General principles

Optogenetics provides a set of techniques which allow millisecond control and sensing of brain processes in targeted populations of neurons using light. There are two types of optogenetic device. Sensors are proteins which transduce physiological signals in cells to light emissions so as to make specific cell functions visible. Actuators are proteins that respond to light signals by altering a physiological process. In many cases the sensor or actuator proteins are produced by animals genetically engineered to manufacture them by introducing the encoding DNA into their genome. Genetic engineering techniques can in some instances ensure that the DNA is restricted to particular cell types. However, the capacity for this is limited to date by our knowledge of gene expression in specific cell types. For example, whilst a requirement of dopaminergic cells is that the gene for the enzyme tyrosine hydroxylase (TH) must be switched on, this is also true of other cat- echolaminergic neurons, so animals engineered so that TH can be light activated or will emit light so as to indicate the enzyme’s activity, cannot be interpreted as just reflecting dopaminergic neuron function.

However, not all optogenetic manipulations can be done by genetically engineering animals specifically. Some   sensors and   actuators require, in addition to genetically encoded proteins, small molecules that must be injected or ingested. Alternatively, the DNA is introduced in the form of plasmids or viruses. These are subsequently taken up by the cells for which these vectors are the targets. The disadvantage of this is that each animal has to be treated individually, making experiments time-consuming and laborious.  However, it is sometimes needed to gain sufficiently high levels of expression of a protein.