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Lloyd, E.

Publications and source records attributed to Lloyd, E..

At least 19 recordsLinked to original sources

Imaging mitral/tufted glomeruli in the mouse olfactory bulb using the genetically encoded voltage indicator ArcLight

In the mammalian olfactory bulb, each olfactory receptor neuron type maps to receptor-specific channels called glomeruli. These input axons interact with the apical dendrites of mitral/tufted cells, which are projection neurons that send axons to the olfactory cortex. Therefore, each glomerulus reflects the input-output relationship for a different olfactory receptor type, which is transformed by a complex synaptic network. While prior 2-photon Ca2+ imaging experiments have shown that the glomerular output is heterogeneous with respect to how odor concentration information is processed, the nature of voltage dynamics remains unclear. Therefore, we used the genetically encoded voltage indicator (GEVI) ArcLight to image the glomerular output in vivo in anesthetized mice. We found that ArcLight could resolve both excitatory and suppressive odor-evoked signals from mitral/tufted glomeruli. ArcLight expression remained stable over multi-week imaging sessions and successfully captured odor- and concentration-specific patterns of activation across a large concentration range. Importantly, this approach allowed us to resolve heterogeneous concentration-response sensitivities and respiratory-coupled dynamics. We also demonstrate that several newer GEVIs can similarly measure odor-evoked signals using epifluorescence imaging. Our study establishes ArcLight and other emerging GEVIs as powerful tools for dissecting how sensory information is encoded and transformed through the mouse olfactory bulb.

neuroscience↗

Machine Learning for Toxicity Prediction in Low-Sample Molecular Classes

Deep learning models such as Chemprop have advanced quantitative molecular property prediction, but their reliance on large training sets limits use in data-scarce domains. We propose a framework that fine-tunes a general baseline model trained on publicly available data on small, class-specific datasets. The resulting models retain the baseline's generalization ability while gaining class-specific accuracy and produce probabilistic outputs that capture uncertainty in the training data. We demonstrate the approach on three toxicity classes defined by a common core structure, target, or mode of action: (i) organophosphates, (ii) androgen receptor antagonists, and (iii) estrogen receptor beta antagonists. Each fine-tuned model outperforms classical machine-learning methods and the EPA TEST tool. The probabilistic nature of the predictions enables prioritization of compounds for experimental validation and seamless integration with data streams of varying quality, supporting iterative decision-making in chemical safety and drug discovery.

biochemistry↗

Enhanced multisensory integration in the olfactory bulb of the Mexican cavefish

Astyanax mexicanus consists of eyed, river-dwelling "surface" fish, and multiple, independently evolved cave populations, which have converged on troglobitic traits such as eye loss and reduced metabolism. However, considerably less is known about constructive adaptations, which include a larger olfactory epithelium in cavefish. It is unknown how this relates to the olfactory bulb (OB), which is the first stage of olfactory sensory processing in the brain. The goal of the present study is to begin to define the structure and functional organization of the OB in A. mexicanus, and to begin to understand how it was transformed via cave adaptation. We addressed these questions using whole-mount immunohistochemistry and in vivo Ca2+ imaging from the OB of developmentally matched surface and Pachon cavefish. The cavefish OB was significantly larger than surface fish by 14 days post fertilization (dpf), which was accompanied by a broad and proportional increase in synaptic input to most glomerular regions. Increases in the size of the OB were accompanied by increases in the number of neurons expressing tyrosine hydroxylase and calretinin, the latter of which occurred primarily in the medial OB and could not be explained as a compensatory response to a larger OB. In vivo Ca2+ imaging from the dorsal OB of surface and cavefish in response to a panel of chemical stimuli revealed odor-evoked responses that were spatially organized and highly conserved across the two populations. Surprisingly, the medial OB was consistently activated by any change in water flow in both populations, although the number of water-responsive neurons was significantly greater in cavefish when measurements were performed using either in vivo imaging or the neuronal activity marker phospho-ERK. Water-responding neurons were similarly present in the olfactory epithelium in both populations, along with neurons expressing the mechanosensitive ion channel Piezo2, with significantly more Piezo2-expressing neurons present in cavefish. Therefore, cavefish exhibit enhanced multisensory integration of olfactory and mechanosensory input in the earliest stage of olfactory sensory processing in the brain.

neuroscience↗

Analysis of multi-trait evolution across independently evolved cavefish populations reveals shared and independent evolution of suites of cave-associated traits

