The brain perceives the outside world, coordinates behavior, regulates emotional states, and forms memories about these experiences. To orchestrate such a diverse array of functions, billions of neurons interact to form circuits with the capacity to compute sensory information and rapidly generate appropriate behavior. Understanding these processes and how the dysregulation of circuits contributes to psychiatric illness is a major goal of neuroscience research and has led to the development of novel tools for circuit-level analysis of the brain in behaving animals (Jennings and Stuber, 2014). One approach for monitoring circuit-specific activity dynamics is in vivo calcium imaging. During periods of increased neural activity, dynamic fluctuations in calcium levels correlate with events such as action potential generation, exocytosis of neurotransmitters, changes in synaptic plasticity, and gene transcription. Thus, monitoring calcium dynamics with genetically encoded calcium indicators, such as GCaMP6, can serve as a proxy for neural activity within defined neurocircuits (Chen et al, 2013). Imaging of neural activity using calcium indicators has largely been accomplished with in vivo two-photon microscopy, which provides unprecedented cellular and subcellular spatial resolution; however, two-photon imaging must be performed in head-fixed animals, greatly limiting the assessment of naturalistic behavior (Svoboda and Yasuda, 2006). To circumvent these limitations, new methods for visualizing and quantifying calcium-mediated fluorescent signals have been developed for use in freely moving animals.

G.D. Stuber has received prototype versions of a mini-epifluorescence microscope system from Inscopix Inc. for testing purposes. The authors declare no conflict of interest.

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