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

• Subject Area: Medicine
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 514483642

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.

• DFG Programme: CRC/Transregios

Current projects

• A01 - Role of dentate gyrus GABAergic interneuron types in long-term information encoding by principal cells (Project Head Bartos, Marlene )
• A02 - MEC GABAeric interneuron coding during spatial learning and contribution of electrical coupling therein (Project Head Monyer, Hannah )
• A03 - Role of medial prefrontal cortex GABAergic interneuron types in context and rule encoding investigated with 2P-imaging and holographic stimulation (Project Heads Bödecker, Joschka ;  Diester, Ilka )
• A04 - Inhibitory control of thermal perception in mouse posterior insular cortex (Project Head Poulet, Ph.D., James F.A. )
• A05 - Role of GABAergic interneuron types in the encoding of local and global motion (Project Head Veit, Julia )
• A06 - Learning inhibition for pattern separation (Project Head Leibold, Christian )
• A07 - Complementary inhibitory control of dendritic top-down information processing in auditory cortex (Project Head Letzkus, Ph.D., Johannes )
• A08 - Optimizing cortical interneuron circuits for flexible integration of information streams (Project Head Sprekeler, Henning )
• B01 - Dendritic mechanisms underlying a sparse spatial code in the dentate gyrus (Project Heads Elgueta, Claudio ;  Kulik, Akos )
• B02 - Rewiring of GABAergic inhibitory cells recruited during spatial encoding (Project Heads Haberl, Matthias ;  Viana da Silva, Ph.D., Silvia )
• B03 - Modulation of cortical inhibition by transcranial magnetic stimulation in rodents and humans – network effects and molecular mechanisms (Project Heads Geiger, Jörg ;  Vlachos, Andreas )
• B04 - Investigating the fast-spiking interneuron microcircuit topology of mouse and human neocortex (Project Head Geiger, Jörg )
• B05 - Inhibitory neurons of different dynamical types: critical network states and homeostasis (Project Head Schreiber, Susanne )
• B06 - Role of microglia-interneuron interactions in shaping network function (Project Heads Madry, Christian ;  Sauer, Jonas-Frederic )
• B07 - Anatomical organization of inhibitory microcircuits in the human temporal cortex (Project Heads Grosser, Sabine ;  Vida, Imre )
• B08 - The influence of interneurons’ active dendritic properties on neuronal information encoding in the neocortex (Project Head Larkum, Matthew )
• INF - Research Data Management infrastructure for collaborative data analyses (Project Heads Binder, Harald ;  Schmoranzer, Jan )
• V01 - Central Task (Project Head Bartos, Marlene )
• Z01 - Machine and deep learning for population data analysis (Project Heads Binder, Harald ;  Sprekeler, Henning )
• Z02 - Light and electron microscopic imaging and morphometric analysis of inhibitory neuronal circuits and signaling proteins (Project Heads Kulik, Akos ;  Vida, Imre )

• Applicant Institution: Albert-Ludwigs-Universität Freiburg
• Co-Applicant Institution: Charité - Universitätsmedizin Berlin; Freie Universität Berlin; Humboldt-Universität zu Berlin
• Participating University: Ruprecht-Karls-Universität Heidelberg; Technische Universität Berlin
• Participating Institution: Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE)
• Spokesperson: Professorin Dr. Marlene Bartos