose Congênita de Leber/terapia , Amaurose Congênita de Leber/fisiopatologia , Adulto Jovem , Estimulação Luminosa/métodos , Pessoa de Meia-Idade , cis-trans-Isomerases/genéticaRESUMO
Humans make sense of the world by organizing things into categories. When and how does this process begin? We investigated whether real-world object categories that spontaneously emerge in the first months of life match categorical representations of objects in the human visual cortex. Using eye tracking, we measured the differential looking time of 4-, 10-, and 19-mo-olds as they looked at pairs of pictures belonging to eight animate or inanimate categories (human/nonhuman, faces/bodies, real-world size big/small, natural/artificial). Taking infants' looking times as a measure of similarity, for each age group, we defined a representational space where each object was defined in relation to others of the same or of a different category. This space was compared with hypothesis-based and functional MRI-based models of visual object categorization in the adults' visual cortex. Analyses across different age groups showed that, as infants grow older, their looking behavior matches neural representations in ever-larger portions of the adult visual cortex, suggesting progressive recruitment and integration of more and more feature spaces distributed over the visual cortex. Moreover, the results characterize infants' visual categorization as an incremental process with two milestones. Between 4 and 10 mo, visual exploration guided by saliency gives way to an organization according to the animate-inanimate distinction. Between 10 and 19 mo, a category spurt leads toward a mature organization. We propose that these changes underlie the coupling between seeing and thinking in the developing mind.
Assuntos
Cognição/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Adulto , Fatores Etários , Mapeamento Encefálico/métodos , Tecnologia de Rastreamento Ocular , Feminino , Fixação Ocular/fisiologia , Humanos , Lactente , Imageamento por Ressonância Magnética/métodos , Masculino , Estimulação Luminosa , Pensamento/fisiologia , Visão Ocular/fisiologia , Córtex Visual/fisiologia , Percepção Visual/fisiologiaRESUMO
To explore how neural circuits represent novel versus familiar inputs, we presented mice with repeated sets of images with novel images sparsely substituted. Using two-photon calcium imaging to record from layer 2/3 neurons in the mouse primary visual cortex, we found that novel images evoked excess activity in the majority of neurons. This novelty response rapidly emerged, arising with a time constant of 2.6 ± 0.9 s. When a new image set was repeatedly presented, a majority of neurons had similarly elevated activity for the first few presentations, which decayed to steady state with a time constant of 1.4 ± 0.4 s. When we increased the number of images in the set, the novelty response's amplitude decreased, defining a capacity to store â¼15 familiar images under our conditions. These results could be explained quantitatively using an adaptive subunit model in which presynaptic neurons have individual tuning and gain control. This result shows that local neural circuits can create different representations for novel versus familiar inputs using generic, widely available mechanisms.
Assuntos
Neurônios/fisiologia , Córtex Visual Primário/fisiologia , Percepção Visual/fisiologia , Adaptação Biológica/fisiologia , Animais , Encéfalo , Masculino , Camundongos , Camundongos Transgênicos , Estimulação Luminosa/métodos , Córtex Visual/fisiologiaRESUMO
Priority map theory is a leading framework for understanding how various aspects of stimulus displays and task demands guide visual attention. Per this theory, the visual system computes a priority map, which is a representation of visual space indexing the relative importance, or priority, of locations in the environment. Priority is computed based on both salience, defined based on image-computable properties; and relevance, defined by an individual's current goals, and is used to direct attention to the highest-priority locations for further processing. Computational theories suggest that priority maps identify salient locations based on individual feature dimensions (e.g., color, motion), which are integrated into an aggregate priority map. While widely accepted, a core assumption of this framework, the existence of independent feature dimension maps in visual cortex, remains untested. Here, we tested the hypothesis that retinotopic regions selective for specific feature dimensions (color or motion) in human cortex act as neural feature dimension maps, indexing salient locations based on their preferred feature. We used fMRI activation patterns to reconstruct spatial maps while male and female human participants viewed stimuli with salient regions defined by relative color or motion direction. Activation in reconstructed spatial maps was localized to the salient stimulus position in the display. Moreover, the strength of the stimulus representation was strongest in the ROI selective for the salience-defining feature. Together, these results suggest that feature-selective extrastriate visual regions highlight salient locations based on local feature contrast within their preferred feature dimensions, supporting their role as neural feature dimension maps.SIGNIFICANCE STATEMENT Identifying salient information is important for navigating the world. For example, it is critical to detect a quickly approaching car when crossing the street. Leading models of computer vision and visual search rely on compartmentalized salience computations based on individual features; however, there has been no direct empirical demonstration identifying neural regions as responsible for performing these dissociable operations. Here, we provide evidence of a critical double dissociation that neural activation patterns from color-selective regions prioritize the location of color-defined salience while minimally representing motion-defined salience, whereas motion-selective regions show the complementary result. These findings reveal that specialized cortical regions act as neural "feature dimension maps" that are used to index salient locations based on specific features to guide attention.