Environmental perturbations often lead to the evolution of multiple traits. Determining whether shared genetic factors underlie multi-trait evolution is a central question in evolutionary biology. In the Mexican tetra, Astyanax mexicanus, cave-dwelling populations have repeatedly evolved multiple traits. The repeated evolution of these traits, paired the robust environmental differences between the surface and cave habitats, provide an opportunity to investigate the genetic basis of multi-trait evolution. Here, we investigate the extent to which shared genetic mechanisms underlie the repeated evolution of multiple traits in cavefish. Across cave populations, we find evidence for shared and distinct genetic mechanisms contributing to the evolution of individual traits. Further, multiple traits covary in cave-surface F2 hybrids and many of the same trait correlations are found across independently evolved cave populations. Finally, we assessed traits that differ between pigmented and albino F2 fish in surface fish with mutations in the albinism gene oculocutaneous albinism 2 (oca2). This revealed that mutations in oca2 reduce bottom-dwelling behavior in A. mexicanus. Together, these findings suggest that multi-trait evolution occurs repeatedly through shared genetic factors across A. mexicanus cave populations. These results are consistent with pleiotropy or linkage playing a large role in multi-trait evolution in this species.

evolutionary biology↗

Microenvironmental TGF-β is an early driver of NF1-associated tumour formation

Neurofibromatosis Type 1 (NF1) is a common tumour predisposition syndrome characterised by neurofibromas - Nf1-/- Schwann cell (SC)-derived tumours of peripheral nerves. We and others have shown that Nf1 loss in SCs is insufficient for neurofibroma formation but cooperates with an injury microenvironment to form tumours, but the mechanisms remained unknown. Here, we identify macrophage-secreted TGF-{beta} as the microenvironmental injury signal that is essential for tumourigenesis. Analysis of the earliest stages of neurofibroma formation showed that tumours arise from a population of Nf1-/- SCs that escape the regenerating nerve shortly after injury. Here, they reside in a distinct microenvironment conducive for tumourigenesis, where TGF-{beta} disrupts SC/axonal interactions and SC re-differentiation. Pharmacological inhibition of TGF-{beta} for a short therapeutic window during this early stage inhibited tumour formation, highlighting the potential to normalise Nf1-/- SCs and identifying TGF-{beta} as a potential therapeutic target to both treat and prevent neurofibroma formation.

cell biology↗

Tac1 Deficiency Reduces the Severity of Enteric Bacterial Infection

BackgroundInfection with enteric bacterial pathogens continues to cause significant morbidity and mortality throughout the world. These pathogens include enterohemorrhagic and enteropathogenic Escherichia coli, which transit the intestinal tract, efface microvilli, and attach firmly to intestinal epithelial cells predominantly in the colon. Investigation of these human-adapted pathogens has been greatly aided by mouse models of infection. The mouse-adapted attaching and effacing pathogen Citrobacter rodentium utilizes many similar mechanisms of pathogenesis, including the use of a type III secretion system, and virulence factors encoded in a locus of enterocyte effacement. Although this model has allowed for assessing the complexity of the host response, the complex interplay between the nervous and immune systems in response to infection remains incomplete. MethodsWe assessed the role of sensory neurotransmitters encoded by the Tac1 gene in the host response to C. rodentium. ResultsTac1-deficient mice had significantly reduced pathogen shedding and colonic bacterial burden, accompanied by decreased expression of inflammatory cytokines and chemokines. In accordance with reduced chemokine production, we observed reduced colonic recruitment of specific immune cell populations in Tac1-/- compared to WT mice. ConclusionsSensory neuropeptides regulate key aspects of enteric bacterial infection and may serve as unique targets in the treatment of enteric disease.

immunology↗

Cryptic and Ecologically Relevant Locomotor Activity Patterns in Lake Malawi Cichlids Revealed Through Computer Vision Pipeline

