Doctors have long used pupil response to gauge levels of consciousness, and those of us on common antidepressants may have noticed the saucer-eyed look in response to increased levels of serotonin floating around our brains. A new mouse study conducted by ETH Zurich has just worked out the mechanism behind these responses.
"The effect was so strong, we knew immediately that we were onto something important," says neuroscientist Nikola Grujic
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The neurotransmitter orexin, also known as hypocretin, may be behind all these changes through cells called orexin neurons. These cells extend from the hypothalamus, the tiny structure deep inside our brains that channels our body's hormone responses to the rest of the organ.
Orexin neurons project across different brain regions with particularly strong connections within our arousal and reward brain areas. With these connections, we already know they regulate the switch between our conscious, awake systems to automatic sleeping states, but their role in more fleeting states of arousal wasn't fully understood until now.
Grujic and colleagues stimulated these specific cells in living mice and, with the help of two-photon microscopy, observed how their activities compared to pupil size.
When the team activated some of these neurons, pupils expanded.
"Quite often, the effects of neurostimulation get lost in the noise of measurement data, which we then have to painstakingly filter in order to find them. This time was different. The effect was plain to see," says Grujic.
Some groups of these neurons did not alter pupil size but affected reward systems, while others influenced pupil activation and reward systems. Both pupil dilation and constriction were also dose-dependent. All of this reveals a direct relationship between the orexinergic neuron system and the control of pupil dilation.
"The pupils show us precisely how active the orexin neurons in the hypothalamus are," explains neuroscientist Denis Burdakov.
What's more, "noradrenaline neurons are slaves to orexin neurons," continues Burdakov. The noradrenaline system was previously thought to control our pupils' reactions, but the team's data indicate these cells actually modulate the orexin neurons' responses.
However, their involvement links our heightened emotional states (like our adrenalin response to fear) and many drug effects to our pupils' states.
Strangely though, mice without orexin neurons still had constricted pupils while they rested; but when they were running, their pupils were more normally dilated. This suggests there is another neural system opening these windows to our souls during this different state of arousal, the researchers explain.
As orexin neurons play a central role in so many systems, damage or loss to these cells could contribute to multiple neurological disorders, including sleep disorders like narcolepsy and Alzheimer's. The researchers are keen to explore this further.
This research was published in Nature Neuroscience.
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