A wireless optogenetic setup in freely moving mice for evaluation of cortical spreading depolarization in a chronic disease model.

Abstract

Background: Spreading depolarization (SD) is an electrophysiological phenomenon of massive neuronal depolarization that occurs in a multitude of brain injuries. Clinical studies and experimental data have linked the occurrence of SDs with secondary brain damage. However, there is a translational gap because of methodological limitations between clinical and experimental approaches focusing on short-term effects. Moreover, usage of highly invasive SD triggers has put into question to what extent SDs themselves or the induction method had caused emergence of tissue damage.

New method: To overcome this gap, we here show the successful realization of an experimental approach for long-term SD induction in a wireless setup of minimal invasive optogenetic stimulation in freely behaving mice.

Results: The proposed method allows for reliable SD induction over the course of three weeks. SD characteristics induced with the wireless setup were comparable to SDs elicited by KCl or cable-bound optogenetic systems. Immunohistological analysis of c-Fos expression revealed neuronal depolarization across the stimulated hemisphere, whereas TUNEL staining revealed no stimulation related apoptosis.

Comparison with existing methods: Optogenetic SD induction so far relied on cable- or fiber-bound systems which restrict experimental possibilities. The proposed model relies on wireless stimulation that allows SD induction in the home cage. In contrast to existing systems, the wireless setup also allows cage enrichment and group housing, therefore allowing behavioral analyses.

Conclusion: This experimental setup has excellent potential to investigate the question of possible long-term SD effects in mouse models of different acute pathologies like traumatic brain injury or migraine.