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1.
Nat Commun ; 15(1): 2466, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38503746

RESUMEN

How the activity of neurons gives rise to natural vision remains a matter of intense investigation. The mid-level visual areas along the ventral stream are selective to a common class of natural images-textures-but a circuit-level understanding of this selectivity and its link to perception remains unclear. We addressed these questions in mice, first showing that they can perceptually discriminate between textures and statistically simpler spectrally matched stimuli, and between texture types. Then, at the neural level, we found that the secondary visual area (LM) exhibited a higher degree of selectivity for textures compared to the primary visual area (V1). Furthermore, textures were represented in distinct neural activity subspaces whose relative distances were found to correlate with the statistical similarity of the images and the mice's ability to discriminate between them. Notably, these dependencies were more pronounced in LM, where the texture-related subspaces were smaller than in V1, resulting in superior stimulus decoding capabilities. Together, our results demonstrate texture vision in mice, finding a linking framework between stimulus statistics, neural representations, and perceptual sensitivity-a distinct hallmark of efficient coding computations.


Asunto(s)
Corteza Visual , Vías Visuales , Animales , Ratones , Estimulación Luminosa/métodos , Vías Visuales/fisiología , Corteza Visual/fisiología , Neuronas/fisiología , Percepción Visual/fisiología
2.
Nat Commun ; 14(1): 6077, 2023 09 28.
Artículo en Inglés | MEDLINE | ID: mdl-37770450

RESUMEN

Excitatory spiny stellate neurons are prominently featured in the cortical circuits of sensory modalities that provide high salience and high acuity representations of the environment. These specialized neurons are considered developmentally linked to bottom-up inputs from the thalamus, however, the molecular mechanisms underlying their diversification and function are unknown. Here, we investigated this in mouse somatosensory cortex, where spiny stellate neurons and pyramidal neurons have distinct roles in processing whisker-evoked signals. Utilizing spatial transcriptomics, we identified reciprocal patterns of gene expression which correlated with these cell-types and were linked to innervation by specific thalamic inputs during development. Genetic manipulation that prevents the acquisition of spiny stellate fate highlighted an important role for these neurons in processing distinct whisker signals within functional cortical columns, and as a key driver in the formation of specific whisker-related circuits in the cortex.


Asunto(s)
Neuronas , Vibrisas , Animales , Vibrisas/fisiología , Neuronas/metabolismo , Células Piramidales/fisiología , Neuritas , Corteza Somatosensorial/fisiología , Tálamo/fisiología
3.
Nat Commun ; 14(1): 192, 2023 01 12.
Artículo en Inglés | MEDLINE | ID: mdl-36635318

RESUMEN

Choice information appears in multi-area brain networks mixed with sensory, motor, and cognitive variables. In the posterior cortex-traditionally implicated in decision computations-the presence, strength, and area specificity of choice signals are highly variable, limiting a cohesive understanding of their computational significance. Examining the mesoscale activity in the mouse posterior cortex during a visual task, we found that choice signals defined a decision variable in a low-dimensional embedding space with a prominent contribution along the ventral visual stream. Their subspace was near-orthogonal to concurrently represented sensory and motor-related activations, with modulations by task difficulty and by the animals' attention state. A recurrent neural network trained with animals' choices revealed an equivalent decision variable whose context-dependent dynamics agreed with that of the neural data. Our results demonstrated an independent, multi-area decision variable in the posterior cortex, controlled by task features and cognitive demands, possibly linked to contextual inference computations in dynamic animal-environment interactions.


Asunto(s)
Corteza Cerebral , Toma de Decisiones , Animales , Ratones , Redes Neurales de la Computación , Conducta de Elección
4.
PLoS Comput Biol ; 18(3): e1009928, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35286305

RESUMEN

Our ability to perceive a stable visual world in the presence of continuous movements of the body, head, and eyes has puzzled researchers in the neuroscience field for a long time. We reformulated this problem in the context of hierarchical convolutional neural networks (CNNs)-whose architectures have been inspired by the hierarchical signal processing of the mammalian visual system-and examined perceptual stability as an optimization process that identifies image-defining features for accurate image classification in the presence of movements. Movement signals, multiplexed with visual inputs along overlapping convolutional layers, aided classification invariance of shifted images by making the classification faster to learn and more robust relative to input noise. Classification invariance was reflected in activity manifolds associated with image categories emerging in late CNN layers and with network units acquiring movement-associated activity modulations as observed experimentally during saccadic eye movements. Our findings provide a computational framework that unifies a multitude of biological observations on perceptual stability under optimality principles for image classification in artificial neural networks.


