Program Summary

The overarching goal of the CRC is to understand how behavior is generated by coordinated activity of neuronal circuits, and how this is disrupted in neurological disorders. The past decade has seen significant advances in this field, with the refinement of techniques for measuring and manipulating the activity of large populations of neurons in behaving animals, as well as the ability to quantify behavior in novel, extremely precise ways. This has allowed to formulate and test new hypotheses about how neuronal activity represents features of the outside world, how neuronal circuits integrate environmental information with internal states, and how this leads to goal-directed behavior.

Notably, even simple behaviors rely on the orchestrated performance of neuronal circuits spanning multiple brain regions. The CRC will, therefore, leverage the critical mass of projects designed to investigate different brain areas for the examination of extended neuronal systems spanning multiple brain regions. We will focus on how these systems work together and how neuromodulation, which we consider to be a key factor in mediating state-dependent modulation in multiple brain regions, contributes to behaviorally relevant circuit activity. These approaches lead to the acquisition of rich behavioral and cellular data, which have to be integrated into a theoretical framework that allows us to rigorously link behavior to neuronal activity patterns. The CRC will mount a coordinated effort to develop methods for the precise observation of behavior and identification of behavioral syntax. Moreover, both within individual projects and within the central project, the CRC will implement a range of mathematical and theoretical methods that link neuronal activity to behavioral features. Finally, the CRC will use novel behavioral opto-tagging and imaging approaches combined with transcriptomic/connectomic approaches to obtain more precise, cellular, and synapse-level connectivity data from neurons identified as behavior-related in vivo.

We will continue to apply these interdisciplinary approaches to the study of CNS disorders, most notably epilepsy and Alzheimer’s disease. We are convinced that understanding the basis of disease-related phenotypes across scales, down to the level of single neurons, is crucial to gaining a true understanding of neurological diseases and developing novel treatments.