A computer game that induces mice to experience hallucination-like events could be a key to understanding the neurobiological roots of psychosis, according to a study from Washington University School of Medicine in St. Louis. Credit: J. Kuhl
An increase of dopamine in the brain’s striatum triggers auditory hallucination-like experiences in mice, revealing a possible causal role for dopamine-dependent neurological circuits in symptoms of psychosis. These findings from a new study could inform novel targeted approaches to treating those with psychotic disorders, like schizophrenia.
Auditory and visual hallucinations — perceptions of hearing or seeing something without observing external sensory stimuli — are central symptoms of psychotic disorders and are thought by some to be caused by excessive dopamine in the brain. However, evaluating the dopamine hypothesis of psychosis is particularly challenging, as hallucinatory experiences often rely on self-reporting, an ability that model organisms like mice lack. As a result, understanding how best to effectively treat psychotic disorders remains limited.
Katharina Schmack and colleagues developed a behavioral model to quantify hallucination-like perception in mice. Schmack et al. trained mice to respond to both visual and auditory cues, thus creating conditioned hallucination-like responses when the cues were altered. Then, using dopamine-sensor measurements and pharmacological manipulations, the authors demonstrated a brain circuit link between excessive striatal dopamine and hallucination-like experience in the mice.
According to the authors, the novel behavioral approach opens the door for mice to be used as a promising translational model of common psychotic symptoms and, perhaps, therapeutic approaches based on selective modulation of dopamine function.
“Although much remains to be explored in these circuits, the findings of Schmack et al. add to a growing body of literature indicating that beyond striatal dopamine’s function in reinforcement of learning and decision-making, it also plays a key role in the neuromodulation of perception,” writes Miriam Matamales in a related Perspective.
“Nevertheless, it is starting to become clear that elegantly designed behavioral neuroscience experiments can effectively bridge the gap between complex psychiatric disorders and the neural systems that underpin them.”
For more on this research, read Mice With Hallucination-Like Behaviors Reveal Insights Into Psychotic Illnesses.
Reference: “Striatal dopamine mediates hallucination-like perception in mice” by K. Schmack, M. Bosc, T. Ott, J. F. Sturgill and A. Kepecs, 2 April 2021, Science.
DOI: 10.1126/science.abf4740