Asunto(s)
Redes Neurales de la Computación , Percepción Visual , Animales , Aprendizaje , Mamíferos , Visión Ocular
5.
Cell Rep ; 36(2): 109377, 2021 07 13.
Artículo en Inglés | MEDLINE | ID: mdl-34260937

RESUMEN

Visually guided behaviors depend on the activity of cortical networks receiving visual inputs and transforming these signals to guide appropriate actions. However, non-retinal inputs, carrying motor signals as well as cognitive and attentional modulatory signals, also activate these cortical regions. How these networks integrate coincident signals ensuring reliable visual behaviors is poorly understood. In this study, we observe neural responses in the dorsal-parietal cortex of mice during a visual discrimination task driven by visual stimuli and movements. We find that visual and motor signals interact according to two mechanisms: divisive normalization and separation of responses. Interactions are contextually modulated by the animal's state of sustained attention, which amplifies visual and motor signals and increases their discriminability in a low-dimensional space of neural activations. These findings reveal computational principles operating in dorsal-parietal networks that enable separation of incoming signals for reliable visually guided behaviors during interactions with the environment.


Asunto(s)
Atención/fisiología , Actividad Motora/fisiología , Sensación/fisiología , Corteza Visual/fisiología , Animales , Conducta Animal , Discriminación en Psicología , Ratones Endogámicos C57BL , Movimiento/fisiología , Neuronas/fisiología , Dinámicas no Lineales
6.
Proc Natl Acad Sci U S A ; 118(30)2021 07 27.
Artículo en Inglés | MEDLINE | ID: mdl-34301903

RESUMEN

During perceptual decision-making, the brain encodes the upcoming decision and the stimulus information in a mixed representation. Paradigms suitable for studying decision computations in isolation rely on stimulus comparisons, with choices depending on relative rather than absolute properties of the stimuli. The adoption of tasks requiring relative perceptual judgments in mice would be advantageous in view of the powerful tools available for the dissection of brain circuits. However, whether and how mice can perform a relative visual discrimination task has not yet been fully established. Here, we show that mice can solve a complex orientation discrimination task in which the choices are decoupled from the orientation of individual stimuli. Moreover, we demonstrate a typical discrimination acuity of 9°, challenging the common belief that mice are poor visual discriminators. We reached these conclusions by introducing a probabilistic choice model that explained behavioral strategies in 40 mice and demonstrated that the circularity of the stimulus space is an additional source of choice variability for trials with fixed difficulty. Furthermore, history biases in the model changed with task engagement, demonstrating behavioral sensitivity to the availability of cognitive resources. In conclusion, our results reveal that mice adopt a diverse set of strategies in a task that decouples decision-relevant information from stimulus-specific information, thus demonstrating their usefulness as an animal model for studying neural representations of relative categories in perceptual decision-making research.


Asunto(s)
Toma de Decisiones , Orientación Espacial , Animales , Ratones
7.
Cell Rep ; 29(12): 3835-3846.e5, 2019 12 17.
Artículo en Inglés | MEDLINE | ID: mdl-31851917

RESUMEN

The long-term storage of episodic memory requires communication between prefrontal cortex and hippocampus. However, how consolidation alters dynamic interactions between these regions during subsequent recall remains unexplored. Here we perform simultaneous electrophysiological recordings from anterior cingulate cortex (ACC) and hippocampal CA1 in mice during recall of recent and remote contextual fear memory. We find that, in contrast to recent memory, remote memory recall is accompanied by increased ACC-CA1 synchronization at multiple frequency bands. The augmented ACC-CA1 interaction is associated with strengthened coupling among distally spaced CA1 neurons, suggesting an ACC-driven organization of a sparse code. This robust shift in physiology permits a support vector machine classifier to accurately determine memory age on the basis of the ACC-CA1 synchronization pattern. Our findings reveal that memory consolidation alters the dynamic coupling of the prefrontal-hippocampal circuit and results in a physiological signature of memory age.


