Related Experiment Video
Updated: Jun 1, 2025
Optogenetic Manipulation of Neuronal Activity to Modulate Behavior in Freely Moving Mice
Published on: October 27, 2020
A wireless optogenetic setup in freely moving mice for evaluation of cortical spreading depolarization in a chronic
Annika Köhne1, Simeon O A Helgers1, Bettina Kewitz1
1Department of Neurosurgery, Carl-von-Ossietzky University Oldenburg, Oldenburg, Germany.
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.
Insights
Researchers developed a wireless optogenetic method for long-term induction of spreading depolarization (SD) in mice. This technique enables studying SD effects without invasive triggers, bridging a critical gap in brain injury research.
Area of Science:
- Neuroscience
- Electrophysiology
- Optogenetics
Background:
- Spreading depolarization (SD) is linked to secondary brain damage in various injuries.
- Existing research faces a translational gap due to short-term studies and invasive SD induction methods.
- The cause of tissue damage in prior studies is unclear due to the invasive nature of SD triggers.
Purpose of the Study:
- To develop a minimally invasive, wireless optogenetic method for long-term Spreading Depolarization (SD) induction.
- To overcome limitations of existing cable-bound or fiber-bound optogenetic systems.
- To enable SD induction in freely behaving mice within their home cages.
Main Methods:
- Utilized a wireless optogenetic stimulation setup for Spreading Depolarization (SD) induction.
- Enabled reliable SD induction over a three-week period in freely behaving mice.
- Allowed for home cage stimulation, cage enrichment, and group housing.
Main Results:
- Successfully induced Spreading Depolarization (SD) wirelessly over three weeks.
- SD characteristics were comparable to those induced by KCl or cable-bound optogenetics.
- Demonstrated widespread neuronal depolarization (c-Fos) without significant apoptosis (TUNEL staining).
Conclusions:
- The wireless optogenetic setup facilitates long-term Spreading Depolarization (SD) studies.
- This method overcomes limitations of invasive and restrictive previous techniques.
- It offers significant potential for investigating long-term SD effects in acute brain injury models.
