EVOLUTION OF CELL TYPES AND NEURONAL DIVERSITY
Neurons are the building blocks of the brain and also units of brain evolution.
We study the evolution of neuron types in vertebrate brains, focusing on the forebrain – a region involved in complex behaviors.
In the forebrain, the anatomy of the dorsal telencephalon or pallium is remarkably diverse across vertebrate species; examples are the six-layered neocortex in mammals and nuclear structures in non-mammals. The evolutionary relationships of these brain regions have been debated for decades. Recently, the advent of high-throughput single-cell RNA sequencing has enabled, for the first time, the systematic molecular comparison of neuron types across species. Using this approach, we have compared excitatory and inhibitory neurons in the mammalian cortex and equivalent brain regions in reptiles and amphibians. Our work demonstrated that these brain regions include ancient neuron types and new types of neurons that diversified independently in each vertebrate lineage.
How does this extreme neuronal diversity evolve? Neurons are specified during development by complex developmental programs. We are currently exploring how the evolution of these developmental programs produced vastly different sets of neuron types in the forebrains of various vertebrate species.
EVOLUTION OF NEURAL CIRCUITS
Do ancient neuron types belong to conserved circuit motifs with conserved functions? And do new types of neurons assemble into new circuits that take on new functions?
We are interested in linking the molecular and functional evolution of neuron types to gain new insights into the evolutionary forces that favor the emergence of neuronal diversity and learn how neural circuits evolve.
For these projects, we are taking advantage of the simplicity, experimental amenability, and interesting phylogenetic position of a salamander, the Iberian ribbed newt Pleurodeles waltl. We have optimized using adeno-associated viruses (AAVs) in Pleurodeles to label neurons and manipulate their activity, enabling circuit-level investigations. With large-scale imaging techniques coupled with behavioral paradigms, we study how circuits evolved in the vertebrate brain to support fundamental behavioral and physiological needs.
MECHANISMS OF BRAIN REGENERATION
Salamanders have the remarkable ability to regrow entire limbs, the heart, ocular tissue, and substantial parts of their nervous system — including the brain. What enables these marvelous regenerative abilities remains mysterious. Even more mysterious is how regeneration has evolved: why we cannot repair our brains?
We use immunohistochemistry, hybridization chain reaction (HCR), single-cell RNAseq, and clonal labeling to analyze neurogenesis in the presence and absence of a brain injury. By studying salamander neural stem cells' molecular and cellular properties within an evolutionary framework, we aim to learn about the evolution of regeneration mechanisms.
PLASTICITY ACROSS ENVIRONMENTS
Newts like Pleurodeles waltl are semiaquatic animals — the pools they inhabit dry up seasonally, forcing them to go on land. Such a change poses great challenges for the nervous system, as sound, light, and odor all travel differently in water and air.
With behavioral paradigms and molecular approaches, we are investigating how Pleurodeles change their body morphology, brain, and behavior in response to changing environmental conditions.
Pleurodeles succeed in two very different environments during their lifetime, and with such a capacity for plasticity, they provide a unique outlook into the circuits and molecular mechanisms of neuroplasticity.