Assuntos
Mapeamento Encefálico , Córtex Visual , Humanos , Masculino , Feminino , Visão Ocular , Córtex Visual/fisiologia , Estimulação Luminosa/métodos , Percepção Visual/fisiologiaRESUMO
Semaphorins and Plexins form ligand/receptor pairs that are crucial for a wide range of developmental processes from cell proliferation to axon guidance. The ability of semaphorins to act both as signaling receptors and ligands yields a multitude of responses. Here, we describe a novel role for Semaphorin-6D (Sema6D) and Plexin-A1 in the positioning and targeting of retinogeniculate axons. In Plexin-A1 or Sema6D mutant mice of either sex, the optic tract courses through, rather than along, the border of the dorsal lateral geniculate nucleus (dLGN), and some retinal axons ectopically arborize adjacent and lateral to the optic tract rather than defasciculating and entering the target region. We find that Sema6D and Plexin-A1 act together in a dose-dependent manner, as the number of the ectopic retinal projections is altered in proportion to the level of Sema6D or Plexin-A1 expression. Moreover, using retinal in utero electroporation of Sema6D or Plexin-A1 shRNA, we show that Sema6D and Plexin-A1 are both required in retinal ganglion cells for axon positioning and targeting. Strikingly, nonelectroporated retinal ganglion cell axons also mistarget in the tract region, indicating that Sema6D and Plexin-A1 can act non-cell-autonomously, potentially through axon-axon interactions. These data provide novel evidence for a dose-dependent and non-cell-autonomous role for Sema6D and Plexin-A1 in retinal axon organization in the optic tract and dLGN.SIGNIFICANCE STATEMENT Before innervating their central brain targets, retinal ganglion cell axons fasciculate in the optic tract and then branch and arborize in their target areas. Upon deletion of the guidance molecules Plexin-A1 or Semaphorin-6D, the optic tract becomes disorganized near and extends within the dorsal lateral geniculate nucleus. In addition, some retinal axons form ectopic aggregates within the defasciculated tract. Sema6D and Plexin-A1 act together as a receptor-ligand pair in a dose-dependent manner, and non-cell-autonomously, to produce this developmental aberration. Such a phenotype highlights an underappreciated role for axon guidance molecules in tract cohesion and appropriate defasciculation near, and arborization within, targets.
Assuntos
Células Ganglionares da Retina , Semaforinas , Animais , Camundongos , Axônios/fisiologia , Ligantes , Células Ganglionares da Retina/metabolismo , Semaforinas/genética , Semaforinas/metabolismoRESUMO
K+ channel Kir7.1 expressed at the apical membrane of the retinal pigment epithelium (RPE) plays an essential role in retinal function. An isoleucine-to-threonine mutation at position 120 of the protein is responsible for blindness-causing vitreo-retinal dystrophy. We have studied the molecular mechanism of action of Kir7.1-I120T in vitro by heterologous expression and in vivo in CRISPR-generated knockin mice. Full-size Kir7.1-I120T reaches the plasma membrane but lacks any activity. Analysis of Kir7.1 and the I120T mutant in mixed transfection experiments, and that of tandem tetrameric constructs made by combining wild type (WT) and mutant protomers, leads us to conclude that they do not form heterotetramers in vitro. Homozygous I120T/I120T mice show cleft palate and tracheomalacia and do not survive beyond P0, whereas heterozygous WT/I120T develop normally. Membrane conductance of RPE cells isolated from WT/WT and heterozygous WT/I120T mice is dominated by Kir7.1 current. Using Rb+ as a charge carrier, we demonstrate that the Kir7.1 current of WT/I120T RPE cells corresponds to approximately 50% of that in cells from WT/WT animals, in direct proportion to WT gene dosage. This suggests a lack of compensatory effects or interference from the mutated allele product, an interpretation consistent with results obtained using WT/- hemizygous mouse. Electroretinography and behavioral tests also show normal vision in WT/I120T animals. The hypomorphic ion channel phenotype of heterozygous Kir7.1-I120T mutants is therefore compatible with normal development and retinal function. The lack of detrimental effect of this degree of functional deficit might explain the recessive nature of Kir7.1 mutations causing human eye disease.NEW & NOTEWORTHY Human retinal pigment epithelium K+ channel Kir7.1 is affected by generally recessive mutations leading to blindness. We investigate one such mutation, isoleucine-to-threonine at position 120, both in vitro and in vivo in knockin mice. The mutated channel is inactive and in heterozygosis gives a hypomorphic phenotype with normal retinal function. Mutant channels do not interfere with wild-type Kir7.1 channels which are expressed concomitantly without hindrance, providing an explanation for the recessive nature of the disease.
