Biology subjects

Duboue, E. R.

Publications and source records attributed to Duboue, E. R..

23 records · Page 2Linked to original sources

bioRxiv2019

Cavefish brain atlases reveal functional and anatomical convergence across independently evolved populations

Environmental perturbation can drive the evolution of behavior and associated changes in brain structure and function. The generation of computationally-derived whole-brain atlases have provided insight into neural connectivity associated with behavior in many model systems. However, these approaches have not been used to study the evolution of brain structure in vertebrates. The Mexican tetra, A. mexicanus, comprises river-dwelling surface fish and multiple independently evolved populations of blind cavefish, providing a unique opportunity to identify neuroanatomical and functional differences associated with behavioral evolution. We employed intact brain imaging and image registration on 684 larval fish to generate neuroanatomical atlases of surface fish and three different cave populations. Analyses of brain regions and neural circuits associated with behavioral regulation identified convergence on hypothalamic expansion, as well as changes in transmitter systems including elevated numbers of catecholamine and hypocretin neurons in cavefish populations. To define evolutionarily-derived changes in brain function, we performed whole brain activity mapping associated with feeding and sleep. Feeding evoked neural activity in different sensory processing centers in surface and cavefish. We also identified multiple brain regions with sleep-associated activity across all four populations, including the rostral zone of the hypothalamus and tegmentum. Together, these atlases represent the first comparative brain-wide study of intraspecies variation in a vertebrate model, and provide a resource for studying the neural basis underlying behavioral evolution.

neuroscience↗

bioRxiv2019

Evolution of the acoustic startle response of Mexican cavefish

The ability to detect threatening sensory stimuli and initiate an escape response is essential for survival and under stringent evolutionary pressure. In diverse fish species, acoustic stimuli activate Mauthner neurons, which initiate a stereotypical C-start escape response. This reflexive behavior is highly conserved across aquatic species and provides a model for investigating the neural mechanism underlying the evolution of escape behavior. Here, we define evolved differences in the C-start response between populations of the Mexican cavefish, Astyanax mexicanus. Cave populations of A. mexicanus inhabit in an environment devoid of light and macroscopic predation, resulting in evolved differences in diverse morphological and behavioral traits. We find that the C-start is present in multiple populations of cavefish and river-dwelling surface fish, but response kinematics and probability differ between populations. The Pachon population of cavefish have an increased response probability, a slower response and reduction of the maximum bend angle, revealing evolved differences between surface and cave populations. In two other independently evolved populations of cavefish, the response probability and the kinematics of the response differ from one another, as well as from surface fish, suggesting the independent evolution of differences in the C-start response. Investigation of surface-cave hybrids reveals a relationship between angular speed and peak angle, suggesting these two kinematic characteristics are related at the genetic or functional levels. Together, these findings provide support for the use of A. mexicanus as a model to investigate the evolution of escape behavior.

neuroscience↗

bioRxiv2019

An adult brain atlas reveals broad neuroanatomical changes in independently evolved populations of Mexican cavefish

A shift in environmental conditions impacts the evolution of complex developmental and behavioral traits. The Mexican cavefish, Astyanax mexicanus, is a powerful model for examining the evolution of development, physiology, and behavior because multiple cavefish populations can be compared to an extant and ancestral-like surface population of the same species. Many behaviors have diverged in cave populations of A. mexicanus, and previous studies have shown that cavefish have a loss of sleep, reduced stress, an absence of social behaviors, and hyperphagia. Despite these findings, surprisingly little is known about the changes in neuroanatomy that underlie these behavioral phenotypes. Here, we use serial sectioning to generate a brain atlas of surface fish and three independent cavefish populations. Volumetric reconstruction of serial-sectioned brains confirms convergent evolution on reduced optic tectum volume in all cavefish populations tested. In addition, we quantified volumes of specific neuroanatomical loci within several brain regions, which have previously been implicated in behavioral regulation, including the hypothalamus, thalamus, and habenula. These analyses reveal an expansion of the hypothalamus across all three cavefish populations relative to surface fish, as well as subnuclei-specific differences within the thalamus and habenulae. Taken together, these analyses support the notion that changes in environmental conditions are accompanied by neuroanatomical changes in brain structures associated with behavior. This atlas provides a resource for comparative neuroanatomy of additional brain regions and the opportunity to associate brain anatomy with evolved changes in behavior.

neuroscience↗

bioRxiv2019

Stable transgenesis in Astyanax mexicanus using the Tol2 transposase system.

Astyanax mexicanus is a well-established and widely used fish model system for evolutionary and developmental biology research. These fish exist as surface forms that inhabit rivers and 30 different populations of cavefish. The establishment of A. mexicanus as an emergent model organism for understanding the evolutionary basis of development and behavior has been accelerated by an increasing availability of genomic approaches to identify genotype-phenotype associations. Despite important progress in the deployment of new technologies, deep mechanistic insights into A. mexicanus evolution and development have been limited by a lack of transgenic lines commonly used in genetic model systems. Here, we expand the toolkit of transgenesis by characterizing two novel stable transgenic lines that were generated using the highly efficient Tol2 system, commonly used to generate transgenic zebrafish. A stable transgenic line consisting of the zebrafish ubiquitin promoter fused to eGFP expressed eGFP ubiquitously throughout development in a surface population of Astyanax. To define specific cell-types, we injected fish with a Cntnap2-mCherry construct that labels lateral line mechanosensory neurons in zebrafish. Strikingly, both constructs appear to label the predicted cell types, suggesting many genetic tools and defined promoter regions in zebrafish are directly transferrable to cavefish. The lines provide proof-of-principle for the application of Tol2 transgenic technology in A. mexicanus. Expansion on these initial transgenic lines will provide a platform to address broadly important problems in the quest to bridge the genotype to phenotype gap.

developmental biology↗

bioRxiv2017

Hypocretin underlies the evolution of sleep loss in the Mexican cavefish

The duration of sleep varies dramatically between species, yet little is known about genetic bases or evolutionary factors driving this variation in behavior. The Mexican cavefish, Astyanax mexicanus, exists as surface populations that inhabit rivers, and multiple independently derived cave populations with convergent evolution on sleep loss. The number of Hypocretin/Orexin (HCRT)-positive hypothalamic neurons is increased significantly in cavefish, and HCRT is upregulated at both the transcript and protein levels. Pharmacological or genetic inhibition of HCRT signaling increases sleep duration in cavefish without affecting sleep in surface fish, suggesting enhanced HCRT signaling underlies sleep loss in cavefish. Ablation of the lateral line or starvation, manipulations that selectively promote sleep in cavefish, inhibit hcrt expression in cavefish while having little effect in surface fish. These findings provide the first evidence of genetic and neuronal changes that contribute to the evolution of sleep loss, and support a conserved role for HCRT in sleep regulation.

genomics↗