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

Abstract

Environmental perturbation can drive behavioral evolution and associated changes in brain structure and function. The Mexican fish species, Astyanax mexicanus, includes eyed river-dwelling surface populations and multiple independently evolved populations of blind cavefish. We used whole-brain imaging and neuronal mapping of 684 larval fish to generate neuroanatomical atlases of surface fish and three different cave populations. Analyses of brain region volume and neural circuits associated with cavefish behavior identified evolutionary convergence in hindbrain and hypothalamic expansion, and changes in neurotransmitter systems, including increased numbers of catecholamine and hypocretin/orexin neurons. To define evolutionary changes in brain function, we performed whole-brain activity mapping associated with behavior. Hunting behavior evoked activity in sensory processing centers, while sleep-associated activity differed in the rostral zone of the hypothalamus and tegmentum. These atlases represent a comparative brain-wide study of intraspecies variation in vertebrates and provide a resource for studying the neural basis of behavioral evolution.

Unique transcriptional signatures of sleep loss across independently evolved cavefish populations

“…We have previously shown that treatment of cavefish with the beta‐adrenergic inhibitor propranolol restores sleep to cavefish, suggesting a critical role for enhanced norepinephrine signaling in cavefish (Duboué et al, 2012; J. Jaggard, Lloyd, Yuiska, et al, 2019). Our findings show some components of β‐adrenergic signaling are differentially expressed but the overall links to this pathway are not conclusive.…”

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

“…To study changes in the function of the optic tectum in A. mexicanus, we generated surface and cave populations harboring the genetically encoded Ca 2+ indicator (GCaMP6s) of the pan-neuronal promoter elavl3/HuC (37). The surface and Molino populations have previously been described (6); here, we also utilizea HuC:GCaMP6s Pachón line, allowing for direct comparison of brain function in independently evolved cavefish populations. Fish from the surface, Pachón, and Molino populations expressed the reporter as early as 1.5 dpf through 8.5 dpf (Fig 1B…”

“…In sighted species, visual processing within the tectum is essential for generating appropriate visuomotor behaviors including prey capture and predator avoidance (21)(22)(23). In comparison to surface fish, the size of the tectum is reduced in cavefish from multiple populations, revealing co-evolution of reduced inputs of the retina and its target centers within the brain (6). Recently, we generated a quantitative neuroanatomical atlas of surface fish and multiple cavefish populations that revealed that despite eye loss, the optic tectum is only reduced by ~20% across populations, raising the possibility that this brain region has been repurposed for functions other than vision (6,24).…”

“…Adaptation to novel environments often results in modifications of sensory processing governing vital behaviors, including foraging and avoidance of predation (3,4). The reliance on different sensory cues has been widely documented to be accompanied by changes in the anatomy of the primary sense organ, such as a tradeoff between expansion of the eye or olfactory epithelium, or changes in cortical area devoted to processing sensory information (5)(6)(7)(8)(9). However, little is known about the evolution of neural circuitry in downstream sensory processing centers.…”

The Digital 3D-Atlas MAKER (DAMAKER): a dynamic and expandable digital 3D-tool for monitoring the temporal changes in tissue growth during hindbrain morphogenesis

“…Thus, one of the main unsolved questions is how gene expression and morphogenesis are coordinated (that is, the generation and maintenance of multiple cell types, in highly organized spatial patterns during brain embryonic development). Existing gene expression and marker atlases in fish provide valuable tools (Chow et al, 2020; Jaggard et al, 2020; Ronneberger et al, 2012; Tabor et al, 2019), but they typically have some limitations in addressing the question of spatiotemporal coordination, including: i) they are based on images from fixed samples acquired at late developmental stages and aligned through non-rigid registration, which is suboptimal for morphogenesis studies; ii) they use filters and are unable to quantify patterns, partially due to the lack of a standardized quantification method; iii) accessing the data is difficult; iv) user-upgrades are difficult, as data usually need to be sent to the atlas-makers for processing; v) atlases are usually hosted on individual platforms, making access to the data challenging; and vi) they lack 3D quantifications. Here, we developed a new “atlas-builder” pipeline that overcomes most of these limitations and can be used to create an expandable atlas of any tissue in any organism.…”