Asunto(s)
Región CA1 Hipocampal/fisiología , Miedo/fisiología , Giro del Cíngulo/fisiología , Memoria a Largo Plazo/fisiología , Memoria/fisiología , Recuerdo Mental/fisiología , Neuronas/fisiología , Animales , Conducta Animal , Aprendizaje Automático , Masculino , Consolidación de la Memoria/fisiología , Ratones , Vías Nerviosas/fisiología , Máquina de Vectores de Soporte
8.
Neurosci Res ; 140: 14-22, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30465783

RESUMEN

In recent years, the number of studies on decision-making in mice has increased dramatically. Many of these studies focus on the posterior parietal cortex (PPC), an area that has been implicated in sensory and multisensory processing, navigation, motion planning, and decision-making. In this review we summarize recent anatomical and functional studies of mouse PPC. First, we make a note of the existing variability in the nomenclature and its anatomical localization. Based on the commonalities across different studies we then describe the connectivity of PPC and discuss its place within several functional brain networks. In view of the examined connectivity, we go on to discuss the role of PPC for the encoding of single-modality and multimodal stimuli as well as its role in navigation. Finally, we summarize the literature on the choice-related activity: we discuss the variety of behavioral protocols and sensory modalities used in these studies, and we note that the response properties of PPC and its causal involvement in decision-making may depend substantially on these conditions. We conclude that, although more research should be devoted to creating a more complete and consistent image of the mouse PPC, this area should rightfully be considered a convenient model system for a circuit-level understanding of the mammalian parietal cortex.


Asunto(s)
Lóbulo Parietal/anatomía & histología , Lóbulo Parietal/fisiología , Animales , Toma de Decisiones/fisiología , Ratones , Percepción Visual/fisiología
9.
Nat Commun ; 8(1): 1196, 2017 10 30.
Artículo en Inglés | MEDLINE | ID: mdl-29084948

RESUMEN

Recording neural activity during animal behavior is a cornerstone of modern brain research. However, integration of cutting-edge technologies for neural circuit analysis with complex behavioral measurements poses a severe experimental bottleneck for researchers. Critical problems include a lack of standardization for psychometric and neurometric integration, and lack of tools that can generate large, sharable data sets for the research community in a time and cost effective way. Here, we introduce a novel mouse behavioral learning platform featuring voluntary head fixation and automated high-throughput data collection for integrating complex behavioral assays with virtually any physiological device. We provide experimental validation by demonstrating behavioral training of mice in visual discrimination and auditory detection tasks. To examine facile integration with physiology systems, we coupled the platform to a two-photon microscope for imaging of cortical networks at single-cell resolution. Our behavioral learning and recording platform is a prototype for the next generation of mouse cognitive studies.


Asunto(s)
Percepción Auditiva/fisiología , Conducta Animal/fisiología , Cabeza/fisiología , Aprendizaje/fisiología , Percepción Visual/fisiología , Algoritmos , Animales , Masculino , Ratones Endogámicos C57BL , Ratones Transgénicos , Análisis y Desempeño de Tareas
10.
J Neurophysiol ; 115(6): 2931-6, 2016 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-26984421

RESUMEN

Imaging techniques such as functional magnetic resonance imaging seek to estimate neural signals in local brain regions through measurements of hemodynamic activity. However, hemodynamic activity is accompanied by large vascular fluctuations of unclear significance. To characterize these fluctuations and their impact on estimates of neural signals, we used optical imaging in visual cortex of awake mice. We found that hemodynamic activity can be expressed as the sum of two components, one local and one global. The local component reflected presumed neural signals driven by visual stimuli in the appropriate retinotopic region. The global component constituted large fluctuations shared by larger cortical regions, which extend beyond visual cortex. These fluctuations varied from trial to trial, but they did not constitute noise; they correlated with pupil diameter, suggesting that they reflect variations in arousal or alertness. Distinguishing local and global contributions to hemodynamic activity may help understand neurovascular coupling and interpret measurements of hemodynamic responses.


