TY - JOUR A1 - Tretter, Verena A1 - Mukherjee, Jayanta A1 - Maric, Hans-Michael A1 - Schindelin, Hermann A1 - Sieghart, Werner A1 - Moss, Stephen J. T1 - Gephyrin, the enigmatic organizer at GABAergic synapses JF - Frontiers in Cellular Neuroscience N2 - GABA(A) receptors are clustered at synaptic sites to achieve a high density of postsynaptic receptors opposite the input axonal terminals. This allows for an efficient propagation of GABA mediated signals, which mostly result in neuronal inhibition. A key organizer for inhibitory synaptic receptors is the 93 kDa protein gephyrin that forms oligomeric superstructures beneath the synaptic area. Gephyrin has long been known to be directly associated with glycine receptor beta subunits that mediate synaptic inhibition in the spinal cord. Recently, synaptic GABA(A) receptors have also been shown to directly interact with gephyrin and interaction sites have been identified and mapped within the intracellular loops of the GABA(A) receptor alpha 1, alpha 2, and alpha 3 subunits. Gephyrin-binding to GABA(A) receptors seems to be at least one order of magnitude weaker than to glycine receptors (GlyRs) and most probably is regulated by phosphorylation. Gephyrin not only has a structural function at synaptic sites, but also plays a crucial role in synaptic dynamics and is a platform for multiple protein-protein interactions, bringing receptors, cytoskeletal proteins and downstream signaling proteins into close spatial proximity. KW - scaffolding protein gephyryrin KW - containing GABA(A) receptors KW - GABA(A) receptors KW - inhibitory synapse KW - gamma-aminobutyric-acid KW - receptor-beta subunits KW - molybdenum cofactor biosynthesis KW - temporal-lobe epilepsy KW - cultured hippocampal-neurons KW - exchange factor collybistin KW - rat spinal-cord KW - glycine KW - gephyrin KW - receptor clustering KW - synapse formation Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133356 VL - 6 IS - 23 ER - TY - JOUR A1 - Martens, Suzanne A1 - Bensch, Michael A1 - Halder, Sebastian A1 - Hill, Jeremy A1 - Nijboer, Femke A1 - Ramos-Murguialday, Ander A1 - Schoelkopf, Bernhard A1 - Birbaumer, Niels A1 - Gharabaghi, Alireza T1 - Epidural electrocorticography for monitoring of arousal in locked-in state JF - Frontiers in Human Neuroscience N2 - Electroencephalography (EEG) often fails to assess both the level (i.e., arousal) and the content (i.e., awareness) of pathologically altered consciousness in patients without motor responsiveness. This might be related to a decline of awareness, to episodes of low arousal and disturbed sleep patterns, and/or to distorting and attenuating effects of the skull and intermediate tissue on the recorded brain signals. Novel approaches are required to overcome these limitations. We introduced epidural electrocorticography (ECoG) for monitoring of cortical physiology in a late-stage amytrophic lateral sclerosis patient in completely locked-in state (CLIS) Despite long-term application for a period of six months, no implant related complications occurred. Recordings from the left frontal cortex were sufficient to identify three arousal states. Spectral analysis of the intrinsic oscillatory activity enabled us to extract state-dependent dominant frequencies at <4, similar to 7 and similar to 20 Hz, representing sleep-like periods, and phases of low and elevated arousal, respectively. In the absence of other biomarkers, ECoG proved to be a reliable tool for monitoring circadian rhythmicity, i.e., avoiding interference with the patient when he was sleeping and exploiting time windows of responsiveness. Moreover, the effects of interventions addressing the patient's arousal, e.g., amantadine medication, could be evaluated objectively on the basis of physiological markers, even in the absence of behavioral parameters. Epidural ECoG constitutes a feasible trade-off between surgical risk and quality of recorded brain signals to gain information on the patient's present level of arousal. This approach enables us to optimize the timing of interactions and medical interventions, all of which should take place when the patient is in a phase of high arousal. Furthermore, avoiding low responsiveness periods will facilitate measures to implement alternative communication pathways involving brain-computer interfaces (BCI). KW - temporal-lobe epilepsy KW - neuroprosthetic devices KW - brain computer interface KW - event-related potentials KW - intraoperative electrocoicography KW - electrocorticography KW - epidural recording KW - locked-in state KW - coma KW - consciousness KW - paralyzed patients KW - EEG KW - sleep KW - communication KW - frequencies KW - amyotrophic-lateral-sclerosis Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-114863 VL - 8 ER -