Neurotransmitters and their receptors are key molecules for signal transmission between neurons, and provide the molecular basis for structure-function relationships in the brain. Brain areas contain neurons, each of which express various inhibitory, excitatory, and modulatory receptor types. The concentrations of the receptors vary by up to an order of 1 to 2 depending on the receptor types and brain regions. Since all receptors are involved in the signal transmission process within a brain region, we hypothesize that the balance between the densities of the different receptors in a given region (receptor fingerprint) indicates the functionality of the respective brain region. This is supported by our results demonstrating different receptor fingerprints between brain regions with sensory, motor or multimodal associational functions. Furthermore, since these functions are realized by numerous interconnected brain regions forming complex neural systems, the hierarchical organization of the cortical areas (primary sensory, higher sensory, multimodal association regions), the different modalities of the systems (e.g., vision vs. audition vs. feeling), and the implication in various resting state systems (e.g., attention, executive function) may be reflected by different receptor fingerprints.
Differences in regional and laminar distribution patterns of single receptors, and particularly different receptor fingerprints can be detected by means of quantitative in vitro receptor autoradiography and in situ hybridization.
In neurological and psychiatric disorders like epilepsy, hepatic encephalopathy, Alzheimer’s or Parkinson’s disease, we find characteristic changes of the receptor fingerprints which provide the molecular basis for respective disease processes. In order to understand the underlying mechanisms of these alterations, we study the receptor fingerprints in transgenic animal models of human diseases and conditional receptor knock-out animals.
Graebenitz, S., Kedo, O., Speckmann, E.-J., Gorji, A., Panneck, H., Hans, V., Palomero-Gallagher, N., Schleicher, A., Zilles, K., Pape, H.-C.: Interictal-like network activity and receptor expression in the epileptic human lateral amygdala. Brain 134: 2929-2947 (2011)
Palomero-Gallagher, N., Schleicher, A., Bidmon, H.-J., Pannek, H.-W., Hans, V., Gorji, A., Speckmann, E.-J., Zilles, K.: Multi-receptor analysis in human neocortex reveals complex alterations of receptor ligand binding in focal epilepsies. Epilepsia 53(11): 1987-1997 (2012)
Palomero-Gallagher, N., Zilles, K.: Neurotransmitter receptor alterations in hepatic encephalopathy: A review. Arch. Biochem. Biophys. 536: 109-121 (2013)
The analysis of regional and laminar distribution patterns of multiple receptors enables not only the identification of functional systems and the parcellation of the cerebral cortex at the molecular basis, but also indicates structural and functional principles of neuronal networks. Therefore, we combine the receptor analysis with studies of the structural and functional connectivity (Connectome) by using diffusion-weighted MRT imaging, fMRT (Brain Network Modeling) and ultra-high resolution visualization by polarized light imaging of myelinated fibres and fiber tracts in vivo and post mortem (Polarolaized Light Imaging) in the human brain, and brains of non-human primates and rodents. This multimodal approach will enable a comprehensive analysis of the connectome and the creation of a multimodal human brain model (Architecture and Brain Function).