Synapse and Neural Circuit Physiology
Our research has two fundamental objectives: The first goal is to bridge the gap between molecular and systemic neurophysiology by a systematic analysis of the different levels of neural organization and their interactions - from molecules via synapses, neurons and neuronal circuits up to higher brain function. In principle, the function of neurons in the neural circuit is defined by i) their connectivity (ii) the strength and plasticity of their synapses, and iii) the rules of integration of synaptic inputs that determine if action potentials are generated and signals are transmitted to downstream neurons. While these principles are well established, they are only loosely connected and specific details in most brain areas during behavior remain often poorly understood especially in mammalian model systems and humans.
The second goal is to identify neurobiological mechanisms by which risk alleles of risk genes for neuropsychiatric diseases lead to cognitive impairments. This information can be an important key for the development of new therapies. Risk alleles often affect synaptic transmission and the function of neurons. Extrapolating from the isolated analysis of synapses and neurons to systemic, cognitive impairments is difficult because of the complex organization of neural circuits.
Our fundamental research themes are:
What are the molecular and biophysical principles that underlie both the stability and the plasticity of synapses as a supra-molecular protein complex?
How does neuronal function at the molecular, synaptic, cellular and circuit level translate into higher brain function?
What are the causal relationships between genetic, molecular, synaptic, cellular and systemic disease mechanisms in neuropsychiatric diseases?
The mouse serves here as model system for applying genetic tools and analyzing genetic models of neuropsychiatric disease. Starting point is the mouse primary visual cortex, which provides complex processing of visual stimuli similar to higher mammals. Mice are capable of solving vision based behavioral tasks, which test cognitive function and involve higher brain areas such as the frontal cortex.
We apply state-of-the-art electro- and optophysiological methods, such as in vivo and in vitro 2-photon microscopy, 2-photon calcium imaging and glutamate uncaging, optogenetics, circuit mapping by laser-scanning-photostimulation, correlated light and electron microscopy and patch-clamp recordings.