Bidirectional Optogenetic Control of Inhibitory Neurons in Freely-moving Mice

Optogenetic manipulations of excitable cells enable activating or silencing specific types of neurons in the brain of freely-moving animals. By expressing two types of exogenous proteins, a single neuron can be depolarized using light of one wavelength and hyperpolarized with another. However, routing two distinct light wavelengths into the same brain locality typically requires bulky optics that cannot be implanted on the head of a freely-moving animal.

We developed a lens-free approach for constructing dual-color head-mounted, fiber-based optical units. Each unit was comprised of one 450 nm and one 638 nm laser diode, yielding light power of 0.4 mW and 8 mW, respectively. To create a multi-color/multi-site optoelectronic device, a four-shank silicon probe mounted on a movable microdrive was equipped with two dual-color and two single-color units.

Devices were implanted in mice expressing the blue-light sensitive cation channel ChR2 and the red-light sensitive chloride pump Jaws in parvalbumin-immunoreactive (PV) inhibitory neurons. The combination of dual-color units with recording electrodes was free from electromagnetic interference, and device heating was under 7 °C even after prolonged operation. Using these devices, a single cortical PV cell could be both activated and silenced.

This was achieved for multiple cells both in the neocortex and the hippocampus of freely-moving mice. Funded by a CRCNS grant (#2015577) from the United States-Israel Binational Science Foundation (BSF), Jerusalem, Israel, and the United States National Science Foundation (NSF); and by an ERC Starting Grant (#679253).