Mechanisms for the light-cell interface in optical neurostimulation
Advances in the field of biomedical engineering have pushed optical methods of neurostimulation further to the edge of therapeutic applications. Different ap-proaches have revealed a broad spectrum of possibilities, and the underlying mechanisms have largely been unraveled. Considerable effort is made to refine the methods and introduce additional flexibility. However, the overall cellular re-action is not always sufficiently understood. The safety and reliability of a new therapeutic device can only be assessed if its effects on the targeted cells, tissue or organ is known. Direct or nanoparticle-mediated laser stimulation of neurons presents an uncomplicated way of performing laser-based cell manipulation. An increase of membrane capacity has been detected as a way to evoke action po-tentials in response to a laser stimulus. The method might therefore be suited for applications in neuroprosthesis. But before it can be introduced into a patient, the processes at the light-cell interface need to be fully understood. In this thesis, calcium signaling, formation of reactive oxygen species and membrane perfora-tion in response to gold nanoparticle-mediated laser stimulation have been stud-ied. Also, the influence of different inhibitors and surrounding media was tested. Single cell manipulation of a large number of neuro-2a cells and primary mouse cortical neurons has revealed a multicomponent cellular reaction involving intra-cellular calcium release, calcium influx through transient receptor potential chan-nels and calcium-induced calcium release. These findings imply a serious inter-ference of the external stimulus with cellular homeostasis, potentially leading to long-term damage. While the effect depends on the cell type and the physiologi-cal environment, any long-term in vivo application of nanoparticle-mediated laser stimulation must be evaluated with great care.