Optogenetic dissection of neural circuitry: from synaptic causalities to blue prints for novel treatments of behavioral diseases

- Behavioral brain diseases are best explained by altered function of neuronal circuits.
- Addiction starts with an increase of mesolimbic dopamine that drives synaptic plasticity.
- Drug-evoked synaptic plasticity alters mesolimbic circuit function.
- Excitatory transmission onto dopamine neurons of the VTA is potentiated within hours.
- Drug-evoked synaptic potentiation in the NAc causes drug-adaptive behavior.
- Optogenetic reversal protocols are used to establish causality.
- The same protocols serve as template to refine deep brain stimulation protocols.

Optogenetics has enabled the characterization of the neural circuits involved in brain diseases, such as addiction, depression or obsessive compulsive disorders. Recently, the technique has also been used to propose blueprints for novel treatments aiming at restoring circuit function through the reversal of specific forms of synaptic plasticity. Since optogenetic manipulations cannot be immediately translated to human use, we argue that an intermediate strategy could consist of emulating optogenetic protocols with deep brain stimulation (DBS). This translational path to rational, optogenetically inspired DBS protocols starts by refining existing approaches and carries the hope to expand to novel indications.