Currently, optogenetics is a blunt-force instrument for manipulating neural activity, which limits its usefulness in the delicate environment of the brain. Researchers have demonstrated that optogenetics can be used as a finely tempered tool to observe and manipulate neural activity. Recent reports have emerged providing the opportunity to balance out excitation and inhibition of neural circuits using optogenetic techniques.
However, this approach is currently limited by non-linear interactions between co-expressed opsins, the proteins used for most optogenetic studies. Although optogenetics is progressing towards using co-activated opsins to modulate neural activity, the mechanisms underlying their interaction have not been studied.
The EU-funded COMP-OPTOGEN (Computational optogenetics for the characterisation and control of cortical activity) initiative measured the effects of a knowledge gap in optogenetics to move the technology towards being useful in more finely controlled experiments.
COMP-OPTOGEN used in vitro and in vivo models to study the effects of co-activated opsins in isolated neurons and networks, respectively. They also used computer models of co-activated opsins in single cells and in a model representing circuitry of the brain.
The researchers matched opsin characteristics with neuron dynamics so that their kinetics were best matched with neuron characteristics. COMP-OPTOGEN studied co-expression and co-activation of opsins in neuronal populations to investigate inclusion of both excitatory and inhibitory opsins within a single neuron.
With the computational models and the experimental results combined, COMP-OPTOGEN produced important findings. Firstly, the researchers found a clear relationship between how the opsin interacted with types of neurons in different ways.
Secondly, they found that it was possible to modulate neurons using dual activation. The team also established protocols to alter the firing rates of neuron groups without disturbing their firing characteristics. These results demonstrate that optogenetics can be used for fine manipulation of neural activity.