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Biology subjects

Bhandari, A.

Publications and source records attributed to Bhandari, A..

At least 19 recordsLinked to original sources

Varietal Evaluation of Coffee Genotype in Subtropical Nepal

Coffee (Coffea arabica L.) is an emerging high-value crop in Nepal, but national productivity remains far below genetic potential, partly due to the lack of locally validated variety recommendations. This study evaluated and compared the morphological and yield-attributing characteristics of 19 Arabica genotypes at the Horticulture Research Station, Malepatan, Pokhara (848 m above sea level) from January to June 2026 using a Randomized Complete Block Design with three replications. Yellow Caturra recorded the highest total fresh cherry yield (5.34 kg/plant), followed by Caturra Amarillo (3.56 kg/plant), Catuai Vermelo (3.19 kg/plant), and Catuai Amarillo (3.10 kg/plant). Catuai Amarillo and Caturra Amarillo produced the most bearing branches (76 and 72, respectively), while Caturra Amarillo and Yellow Caturra had the most cherries per node (7.73 and 7.47). Pacamara and Selection-10 achieved the maximum 100-cherry weight (167.67 g), while Indonesia had the largest cherry diameter (13.38 mm). Catuai Amarillo had the highest total soluble solids (25.97 degree Brix), while Tekisic had the lowest (16.80 degree Brix). Coffee leaf rust severity increased from a mean of 7.49% at 30 days after incidence (DAI) to 37.58% at 120 DAI. Selection-10 was the least affected genotype across the severity assessments and recorded the lowest area under the disease progress curve (AUDPC; 25.03 rating-days), whereas Caturra Amarillo had the highest AUDPC (347.95 rating-days). Overall, Yellow Caturra showed the strongest yield performance, while Selection-10 combined low disease development with a high 100-cherry weight. These results indicate that genotype selection should consider productivity, quality-related traits, and CLR response together.

plant biology↗

Management of Root-Knot Nematode-Fusarium Wilt Complex with different Bio-management methods in Tomato (Solanum lycopersicum L.) var Srijana

The root-knot nematode-Fusarium complex is a major constraint to protected tomato cultivation in Nepal, particularly on the widely grown Srijana hybrid, which lacks Mi-mediated nematode resistance. The present study was conducted to identify the most effective biocontrol agent, to identify the most effective Solanum rootstock, and to compare the overall efficacy of grafting versus biocontrol agents under polyhouse conditions. For the management of the root knot nematode-Fusarium complex, a pot experiment was set up in a completely randomized design at Pokhara, Kaski. Treatments comprised Trichoderma viride, Pseudomonas fluorescens, their half-dose combination, self-grafted Srijana, and four resistant rootstocks (S. sisymbriifolium, S. melongena, S. torvum, and VNRRs-10), together with nematode-only, Fusarium-only, complex (Nematode + Fusarium), and disease-free controls. Each plant was inoculated with approximately 2,000 nematode eggs, followed by 25 ml of 10^6 spores per ml of Fusarium seven days later to mimic the field complex. Plant growth parameters and nematode infestation data were recorded and analyzed via RStudio v. 2026.04.0. The root knot nematode-Fusarium complex caused significantly greater reductions in vegetative biomass than root knot nematode and Fusarium alone (20.32 gm vs 38.40 gm vs 51.32 gm) at 45 DAT. Single-agent biocontrol gave intermediate protection (T. viride 64.9%; P. fluorescens 47.9% nematode management efficiency), whereas combined T. viride + P. fluorescens treatment produced the highest vegetative biomass but the weakest nematode suppression (320 galls, reproduction factor: 38). Grafting onto S. torvum and S. melongena resulted in the greatest nematode suppression, achieving 97.9% and 93.6% management efficiency, respectively, while S. torvum alongside VNRRs-10 maintained the highest Fusarium suppression (92.5%). Overall resistant rootstocks consistently outperformed biological control in reducing disease severity. These findings indicate that grafting onto resistant solanum rootstocks, particularly S. torvum and S. melongena, was observed as the most effective strategy for managing the root knot nematode-Fusarium complex under protected cultivation, offering a viable chemical-free management option. Keywords: Root-Knot Nematode, Fusarium oxysporum, RKN-Fusarium-complex, Solanum torvum

pathology↗

CXCR3 on transferred T cells enables vaccine-boosted adoptive T-cell therapy in solid tumors

