Thursday, June 03, 2021

Optogenetics used to induce pair bonding and restore vision.

I want to note two striking technical advances that make use of the light activated protein rhodopsin that I spent 36 years of my laboratory life studying. Using genetic techniques, a version of this protein found in algae, called channelrhodopsin, can be inserted into nerve cells so that they become activated by light. Hughes does a lucid explanation of a technical tour de force in bioengineering reported by Yang et al. They used transgenic mice in which light sensitive dopaminergic (DA) neurons in the ventral tegmental area (VTA) brain region (involved in processing reward and promoting social behavior) can be activated by blue light pulses from a tiny LED device implanted under the skull. It is known that some VTA areas fire in synchrony when two mice (or humans) are cooperating or bonding. When two male mice were dropped into a cage, they exhibited mild animus towards each other, but when both were zapped with blue light at the same high frequency they clung to and started grooming each other! (Aside from being forbidden and impractical in humans, how about this means of getting someone to like you!...all you would have to do is control the transmitters controlling VTA DA neuron activity in yourself and your intended.) 

A second striking use of optogenetics is reported in Zimmer's summary of work of Sahel et al., who have partially restored sight in one eye of a blind man with retinitis pigmentosa, a hereditary disease that destroys light sensitive photoreceptor cells in the retina but spares the ganglion cell layer whose axons normally send visual information to the brain. Here is the Sahel et. al. abstract:

Optogenetics may enable mutation-independent, circuit-specific restoration of neuronal function in neurological diseases. Retinitis pigmentosa is a neurodegenerative eye disease where loss of photoreceptors can lead to complete blindness. In a blind patient, we combined intraocular injection of an adeno-associated viral vector encoding ChrimsonR with light stimulation via engineered goggles. The goggles detect local changes in light intensity and project corresponding light pulses onto the retina in real time to activate optogenetically transduced retinal ganglion cells. The patient perceived, located, counted and touched different objects using the vector-treated eye alone while wearing the goggles. During visual perception, multichannel electroencephalographic recordings revealed object-related activity above the visual cortex. The patient could not visually detect any objects before injection with or without the goggles or after injection without the goggles. This is the first reported case of partial functional recovery in a neurodegenerative disease after optogenetic therapy.

1 comment:

  1. Both the Times write-up and the article itself seem to lean pretty heavily on the stimulation frequency aspect and don't really bother mentioning that they're stimulating the part of the brain associated with incentive salience at the end of the reward pathways.

    I'd bet there isn't actually an effect of "frequency synchrony" at all and it's just that there's one optical frequency for entraining the VTA dopaminergic neurons to fire and when it's sub-optimal (ie, both not being optimal freq) they don't see as much effect.