Asunto(s)
Hemodinámica/fisiología , Corteza Visual/irrigación sanguínea , Corteza Visual/fisiología , Animales , Medidas del Movimiento Ocular , Movimientos Oculares/fisiología , Masculino , Ratones Endogámicos C57BL , Imagen Óptica , Estimulación Luminosa , Pupila/fisiología , Percepción Visual/fisiología
12.
Neuron ; 85(5): 942-58, 2015 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-25741722

RESUMEN

An increasingly powerful approach for studying brain circuits relies on targeting genetically encoded sensors and effectors to specific cell types. However, current approaches for this are still limited in functionality and specificity. Here we utilize several intersectional strategies to generate multiple transgenic mouse lines expressing high levels of novel genetic tools with high specificity. We developed driver and double reporter mouse lines and viral vectors using the Cre/Flp and Cre/Dre double recombinase systems and established a new, retargetable genomic locus, TIGRE, which allowed the generation of a large set of Cre/tTA-dependent reporter lines expressing fluorescent proteins, genetically encoded calcium, voltage, or glutamate indicators, and optogenetic effectors, all at substantially higher levels than before. High functionality was shown in example mouse lines for GCaMP6, YCX2.60, VSFP Butterfly 1.2, and Jaws. These novel transgenic lines greatly expand the ability to monitor and manipulate neuronal activities with increased specificity.


Asunto(s)
Marcación de Gen/métodos , Integrasas/genética , Neuronas/fisiología , Optogenética/métodos , Animales , Hipocampo/química , Hipocampo/fisiología , Integrasas/biosíntesis , Ratones , Ratones Transgénicos , Neuronas/química , Técnicas de Cultivo de Órganos , Corteza Visual/química , Corteza Visual/fisiología
13.
J Neurosci ; 35(1): 53-63, 2015 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-25568102

RESUMEN

Genetically encoded voltage indicators (GEVIs) promise to reveal the membrane potential of genetically targeted neuronal populations through noninvasive, chronic imaging of large portions of cortical space. Here we test a promising GEVI in mouse cortex during wakefulness, a challenging condition due to large hemodynamic activity, and we introduce a straightforward projection method to separate a signal dominated by membrane voltage from a signal dominated by hemodynamic activity. We expressed VSFP-Butterfly 1.2 plasmid in layer 2/3 pyramidal cells of visual cortex through electroporation in utero. We then used wide-field imaging with two cameras to measure both fluorophores of the indicator in response to visual stimuli. By taking weighted sums and differences of the two measurements, we obtained clear separation of hemodynamic and voltage signals. The hemodynamic signal showed strong heartbeat oscillations, superimposed on slow dynamics similar to blood oxygen level-dependent (BOLD) or "intrinsic" signals. The voltage signal had fast dynamics similar to neural responses measured electrically, and showed an orderly retinotopic mapping. We compared this voltage signal with calcium signals imaged in transgenic mice that express a calcium indicator (GCaMP3) throughout cortex. The voltage signal from VSFP had similar signal-to-noise ratios as the calcium signal, it was more immune to vascular artifacts, and it integrated over larger regions of visual space, which was consistent with its reporting mostly subthreshold activity rather than the spiking activity revealed by calcium signals. These results demonstrate that GEVIs provide a powerful tool to study the dynamics of neural populations at mesoscopic spatial scales in the awake cortex.


