Mesh electronics for understanding space encoding in the amphibian brain

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PROJECT SUMMARY/ABSTRACT Many animals rely on spatial cognition for daily survival in order to recognize familiar places and process movements through or between locations. A variety of space-encoding cells in the hippocampus are important for spatial behaviors in mammals. However, neural encoding of space remains uncharacterized in other vertebrate taxa, including amphibians, whose simpler brain structure suggests alternative mechanisms of encoding space. The severe gap in our understanding of how the simple amphibian brain functions stems, in part, from difficulty in recording neural activity. The amphibian brain exhibits a greater degree of movement within the skull than other vertebrates, which could lead to an instability of electrophysiology recordings in moving animals using conventional implantable neural probes. Recently our labs have developed 1) a new form of electronics with tissue-like flexibility and stretchability for chronically stable neural recording with single-neuron resolution, and 2) cane toads as a model to study the neural basis of amphibian spatial behaviors. We propose to develop stretchable mesh electronic neural probes for in vivo electrophysiological recording of single neurons in the medial pallium, the proposed homolog of the mammalian hippocampus, in freely moving toads. We hypothesize that the medial pallium contains neurons that fire with spatial specificity, similar to place cells or head direction cells in the mammalian hippocampus, but with lower resolution and high correlation with specific environmental features (e.g., borders). We predict that single-cell activity of some neurons in the medial pallium, which is measured by mesh electronics in freely moving toads, will be correlated with spatial position within a behavioral arena, while neurons recorded from another region will not. Prior to recording from the medial pallium, we will establish mesh recordings in the optic tectum, a region easily accessible on the dorsal side of the brain which has been a target for previous electrophysiology studies. We will validate the results with rigorous statistical analyses and comparison of neural recording data with immunohistological imaging of brain slices. Understanding how amphibians learn and encode spatial information will reveal either alternative mechanisms for learning and encoding of spatial experiences or which paradigms are ancestral features of vertebrate brain function and how neurobiological principles of space coding might generalize across vertebrate taxa. Importantly, our approach will result in the development of chronically stable recording techniques in brains with large movements in the skull. This advance will be a valuable research tool for expanding the scope and possibility of electrophysiology studies in other animals. Successful completion of this project will allow us to obtain proof-of-principle data elucidating fundamental questions relating neuroanatomy to neuronal functions, which is crucial for future R01 applications. Furthermore, establishing a recording protocol in cane toads will allow for other aspects of neural function in amphibians, a research area that has thus far been limited due to technological constraints. In summary, our proposed research will help elucidate the core coding principles in the relatively simple amphibian brain and reveal how these principles for spatial encoding might generalize across vertebrate taxa.