Adoptive T-cell therapy (ACT) has demonstrated marked clinical benefit in hematological malignancies but has limited efficacy against solid tumors. Cancer vaccines can improve ACT, but the mechanisms underlying this combination are poorly understood. Here, we combined ACT with chimpanzee adenovirus ChAdOx1 (ChAd) and modified vaccinia Ankara (MVA) encoding tumor antigens. Whereas PD1 blockade failed to improve ACT, the combination with ChAd/MVA vaccination drove durable regression of established tumors, correlating with expansion of tumor-reactive T cells in lymphoid organs and increased tumor infiltration by T cells. Mechanistically, ChAd priming induced CXCR3 ligands (CXCL10 and CXCL9) in the vaccine-draining lymph node, thereby recruiting transferred T cells to this node independently of cognate antigen. CXCR3 expression on the transferred T cells, but not on host cells, was required for the anti-tumor effect of the combination therapy and favored T-cell accumulation in the vaccine-draining lymph node and the tumor. These findings identify CXCR3 on the transferred T cells as a determinant of ACT plus vaccination synergy and provide a rationale for combining viral-vector vaccines with TCR-T therapies, and for selecting or engineering T cells to retain CXCR3 expression.

immunology↗

Task context is broadly encoded in the human brain

Cognitive control depends on the task context as a top-down modulatory influence on ongoing processing. Cognitive neuroscience theories of cognitive control have associated the maintenance of context, and its deployment as a control signal, with neural populations in the dorsolateral prefrontal cortex (DLPFC). Importantly, however, the way information about the task context is propagated and used throughout the brain remains largely unspecified. A longstanding hypothesis is that neural representations of context in DLPFC directly influence neural processing only where this information is needed to resolve competition, integrating top-down context inputs from DLPFC conjunctively with local processing. However, an alternative hypothesis is that context is broadcast and maintained more widely throughout the brain than necessary. In this way, context is available for integration with local populations when needed. Here, we tested these hypotheses by analyzing a large multisession fMRI data set collected while participants performed a context-dependent task using a hierarchical rule that features one superordinate context versus a control task that used a non-hierarchical, flat rule. Across a range of analyses, we found that the superordinate task context is robustly and widely coded throughout the cortex, evident in every largescale cortical network. Across a range of controls, the superordinate context was the only task feature to show this property. Indeed, context accounted for the most variance in cortex-wide activity patterns across analyses. In contrast, the integration of this context with coding of other task features was evident in only a subset of context-coding regions, principally those in higher-order control and attentional networks and visual perceptual stream areas. These latter areas showed interactions with context that were consistent with object-based attentional modulation, as needed by the task. These results provide initial empirical support for a context broadcast model of top-down control in the brain.

neuroscience↗

MAIT cells derived ligands signal via VEGFR2 to promote tissue repair and liver regeneration

MAIT are a highly versatile population of innate-like T cells that have been implicated in promoting tissue repair-associated process in a variety of tissue and diseases settings in the last years. While certain specific effector molecules responsible for MAIT-cell mediated have been identified, the mechanisms by which MAIT cells exert repair functions remain incompletely understood. Here, we show that hepatic MAIT cells express VEGFA, VEGFB and vimentin, an alternative ligand for the VEGFA-receptor VEGFR2 in both, regenerating and heathy tissue. Expression and secretion of these factors were induced in vitro by combined T cell receptor and cytokine stimulation. Supernatants of activated MAIT cells were able to promote proliferation of different epithelial and endothelial cells, including a liver sinusoidal endothelial-derived cell line in an VEGFR2-dependent manner. Together, our findings expand our understanding of MAIT cell function, especially in the liver and open new opens avenues for exploring MAIT therapeutic potential in modulating tissue repair.

immunology↗

Single-Cell Characterization of Anterior Segment Development: Cell Types, Pathways, and Signals Driving Formation of the Trabecular Meshwork and Schlemm's Canal