Assuntos
Isoleucina , Retina , Camundongos , Humanos , Animais , Isoleucina/metabolismo , Retina/metabolismo , Cegueira/metabolismo , Mutação/genética , Treonina/metabolismoRESUMO
The increase of brain neuron number in relation with brain size is currently considered to be the major evolutionary path to high cognitive power in amniotes. However, how changes in neuron density did contribute to the evolution of the information-processing capacity of the brain remains unanswered. High neuron densities are seen as the main reason why the fovea located at the visual center of the retina is responsible for sharp vision in birds and primates. The emergence of foveal vision is considered as a breakthrough innovation in visual system evolution. We found that neuron densities in the largest visual center of the midbrain - i.e., the optic tectum - are two to four times higher in modern birds with one or two foveae compared to birds deprived of this specialty. Interspecies comparisons enabled us to identify elements of a hitherto unknown developmental process set up by foveate birds for increasing neuron density in the upper layers of their optic tectum. The late progenitor cells that generate these neurons proliferate in a ventricular zone that can expand only radially. In this particular context, the number of cells in ontogenetic columns increases, thereby setting the conditions for higher cell densities in the upper layers once neurons did migrate.
Assuntos
Columbidae , Retina , Animais , Retina/fisiologia , Neurônios , Colículos Superiores , MorfogêneseRESUMO
Organization of neuronal connections into topographic maps is essential for processing information. Yet, our understanding of topographic mapping has remained limited by our inability to observe maps forming and refining directly in vivo. Here, we used Cre-mediated recombination of a new colorswitch reporter in zebrafish to generate the first transgenic model allowing the dynamic analysis of retinotectal mapping in vivo. We found that the antero-posterior retinotopic map forms early but remains dynamic, with nasal and temporal retinal axons expanding their projection domains over time. Nasal projections initially arborize in the anterior tectum but progressively refine their projection domain to the posterior tectum, leading to the sharpening of the retinotopic map along the antero-posterior axis. Finally, using a CRISPR-mediated mutagenesis approach, we demonstrate that the refinement of nasal retinal projections requires the adhesion molecule Contactin 2. Altogether, our study provides the first analysis of a topographic map maturing in real time in a live animal and opens new strategies for dissecting the molecular mechanisms underlying precise topographic mapping in vertebrates.
Assuntos
Axônios/metabolismo , Contactina 2/metabolismo , Células Ganglionares da Retina/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/embriologia , Animais , Animais Geneticamente Modificados/embriologia , Animais Geneticamente Modificados/genética , Contactina 2/genética , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/genéticaRESUMO
Artificial optoelectronic synapses (OES) have attracted extensive attention in brain-inspired information processing and neuromorphic computing. However, OES at near-infrared wavelengths have rarely been reported, seriously limiting the application in modern optical communication. Herein, high-performance near-infrared OES devices based on VO2/MoO3 heterojunctions are presented. The textured MoO3 films are deposited on the sputtered VO2 film by using the glancing-angle deposition technique to form a heterojunction device. Through tuning the oxygen defects in the VO2 film, the fabricated VO2/MoO3 heterojunction exhibits versatile electrical synaptic functions. Benefiting from the highly efficient light harvesting and the unique interface effect, the photonic synaptic characteristics, mainly including the short/long-term plasticity and learning experience behavior are successfully realized at the O (1342 nm) and C (1550 nm) optical communication wavebands. Moreover, a single OES device can output messages accurately by converting light signals of the Morse code to distinct synaptic currents. More importantly, a 3 × 3 artificial OES array is constructed to demonstrate the impressive image perceiving and learning capabilities. This work not only indicates the feasibility of defect and interface engineering in modulating the synaptic plasticity of OES devices, but also provides effective strategies to develop advanced artificial neuromorphic visual systems for next-generation optical communication systems.
