Commentary: Lack of functional specialization of neurons in the mouse primary visual cortex that have expressed calretinin

Citation: Barinka F (2016) Commentary: Lack of functional specialization of neurons in the mouse primary visual cortex that have expressed calretinin. The intracellular protein calretinin (CR) is frequently used as a marker of specific (albeit heterogeneous) cortical interneuronal population (see Cauli et al., 2014; Schwaller, 2014 for recent reviews). A large body of data on connectivity of calretinin expressing (CR+) neocortical interneurons in various areas and species has been collected in the last two decades. However, remarkably little is yet known about their reactions to physiological stimuli during information processing in neocortical networks. Furthermore, we still lack precise data about the physiological roles of calretinin in neocortical neurons and we also do not know whether the presence of calretinin protein in these neurons is directly coupled to any special physiological feature of these cells. In other words, are there any common functional attributes, shared (exclusively?) by (all?) CR+ neocortical neurons? Alexander Heimel from the Netherlands Institute for Neuroscience with his research group decided to challenge this topic by characterizing the physiological response properties of CR+ interneurons in the primary visual cortex of the mouse in vivo (Camillo et al., 2014). They intended to figure out, whether these cells differ in their receptive field properties from the general neuronal population in this area. With this intention, a very elegant study design was elaborated, combining various methods: the use of genetically modified mouse lines, two-photon calcium imaging, immunohistochemistry as well as in situ hybridization [the last one retrieved as " ready-made " in situ hybridization images from the Allen Mouse Brain Atlas (Lein et al., 2007; Oh et al., 2014)]. Firstly, two genetically engineered mouse lines were crossed: a Cre-dependent reporter mouse line expressing the red fluorescent protein tdTomato (tdTom) with a CR-ires-Cre mouse line, which expresses the enzyme Cre-recombinase in a fashion similar to endogenous CR expression. In the offspring from this cross, the cellular expression of the tdTom label was indirectly activated by the expression of CR. In these animals, the orientation selectivity, size tuning, and temporal and spatial frequency tuning of tdTom+ cells were estimated in vivo by measuring the intracellular calcium changes via two-photon calcium imaging using the genetically encoded calcium indicator GCaMP6s, while showing standardized visual stimuli.