Astrocytes Play Critical Role in Regulating Behavior

Summary: Researchers made a groundbreaking discovery in identifying a unique group of astrocytes, located in the brain’s central striatum, that play a crucial role in regulating behaviors linked to neuropsychiatric disorders. This distinct subset of astrocytes expresses the gene Crym, coding for μ-crystallin, a protein associated with various human diseases.

By experimentally reducing Crym expression in these astrocytes, the study observed increased repetitive behaviors in mice, akin to human perseveration seen in conditions like autism and OCD. This novel finding not only challenges the neuron-centric view of brain function but also opens up new avenues for potential treatments targeting specific astrocyte populations.

Key Facts:

  1. Discovery of Behavior-Regulating Astrocytes: Researchers identified astrocytes expressing the Crym gene in the central striatum as key players in behavior regulation.
  2. Link to Neuropsychiatric Disorders: Reduced expression of Crym in these astrocytes led to behaviors in mice that mirror human perseveration, associated with disorders such as autism and OCD.
  3. Potential for New Therapies: The findings offer a new target for developing therapies aimed at alleviating symptoms of various neuropsychiatric conditions by modulating astrocyte function.

Source: UCLA

UCLA Health researchers have discovered a group of specialized support cells in the brain that can regulate behaviors associated with human neuropsychiatric disorders.

The study, published in the journal Nature, focused on a group of cells known as astrocytes – star-shaped cells that tile the central nervous system and provide a support structure for the neural communication networks. 

This shows astrocytes.
The study found that Crym-positive astrocytes in the central striatum regulated neurotransmitter communication at synapses from the cortex to the center of the brain within the striatum. Credit: Neuroscience News

While neurons have long been understood to have primary control of behavior, the study found that a distinct group of astrocytes located deep in the central region of the brain, known as the central striatum, may also regulate communications between neurons.

Unlike other astrocytes, this group of astrocytes express the gene Crym, which encodes for the protein known as μ-crystallin. This protein has been associated with several human diseases including neuropsychiatric disorders, but its influence on brain function has remained largely unknown.

“Several years ago the lab identified that astrocytes in the striatum express Crym. It was my job to find out what it did. By reducing expression of this gene in astrocytes of the central striatum, I uncovered mechanisms related to a specific behavior called perseveration,” said Matthias Ollivier, the study’s first author and postdoctoral scholar at the David Geffen School of Medicine at UCLA.

In the study, researchers genetically reduced the expression of the gene in this group of astrocytes in mice. Studying the behavior of mice, the researchers found they had significant increases in repetitive behavioral patterns or activities that serve little purpose or made it difficult for the mice to transition to other activities.

This behavior, known as perseveration, is associated with neurological and psychiatric disorders including autism, obsessive-compulsive disorder, Huntington’s disease and Tourette syndrome.

The study found that Crym-positive astrocytes in the central striatum regulated neurotransmitter communication at synapses from the cortex to the center of the brain within the striatum.

“At a basic biology level, the study provides evidence that distinct types of astrocytes have important neurobiological functions,” said Baljit Khakh, the senior author of the study and professor of physiology and neurobiology at the David Geffen School of Medicine at UCLA.

Researchers say the findings could be starting points in the development of potential therapies to alleviate perseveration in different disorders. Further research is underway to understand the interactions and signaling cascades regulated by μ-crystallin.

About this neuroscience and mental health research news

Author: Will Houston
Source: UCLA
Contact: Will Houston – UCLA
Image: The image is credited to Neuroscience News

Original Research: Open access.
Crym-positive striatal astrocytes gate perseverative behaviour” by Matthias Ollivier et al. Nature


Crym-positive striatal astrocytes gate perseverative behaviour

Astrocytes are heterogeneous glial cells of the central nervous system. However, the physiological relevance of astrocyte diversity for neural circuits and behaviour remains unclear.

Here we show that a specific population of astrocytes in the central striatum expresses μ-crystallin (encoded by Crym in mice and CRYM in humans) that is associated with several human diseases, including neuropsychiatric disorders.

In adult mice, reducing the levels of μ-crystallin in striatal astrocytes through CRISPR–Cas9-mediated knockout of Crym resulted in perseverative behaviours, increased fast synaptic excitation in medium spiny neurons and dysfunctional excitatory–inhibitory synaptic balance.

Increased perseveration stemmed from the loss of astrocyte-gated control of neurotransmitter release from presynaptic terminals of orbitofrontal cortex–striatum projections. We found that perseveration could be remedied using presynaptic inhibitory chemogenetics, and that this treatment also corrected the synaptic deficits.

Together, our findings reveal converging molecular, synaptic, circuit and behavioural mechanisms by which a molecularly defined and allocated population of striatal astrocytes gates perseveration phenotypes that accompany neuropsychiatric disorders.

Our data show that Crym-positive striatal astrocytes have key biological functions within the central nervous system, and uncover astrocyte–neuron interaction mechanisms that could be targeted in treatments for perseveration.

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