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The Evolution and Function of Ancestral Brain States

Periodic Reporting for period 2 - reptiCode (The Evolution and Function of Ancestral Brain States)

Reporting period: 2022-08-01 to 2024-01-31

Our brain exhibits dramatic transitions in activity patterns. These transitions, or brain states, are observed during wakefulness but, strikingly, are even more prominent during sleep, when interaction with the environment is limited. To date, the function of these state transitions remains elusive.
The ReptiCode project is motivated by the understanding that our brains are not a product of careful design but rather of a long series of random modifications shaped by evolution. Thus, to understand fundamental properties of neuronal system, we must understand their evolutionary story. Further, evolution produces highly complex biological systems with large variations between multiple components. To understand the general principles underlying function we need a methodology to separate between details that are fundamental to those that are species specific. Comparative studies between animals provide the tools to achieve this. Finally, the diversity of species gives us a rich repertoire of manifestations for different biological phenomena. From those we can identify valuable animal models in which the biological question is more simply manifested or easier to study. The considerations above led us to focus our study on the brain of reptiles.
Our aim is to utilize the simpler and highly structured organization of brain states in the lizard Pogona Vitticeps, to expose the full repertoire of brain states in a naturally behaving animal. We will take advantage of the limited diversity of motor movements in Pogona, to expose the link between brain activity and behavior. Reptiles are located in a unique position in the evolutionary tree. This position allows us to understand the common vertebrate ancestor of all mammals, reptiles, and birds – the first vertebrates that became fully terrestrial and “solved” the challenges of life on land. We will therefore exploit this unique evolutionary position to reveal the forces that pushed the emergence of brain states during evolution. Finally, through a comparative analysis of brain state properties between different reptiles and mammals we will extract the fundamental properties and functions of brain states and the brain network that supports them.
Since the beginning of the project, we were able to establish a flourishing and collaborative research group aimed at addressing our research goals. We have also built the unique infrastructure and experimental setups required for the completion of this project. Finally, we've devised innovative methodologies that have yielded novel findings.
Reptiles are non-conventional model systems in neuroscience. Studying them holds great potential but this potential comes at the expense of lack of existing methodologies. Many of the scientific tools we needed to employ were never used in reptiles. We therefore established a set of new approaches and tools that dramatically improve our ability to study reptiles. We developed new approaches that allow us to measure the activity patterns in the brains of awake and sleeping reptiles with unprecedented detail. We also constructed a new set of automated behavioral approaches that allow us to substantially increase reptile engagement in behavioral tasks and to systematically study their cognition, and link it to brain patterns. In addition to the contribution of these tools to our project, they will provide a platform for studying many other questions in reptile (and other cold blood animal) behavior and brain function.
The project has already advanced the state of the art by providing a new set of experimental tools for studying cold blooded animals. In addition, we were able to make the following discoveries:
1. We found clear and simply organized brains states in a set of lizards. These results considerably improve our understanding of the evolution of sleep.
2. Brain states in reptiles are persistent across a wide range of temperatures. Such persistence is not trivial, and it does not exist in mammals in which brain state is dramatically perturbed following small temperature changes. This highlights the importance of these states for reptiles that possess mechanisms to sustain them across temperatures.
3. During the development of our behavioral tasks, we found that reptiles can learn complex models of their prey’s movement. We hypothesize that these models may reside in the brain areas from which we record state changes. Finding this will open the door to shedding light on brain state function.