Lightweight, wireless LED implant for chronic manipulation in vivo of spontaneous activity in neonatal mice

Background: Long-term manipulation of activity in the neonatal rodent brain can help us understand healthy development, but also involves a set of challenges unique to the neonatal animal. As pups are small, cannot be separated from their mother for long periods of time, and must be housed in a nest, many traditional techniques are unusable during the first two postnatal weeks. New method: Here, we describe the use of magnetic resonance induction to allow wireless and chronic optogenetic manipulation of spontaneous activity in mouse pups during the second postnatal week. Results: Pups were implanted with a lightweight receiver coupled to an LED and successfully returned to the homecage. A transmitter coil surrounding the homecage drove the implanted LED and was regulated by a microcontroller to allow flexible, precisely-timed and wireless control over neuronal manipulation. In vivo patch-clamp recordings verified that activation of the LED triggered bursts of action potentials in layer 2/3 neurons that expressed channelrhodopsin-2 in the visual cortex without directly affecting neighboring, non-expressing neurons. The implants are stable and functional for at least 10 days and do not have an impact on the weight gain of pups. Implanted pups’ behavior is mildly affected only briefly after surgery, while maternal behavior of dams remains unaffected. Comparison with existing method(s): In contrast to most other methods for wireless optogenetic stimulation, the small size and low weight of the receiver allow complete implantation in animals that are as small as a newborn mouse. Conclusions: This method is ideal for investigating the function and development of cortical circuits in small and developing animals. Furthermore, our method is economical and easy to adapt to diverse experimental designs.