RESUMO
Vision plays a vital biological role in organisms, which depends on the visual pigment molecules (opsin plus chromophore). The expansion or reduction of spectral channels in the organisms is determined by distinct opsin classes and copy numbers resulting from duplication or loss. Within Coleoptera, the superfamily Elateroidea exhibits a great diversity of morphological and physiological characteristics, such as bioluminescence, making this group an important model for opsin studies. While molecular and physiological studies have been conducted in Lampyridae and Elateridae, other families remain unexplored. Here, we reused transcriptome datasets from Elateroidea species, including members of Elateridae, Lampyridae, Phengodidae, Rhagophthalmidae, Cantharidae, and Lycidae, to detect the diversity of putative opsin genes in this superfamily. In addition, we tested the signature of sites under positive selection in both ultraviolet (UV)- and long-wavelength (LW)-opsin classes. Although the visual system in Elateroidea is considered simple, we observed events of duplication in LW- and UV-opsin, as well as the absence of UV-opsin in distinct families, such as larval Phengodidae individuals. We detected different copies of LW-opsins that were highly expressed in the eyes of distinct tribes of fireflies, indicating the possible selection of each copy during the evolution of the sexual mating to avoid spectrum overlapping. In Elateridae, we found that the bioluminescent species had a distinct LW-opsin copy compared with the non-bioluminescent species, suggesting events of duplication and loss. The signature of positive selection showed only one residue associated with the chromophore binding site in the Elateroidea, which may produce a bathochromic shift in the wavelength absorption spectra in this family. Overall, this study brings important content and fills gaps regarding opsin evolution in Elateroidea.
Assuntos
Besouros , Opsinas , Humanos , Animais , Opsinas/genética , Transcriptoma , Filogenia , Besouros/genética , Larva , Evolução MolecularRESUMO
Vision is formed by the transmission of light stimuli to the brain through axons extending from photoreceptor cells. Damage to these axons leads to loss of vision. Despite research on neural circuit regeneration through transplantation, achieving precise axon projection remains challenging. To achieve optic nerve regeneration by transplantation, we employed the Drosophila visual system. We previously established a transplantation method for Drosophila utilizing photoreceptor precursor cells extracted from the eye disc. However, little axonal elongation of transplanted cells into the brain, the lamina, was observed. We verified axonal elongation to the lamina by modifying the selection process for transplanted cells. Moreover, we focused on N-cadherin (Ncad), a cell adhesion factor, and Twinstar (Tsr), which has been shown to promote actin reorganization and induce axon elongation in damaged nerves. Overexpression of Ncad and tsr promoted axon elongation to the lamina, along with presynaptic structure formation in the elongating axons. Furthermore, overexpression of Neurexin-1 (Nrx-1), encoding a protein identified as a synaptic organizer, was found to not only promote presynapse formation but also enhance axon elongation. By introducing Ncad, tsr, and Nrx-1, we not only successfully achieved axonal projection of transplanted cells to the brain beyond the retina, but also confirmed the projection of transplanted cells into a deeper ganglion, the medulla. The present study offers valuable insights to realize regeneration through transplantation in a more complex nervous system.
Assuntos
Actinas , Adesão Celular , Drosophila , Células Fotorreceptoras , Animais , Actinas/metabolismo , Axônios/metabolismo , Drosophila/genética , Drosophila/metabolismo , Células Fotorreceptoras/metabolismo , Sinapses/metabolismoRESUMO
BACKGROUND: Numerous studies have indicated altered temporal features of the brain function in Parkinson's disease (PD), and the autocorrelation magnitude of intrinsic neural signals, called intrinsic neural timescales, were often applied to estimate how long neural information stored in local brain areas. However, it is unclear whether PD patients at different disease stages exhibit abnormal timescales accompanied with abnormal gray matter volume (GMV). PURPOSE: To assess the intrinsic timescale and GMV in PD. STUDY TYPE: Prospective. POPULATION: 74 idiopathic PD patients (44 early stage (PD-ES) and 30 late stage (PD-LS), as determined by the Hoehn and Yahr (HY) severity classification scale), and 73 healthy controls (HC). FIELD STRENGTH/SEQUENCE: 3.0 T MRI scanner; magnetization prepared rapid acquisition gradient echo and echo planar imaging sequences. ASSESSMENT: The timescales were estimated by using the autocorrelation magnitude of neural signals. Voxel-based morphometry was performed to calculate GMV in the whole brain. Severity of motor symptoms and cognitive impairments were assessed using the unified PD rating scale, the HY scale, the Montreal cognitive assessment, and the mini-mental state examination. STATISTICAL TEST: Analysis of variance; two-sample t-test; Spearman rank correlation analysis; Mann-Whitney U test; Kruskal-Wallis' H test. A P value <0.05 was considered statistically significant. RESULTS: The PD group had significantly abnormal intrinsic timescales in the sensorimotor, visual, and cognitive-related areas, which correlated with the symptom severity (ρ = -0.265, P = 0.022) and GMV (ρ = 0.254, P = 0.029). Compared to the HC group, the PD-ES group had significantly longer timescales in anterior cortical regions, whereas the PD-LS group had significantly shorter timescales in posterior cortical regions. CONCLUSION: This study suggested that PD patients have abnormal timescales in multisystem and distinct patterns of timescales and GMV in cerebral cortex at different disease stages. This may provide new insights for the neural substrate of PD. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 1.
