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Aufgabenstellung: Die außeruniversitären Forschungseinrichtungen in Deutschland verfügen dank ihrer in zahlreichen Bereichen durchgeführten Spitzenforschung über ein beachtliches Innovationspotenzial. Eine gezielte Erschließung dieses Potenzials scheitert allerdings nicht selten an dem Fehlen geeigneter Verwertungsmodelle bzw. -strukturen, welche in der Lage sind, die Interessenslage sowohl der Wissenschaftler und der Wissenschaftseinrichtungen als auch der Wirtschaft und gegebenenfalls von Investoren zu vereinen. Die Aufgabenstellung des Projekts lag darin, im Rahmen dieses Vorhabens ein auf die spezifischen Bedürfnisse des INM angepasstes Verwertungskonzept zu erarbeiten und umzusetzen.
Aufgabenstellung: Ziel des Vorhabens ist es, systematische und auf das INM abgestimmte Prozesse zu entwicklne, die das Institut langfristig in die Lage versetzen, autonom und nachhaltig Verwertungsmöglichkeiten zu identifizieren. In der Folge sollen die Kosten des Verwertungspartners auf ein Maß gebracht werden, welches eine kontinuierliche Zusammenarbeit in bestimmten Bereichen auch nach dem Förderzeitraum und durch Eigenmittel realisierbar macht. Ein weiteres Ziel ist, Prozesse und die dazugehörigen Rahmenbedingungen zu schaffen, mit denen FuE-Ergebnisse verwertet werden können, die einen hohen Technical Readyness Leve besetzen und im Rahmen der weiteren Schritte noch zusätzlich Erfordernisse erfüllen. Die zu schaffenden Strukturen und die damit einhergehenden Prozesse müssen sowohl die Rahmenbedingungen der INM-Zuwendungsgeber und die gesetzlichen Vorschriften als auch die jeweiligen technischen und infrastrukturellen Aspekte zwingend berücksichtigen.
Modeling the Effects of Nanoparticles on Neuronal Cells : From Ionic Channels to Network Dynamics
(2014)
Background: Besides the promising application potential of nanotechnologies in engineering, the use of nanomaterials in medicine is growing. New therapies employing innovative nanocarrier systems to increase specificity and efficacy of drug deliveryschemes to reach non-operable structures are already in clinical trials. However the influence of the nanoparticles (NPs) themselves is still unknown in medical applications, especially for complex interactions in least investigatable neural systems. The aim of this study was to investigate in vitro effects of coated silvernanoparticles (cAg-NPs) on the excitability of single neuronal cells and to integrate those findings into an in silico model to predict possible effects from single cells up to neuronal circuits and finally toneural field potentials generated by those circuits.
Methods: First, patch-clamp measurements were performed to investigate the effects of nano-sized silver particles, surrounded by an organic coating, on excitability of single cells. Second, it was determined which parameters were altered by exposure to those
nanoparticles using the Hodgkin-Huxley model of the sodium current. As a third step those findings were integrated into a well defined neuronal circuit of thalamocortical interactions to predict possible changes in network signaling due to the applied cAg-NPs, in silico. Fourthly, the model was extended to observe neural fields originating from Hodgkin-Huxley type neurons. Therefore it was investigated how the neural field potentials influence the spike generation in neurons that are physically located within these fields, if this feedback causes relevant changes in the underlying neuronal signaling within the circuit, and most important if the cAg-NPs effects on single neurons of the network are strong enough to cause observable changes in the generated field potentials themselves.
Results: A rapid suppression of sodium currents was observed after exposure to cAg-NPs in the in vitro recordings. In numerical simulations of sodium currents the parameters most likely affected by cAg-NPs were identified. The effects of such changes on the activity of networks were then examined. In silico network modeling indicated effects of local cAg-NP application on firing patterns in all neurons in the circuit. It has been shown that field potentials have strong effects on the action potential generation of neurons that are exposed to those fields. Furthermore, it was also shown that this is also affecting the underlying neuronal signaling. The assumed cAg-NPs presence in the circuit’s thalamic cells were finally found to also have distinctive effects on the emerging neural field potentials.
Conclusion: The sodium current measurements and simulations show that suppression of sodium currents by cAg-NPs results primarily in a reduction in the current amplitude right after a few seconds of particle addition. The network simulations on larger scale
show that locally cAg-NPs induced changes result in diversification of activity in the entire circuit. This was also found for the field potential simulations on a more larger scale. The results indicated that local application of cAg-NPs may influence the activity throughout the network and may cause distortions in cortical field potentials in vivo. This multiscale model may subserve as basic approach to estimate the NPs affected spatiotemporal dynamics of cortical field potentials on a very small cortical patch. The electrophysiological detection of this simulated effect by utilizing the voltage sensitive dyes technique is part of the future work that will be carried out by the group ”Systems Neuroscience and Neurotechnology Unit”
Background: Beside the promising application potential of nanotechnologies in engineering, the use of nanomaterials in medicine is growing. New therapies employing innovative nanocarrier systems to increase specificity and efficacy of drug delivery schemes are already in clinical trials. However the influence of the nanoparticles themselves is still unknown in medical applications, especially for complex interactions in neural systems. The aim of this study was to investigate in vitro effects of coated silver nanoparticles (cAgNP) on the excitability of single neuronal cells and to integrate those findings into an in silico model to predict possible effects on neuronal circuits. Methods: We first performed patch clamp measurements to investigate the effects of nanosized silver particles, surrounded by an organic coating, on excitability of single cells. We then determined which parameters were altered by exposure to those nanoparticles using the Hodgkin-Huxley model of the sodium current. As a third step, we integrated those findings into a well-defined neuronal circuit of thalamocortical interactions to predict possible changes in network signaling due to the applied cAgNP, in silico. Results: We observed rapid suppression of sodium currents after exposure to cAgNP in our in vitro recordings. In numerical simulations of sodium currents we identified the parameters likely affected by cAgNP. We then examined the effects of such changes on the activity of networks. In silico network modeling indicated effects of local cAgNP application on firing patterns in all neurons in the circuit. Conclusion: Our sodium current simulation shows that suppression of sodium currents by cAgNP results primarily by a reduction in the amplitude of the current. The network simulation shows that locally cAgNP-induced changes result in changes in network activity in the entire network, indicating that local application of cAgNP may influence the activity throughout the network.
Im Rahmen des Projektes sollen geeignete Vorgehensweisen, sowie praxistaugliche Methoden zur erfolgreichen Gewinnung von KMUs für gemeinsame Innovationsprojekte konzipiert und erprobt werden. Bei den Methoden wurde Augenmerk auf die Identifizierung von innovationsfähigen und –willigen Firmen gelegt; sowie deren gezielte Ansprache. Ferner sollte ein Kooperationsmodell zwischen INM und spezifischen Unternehmen erstellt werden, das den jeweiligen Zielen, Anforderungen und Rahmenbedingungen beider Partner gerecht wird.[...]