Reward Lasers

Our ability to feel pleasure in rewarding situations depends on a delicate balance of two specific types of brain circuits, a new study reports.

By using targeted lasers to activate specific cells in a mouse brain, researchers can disrupt and reactivate small sections of that brain’s reward pathway, causing mice to drastically change their behavior. A lot of the cells that activate the brain’s main pleasure highway – particularly neurons in the ventral tegmental area (VTA) – respond to the neurotransmitter chemical dopamine; but other cells in that area – neurons that respond to the neurotransmitter gamma-aminobutyric acid (GABA) – can block those dopaminergic neurons from passing their signals on.

Yep, it’s time for a story about controlling brains with lasers. Pew pew pew!

Though we’ve known for years that dopamine is a crucial chemical for feelings of reward, scientists have had to figure that out either by injecting brains with drugs that block dopamine chemically, or by dissecting the brains of dead animals injected with special dye that lights up in the presence of that particular chemical. Those processes have some obvious drawbacks, though: once you’ve sacrificed a lab rat, you can’t exactly keep studying its behavior – and while the rat’s alive and running around in a maze, you can’t get a very clear look at individual neurons inside its head.

Some new technologies are changing that, though. Not only are there cool devices like the tiny microscope hat – scientists can now use lasers to activate cells of a specific genetic makeup… on command. The emerging field of optogenetics is giving birth to all kinds of weird discoveries – from light-controlled fly brains to non-invasive therapies for disorders like epilepsy and schizophrenia.

And now, a team led by Garret D. Stuber at the University of North Carolina at Chapel Hill School of Medicine have used this technology to study the impact of GABAergic neurons on dopaminergic neurons, the journal Neuron reports.

Lasermaus wants his 15 minutes of fame (and maybe some sugar water).

After recording the behavior of a group of mice in rewarding situations (they were given sugar water for completing simple memory tasks), the researchers shined lasers into the animals’ brains via fiber-optic cables. And since these mice had been genetically engineered to produce opsins – light-sensitive proteins – in their GABAeric neurons, the scientists could activate just those neurons with tiny pulses of light.

When they did this, the team found that the mice took on some unusual behavior:

Optogenetic activation of VTA GABA neurons disrupts reward consummatory behavior but not conditioned anticipatory behavior in response to reward-predictive cues.

In other words, the mice still performed the tasks they remembered would earn them a taste of sugar water – but they stopped wanting to drink it.

What’s more, scientists found they could reactivate the animals’ desire to drink by laser-activating another area of the reward pathway – the nucleus accumbens (NAc):

Direct activation of VTA GABA projections to the nucleus accumbens (NAc) resulted in detectable GABA release but did not alter reward consumption.

And in a final flourish, the team figured out exactly how those GABAergic neurons in the VTA were preventing the mice from enjoying their drinks:

Optogenetic stimulation of VTA GABA neurons directly suppressed the activity and excitability of neighboring DA neurons as well as the release of DA in the NAc, suggesting that the dynamic interplay between VTA DA and GABA neurons can control the initiation and termination of reward-related behaviors.

In short, GABA neurons in the VTA block the activity of dopamine, both in the VTA and in the NAc. Since the VTA and the NAc are clearly communicating with each other, this seems to suggest that a delicate balance between dopamine and GABA in these areas is necessary for us to both want rewards and enjoy them once we get them.

That’s the balance that becomes upset in the brains of drug abusers and chronically depressed people: their brain might not produce enough dopamine, it might produce too much, and/or their reward pathway might not be as responsive to the chemical as it would be in a healthy brain. So hopefully, targeted laser therapy won’t be too far in the future for people suffering from problems like these.

(Many thanks to Mike Robinson for sharing the brain image at the top of the article!)



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