Viral Tools Enable First Detailed Study of Amphibian Neural Circuits

Scientists at the Institute of Science and Technology Austria (ISTA) have made a breakthrough in amphibian neurobiology. By using adeno-associated viruses (AAVs), the research provides new insights into the nervous system of amphibians, particularly frogs, throughout their development. The findings, recently published in Developmental Cell, hold promise for comparative studies of nervous system development across species.

Viral tools in basic research

AAVs are non-pathogenic viruses often used in basic neuroscience research to trace and visualize neuronal circuits. By genetically modifying these viruses, scientists can introduce fluorescent markers that illuminate nerve cells, revealing how neurons are connected. While this technique has been widely applied in mammals such as mice, applying it to amphibians was considered a significant challenge – until now.

Researchers have successfully optimized AAVs for amphibians, allowing detailed tracking of neural development during the metamorphic transition from tadpole to adult frog. This method enables scientists to explore how nervous systems adapt as locomotion changes from swimming to walking.

Neural circuits: connecting neurons like electrical systems

The nervous system is often compared to an electrical circuit, where neurons transmit signals via connections known as synapses. Using AAVs, scientists can map these pathways in amphibians, revealing how circuits are established and modified during development. By labeling neurons, researchers can visualize the direction of signal transmission, either from synapse to cell body (retrograde) or from cell body to synapse (anterograde).

This is particularly important in understanding changes in the nervous system as amphibians undergo metamorphosis. For instance, tadpoles rely on swimming as their primary mode of movement, while adult frogs develop limb-based locomotion. These behavioral transitions are mirrored by significant changes in neural connectivity.

Collaborative efforts and technical advancements

This achievement was made possible through an international consortium involving institutions such as Columbia University, Tel Aviv University and the University of Utah. The team adapted AAVs to infect amphibian cells effectively, creating a step-by-step guide for applying these tools across different developmental stages. Starting with young tadpoles, the approach was refined for adult frogs and even newts. The collaboration highlights the importance of shared expertise in advancing research in less-studied organisms.

Implications for understanding human neurobiology

Although humans and amphibians last shared a common ancestor approximately 360 million years ago, comparative studies can shed light on the evolution of the nervous system. By examining the frog nervous system, researchers can identify traits shared with mammals and those that are unique.

The newly developed technique also offers a way to study neuronal progenitor cells – cells that develop into neurons – and their role in constructing neural circuits. This knowledge could provide foundational insights into how nervous systems adapt and evolve, offering broader implications for understanding and treating diseases or injuries in humans.

Reference: Jaeger ECB, Vijatovic D, Deryckere A, et al. Adeno-associated viral tools to trace neural development and connectivity across amphibians. Developmental Cell. doi: 10.1016/j.devcel.2024.10.025

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