Neocortical Circuit Interrogation with Optogenetics

Optogenetic tools have gained popularity for enabling manipulation of specified populations of neurons on a precise temporal scale. These opsins, as the proteins are known, utilize retinal (Vitamin A) as a co-factor—in a form related to the same molecule used by the human retina as a light-sensing moiety; opsin function does not require (at least in vertebrates) exogenous supplementation of this molecule [1]. Taken together, these properties of optogenetic tools situate them ideally for the interrogation of neural circuits in the settings of acute slice preparations, in vivo single and multiunit recordings, and behaving animals. Robust and diverse tools now exist to allow for both gain and loss of function experiments in all of these settings; for example, recent engineering and genomic approaches have introduced diversity in the spectral properties of both excitatory and inhibitory opsins, opening the door to combinatorial optogenetic experiments and simultaneous manipulation of multiple populations of neurons in the same physical volume [2] (see Chapter 5 in this volume). Here we discuss circuit-targeting strategies with examples from the recent literature, focusing particularly on approaches and results in the study of mammalian neocortex.