Cichlid fishes have long been a popular model for ecology and evolutionary biology. Not only do they exhibit nearly unparalleled taxonomic diversity, but their community structures are both complex and extremely dense. Niche partitioning along dietary axes has been credited in maintaining cichlid biodiversity in a broad sense; however, it is common for cichlid species with overlapping diets to co-exist, leading to the search for other mechanisms to explain the maintenance of cichlid biodiversity. Behavioral variation has the potential to lead to fine-scale (i.e., micro-) habitat partitioning, but analyzing complex animal behavior poses several challenges, including time, cost and reproducibility. Modern tools, such as Machine Learning (ML), ease the burden of behavioral analyses, and are increasingly used in the field. Here, we present the application of tools from a well-developed sub-field of ML, Computer Vision (CV), to extract locomotor behavioral data from four Lake Malawi cichlid species. Our dataset consisted of low-resolution (320x240), twenty-four-hour infrared videos of activity in 4 cichlid species. We first analyzed a pair of species with divergent behaviors, diets and habitats (i.e., Abactochromis labrosus versus Tropheops kumwera), representing a proof-of-concept comparison. Next we analyzed activity in two closely related species with broadly similar behaviors and overlapping diets and habitats (i.e., Maylandia sp. Daktari versus Maylandia faiaziberi). In both comparisons, our analysis involved the quantification of tank usage patterns and stop/rest activity. Not only did our data align with the known ecologies and behaviors of the species in our proof-of-concept comparison, but they revealed novel behavioral differences between all species, especially as related to variation in tank usage from day to night. Our approach provides a window into potential cryptic behavioral niche partitioning, as well as a foundation for future, high-throughput analyses to study the genetic basis and evolution of behavior.

animal behavior and cognition↗

Sleep rescues age-associated loss of glial engulfment

Neuronal injury due to trauma or neurodegeneration is a common feature of aging. The clearance of damaged neurons by glia is thought to be critical for maintenance of proper brain function. Sleep loss has been shown to inhibit the motility and function of glia that clear damaged axons while enhancement of sleep promotes clearance of damaged axons. Despite the potential role of glia in maintenance of brain function and protection against neurodegenerative disease, surprisingly little is known about how sleep loss impacts glial function in aged animals. Axotomy of the Drosophila antennae triggers Wallerian degeneration, where specialized olfactory ensheathing glia engulf damaged neurites. This glial response provides a robust model system to investigate the molecular basis for glial engulfment and neuron-glia communication. Glial engulfment is impaired in aged and sleep-deprived animals, raising the possibility that age-related sleep loss underlies deficits in glial function. To define the relationship between sleep- and age-dependent reductions in glial function, we restored sleep to aged animals and examined the effects on glial clearance of damaged axons. Both pharmacological and genetic induction of sleep restores clearance of damaged neurons in aged flies. Further analysis revealed that sleep restored post-injury induction of the engulfment protein Draper to aged flies, fortifying the notion that loss of sleep contributes to reduced glial-mediated debris clearance in aged animals. To identify age-related changes in the transcriptional response to neuronal injury, we used single-nucleus RNA-seq of the central brains from axotomized young and old flies. We identified broad transcriptional changes within the ensheathing glia of young flies, and the loss of transcriptional induction of autophagy-associated genes. We also identify age-dependent loss of transcriptional induction of 18 transcripts encoding for small and large ribosomal protein subunits following injury in old flies, suggesting dysregulation of ribosomal biogenesis contributes to loss of glial function. Together, these findings demonstrate a functional link between sleep loss, aging and Wallerian degeneration.

neuroscience↗

Postprandial sleep in short-sleeping Mexican cavefish

Interaction between sleep and feeding behaviors are critical for adaptive fitness. Diverse species suppress sleep when food is scarce to increase the time spent foraging. Post-prandial sleep, an increase in sleep time following a feeding event, has been documented in vertebrate and invertebrate animals. While interactions between sleep and feeding appear to be highly conserved, the evolution of postprandial sleep in response to changes in food availability remains poorly understood. Multiple populations of the Mexican cavefish, Astyanax mexicanus, have independently evolved sleep loss and increased food consumption compared to surface-dwelling fish of the same species, providing the opportunity to investigate the evolution of interactions between sleep and feeding. Here, we investigate effects of feeding on sleep in larval and adult surface fish, and two parallelly evolved cave populations of A. mexicanus. Larval surface and cave populations of A. mexicanus increase sleep immediately following a meal, providing the first evidence of postprandial sleep in a fish model. The amount of sleep was not correlated to meal size and occurred independently of feeding time. In contrast to larvae, postprandial sleep was not detected in adult surface or cavefish, that can survive for months without food. Together, these findings reveal that postprandial sleep is present in multiple short-sleeping populations of cavefish, suggesting sleep-feeding interactions are retained despite the evolution of sleep loss. These findings raise the possibility that postprandial sleep is critical for energy conservation and survival in larvae that are highly sensitive to food deprivation.

