CRC/TRR 384: Inhibitory neurons: shaping the cortical code (IN-CODE)

The brain enables us to feel, act, learn and remember, to process and store information with an effi-ciency and flexibility that by far surpasses any machine. At the same time, dysfunctions of the brain cause a number of devastating cognitive disorders. Cognitive functions depend on the cortex. Since ~80% of cortical cells are excitatory principal neurons (PNs), they have received greatest attention. This work revealed that even individual PNs represent significant information, such as place cells in the hippocampus or PNs in sensory areas tuned to stimulus features (single neuron code). Advances in large-scale recordings started to uncover how PNs combine to represent information at the popula-tion level (population code). However, the activity of PNs is markedly shaped by GABAergic inhibitory interneurons, a smaller but highly diverse class of cortical cells. Inhibition has recently emerged as an essential factor that plays complex roles in cortical networks. Indeed, through their great diversity and specific connectivity, interneurons can determine not only if, but also when and where individual PNs fire to encode information. Thus, the emerging picture suggests that, while PN assemblies sus-tain the information content, interneurons offer key mechanisms that sculpt the activity of neuronal subpopulations in space and time and thereby contribute to the process of information encoding in the brain. Driven by this hypothesis, the proposed CRC/TRR aims to investigate in what ways inter-neurons tune cortical network computations and thereby shape the cortical population code. Interneurons are characterized by diverse morphologies, molecular and synaptic properties, connectivities and activity profiles, and may tune cortical cods according to the changing computational demands. Using mouse models for genetic circuit dissection and human tissue, we will focus on a number of cortical areas, vital for higher brain functions. By combining state-of-the-art optical and electrical recordings with pharmaco- and optogenetic perturbation, quantitative behavior, computa-tional modeling, high-dimensional data analysis and deep learning, the proposed CRC/TRR will pro-vide multidisciplinary insights on a number of central questions in neuroscience: How do interneurons shape cortical codes in relation to experience? How do structural-functional interneurons properties contribute to encoding of information? How is the encapsulation of information in the neuronal population code controlled by interneurons? Addressing these questions critically depends on synergies between our members in terms of tools, methods, concepts, computational and translational integration. The proposed topic is timely as reflected by the continuous rise of related publications in high impact journals in the last 10 years. We strongly believe that our work will build a foundation on the role of interneurons in controlling encoding of behaviorally relevant information in cortical circuits.