About

Calbindin- (white), Parvalbumin- (green) and KCC2- (red) labeling in dentate gyrus (blue nuclei). Fluorescence confocal microscopy. From C. Elgueta

Apr 2024 – Dec 2027

The Research Program

The brain is the most complex information processing system known to humankind. It enables thoughts, learning and memories, perceptions and actions with an efficiency and flexibility that by far surpasses any machine. Brain processes are controlled by a complex system of neurons, among which inhibitory neurons play a crucial role.

Interneurons are characterized by a great morphological and physiological diversity as well as a highly specific connectivity. This great diversity is thought to mediate the comprehensive functional repertoire of inhibitory processes, which in turn enable fine-tuned control of the activity of single cells. Thus, interneurons can determine not only if, but also when and where in the network individual excitatory principal neurons fire to encode information.

The emerging picture suggests that, while principal cell assemblies primarily sustain the information content of neuronal representation, inhibitory 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.

Area A – Encoding

In Research Area A, we will examine how inhibitory interneurons shape the cortical code in a ‘top down’ approach by recording activity of individual cells, cell assemblies and large-scale neuron populations during behaviour. We will apply state-of-the-art electrophysiological, imaging, optogenetic and chemogenetic techniques to record from neuronal populations and to perturb the activity of defined interneuron types to thereby identify their influence on the neuronal code and the guidance of behavior.

Neuronal encoding of information is not a static process, but instead undergoes temporally dynamic changes in dependence on internal states such as motivation, and previous experiences and memories on past events. Thus, in this research area, we will further examine how interneuron types contribute to dynamic changes in information encoding.

On a computational level, experimental data will be used to characterize internal representations of behavioral variables in high-dimensional neuronal data. Finally, by comparing different cortical areas in rodents, we aim to identify brain area-specific and more general principles in how interneurons shape the cortical code.

Marlene Bartos about Area A.

Mouse running through a virtual reality shows activity in dentate gyrus Somatostatin interneurons (green). 2-photon microscopy. Graphic from A. Cazala; Recording from A. Kilias.

Area B – Structure and Function

Complementing research in the A section, in research area B, we will employ a ‘bottom-up’ approach to examine the structural & functional basis of inhibitory processes sculpting neuronal responses in cortical networks. We will identify physiological, synaptic, morphological and molecular properties of interneuron types, their functional and structural embedding in cortical microcircuits as well as activity- and experience-dependent dynamic changes in these properties.

We will apply a wide range of methods including recordings from multiple neurons in brain tissue, recordings from neuronal compartments, electron microscopy and array tomography to support the identification of the structural organization of the inhibitory network as well as microcircuit topologies.

By comparing data obtained from rodent and human tissue, as well as various cortical brain areas, we will identify species-specific, brain area-specific and more general principles in the structural and functional organization of interneuron networks underlying the specific functions of the brain areas under investigation. Both elementary and dynamic processes of inhibition are joint themes of both sections thereby synergizing between research areas A and B.

Prof. Geiger about Area B.

Expression of glutamate receptors mGluR1α (blue) and mGluR5 (magenta) in dendrites of somatostatin interneurons (white label) is crucial for synaptic plasticity. Immunoelectron Microscopy. From Grigoryan et al., 2023.

Areas Z/INF – Methods and Services

The service projects will maximize synergies between Research Areas A and B and are divided in three parts. In one part, we will integrate the findings obtained from both sections in data-constrained single-cell and network models.

By employing dimensionality reduction and decoding methods, we will explore population dynamics to study the neuronal mechanisms and principles underlying encoding across brain regions. In the second part, we will focus on the support of the consortium through qualitative and quantitative neuroanatomical and molecular characterization of neuron types that have been recorded in both sections, by applying light- and electron microscopy, array tomography as well as single cell RNA sequencing.

In the third part, we will establish information infrastructures for the long-term storage of and the reliable access to original data, as well as the documentation of metadata, thereby supporting a reliable and save exchange of data within the consortium.

Glowing geometric shapes in bright multi colors motion generated by artificial intelligence

Collaborations
& Partner

International
We maintain international partnerships with numerous international universities and research institutes.
National

The visualizations show the diverse national and international scientific connections.

Universität Freiburg

Freiburg, Germany

Uniklinik Freiburg

Freiburg, Germany

Charité

Berlin, Germany

Humboldt Universität

Berlin, Germany

Technische Universität Berlin

Berlin, Germany

Max Delbrück Center

Berlin, Germany

Universitätsklinikum

Heidelberg, Germany

DZNE

Berlin, Germany