Morphogenesis of the anterior segment (AS) is crucial for healthy ocular physiology and vision but is only partially understood. The Schlemms canal (SC) and trabecular meshwork (TM) are essential drainage tissues within the AS, and their proper development and function are critical for maintaining normal intraocular pressure; abnormalities in either tissue can result in elevated pressure and glaucoma. Here, we use single-cell transcriptomic profiling to provide high-resolution molecular detail of AS development with a particular focus on SC and TM. We report transcriptomes for [~]130,000 single cells at key developmental stages from postnatal day 2 (P2) to P60. We provide the first annotation of cell types across these developmental stages and crucial information about dynamic changes in pathways/gene expression. Further, we trace developmental trajectories for TM cell and SC endothelial cell (SEC) subtypes and determine genes and signaling networks driving their specific cell fates. We demonstrate dynamic changes in signaling interactions between SC and the TM cells during their synchronized development. Collectively, our data lay a deep molecular foundation for AS development that will direct understanding of normal ocular physiology, glaucoma, and other AS conditions.

developmental biology↗

Optimised genome editing for precise DNA insertion and substitution using Prime Editors in zebrafish

CRISPR/Cas9-mediated genome editing has rapidly become a popular tool for studying gene functions and generating genetically modified organisms. However, using this system, stochastic integration of random insertions and deletions restricts precise genome manipulation. Advanced CRISPR/Cas9 technologies using Prime Editors (PEs), Cas9 proteins fused with reverse transcriptase, enable programmed integration of short DNA modifications into the genome. However, its application in precise genome editing in animal models is challenging. Here, we utilise a nickase-and a nuclease-based PE to perform programmed short DNA substitution and insertion in various loci in the zebrafish genome. Whereas nickase-based PE2 mediated a higher ratio of precise prime edits to the total edits, nuclease-based PEn was more efficient for short DNA modifications, achieving up to 27.3% precise insertion. To further evaluate our approach, we inserted a nuclear localisation signal into a reporter transgene to incorporate longer fragments by prime editing. These gene modifications were transmitted to the next generation. We show that PE-mediated prime editing can efficiently manipulate genome information in zebrafish without using exogenous donor DNA. Prime editing, CRISPR/Cas9, zebrafish, PE2, PEn

molecular biology↗

Medial temporal lobe encodes cognitive maps of real-world social networks

People routinely navigate their complex social networks1: From gossiping strategically with others2-4 to brokering connections between siloed groups5,6, our ability to make adaptive social choices hinges on whether we can construct useful mental representations of the social ties within our communities7. While decades of neuroscience research have shown that the medial temporal lobe encodes cognitive maps of physical8-10 or conceptual space11, how the brain represents our social networks in the wild to solve social problems remains unknown. By combining computational models with functional neuroimaging and longitudinal measurement of an evolving and densely interconnected real-world human network (N=187), we show that the entorhinal cortex encodes a cognitive map of the long-range connectivity between pairs of network members. This social map reflects the particular demands of social navigation and is specifically formatted to encode the simultaneous connectivity between network members, which critically enables tracking how information diffuses across the network. Moreover, the strength of its encoding in the entorhinal cortex aids in brokering connections that improve cohesion within peoples social communities. Our results illuminate how a domain-general neural mechanism12,13 is tailored to prioritize the natural dynamics of social phenomena in order to support adaptive navigation through these highly complex environments.

neuroscience↗

A framework for evaluating predicted sperm trajectories in crowded microscopy videos

Since the 1980s, semi-automated sperm motility analysis of phase contrast microscopy videos has been used to measure and categorize sperm motility patterns. Motility categories are determined from various kinematic parameters such as Curvilinear Velocity (VCL) and Beat Cross Frequency (BCF). These measures ultimately rely on the quality of the tracking for each individual sperm in the microscopy video. However, common approaches to sperm tracking require sample dilution and shortening the time window of observation (less than 1 to 2 seconds) to avoid tracking errors that occur when sperm cross paths. The post-ejaculatory lifespan of sperm can exceed several hours to days in some species, and long-term adaptive changes in motility pattern may be an important distinguishing factor for predictive modeling of sperm fertilizing competence. Improving the predictive value of computer assisted semen analysis will require accurate tracking of sperm trajectories over physiologically-relevant time scales and at the high cell densities typically found in semen. In this work, we identify a framework for accurately assessing the quality of sperm trajectory tracking that is independent of standard motility measures. We utilize cell tracking metrics adapted from the more common task of tracking adherent somatic cells and propose modifications based on the unique challenges of sperm video-microscopy. We also provide a small dataset of labeled microscopy videos to allow for future comparisons and developments. Author summaryThis report develops a computer vision framework to track individual sperm cells in crowded (high cell-density) microscopy videos, with the goal of improving automated analysis of sperm motility patterns. The task of accurately analyzing sperm movement is deceptively challenging due to the high rate of cell crossovers, an issue that has long impeded long-term tracking of sperm trajectories. Here, we introduce new evaluation metrics and provide a labeled dataset to serve as a baseline for future improvements.

