In vivo Photometry during Movement Changes Our Understanding of the Direct and Indirect Pathways

between these pathways. To do so we need to observe the activity of the direct and indirect pathway spiny projection neurons in “behaving” animal models (1). However, it is difficult to distinguish direct and indirect spiny projection neuron firing using electrophysiological recordings and antidromic stimulation is unreliable and difficult due to “cross talk” between axons of both pathways (1). The authors highlight that optogenetic technology in vivo facilitates the identification of specific cell types and the monitoring of activity of specific cell types (1). Limitations of this technology include the requirement for head restraint, which limits the study of structures involved in movement and the technology does not penetrate to subcortical structures therein limiting the ability to study the basal ganglia (1). Cui et al. developed an experimental paradigm utilizing in vivo photometry to optically record neural activity within the striatum during free movement in a mouse model (1). They implanted a fiber-optic probe to deliver laser pulses and record emitted photons in the dorsal striatum over time. The optical indicator was a genetically encoded calcium indicator (GECI), selectively expressed in the direct pathway spiny projection neurons by injection with a recombinant viral vector to produce D1-Cre mice (2). A similar technique was used to selectively express the indicator in the indirect pathway spiny projection neurons of A2A-Cre mice (1). Focusing specifically on their examination of the relationship between activity in the direct and indirect pathway spiny projection neurons during movement, the authors measured fluorescence whilst mice performed a lever-pressing task. They demonstrated time-locked increases in fluorescence during the initiation of the task with a similar temporal profile in both the direct A commentary on