neuroscience↗

Mutations in the albinism gene oca2 alter vision-dependent prey capture behavior in the Mexican tetra

Understanding the phenotypic consequences of naturally occurring genetic changes, as well as their impact on fitness, is fundamental to understanding how organisms adapt to an environment. This is critical when genetic variants have pleiotropic effects, as determining how each phenotype impacted by a gene contributes to fitness is essential to understand how and why traits have evolved. A striking example of a pleiotropic gene contributing to trait evolution is the oca2 gene, coding mutations in which underlie albinism and reductions of sleep in the blind Mexican cavefish, Astyanax mexicanus. Here, we characterize the effects of mutations in the oca2 gene on larval prey capture. We find that when conspecific surface fish with engineered mutations in the oca2 allele are hunting, they use cave-like, wide angle strikes to capture prey. However, unlike cavefish or surface fish in the dark, which rely on lateral line mediated hunting, oca2 mutant surface fish use vision when striking at prey from wide angles. Finally, we find that while oca2 mutant surface fish do not outcompete pigmented surface siblings in the dark, pigmented fish outcompete albino fish in the light. This raises the possibility that albinism is detrimental to larval feeding in a surface-like lighted environment, but does not have negative consequences for fish in cave-like, dark environments. Together, these results demonstrate that oca2 plays a role in larval feeding behavior in A. mexicanus. Further, they expand our understanding of the pleiotropic phenotypic consequences of oca2 in cavefish evolution.

animal behavior and cognition↗

Elevated DNA Damage without signs of aging in the short-sleeping Mexican Cavefish

Dysregulation of sleep has widespread health consequences and represents an enormous health burden. Short-sleeping individuals are predisposed to the effects of neurodegeneration, suggesting a critical role for sleep in the maintenance of neuronal health. While the effects of sleep on cellular function are not completely understood, growing evidence has identified an association between sleep loss and DNA damage, raising the possibility that sleep facilitates efficient DNA repair. The Mexican tetra fish, Astyanax mexicanus provides a model to investigate the evolutionary basis for changes in sleep and the consequences of sleep loss. Multiple cave-adapted populations of these fish have evolved to sleep for substantially less time compared to surface populations of the same species without identifiable impacts on healthspan or longevity. To investigate whether the evolved sleep loss is associated with DNA damage and cellular stress, we compared the DNA Damage Response (DDR) and oxidative stress levels between A. mexicanus populations. We measured markers of chronic sleep loss and discovered elevated levels of the DNA damage marker {gamma}H2AX in the brain, and increased oxidative stress in the gut of cavefish, consistent with chronic sleep deprivation. Notably, we found that acute UV-induced DNA damage elicited an increase in sleep in surface fish but not in cavefish. On a transcriptional level, only the surface fish activated the photoreactivation repair pathway following UV damage. These findings suggest a reduction of the DDR in cavefish compared to surface fish that coincides with elevated DNA damage in cavefish. To examine DDR pathways at a cellular level, we created an embryonic fibroblast cell line from the two populations of A. mexicanus. We observed that both the DDR and DNA repair were diminished in the cavefish cells, corroborating the in vivo findings and suggesting that the acute response to DNA damage is lost in cavefish. To investigate the long-term impact of these changes, we compared the transcriptome in the brain and gut of aged surface fish and cavefish. Strikingly, many genes that are differentially expressed between young and old surface fish do not transcriptionally vary by age in cavefish. Taken together, these findings suggest that cavefish have developed resilience to sleep loss, despite possessing cellular hallmarks of chronic sleep deprivation.

