About
Painting by Ke Tan
Mission Statement
The Center for Neuroethology & Physiological Plasticity harnesses the extraordinary adaptations of specialized, non-traditional vertebrate organisms to uncover fundamental biological principles driving the plasticity and resilience of neurophysiological, metabolic, sensory, and reproductive systems—principles with relevance to human health, aging, and therapeutic innovation that would remain hidden in conventional laboratory models.
Core Approach
The center employs a comparative strategy that capitalizes on non-traditional model species from diverse vertebrate clades displaying robust and trackable adaptations to environmental, ecological, and pathophysiological challenges and integrates theoretical modeling to accelerate the discovery of broadly applicable biological mechanisms.
A deep understanding of the basic biological principles governing organismal functions is essential for developing innovative therapies. Yet the overwhelming focus of biomedical research on a handful of conventional model organisms delays the discovery of general unifying principles and slows progress against complex human disorders.
This center is a pioneering initiative that combines experimentation, tool development, and theoretical modeling to decipher the fundamentals of biological processes through the lens of naturalistic, ecologically relevant animal models. The center addresses major barriers in the field:
- Overreliance on a small number of model organisms
- Limited tools for non-traditional models
- A persistent disconnect between experimental and theoretical research
By strategically expanding the toolkit of model vertebrates, the center complements rather than replaces existing model-organism research, delivering a new perspective that can be rapidly translated into new therapeutic strategies.
The center builds a comparative neurophysiological program using non-standard model species from different clades with robust, trackable adaptations, including:
- Mammalian hibernators and aestivators — species with highly plastic metabolic, neurophysiological and reproductive functions that enable survival dunder extreme conditions of prolonged hypothermia, fasting and dehydration.
- Diverse bird lineages with specialized behavioral, cognitive, and sensory systems.
- Amphibians exhibiting remarkable ecological and evolutionary physiological plasticity.
- Specialized fish lineages with unique metabolic and sensory adaptations
The center leverages molecular, cellular, and circuitry adaptations to external and internal challenges and synergizes experimental data with information theory to build theoretical models connecting species’ adaptive capacity with interoceptive and exteroceptive states.
The core mission of the center is enabled through integration of Research, Tool Development, and Theoretical Modeling efforts. The center operates as a cross-disciplinary hub within Yale’s research ecosystem, fostering collaboration and serving as a national and international magnet for researchers working on non-standard animal models.
Research directions:
- Neurophysiological reprogramming. Elucidate molecular and neurophysiological adaptations countering environmental and pathophysiological challenges, including food scarcity, changes in nutrient sources, temperature fluctuations, tissue damage, repair, and regeneration.
- Sensory plasticity. Discover the molecular, cellular, and circuit pathways that underlie the adaptability of sensory systems; investigate the mechanisms of interoceptive and exteroceptive sensory receptor functions.
- Reproductive phenology. Understand the mechanisms of heritable traits that balance the constraints of environmental stressors, seasonal timing, food availability, and temperature to achieve optimal reproductive strategy.
- Theoretical modeling. Synergize experimental data with information theory to build theoretical models that link behavioral demands to neurophysiological reprogramming, sensory plasticity, and reproductive strategies and generate testable hypotheses with potential applications in regenerative medicine, neuromodulation, and adaptive therapeutics.
The center houses a dedicated program to create and disseminate gene-editing, viral-delivery, and imaging technologies to foster the adoption of non-standard vertebrate models for mainstream research.
- Viral vectors and cell type–specific promoters
- RNA multiome sequencing that builds functional/genetic pipelines across species
- Comprehensive brain atlases and experimental pipelines
- Shareable resources: organ atlases, transcriptomes, genomes/proteomes, circuitry maps, and baseline physiological measurements
By integrating empirical efforts with theoretical modeling, center outcomes support improved prediction of organismal resilience and inform targeted pharmacology related to:
- Sensory disorders – new therapies for chronic pain, touch and proprioceptive deficits, including age-related sensory decline, inspired by adaptive mechanisms in sensory champion species.
- Metabolic disorders – treatments for obesity, anorexia, cachexia, and related diseases based on reverse engineering of metabolic strategies from hibernators and aestivators.
- Reproductive disorders – improved intervention for infertility and environmentally sensitive reproductive function, drawing on the phenological plasticity of seasonal breeders.
A flagship of the center’s portfolio is the discovery of fundamental principles underlying hibernation. By understanding the molecular, cellular and neural mechanisms that enable torpor, the center aims to foster the development of approach that could:
- Extend safe surgical windows and organ preservation times.
- Induce the state of “suspended animation” for emergency medicine.
- Enable new strategies to induce hibernation in humans to foster extended space exploration.