Summary: Destruction or removal of the cilia in the striatum impairs time perception and judgment, new research suggests. The findings could have implications for a range of diseases including schizophrenia, ASD, and Parkinson’s.
Source: UC Irvine
Researchers at the University of California, Irvine have discovered that removal of cilia from the brain’s striatum region impaired time perception and judgment, revealing 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 across specific mental and neurological disorders is a profound decline in patients’ ability to adjust to variations in their surroundings and accurately estimate the timing and termination of voluntary actions.
The study, recently published online in the journal Molecular Neurobiology, uncovered the first evidence of the important role cilia play in timing-dependent dysfunction.
“Our findings may revolutionize our understanding of brain functions and mental disorders in the context of the critical task performed by these previously unappreciated organelles in the brain’s ‘central clock’ function,” said Amal Alachkar, Ph.D., corresponding author and professor of teaching 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 part of the brain’s circuitry that performs central clock processes, essential in controlling executive functions such as motor coordination, learning, planning and decision-making, as well as working memory and attention. Cilia protrude from the brain cell surfaces like antennae, working as a signaling hub that senses and transmits signals to generate appropriate reactions.
To examine their physiological role, the researchers removed cilia from the striatum in mice using conditional gene manipulation technology. These rodents were not able to learn new motor tasks, showed repetitive motor behavior and exhibited delays in decision-making.
They were also deficient in rapidly recalling information about their location and orientation in space and in their ability to filter 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, usually within a millisecond to a minute,” Alachkar said.
“When that capacity is impaired, it means losing the ability to quickly adjust behavior in response to changes in external stimuli and failing to sustain appropriate, goal-oriented motor responses.
“Our ongoing work is aimed at understanding the mechanisms by which cilia regulate time perception and developing targeted therapies to improve behavioral deficits.”
Team members also included pharmaceutical sciences graduate students Wedad Alhassen, Sammy Alhassen, Kiki Jiaqi Chen and Roudabeh Vakil Monfared.
Funding: This work was funded, in part, by the National Institutes of Health under award numbers R01-HL1473-02S1 and 1F31MH126565-01A1.
About this perception and neuroscience research news
Author: Pat Harriman
Source: UC Irvine
Contact: Pat Harriman – UC Irvine
Image: The image is in the public domain
Original Research: Open access.
“Cilia in the Striatum Mediate Timing-Dependent Functions” by Amal Alachkar et al. Molecular Neurobiology
Abstract
Cilia in the Striatum Mediate Timing-Dependent Functions
Almost all brain cells contain cilia, antennae-like microtubule-based organelles. Yet, the significance of cilia, once considered vestigial organelles, in the higher-order brain functions is unknown.
Cilia act as a hub that senses and transduces environmental sensory stimuli to generate an appropriate cellular response.
Similarly, the striatum, a brain structure enriched in cilia, functions as a hub that receives and integrates various types of environmental information to drive appropriate motor response.
To understand cilia’s role in the striatum functions, we used loxP/Cre technology to ablate cilia from the dorsal striatum of male mice and monitored the behavioral consequences.
Our results revealed an essential role for striatal cilia in the acquisition and brief storage of information, including learning new motor skills, but not in long-term consolidation of information or maintaining habitual/learned motor skills. A fundamental aspect of all disrupted functions was the “time perception/judgment deficit.”
Furthermore, the observed behavioral deficits form a cluster pertaining to clinical manifestations overlapping across psychiatric disorders that involve the striatum functions and are known to exhibit timing deficits. Thus, striatal cilia may act as a calibrator of the timing functions of the basal ganglia-cortical circuit by maintaining proper timing perception.
Our findings suggest that dysfunctional cilia may contribute to the pathophysiology of neuro-psychiatric disorders, as related to deficits in timing perception.
