Forschungsschwerpunkte

We analyze cell-specific function and gene-expression of individual neurons, to identify mechanisms of their selective (dys-)function in health and disease. Selective death or dysfunction of distinct neuronal cell populations is a main feature of many disorders of the central nervous system, like Parkinson's disease, Schizophrenia, or Amyothrophic lateral sclerosis (ALS). We focus on the dopaminergic midbrain system, as well as on analyzing cell-specific roles of ion channels, transporters and receptors (e.g. K-ATP and Ca2+ channels, dopamine and Ca2+ transporters, D2 and NMDA receptors), as their functional expression directly defines individual neuronal activity pattern and transmitter release.

The dopamine midbrain system and the activity of dopamine releasing (DA) neurons is not only essential for motor control, but is also crucial for emotion, reward, and for cognitive functions. Moreover, subtypes of DA midbrain neurons - with different axonal projections and with distinct activity pattern - are differentially affected in diseases: e.g. Substantia nigra (SN) DA neurons are particularly prone to degeneration in Parkinson´s disease (PD), while neighboring DA neurons in the ventral tegmental area (VTA) are significantly less vulnerable to degeneration in PD, but are particularly affected in Schizophrenia and attention deficit hyperactivity disorder (ADHD). The cause for this selective vulnerability of DA neurons to distinct diseases is still unclear; however specific trigger factors, like metabolic stress, mitochondrial dysfucntion and impaired calcium homeostasis have been identified.

We aim to identify cell-specific functional and molecular differences of e.g. SN DA and VTA DA neurons, that define their distinct physiological functions, their selective transitions to disease states (e.g. malfuntion or degeneration), and their selective age-related dysfunctions.

We combine cell-specific functional analysis (e.g. retrograde tracing, in vivo & in vitro electrophysiology, MEA, calcium imaging) of wildtype and transgenic mice, as well as immunohistochemistry and laser-microdissection, with quantitative RNA and DNA analysis of individual neurons.