Asunto(s)
Sondas de ADN/análisis , Electroporación/métodos , Imagen Molecular/métodos , Estimulación Luminosa/métodos , Corteza Visual/química , Corteza Visual/fisiología , Animales , Sondas de ADN/genética , Femenino , Colorantes Fluorescentes/análisis , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Embarazo
14.
J Neurosci ; 35(1): 170-8, 2015 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-25568112

RESUMEN

The response of neurons in sensory cortex to repeated stimulus presentations is highly variable. To investigate the nature of this variability, we compared the spike activity of neurons in the primary visual cortex (V1) of cats with that of their afferents from lateral geniculate nucleus (LGN), in response to similar stimuli. We found variability to be much higher in V1 than in LGN. To investigate the sources of the additional variability, we measured the spiking activity of large V1 populations and found that much of the variability was shared across neurons: the variable portion of the responses of one neuron could be well predicted from the summed activity of the rest of the neurons. Variability thus mostly reflected global fluctuations affecting all neurons. The size and prevalence of these fluctuations, both in responses to stimuli and in ongoing activity, depended on cortical state, being larger in synchronized states than in more desynchronized states. Contrary to previous reports, these fluctuations invested the overall population, regardless of preferred orientation. The global fluctuations substantially increased variability in single neurons and correlations among pairs of neurons. Once this effect was removed, pairwise correlations were reduced and were similar regardless of cortical state. These results highlight the importance of cortical state in controlling cortical operation and can help reconcile previous studies, which differed widely in their estimate of neuronal variability and pairwise correlations.


Asunto(s)
Red Nerviosa/fisiología , Estimulación Luminosa/métodos , Corteza Visual/fisiología , Vías Visuales/fisiología , Animales , Gatos , Femenino , Distribución Aleatoria
15.
J Neurosci ; 33(46): 18343-51, 2013 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-24227743

RESUMEN

Hemodynamic responses in mice and other species are typically measured under anesthesia. However, anesthesia could influence their relationship to neural activity. To investigate this relationship, we used optical imaging in mouse primary visual cortex (V1). Hemodynamic responses yielded clear maps of retinotopy in both anesthetized and awake mice. However, during wakefulness, responses were four times larger and twice as fast. These differences held whether we induced anesthesia with urethane or isoflurane and whether awake mice were stationary or running on a treadmill. With electrode recordings, we established that the effects of wakefulness reflect changes in neurovascular coupling, not in neural activity. By activating V1 directly via optogenetics, we replicated the effects of wakefulness in terms of timing but not of amplitude. We conclude that neurovascular coupling depends critically on anesthesia and wakefulness: during wakefulness, neural activity is followed by much stronger and quicker hemodynamic responses.


Asunto(s)
Hemodinámica/fisiología , Tiempo de Reacción/fisiología , Corteza Visual/fisiología , Vigilia/fisiología , Animales , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos
16.
Nat Neurosci ; 16(6): 724-9, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23603708

RESUMEN

Sensory systems exhibit mechanisms of neural adaptation, which adjust neuronal activity on the basis of recent stimulus history. In primary visual cortex (V1) in particular, adaptation controls the responsiveness of individual neurons and shifts their visual selectivity. What benefits does adaptation confer on a neuronal population? We measured adaptation in the responses of populations of cat V1 neurons to stimulus ensembles with markedly different statistics of stimulus orientation. We found that adaptation served two homeostatic goals. First, it maintained equality in the time-averaged responses across the population. Second, it maintained independence in selectivity across the population. Adaptation scaled and distorted population activity according to a simple multiplicative rule that depended on neuronal orientation preference and on stimulus orientation. We conclude that adaptation in V1 acts as a mechanism of homeostasis, enforcing a tendency toward equality and independence in neural activity across the population.


Asunto(s)
Adaptación Fisiológica/fisiología , Adaptación Psicológica/fisiología , Homeostasis/fisiología , Neuronas/fisiología , Corteza Visual/fisiología , Animales , Gatos , Electrodos Implantados , Electroencefalografía , Femenino , Modelos Neurológicos , Pruebas Neuropsicológicas , Corteza Visual/citología
17.
J Neurosci ; 32(48): 17108-19, 2012 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-23197704

RESUMEN

Cortical circuits encode sensory stimuli through the firing of neuronal ensembles, and also produce spontaneous population patterns in the absence of sensory drive. This population activity is often characterized experimentally by the distribution of multineuron "words" (binary firing vectors), and a match between spontaneous and evoked word distributions has been suggested to reflect learning of a probabilistic model of the sensory world. We analyzed multineuron word distributions in sensory cortex of anesthetized rats and cats, and found that they are dominated by fluctuations in population firing rate rather than precise interactions between individual units. Furthermore, cortical word distributions change when brain state shifts, and similar behavior is seen in simulated networks with fixed, random connectivity. Our results suggest that similarity or dissimilarity in multineuron word distributions could primarily reflect similarity or dissimilarity in population firing rate dynamics, and not necessarily the precise interactions between neurons that would indicate learning of sensory features.


