Striatal dopamine mediates hallucinatory perception in mice
We have established hallucinatory perception as a quantitative behavior in mice to model the subjective experience of basic symptoms of psychosis. They found that hallucinatory perceptions are mediated by elevated dopamine in the striatum, which can be explained by the encoding of different kinds of expectations in different striatal subregions. These findings support the idea that hallucinations arise as false perceptual inferences due to elevated dopamine that creates a bias in favor of prior expectations over current sensory evidence. Our results also provide circuit-level insight into the long-standing dopamine hypothesis of psychosis and provide a rigorous framework for analyzing the neural circuit mechanisms involved in hallucinations.
DOI: 10.1126 / science.abf4740
DESCRIPTION
This study investigated the neural basis of hallucinatory-like perceptions in mice in order to understand how these perceptions are the main symptom of psychosis.
They say that hallucinations are false perceptions experienced with the same subjective confidence as "true" perceptions, and can be assessed quantitatively using a sensory detection task in which individuals report whether they have heard a signal embedded in background noise and indicate how confident they are in their answer. Thus, a hallucinatory perception is defined as a reliable false alarm, a false report that a signal was present.
It is reasoned that such experimentally controlled hallucinatory perceptions involve neural mechanisms that are shared with spontaneously experienced hallucinations in psychosis and can serve as a translational model of psychotic symptoms.
As a result, an auditory detection task similar to that between humans and mice was set up in which auditory stimuli with an embedded tone signal were presented against a noisy background.
For humans, we reported whether they heard the signal by pressing one of two buttons, while the mouse plunged into one of two selection ports. In experiments using genetically encoded dopamine sensors with fiber photometry to monitor dopamine dynamics in the striatum, as well as proximity to these commonalities, they found that elevated dopamine levels before stimulus onset predicted hallucinatory-like perceptions in both the ventral striatum and the tail of the striatum We found that
This experimental model revealed how hallucinatory perceptions arise from fluctuations in two different types of expectations: reward expectations and perceptual expectations. In mice, dopamine fluctuations in the ventral striatum reflected reward expectations, while in the tail of the striatum they resembled perceptual expectations. It was observed that optogenetic boosting of dopamine in the caudal part of the striatum and increased dopamine induced hallucinatory-like perceptions, and this effect was rescued by the administration of haloperidol, an antipsychotic drug that blocks D2 dopamine receptors.