bioinformatics↗

IOP-induced blood-retinal barrier compromise contributes to RGC death in glaucoma

The integrity of the blood-retinal barrier (BRB) has been largely unexplored in glaucoma. We reveal that elevated intraocular pressure (IOP) partially compromises the BRB in two human-relevant inherited mouse models of glaucoma (DBA/2J and Lmx1bV265D). Experimentally increasing IOP in mouse eyes further confirms this. Notably, the compromise induces subtle leakage, happening without bleeding or detected endothelial cell junction disruption, and it precedes neurodegeneration. Leakage occurs from peripheral veins in the retinal ganglion cell layer with a concomitant loss of the transcytosis inhibitor MFSD2A. Importantly, stabilizing {beta}-catenin in retinal endothelial cells prevents both vascular leakage and neurodegeneration in the DBA/2J model. The occurrence of leakage in all 3 high IOP models indicates that BRB compromise may be a common, yet overlooked, mechanism in glaucoma. These findings suggest that IOP-induced BRB compromise plays a critical role in glaucoma, offering a new therapeutic target.

neuroscience↗

Task structure tailors the geometry of neural representations in human lateral prefrontal cortex

How do human brains represent tasks of varying structure? The lateral prefrontal cortex (lPFC) flexibly represents task information. However, principles that shape lPFC representational geometry remain unsettled. We use fMRI and pattern analyses to reveal the structure of lPFC representational geometries as humans perform two distinct categorization tasks- one with flat, conjunctive categories and another with hierarchical, context-dependent categories. We show that lPFC encodes task-relevant information with task-tailored geometries of intermediate dimensionality. These geometries preferentially enhance the separability of task-relevant variables while encoding a subset in abstract form. Specifically, in the flat task, a global axis encodes response-relevant categories abstractly, while category-specific local geometries are high-dimensional. In the hierarchy task, a global axis abstractly encodes the higher-level context, while low-dimensional, context-specific local geometries compress irrelevant information and abstractly encode the relevant information. Trial-by-trial variability in neural patterns along the global coding axes in each task structure was associated with behavioral variability. Comparing these task geometries exposes generalizable principles by which lPFC tailors representations to different tasks.

neuroscience↗

Replay shapes abstract cognitive maps for efficient social navigation

To make adaptive social decisions, people must anticipate how information flows through their social network. While this requires knowledge of how people are connected, networks are too large to have firsthand experience with every possible route between individuals. How, then, are people able to accurately track information flow through social networks? We find that people immediately cache abstract knowledge about social network structure as they learn who is friends with whom, which enables the identification of efficient routes between remotely-connected individuals. These cognitive maps of social networks, which are built while learning, are then reshaped through overnight rest. During these extended periods of rest, a replay-like mechanism helps to make these maps increasingly abstract, which privileges improvements in social navigation accuracy for the longest communication paths that span distinct communities within the network. Together, these findings provide mechanistic insight into the sophisticated mental representations humans use for social navigation.

neuroscience↗

FYN regulates aqueous humor outflow and IOP through the phosphorylation of VE-cadherin

