, 2011 and Ziv et al., 2013). Such CMOS-based miniature microscopes can now provide recordings of up to ∼1,200 neurons concurrently during active mouse behavior (Figure 1). This promises to be a useful tool in the study of rodent models of human brain disorders, CDK inhibitor and perhaps even in primate models. We expect continued

progress in camera technology and image sensor chips, leading to larger sensors, faster image-frame acquisition rates, on-chip imaging analyses, wireless imaging, and even capabilities for three-dimensional imaging. Further improvements in tiny light emitting diodes (LEDs) in combination with CMOS image sensors should enable a new generation of devices capable of both optogenetic manipulation and fluorescence imaging concurrently. This need will provide additional impetus for the ongoing engineering of spectrally compatible sets of

optogenetic control probes and fluorescence-based sensors of neural activity. Even as next-generation optical tools offer increasingly sophisticated technological capabilities, the practice of systems neuroscience will have to remain grounded in rigorous, clever, and insightful behavioral paradigms. Here, digital imaging may help advance the field, as many emerging opportunities exist for high-throughput and high-resolution video tracking GDC-0199 research buy of animal behavior. To maximally leverage the newfound capabilities for optically monitoring individual cells over many weeks in the live brain,

new behavioral assays should be compatible with long-term tracking and quantification of behavior. Machine-learning approaches to scoring digital image sequences of animal behavior (Kabra et al., 2013) might facilitate the combined automation of both brain imaging and behavioral data analyses. Finally, we note that for in vivo animal only experimentation, the demands of small animal surgery often remain a limiting factor on the rate of experimental progress. In recent years there has been exploration of laser surgical methods to perform highly precise surgeries. One candidate approach involves the use of regenerative laser amplifiers that emit high-energy ultrashort pulses of light for highly precise tissue ablation (down to the submicron scale, to cut or ablate individual axons, neurons, and even organelles) (Jeong et al., 2012 and Samara et al., 2010). However, the fine spatial scale of the cutting action is a limiting factor for performing dissections over broad tissue regions. An alternative approach is to make use of ultraviolet lasers, such as those commonly used in clinical ophthalmology for reshaping the cornea (Sinha et al., 2013). Ultraviolet excimer lasers can cut precision holes down to the sub-10-μm scale, with clean-cut edges straight to <1 μm, and at much faster cutting rates than the regenerative laser amplifiers.