Differential function of dopamine midbrain neurons in health and disease: role of ion channels
The dopamine midbrain system and the activity of dopamine releasing (DA) midbrain neurons is not only involved in motor control and movement disorders like Parkinson disease but also plays a crucial role in emotional and cognitive brain functions, and related disorders like schizophrenia, drug addiction, and attention-deficit-hyperactivity-disorder. Our main research goal is to define the functional and molecular mechanisms of different types of DA midbrain neurons, which control their distinct physiological roles and their selective transitions to disease states (Liss and Roeper 2008). By combining in vivo retrograde tracing with in vitro brain slice electrophysiology and UV-lasermicrodissection, as well as with quantitative DNA analysis and RT-PCR based gene expression profiling at the single cell level (Liss and Roeper 2004, Gründemann et al. 2008), we aim to define the pathophysiological signalling-pathways that control DA neuron activity as well as activation and execution of selective disease pathways of the dopamine system, in particular in Parkinson’s disease (PD). The cause for the selective and progressive neurodegeneration of DA midbrain neurons in PD still remains unclear. However, genetic and environmental factors, leading to impaired DNA integrity and mitochondrial dysfunction, as well as altered ion channel activity in DA midbrain neurons, especially of ATP-sensitive K+ -channels (KATP) and L-type calcium channels (LTCCs) have been identified as important factors in PD (Liss and Roeper 2010). We focus on the role of ionchannels and receptors as their cell-specific activity directly defines neuronal activity in health and disease states (Lammel et al. 2008). To address these issues, we analyze cellular function as well as mRNA expression and DNA integrity of individual DA neurons from control mice and from respective disease mouse models as well as from post mortem human brain tissue.
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