How a relatively sparse interneuron population, such as striatal cholinergic interneurons, contributes to in vivo function remains to be elucidated. One challenge we face is that, using conventional techniques it is difficult to achieve selective control of interneuron activities with temporal and spatial precision. Cholinergic interneurons are physically interspersed with the other neurons in the striatum preventing conventional manipulations. However, recently developed optogenetic tools, such as Channelrhodopsin-2 (ChR2) and Halorhodopsin (eNpHr3.0), can be expressed in mammalian neurons and used to enhance or suppress their firing with millisecond precision [58,59,60,61]. The development of transgenic mice expressing ChR2 or Cre specifically in cholinergic interneurons allows selective expression of these optogenetic tools [44,67]. New devices, such as optrodes, have been designed to simultaneously record from cells while delivering light through a fiberoptic in vivo allowing new means of controlling cholinergic interneurons in freely moving behaving mice [63].