neuroscience↗

Aging is associated with a modality-specific decline in taste

Deficits in chemosensory processing are associated with healthy aging, as well as numerous neurodegenerative disorders, including Alzheimers Disease (AD). In many cases, chemosensory deficits are harbingers of neurodegenerative disease, and understanding the mechanistic basis for these changes may provide insight into the fundamental dysfunction associated with aging and neurodegeneration. The fruit fly, Drosophila melanogaster, is a powerful model for studying chemosensation, aging, and aging-related pathologies, yet the effects of aging and neurodegeneration on chemosensation remain largely unexplored in this model, particularly with respect to taste. To determine whether the effects of aging on taste are conserved in flies, we compared the response of flies to different appetitive tastants. Aging impaired response to sugars, but not medium-chain fatty acids that are sensed by a shared population of neurons, revealing modality-specific deficits in taste. Selective expression of the human amyloid beta (A{beta}) 1-42 peptide bearing the Arctic mutation (E693E) associated with early onset AD in the neurons that sense sugars and fatty acids phenocopies the effects of aging, suggesting that the age-related decline in response is localized to gustatory neurons. Functional imaging of gustatory axon terminals revealed reduced response to sugar, but not fatty acids. Axonal innervation of the fly taste center was largely intact in aged flies, suggesting that reduced sucrose response does not derive from neurodegeneration. Conversely, expression of the amyloid peptide in sweet-sensing taste neurons resulted in reduced innervation of the primary fly taste center. A comparison of transcript expression within the sugar-sensing taste neurons revealed age-related changes in 66 genes, including a reduction in odorant-binding protein class genes that are also expressed in taste sensilla. Together, these findings suggest that deficits in taste detection may result from signaling pathway-specific changes, while different mechanisms underly taste deficits in aged and AD model flies. Overall, this work provides a model to examine cellular deficits in neural function associated with aging and AD.

neuroscience↗

Integrated spatial protein and RNA analysis on the same section using MICS technology

Spatial Biology has evolved from the molecular characterization of microdissected cells to high throughput spatial RNA and protein expression analysis at scale. The main limitation of spatial technologies so far is the inability to resolve protein and RNA information in the same histological section. Here, we report for the first time the integration of highly multiplexed RNA and protein detection on the same tissue section. We developed a new, automated, spatial RNA detection method (RNAsky), which is based on targeted rolling circle amplification and iterative staining. We combine RNAsky with MACSima Imaging Cyclic Staining (MICS) based protein analysis and show compatibility with subsequent standard hematoxylin and eosin (H&E) staining. Using both, open-source tools and our recently developed software suite MACS(R) iQ View, we demonstrate our multiomics MICS workflow by characterizing key immune-oncology markers at subcellular resolution across normal and diseased tissues.

molecular biology↗

Ontogeny and social context regulate the circadian activity patterns of Lake Malawi cichlids

Activity patterns tend to be highly stereotyped and critical for executing many different behaviors including foraging, social interactions and predator avoidance. Differences in the circadian timing of locomotor activity and rest periods can facilitate habitat partitioning and the exploitation of novel niches. As a consequence, closely related species often display highly divergent activity patterns, raising the possibility that a shift from diurnal to nocturnal behavior, or vice versa, can occur rapidly. In Africas Lake Malawi alone, there are over 500 species of cichlids, which inhabit diverse environments and exhibit extensive phenotypic variation. We have previously identified a substantial range in activity patterns across adult Lake Malawi cichlid species, from strongly diurnal to strongly nocturnal. In many species, including fishes, ecological pressures differ dramatically across life-history stages, raising the possibility that activity patterns may change over ontogeny. To determine if rest-activity patterns change across life stages we compared the locomotor patterns of six Lake Malawi cichlid species. While total rest and activity did not change between early juvenile and adult stages, rest-activity patterns did, with juveniles displaying distinct activity rhythms that are more robust than adults. One distinct difference between juveniles and adults is the emergence of complex social behavior. To determine whether social context is required for activity rhythms, we next measured locomotor behavior in group housed adult fish. We found that when normal social interactions were allowed, locomotor activity patterns were restored, supporting the notion that social interactions promote circadian regulation of activity in adult fish. These findings reveal a previously unidentified link between developmental stage and social interactions in the circadian timing of cichlid activity.

evolutionary biology↗

Neurofibromin 1 mediates sleep depth in Drosophila

Neural regulation of sleep and metabolic homeostasis are critical in many aspects of human health. Despite extensive epidemiological evidence linking sleep dysregulation with obesity, diabetes, and metabolic syndrome, little is known about the neural and molecular basis for the integration of sleep and metabolic function. The RAS GTPase-activating gene Neurofibromin (Nf1) has been implicated in the regulation of sleep and metabolic rate, raising the possibility that it serves to integrate these processes, but the effects on sleep consolidation and physiology remain poorly understood. A key hallmark of sleep depth in mammals and flies is a reduction in metabolic rate during sleep. Here, we use indirect calorimetry to define the role of Nf1 on sleep-dependent changes in metabolic rate. Flies lacking Nf1 fail to suppress metabolic rate during sleep, raising the possibility that loss of Nf1 prevents flies from integrating sleep and metabolic state. Sleep of Nf1 mutant flies is fragmented with a reduced arousal threshold in Nf1 mutants, suggesting Nf1 flies fail to enter deep sleep. The effects of Nf1 on sleep can be localized to a subset of neurons expressing the GABA receptor Rdl. Selective knockdown of Nf1 in Rdl-expressing neurons increases gut permeability and reactive oxygen species (ROS) in the gut, suggesting a critical role for deep sleep in gut homeostasis. Together, these findings suggest Nf1 acts in GABA-sensitive neurons to modulate sleep depth in Drosophila.

