Irvine, California, 30 November 2022 — Researchers at the University of California, Irvine, have discovered that removing cilia from the striatum region of the brain impairs time perception and judgment, and reveals possible new therapeutic targets for mental and neurological conditions, including schizophrenia, Parkinson’s and Huntington’s diseases, autism spectrum disorder and Tourette syndrome. .
The striatum processes and integrates new environmental sensory information and coordinates the time sequence of motor responses. A common feature of specific mental and neurological disorders is the profound decline in patients’ ability to adapt to changes in their environment and accurately predict the timing and termination of voluntary actions.
this studyrecently published online in the journal Molecular Neurobiologyrevealed the first evidence of an important role that cilia play in timing-related dysfunction.
«Our findings could revolutionize our understanding of brain function and mental disorders in the context of the critical task performed by these organelles that were previously underappreciated in the brain’s ‘central clock’ function,» said Amal Alachkar. Lecturer in UCI’s Department of Pharmaceutical Sciences. «Our results may open new avenues for effective intervention through cilia-targeted therapies for treatment.»
The striatum is the part of the brain circuitry that performs central clock processes essential in controlling executive functions such as working memory and attention, as well as motor coordination, learning, planning and decision making. Cilia protrude from brain cell surfaces like antennae, working as a signal center that senses and transmits signals to create appropriate reactions.
To examine their physiological roles, the researchers removed cilia from the striatum in mice using conditional gene manipulation technology. These rodents failed to learn new motor tasks, showed repetitive motor behaviors and exhibited delays in decision making. They were also incapable of quickly recalling information about their position and orientation in space and filtering out irrelevant environmental sensory information. However, the mice maintained habitual or already learned motor skills and long-term memories.
«Successful performance of working memory, attention, decision making, and executive function requires accurate and precise timing judgment, often in the millisecond to one minute.» Said. «When this capacity is impaired, it means losing the ability to rapidly adjust behavior in response to changes in external stimuli and being unable to maintain appropriate, goal-directed motor responses. Our ongoing work aims to understand the mechanisms by which cilia regulate the perception of time and develop targeted therapies to ameliorate behavioral deficits.»
Team members included pharmaceutical science graduate students Wedad Alhassen, Sammy Alhassen, Kiki Jiaqi Chen, and Roudabeh Vakil Monfared.
This work was partially funded by the National Institutes of Health under award numbers R01-HL1473-02S1 and 1F31MH126565-01A1.
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Cilia in the striatum mediate timing-dependent functions
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