The exact sites and molecules that determine resistance to aqueous humor drainage and control intraocular pressure (IOP) need further elaboration. Proposed sites include the inner wall of Schlemmss canal and the juxtacanalicular trabecular meshwork ocular drainage tissues. The adherens junctions (AJs) of Schlemms canal endothelial cells (SECs) must both preserve the blood-aqueous humor (AQH) barrier and be conducive to AQH drainage. How homeostatic control of AJ permeability in SC occurs and how such control impacts IOP is unclear. We hypothesized that mechano-responsive phosphorylation of the junctional molecule VE-CADHERIN (VEC) by SRC family kinases (SFKs) regulates the permeability of SEC AJs. We tested this by clamping IOP at either 16 mmHg, 25 mmHg, or 45 mmHg in mice and then measuring AJ permeability and VEC phosphorylation. We found that with increasing IOP: 1) SEC AJ permeability increased, 2) VEC phosphorylation was increased at tyrosine-658, and 3) SFKs were activated at the AJ. Among the two SFKs known to phosphorylate VEC, FYN, but not SRC, localizes to the SC. Furthermore, FYN mutant mice had decreased phosphorylation of VEC at SEC AJs, dysregulated IOP, and reduced AQH outflow. Together, our data demonstrate that increased IOP activates FYN in the inner wall of SC, leading to increased phosphorylation of AJ VEC and, thus, decreased resistance to AQH outflow. These findings support a crucial role of mechanotransduction signaling in IOP homeostasis within SC in response to IOP. These data strongly suggest that the inner wall of SC partially contributes to outflow resistance.

cell biology↗

Transcriptomic profiling of Schlemm's canal cells reveals a lymphatic-biased identity and three major cell states

Schlemms canal (SC) is central in intraocular pressure regulation but requires much characterization. It has distinct inner and outer walls, each composed of Schlemms canal endothelial cells (SECs) with different morphologies and functions. Recent transcriptomic studies of the anterior segment added important knowledge, but were limited in power by SEC numbers or did not focus on SC. To gain a more comprehensive understanding of SC biology, we performed bulk RNA sequencing on C57BL/6J SC, blood vessel, and lymphatic endothelial cells from limbal tissue ([~]4500 SECs). We also analyzed mouse limbal tissues by single-cell and single-nucleus RNA sequencing (C57BL/6J and 129/Sj strains), successfully sequencing 903 individual SECs. Together, these datasets confirm that SC has molecular characteristics of both blood and lymphatic endothelia with a lymphatic phenotype predominating. SECs are enriched in pathways that regulate cell-cell junction formation pointing to the importance of junctions in determining SC fluid permeability. Importantly, and for the first time, our analyses characterize 3 molecular classes of SECs, molecularly distinguishing inner wall from outer wall SECs and discovering two inner wall cell states that likely result from local environmental differences. Further, and based on ligand and receptor expression patterns, we document key interactions between SECs and cells of the adjacent trabecular meshwork (TM) drainage tissue. Also, we present cell type expression for a collection of human glaucoma genes. These data provide a new molecular foundation that will enable the functional dissection of key homeostatic processes mediated by SECs as well as the development of new glaucoma therapeutics. Significance statementSchlemms canal is a critical ocular drainage structure that maintains intraocular pressure with important consequences for glaucoma. Despite this, Schlemms canal has been relatively understudied with the molecular process that mediate its function, maintain its health, or that are compromised in glaucoma needing much deeper characterization. This study is important as it provides the most comprehensive molecular characterization of Schlemms canal cells to date providing a wealth of molecular details. In addition to highlighting important biological pathways, this information will guide studies to develop new treatments against glaucoma.

genomics↗

A Transient High-dimensional Geometry Affords Stable Conjunctive Subspaces for Efficient Action Selection

Flexible action selection requires cognitive control mechanisms capable of mapping the same inputs to different output actions depending on the context. From a neural state-space perspective, this requires a control representation that separates similar input neural states by context. Additionally, for action selection to be robust and time-invariant, information must be stable in time, enabling efficient readout. Here, using EEG decoding methods, we investigate how the geometry and dynamics of control representations constrain flexible action selection in the human brain. Participants performed a context-dependent action selection task. A forced response procedure probed action selection different states in neural trajectories. The result shows that before successful responses, there is a transient expansion of representational dimensionality that separated conjunctive subspaces. Further, the dynamics stabilizes in the same time window, with entry into this stable, high-dimensional state predictive of individual trial performance. These results establish the neural geometry and dynamics the human brain needs for flexible control over behavior.

neuroscience↗

Uncertainty aversion predicts the neural expansion of semantic representations

Correctly identifying the meaning of a stimulus requires activating the appropriate semantic representation among many alternatives. One way to reduce this uncertainty is to differentiate semantic representations from each other, thereby expanding the semantic space. In four experiments, we test this semantic-expansion hypothesis, finding that uncertainty averse individuals exhibit increasingly differentiated and separated semantic representations. This effect is mirrored at the neural level, where uncertainty aversion predicts greater distances between activity patterns in the left inferior frontal gyrus when reading words, and enhanced sensitivity to the semantic ambiguity of these words in the ventromedial prefrontal cortex. Two direct tests of the behavioral consequences of semantic-expansion further reveal that uncertainty averse individuals exhibit reduced semantic interference and poorer generalization. Together, these findings demonstrate that the internal structure of our semantic representations is shaped in a principled manner: aversion to uncertainty acts as an organizing principle to make the world more identifiable.

neuroscience↗

Loss of retinogeniculate synaptic function in the DBA/2J mouse model of glaucoma.

