Über

Calbindin- (weiß), Parvalbumin- (grün) und KCC2- (rot) Färbung im Gyrus dentatus (blaue Zellkerne). Konfokale Fluoreszenzmikroskopie. Von C. Elgueta.

Apr 2024 – Dec 2027

Das Forschungsprogramm

Das Gehirn ist das komplexeste Informationssystem, das der Menschheit bekannt ist. Es ermöglicht Gedanken, Lernen und Erinnerungen, Wahrnehmungen und Handlungen mit einer Effizienz und Flexibilität, die bei weitem jede Maschine übertrifft. Gehirnprozesse werden von einem komplexen System von Neuronen kontrolliert, unter denen hemmende Neuronen eine entscheidende Rolle spielen.

Interneuronen zeichnen sich durch eine große morphologische und physiologische Vielfalt sowie eine hochspezifische Konnektivität aus. Diese große Vielfalt ermöglicht das umfassende funktionale Repertoire hemmender Prozesse, welche wiederum eine fein abgestimmte Kontrolle der Aktivität einzelner Zellen ermöglichen. So können Interneuronen nicht nur bestimmen, ob, sondern auch wann und wo im Netzwerk einzelne erregende Prinzipalzellen feuern, um Informationen zu kodieren.

Es zeichnet sich ab, dass, während die Aktivität von Gruppen an Prinzipalzellen vor allem den Informationsgehalt neuronaler Repräsentation aufrecht erhalten, hemmende Interneuronen die Schlüsselmechanismen bieten, die die Aktivität neuronaler Subpopulationen im Raum und in der Zeit modulieren und damit zum Prozess der Informationskodierung im Gehirn beitragen.

 

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 mGluR1α (blue) and mGluR5 (magenta) at the dendritic level of somatostatin-positive interneurons (distinguished by the white label) is crucial for synaptic plasticity expression. 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.

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