Evolution of visual circuits: Astyanax provides a unique system to compare ancestral and derived neural circuits.

Both cave and surface forms are born with eyes and lenses. In the cavefish however, the lens undergoes programmed cell death, leading to the retina to degenerate and the eye to sink into the orbit. Lens and transplantation experiments during development have established the central role of the lens in eye degeneration. When a surface fish lens vesicle is transplanted into a cavefish optic cup, eye development is restored. I have shown that restoring the eye has direct consequences for the rest of the brain circuitry, from the midbrain structures in the optic tectum, to Mauthner cells in the hindbrain involved in escape behavior. Thus, when rescuing one eye in a cavefish we have the ancestral and derived visual systems side by side for comparison. I will continue to use this unique system and to determine the mechanisms in which an ancestral circuit develops to became a derived one. Furthermore, once I determine the changes in circuitry in Astyanax, I will be able to compare them to amblyopsids, which cavefish lineage is much older than Astyanax.

Evolution of sensory novelty

 The discovery of a novelty is one of the most rewarding aspects in Biology. As a graduate student I described a novel mechanosensory organ that detects water ripples in the American Alligator. Recently I have described how teeth located on the dorsal skin of the cavefish Astroblepus phoeleter act as hydrodynamic image sensors (Figure 3). Only by paying attention to the ecology of the animal of study in order to determine the context for the evolution I am have been able to describe novel sensory organs. Sensory adaptation to extreme environments comes in many forms, from evolution of specialized sensory organs, to shifts in modality preferences. In these studies I will test two main hypotheses: 1) Only species that have a developed non-visual sensory repertoire could thrive in caves. Hence, closely related cave and surface species share high sensitivity and similar sensory structures due to preadaptation. 2) Cavefishes are more sensitive and have structures that are not evident in the closest surface relatives due to cave adaptation. Other possible outcomes are a combination or a mixture of these two evolutionary mechanisms and I want to understand where cavefish evolution lies in this continuum. My laboratory continues to take physical measurements of the environment and uses animal tracking to examine the interaction between organism and its ecosystem. Environmental data, combined with ecological approaches, will guide our future studies of sensory structures, neural system function, and behaviors to understand the sensory capabilities of animals within the range of environmental conditions they experience. We have already shown how the soundscape of caves in the United States has molded the hearing characteristics of amblyopsids.

Evolution of feeding behavior

We observed that under laboratory conditions Astyanax cavefish typically have more fat tissue than their surface form. I used a cDNA microarray to show that there are intrinsic differences of gene expression in the brains of the cavefish and surface forms. Among several differentially expressed genes, cave Astyanax expresses the endocannabinoid receptor CB1 in a larger amount. CB1 receptors are part of the endocannabinoid system that, among other roles, controls various aspects of food intake and addiction. One of the effects of endocannabinoids in the brain occurs via a dopaminergic pathway to enhance food intake. Changes in cannabinoids levels have been shown to underlie obesity in rats and humans. The selection for upregulation of this neuromodulator pathway in an extreme environment is not surprising, given role of endocannabinoids in stress and feeding. My laboratory has demonstrated that the increased fat content in cavefish is due to behavioral and not to physiological changes. Our current hypothesis is that cavefishes are driven to excessive feeding via the neuronal pathway involved in addiction in humans. I will continue this study by determining the molecular basis for satiation and cellular and anatomical differences in circuits involved in feeding and addiction.