BackgroundRetinal ganglion cell (RGC) axons comprise the optic nerve and carry information to the dorsolateral geniculate nucleus (dLGN) that is relayed to the cortex for conscious vision. Glaucoma is a blinding neurodegenerative disease that commonly results from intraocular pressure (IOP)-associated injury leading to RGC axonal pathology, disruption of RGC outputs to the brain, and eventual apoptotic loss of RGC somata. The consequences of elevated IOP and glaucomatous pathology on RGC signaling to the dLGN are largely unknown and likely to be important contributors to visual system dysfunction in glaucoma. Thus, the goal of this study was to determine how glaucoma affects RGC outputs to the dLGN. MethodsWe used a combination of anatomical and physiological approaches to study the structure and function of retinogeniculate synapses in male and female DBA/2J mice at multiple ages before and after IOP elevation. These included measures of anterograde axonal transport, immunofluorescence staining of RGC axon terminals, patch-clamp recording retinogeniculate (RG) synapses in living brain slices, Sholl analysis of thalamocortical relay neuron dendrites, measurements of RGC somatic density, and treatment with a topical ophthalmic alpha-2 adrenergic agonist (brimonidine). ResultsDBA/2J mice showed progressive loss of anterograde optic tract transport to the dLGN and vGlut2 labeling of RGC axon terminals. Patch-clamp measurements of RG synaptic function showed that the strength of synaptic transmission was lower in 9 and 12-month DBA/2J mice and that this was the result of loss of individual RGC axon contributions. TC neuron dendrites showed a reduction in complexity at 12 months, suggestive of a delayed reorganization following reduced synaptic input. There was no detectable change in RGC soma density in 11-12m DBA/2J retinas indicating that observed effects occurred prior to RGC somatic loss. Finally, treatment with brimonidine eye drops prevented the loss of vGlut2-labeled RGC terminals in the dLGN. ConclusionsThese findings identify glaucoma- and IOP-associated functional deficits in an important subcortical RGC projection target. This sheds light on the processes linking IOP to vision loss and will be critical for informing future diagnostic approaches and vision-restoration therapies.

neuroscience↗

Bilateral enucleation induces homeostatic plasticity in the dorsolateral geniculate nucleus of mice.

Within the nervous system, plasticity mechanisms attempt to stabilize network activity following disruption by injury, disease, or degeneration. Optic nerve injury and age-related diseases can induce homeostatic-like responses in adulthood. We tested this possibility in the thalamocortical (TC) neurons in the dorsolateral geniculate nucleus (dLGN) using patch-clamp electrophysiology, optogenetics, immunostaining, and single-cell dendritic analysis following loss of visual input via bilateral enucleation. We observed progressive loss of vGlut2-positive retinal terminals in the dLGN indicating degeneration post-enucleation that was coincident with changes in microglial morphology indicative of microglial activation. Consistent with the decline of vGlut2 puncta, we also observed loss of retinogeniculate (RG) synaptic function assessed using optogenetic activation of RG axons while performing whole-cell voltage clamp recordings from TC neurons in brain slices. Surprisingly, we did not detect any significant changes in the frequency of miniature post-synaptic currents (mEPSCs) or corticothalamic feedback synapses. Analysis of TC neuron dendritic structure from single-cell dye fills revealed a gradual loss of dendrites proximal to the soma, where TC neurons receive the bulk of RG inputs. Finally, analysis of action potential firing demonstrated that TC neurons have increased excitability following enucleation, firing more action potentials in response to depolarizing current injections. Our findings show that degeneration of the retinal axons/optic nerve and loss of RG synaptic inputs induces structural and functional changes in TC neurons, consistent with neuronal attempts at compensatory plasticity in the dLGN.

neuroscience↗