Asunto(s)
Potenciales de Acción/fisiología , Red Nerviosa/fisiología , Neuronas/fisiología , Corteza Somatosensorial/fisiología , Animales , Gatos , Masculino , Modelos Neurológicos , Ratas , Ratas Sprague-Dawley
18.
Nat Neurosci ; 12(10): 1317-24, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19749748

RESUMEN

Neuronal populations in sensory cortex represent time-changing sensory input through a spatiotemporal code. What are the rules that govern this code? We measured membrane potentials and spikes from neuronal populations in cat visual cortex (V1) using voltage-sensitive dyes and electrode arrays. We first characterized the population response to a single orientation. As response amplitude grew, the population tuning width remained constant for membrane potential responses and became progressively sharper for spike responses. We then asked how these single-orientation responses combine to code for successive orientations. We found that they combined through simple linear summation. Linearity, however, was violated after stimulus offset, when responses exhibited an unexplained persistence. As a result of linearity, the interactions between responses to successive stimuli were minimal. Our results indicate that higher cortical areas may reconstruct the stimulus sequence from V1 population responses through a simple instantaneous decoder. Therefore, spatial and temporal codes in area V1 operate largely independently.


Asunto(s)
Potenciales de Acción/fisiología , Mapeo Encefálico , Potenciales de la Membrana/fisiología , Neuronas/fisiología , Corteza Visual/citología , Animales , Gatos , Electrodos , Colorantes Fluorescentes/metabolismo , Modelos Neurológicos , Orientación/fisiología , Estimulación Luminosa/métodos , Valor Predictivo de las Pruebas , Tiempo de Reacción/fisiología , Factores de Tiempo
19.
Neuron ; 61(1): 35-41, 2009 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-19146811

RESUMEN

The local field potential (LFP) is increasingly used to measure the combined activity of neurons within a region of tissue. Yet, available estimates of the size of this region are highly disparate, ranging from several hundred microns to a few millimeters. To measure the size of this region directly, we used a combination of multielectrode recordings and optical imaging. We determined the orientation selectivity of stimulus-evoked LFP signals in primary visual cortex and were able to predict it on the basis of the surrounding map of orientation preference. The results show that > 95% of the LFP signal originates within 250 microm of the recording electrode. This quantitative estimate indicates that LFPs are more local than often recognized and provides a guide to the interpretation of the increasing number of studies that rest on LFP recordings.


Asunto(s)
Potenciales Evocados Visuales/fisiología , Neuronas/fisiología , Corteza Visual/fisiología , Animales , Gatos , Electrodos , Electrofisiología/métodos , Corteza Visual/citología , Percepción Visual/fisiología
20.
Neuron ; 57(5): 673-9, 2008 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-18341988

RESUMEN

The organization of primary visual cortex (V1) into functional maps makes individual cells operate in a variety of contexts. For instance, some neurons lie in regions of fairly homogeneous orientation preference (iso-orientation domains), while others lie in regions with a variety of preferences (e.g., pinwheel centers). We asked whether this diversity in local map structure correlates with the degree of selectivity of spike responses. We used a combination of imaging and electrophysiology to reveal that neurons in regions of homogeneous orientation preference have much sharper tuning. Moreover, in both monkeys and cats, a common principle links the structure of the orientation map, on the spatial scale of dendritic integration, to the degree of selectivity of individual cells. We conclude that neural computation is not invariant across the cortical surface. This finding must factor into future theories of receptive field wiring and map development.


Asunto(s)
Mapeo Encefálico/métodos , Neuronas/fisiología , Corteza Visual/fisiología , Animales , Gatos , Macaca fascicularis , Estimulación Luminosa/métodos , Percepción Visual/fisiología
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