neuroscience↗

A brain-wide analysis maps structural evolution to distinct anatomical modules

Brain anatomy is highly variable and it is widely accepted that anatomical variation impacts brain function and ultimately behavior. The structural complexity of the brain, including differences in volume and shape, presents an enormous barrier to define how variability underlies differences in function. In this study, we sought to investigate the evolution of brain anatomy in relation to brain region volume and shape across the brain of a single species with variable genetic and anatomical morphs. We generated a high-resolution brain atlas for the blind Mexican cavefish and coupled the atlas with automated computational tools to directly assess brain region shape and volume variability across all populations. We measured the volume and shape of every neuroanatomical region of the brain and assess correlations between anatomical regions in surface, cavefish and surface to cave F2 hybrids, whose phenotypes span the range of surface to cave. We find that dorsal regions of the brain are contracted in cavefish, while ventral regions have expanded. Interestingly, in hybrid fish the volume and shape of dorsal regions are inversely proportional to ventral regions. This trend is true for both volume and shape, suggesting that these two parameters share developmental mechanisms necessary for remodeling the entire brain. Given the high conservation of brain anatomy and function among vertebrate species, we expect these data to studies reveal generalized principles of brain evolution and show that Astyanax provides a system for functionally determining basic principles of brain evolution by utilizing the independent genetic diversity of different morphs, to test how genes influence early patterning events to drive brain-wide anatomical evolution.

neuroscience↗

Characterizing the genetic basis of trait evolution in the Mexican cavefish

Evolution in response to a change in ecology often coincides with various morphological, physiological, and behavioral traits. For most organisms little is known about the genetic and functional relationship between evolutionarily derived traits, representing a critical gap in our understanding of adaptation The Mexican tetra, Astyanax mexicanus, consists of largely independent populations of fish that inhabit at least 30 caves in Northeast Mexico, and a surface fish population, that inhabits the rivers of Mexico and Southern Texas. The recent application of molecular genetic approaches combined with behavioral phenotyping have established A. mexicanus as a model for studying the evolution of complex traits. Cave populations of A. mexicanus are interfertile with surface populations and have evolved numerous traits including eye degeneration, insomnia, albinism and enhanced mechanosensory function. The interfertility of different populations from the same species provides a unique opportunity to define the genetic relationship between evolved traits and assess the co-evolution of behavioral and morphological traits with one another. To define the relationships between morphological and behavioral traits, we developed a pipeline to test individual fish for multiple traits. This pipeline confirmed differences in locomotor activity, prey capture, and startle reflex between surface and cavefish populations. To measure the relationship between traits, individual F2 hybrid fish were characterized for locomotor behavior, prey-capture behavior, startle reflex and morphological attributes. Analysis revealed an association between body length and slower escape reflex, suggesting a trade-off between increased size and predator avoidance in cavefish. Overall, there were few associations between individual behavioral traits, or behavioral and morphological traits, suggesting independent genetic changes underlie the evolution of behavioral and morphological traits. Taken together, this approach provides a novel system to identify genes that underlie naturally occurring genetic variation in morphological and behavioral traits.

evolutionary biology↗

Blind cavefish retain functional connectivity in the tectum despite loss of retinal input

Sensory systems display remarkable plasticity and are under strong evolutionary selection. The Mexican cavefish, Astyanax mexicanus, consists of eyed river-dwelling surface populations, and multiple independent cave populations which have converged on eye loss, providing the opportunity to examine the evolution of sensory circuits in response to environmental perturbation. Functional analysis across multiple transgenic populations expressing GCaMP6s showed that functional connectivity of the optic tectum largely did not differ between populations, except for the selective loss of negatively correlated activity within the cavefish tectum, suggesting positively correlated neural activity is resistant to an evolved loss of input from the retina. Further, analysis of surface-cave hybrid fish reveals that changes in the tectum are genetically distinct from those encoding eye-loss. Together, these findings uncover the independent evolution of multiple components of the visual system and establish the use of functional imaging in A. mexicanus to study neural circuit evolution.

neuroscience↗