My interest in wireless optogenetics has come up a couple of times. In fact, I’ll start with a quick correction: I prefer to call it fibre-free optogenetics, after multiple people mistook my wireless system I was designing as meaning controlled via Bluetooth or WiFi. Which it ain’t. And, for me at least, the whole point of going “wireless” is to do away with the optic fibres, which really embody all the issues and difficulties with in vivo optogenetics:
- Impacts to the animal – the need to have the animals in an open cage, with an open lid and a sterile environment to prevent damage to the fibres. Also, they tend to be stiff, having severe behavioural impacts.
- Loss of optical power – the optic fibres require additional optical connections, which inevitably leads to light loss, and therefore difficulties obtaining a high enough brightness.
- Expensive and fragile – not much more to say, other than we have spent thousands of pounds maintaining the optic fibres for our optogenetics system. This may be more than is typical, but I think that’s because the Plexon fibres we use are very fine and lightweight – I have used more durable ones that were even worse for the mouse behaviour because of the added stiffness.
The most important reason to do away with the optic fibres, as far as I’m concerned, is the impact to the animal. Quite apart from minding the 3R’s with regards to animal welfare, tethering will inevitably cause stress, which is detrimental to the data you can acquire (Figure 1). In fact, it is to the NC3R’s that I am applying for funding to take my fibre-free opto system to the next level.
There is of course the added bonus with wireless optogenetics that you can do optogenetic stimulation in otherwise impossible setups. For example, I am very keen to use my fibre-free opto’s in our calorimetry system to measure energy expenditure in response to opto stim. This is done in an air-tight sealed container, which to my knowledge this has never been done with optogenetic stimulation in the brain.
After a fair bit of research, I have found 4 commercially available wireless in vivo optogenetics systems (Figure 2).
Helios by Plexon and Teleopto by Amuza are both very similar, except that the Helios headstage attaches to “normal” implants, whereas Teleopto make their own custom implants. Both require you to point an IR remote at the headstage constantly (ie. the flashing stops if the signal stops). Fi-Wi from Doric connects over radio signal to drive opto flashing; similar to Teleopto they use custom implants. Neurolux is a very different system to the other three, and uses electromagnetic induction to remotely power the implants. Hence the Neurolux implants are tiny and custom (the LED is actually on the end of the fibre that gets implanted).
I have collated a summary table of the various systems, including a number of parameters (Table 1). Included is the cost to buy a complete setup to stimulate 1 mouse at a time, which usually comes with a few implants. However, I was unable to find out the irradiance available from the Plexon Helios system, despite asking the sales people for those details.
Overall, the Doric system seems the best of the bunch; despite being the heaviest it is very compact and produces by far the highest irradiance. In fact, it provides higher irradiance than the system I’ve been developing, which comes out around 150 mW/mm2. Stay tuned, and I’ll be talking more about my system in the coming months.
1. Won et al., Nat Biomed Eng (2021) Wireless and battery-free technologies for nanoengineering.