Assuntos
Substância Cinzenta , Doença de Parkinson , Humanos , Doença de Parkinson/complicações , Estudos Prospectivos , Córtex Cerebral , Imageamento por Ressonância Magnética/métodosRESUMO
BACKGROUND: Macular degeneration of the eye is a common cause of blindness and affects 8% of the worldwide human population. In adult cats with bilateral lesions of the central retina, we explored the possibility that motion perception training can limit the associated degradation of the visual system. We evaluated how visual training affects behavioral performance and white matter structure. Recently, we proposed (Kozak et al. in Transl Vis Sci Technol 10:9, 2021) a new motion-acuity test for low vision patients, enabling full visual field functional assessment through simultaneous perception of shape and motion. Here, we integrated this test as the last step of a 10-week motion-perception training. RESULTS: Cats were divided into three groups: retinal-lesioned only and two trained groups, retinal-lesioned trained and control trained. The behavioral data revealed that trained cats with retinal lesions were superior in motion tasks, even when the difficulty relied only on acuity. 7 T-MRI scanning was done before and after lesioning at 5 different timepoints, followed by Fixel-Based and Fractional Anisotropy Analysis. In cats with retinal lesions, training resulted in a more localized and reduced percentage decrease in Fixel-Based Analysis metrics in the dLGN, caudate nucleus and hippocampus compared to untrained cats. In motion-sensitive area V5/PMLS, the significant decreases in fiber density were equally strong in retinal-lesioned untrained and trained cats, up to 40% in both groups. The only cortical area with Fractional Anisotropy values not affected by central retinal loss was area V5/PMLS. In other visual ROIs, the Fractional Anisotropy values increased over time in the untrained retinal lesioned group, whereas they decreased in the retinal lesioned trained group and remained at a similar level as in trained controls. CONCLUSIONS: Overall, our MRI results showed a stabilizing effect of motion training applied soon after central retinal loss induction on white matter structure. We propose that introducing early motion-acuity training for low vision patients, aimed at the intact and active retinal peripheries, may facilitate brain plasticity processes toward better vision.
Assuntos
Imageamento por Ressonância Magnética , Percepção de Movimento , Substância Branca , Animais , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Gatos , Imageamento por Ressonância Magnética/métodos , Percepção de Movimento/fisiologia , Retina/diagnóstico por imagem , Retina/fisiopatologia , Masculino , FemininoRESUMO
Highveld mole-rats (Cryptomys hottentotus pretoriae) are social rodents that inhabit networks of subterranean tunnels. In their natural environment, they are rarely exposed to light, and consequently their visual systems have regressed over evolutionary time. However, in the laboratory they display nocturnal activity, suggesting that they are sensitive to changes in ambient illumination. We examined the robustness of the Highveld mole-rat circadian system by assessing its locomotor activity under decreasing light intensities. Mole-rats were subjected to seven consecutive light cycles commencing with a control cycle (overhead fluorescent lighting at 150 lx), followed by decreasing LED lighting (500, 300, 100, 10 and 1 lx) on a 12 h light:12 h dark (L:D) photoperiod and finally a constant darkness (DD) cycle. Mole-rats displayed nocturnal activity under the whole range of experimental lighting conditions, with a distinct spike in activity at the end of the dark phase in all cycles. The mole-rats were least active during the control cycle under fluorescent light, locomotor activity increased steadily with decreasing LED light intensities, and the highest activity was exhibited when the light was completely removed. In constant darkness, mole-rats displayed free-running rhythms with periods (τ) ranging from 23.77 to 24.38â h, but was overall very close to 24â h at 24.07â h. Our findings confirm that the Highveld mole-rat has a higher threshold for light compared with aboveground dwelling rodents, which is congruent with previous neurological findings, and has implications for behavioural rhythms.