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Elevated dopamine in the striatum can cause hallucinations
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Elevated dopamine in the striatum can cause hallucinations.
Psychotic disorders such as schizophrenia bring a huge burden to human beings, society and the economy.
Over the past few decades, as scientists’ understanding of underlying neurobiology has remained stagnant, the prognosis of mental illness has not substantially improved.
In fact, the subjectivity of hallucinations is a defining symptom of mental illness, which poses a lasting challenge for rigorous research in humans and translation into preclinical animal models.
In a new study, researchers from the Cold Spring Harbor Laboratory in the United States and the University of Washington School of Medicine have developed a cross-species method of calculating mental illness to directly link the behavior of humans and rodents and use this This method is used to study the neural basis of hallucination-like perception in mice.
The relevant research results were published in the Science Journal on April 2, 2021, with the title of the paper “Striatal dopamine mediates hallucination-like perception in mice”.
Similar false perceptions can be quantitatively assessed using the sensory detection task, in which participants report whether they have heard signals embedded in background noise and show how confident they are in their answers.
Therefore, these authors define hallucination-like perceptions as self-confident false alarms—that is, false reports of the presence of signals and high confidence in these reports.
These authors infer that the hallucination-like perception controlled by this experiment has the same neural mechanism as the hallucinations experienced spontaneously in mental illness, and therefore can be used as a transformation model for the symptoms of mental illness.
Given that psychiatric symptoms are thought to be involved in the increase in dopamine transmission in the striatum, they speculate that hallucination-like perception is mediated by an increase in dopamine in the striatum.
These authors set up similar auditory detection tasks for humans and mice.
Both human participants and mice were provided with an auditory stimulus in which a tonal signal was embedded on a noisy background in half of the experiment.
Human participants pressed one of the two buttons to report whether they heard the signal, while mice poked into one of the two selection ports to indicate this.
Human participants placed a cursor on a slider to indicate how confident they were; mice expressed their confidence by investing different durations of rewards.
In humans, hallucination-like perceptions—high-confidence false alarms—are related to the propensity to experience spontaneous hallucinations and can be quantified by self-report questionnaires.
In mice, two known maneuvers that induce hallucinations in humans can increase their hallucination-like perception: ketamine delivery and a strong desire to hear the signal.
Then, the authors used genetically encoded dopamine sensors and fiber optic photometers to monitor the dynamics of dopamine in the striatum.
They found that an increase in dopamine levels before the stimulation started predicts hallucination-like sensations in the ventral striatum and the tail of the striatum.
Hallucination-like perception framework and striatal dopamine. Picture from Science, 2021, doi:10.1126/science.abf4740.
They designed a computational model to explain that when the previous expectations are greater than the sensory evidence, the appearance of hallucination-like perceptions is the result of wrong perception inferences.
This model illustrates how hallucination-like perception arises from fluctuations in two different types of expectations: reward expectation and perceptual expectation.
In mice, dopamine fluctuations in the ventral striatum reflect reward expectations, while dopamine fluctuations in the tail of the striatum reflect perception expectations.
They used optogenetics to increase dopamine in the tail of the striatum, and observed that the increase in dopamine caused hallucinations.
This effect can be rescued by giving haloperidol (an antipsychotic drug that blocks D2 dopamine receptors).
In summary, these authors established hallucination-like perception in mice as a quantitative behavior to simulate the subjective experience of the main symptoms of mental illness.
They found that hallucination-like perception is mediated by an increase in dopamine in the striatum, and this can be explained by encoding different kinds of expectations in different subregions of the striatum.
These findings support the view that hallucinations are caused by the rise of dopamine, which produces a false perception inference that is biased in favor of previous expectations rather than current sensory evidence.
These results also provide new insights at the circuit level for the long-standing mental illness dopamine hypothesis, and provide a rigorous framework to analyze the neural circuit mechanisms involved in hallucinations.
These authors suggest that this approach can guide the development of new treatments for schizophrenia and other mental illnesses.
Elevated dopamine in the striatum can cause hallucinations
(source:internet, reference only)