summary: Researchers have found that the neurotransmitter orexin, but not the stress hormone norepinephrine alone, regulates pupil size, making it difficult to understand until now. Orexin neurons influence pupil size in response to light exposure as well as emotional states and mental tension.
The findings link orexin activity to several neurological conditions, including narcolepsy and Alzheimer’s disease, providing a new diagnostic tool. This study may also clarify our understanding of consciousness and attentional regulation.
Important facts:
- Orexin neurons, rather than noradrenaline, are primarily responsible for regulating pupil size, calling into question long-standing scientific beliefs.
- The researchers found a dose-dependent relationship between orexin neuron activity and pupillary diameter, providing a direct method to measure orexin activity.
- These findings demonstrate links between orexins and several neurological conditions, such as Alzheimer’s disease, narcolepsy, stroke, and Prader-Willi syndrome, and may simplify and improve diagnostic methods.
sauce: ETH Zurich
The way the brain regulates pupil size differs from what was previously thought. The root cause, as researchers at ETH Zurich have now revealed, is the neurotransmitter orexin.
This discovery could revolutionize our understanding of consciousness and diseases such as narcolepsy and Alzheimer’s disease.
“The effect was so strong that we knew right away that we were understanding something important,” recalls Nicola Gruich, a postdoctoral researcher in the Neurobehavioral Dynamics Laboratory at ETH Zurich.
Through a series of early experiments in mice, he studied one of the lab’s main areas of research, known as orexin neurons. He observed that the pupils of mice significantly dilated when nerve cells were stimulated.
“Neurostimulation effects often get lost in the noise in the measurement data, and you have to painstakingly filter to find them. It was obvious,” he says.
First reported in 1998, orexin neurons extend from the hypothalamus to all other brain regions, including those controlling consciousness and autonomic functions. These neurons are involved in regulating sleep-wake switching, attention span, reward system, appetite, energy expenditure, and more.
Essential for normal pupillary condition
Orexin neurons directly influence central features of an individual’s emotional state, as Grutsch’s measurements showed. It is not only light stimuli that cause changes in pupil size, but also mental tension and emotional impressions.
Appropriately called the “window to the soul” in slang, the pupil is routinely used in both medical and psychological testing. Pupil size is an indicator of attention and other unconsciously controlled bodily functions.
Previously, along with light, the main determinants of pupil size were thought to be the noradrenaline, known as the stress hormone, and its receptor system.
Now, however, ETH researchers have shown instead that this role is due to the neurotransmitter orexin and its receptor system.
In fact, noradrenergic neurons cannot maintain a normal pupillary state without orexin neurons. When the orexin system is switched off, the pupil remains highly constricted.
“Essentially, noradrenergic neurons are slaves to orexin neurons,” says ETH professor Denis Buldakov, who explains this dependency in a colorful way.
Links to Narcolepsy
In their experiments, the researchers also established a dose-dependent relationship between neuronal activity and pupil diameter. “Students are showing us exactly how active the orexin neurons in the hypothalamus are,” Buldakov says.
This not only provides brain researchers with a new way to measure orexin activity, but also opens new avenues for medicine. A long association has been established between disruption of orexin regulation and the sleep disorder narcolepsy.
However, recently, associations with other neurological disorders such as Alzheimer’s disease, stroke, and the genetic disorder Prader-Willi syndrome have also been observed.
In this last state, hypothalamic diencephalon or interbrain dysfunction results in severe physical, cognitive, and metabolic symptoms.
All four of these symptoms have an element of sleep disturbance. In the future, examining pupil size may help study the effects of orexin on these conditions more precisely, and may even simplify and improve diagnosis. says Buldakov. At this time, a lumbar puncture is still required to diagnose narcolepsy, which is an invasive procedure.
unleash the limits of consciousness
As a neuroscientist, Gruitch sees his findings primarily as key to a better understanding of how the core functions of our consciousness are regulated.
“Keeping a balance between focusing on the familiar and letting your mind wander and explore the world around you is an important part of our ability to adapt to new situations.” he says.
The prevalence and extent of attention deficit disorders currently being diagnosed shows how difficult it is to maintain this balance, Gruich said.
Orexin is one of several neuromodulatory systems (others such as noradrenaline and serotonin) that regulate this balance. These systems tip the balance one way or another depending on the organism’s needs.
Early in human evolution, for example, hungry hunter-gatherers had to roam in search of food sources. When they were rewarded for finding something edible, they had to shift their focus to their surroundings to be able to scout further that food.
And when early humans were finally satisfied, they could turn their attention to meeting other needs.
Multiple neuron subsets for specific functions
In studying orexin neurons, Buldakov’s group succeeded in identifying subsets involved in different neuronal functions and thus different components of this balance.
The researchers used a special kind of fluorescence microscopy to observe the responses of individual orexin neurons in mice and compared this to variations in pupil size. They used two-photon microscopy. This made it possible to observe the activity of individual cells in the brain.
The researchers found some neurons whose activity was positively correlated with pupil size, the level of arousal in mice, and others whose activity was negatively correlated.
They also encountered cells that affect pupil size, respond to reward, and cells that are associated with only one of the two factors.
Candidates for Higher Level Regulation
Identification of these specialized subsets within orexin neurons provides the first insight into how they are wired to support the central functions of our consciousness.
In addition, Grutsch said, orexins’ effects on a variety of behavioral states, from attention, sleep-wake switching, and reward seeking to appetite and energy expenditure, make them prime candidates for higher-order regulation. there is
The findings of the ETH researchers will further the scientific research into identifying additional neuronal subsets and how they interact and how they interact with the serotonin and noradrenergic systems. Open the door to the road.
Researchers believe that answering questions like this will not only lead to a more detailed understanding of how our vital functions are regulated.
They also predict benefits in diagnosing and treating attention and sleep disorders and related conditions. And as the examples of Alzheimer’s disease and stroke suggest, these benefits may be greater than they seem.
About this neuroscience research news
author: Daniel Meyerhans
sauce: ETH Zurich
contact: Daniel Meyerhans – ETH Zurich
image: Image credited to Neuroscience News
Original research: open access.
“Regulation and coding of pupil size by hypothalamic orexin neurons” Grujic N et al. natural neuroscience
overview
Regulation and coding of pupil size by hypothalamic orexin neurons
Orexin (hypocretin) neurons in the brain are involved in sleep-wake switching and reward seeking, but their role in rapid wake dynamics and reward perception is unclear.
Cell-specific stimulation, deletion, and in vivo recordings now reveal a strong correlation and causal relationship between the quantitative arousal marker pupillary dilation and orexin cell activity.
Arousal and reward coding are distributed throughout orexin cells, indicating that orexin cells are specialized for rapid multiplexing of momentary arousal and reward states.
