Abstract
Here we characterize several new lines of transgenic mice useful for optogenetic analysis of brain circuit function. These mice express optogenetic probes, such as enhanced halorhodopsin or several different versions of channelrhodopsins, behind various neuron-specific promoters. These mice permit photoinhibition or photostimulation both in vitro and in vivo. Our results also reveal the important influence of fluorescent tags on optogenetic probe expression and function in transgenic mice.
Highlights
One of the fundamental goals of neuroscience is to understand how the high-order functions of the brain emerge from the complex networks formed by many types of neurons with diverse genetic, physiological, and anatomical properties
Several optogenetic actuators have been identified that allow photostimulation or photoinhibition of genetically defined populations of neurons with high temporal and spatial resolution
To inhibit forelimb movement, the activity of many neurons in a large area (>0.66 × 0.66 mm) must be silenced. These results show that cortical activity and limb movement can be photoinhibited in vivo using the Thy1eNpHR2.0 mouse, indicating that this mouse is an excellent tool for disruption of neural circuit activity in vivo
Summary
One of the fundamental goals of neuroscience is to understand how the high-order functions of the brain emerge from the complex networks formed by many types of neurons with diverse genetic, physiological, and anatomical properties. Optogenetic tools provide unprecedented opportunities for approaching this goal by causally linking the activity of specific types of neurons or neural circuits to behavioral output. Several optogenetic actuators have been identified that allow photostimulation or photoinhibition of genetically defined populations of neurons with high temporal and spatial resolution. The ability to selectively photostimulate defined populations of neurons enables high-speed mapping of the spatial organization of circuits by photostimulating presynaptic neurons with a scanned laser beam while using electrophysiology to detect postsynaptic responses in downstream neurons (Petreanu et al, 2007; Wang et al, 2007; Mao et al, 2011; Kim et al, in revision). Probes have been developed to enable optogenetic photoinhibition of neurons. The first example of this class of probes was the light-driven chloride pump, halorhodopsin, from Natronomonas pharaonis (NpHR; Han and Boyden, 2007; Zhang et al, 2007) and its improved versions eNpHR 2.0 and eNpHR 3.0 (Gradinaru et al, 2008, 2010; Zhao et al, 2008), as well as light-driven proton pumps such as archaerhodopsin-3 from Halorubrum sodomense (Arch; Chow et al, 2010) and bacteriorhodopsin (Gradinaru et al, 2010) have been harnessed for photoinhibition
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