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The Attentional Set Shifting Task: A Measure of Cognitive Flexibility in Mice

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Crym-positive striatal astrocytes gate perseverative behaviour.

Matthias Ollivier¹, Joselyn S Soto¹, Kay E Linker¹

¹Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.

|February 28, 2024

Summary

This summary is machine-generated.

Specific striatal astrocytes control perseveration behaviors. Loss of μ-crystallin in these astrocytes causes perseveration and synaptic issues, highlighting astrocyte diversity

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Area of Science:

Neuroscience
Astrocyte Biology
Neuropsychiatric Disorders

Background:

Astrocytes are diverse glial cells in the central nervous system.
The functional significance of astrocyte heterogeneity in neural circuits and behavior is not well understood.
A specific astrocyte population in the striatum expresses μ-crystallin (Crym), linked to human diseases.

Purpose of the Study:

To investigate the physiological role of μ-crystallin-expressing striatal astrocytes.
To determine the impact of μ-crystallin loss on neural circuits and behavior.
To explore mechanisms underlying perseverative behaviors in neuropsychiatric disorders.

Main Methods:

CRISPR-Cas9-mediated knockout of Crym in adult mice to reduce μ-crystallin levels in striatal astrocytes.
Behavioral analysis to assess perseverative behaviors.
Electrophysiological recordings to examine synaptic function in medium spiny neurons.
Presynaptic inhibitory chemogenetics to test therapeutic interventions.

Main Results:

Knockout of Crym in striatal astrocytes led to perseverative behaviors and increased fast synaptic excitation.
Synaptic deficits included a dysfunctional excitatory-inhibitory balance in medium spiny neurons.
Perseveration resulted from impaired astrocyte-mediated control of neurotransmitter release from orbitofrontal cortex-striatum projections.

Conclusions:

Crym-positive striatal astrocytes play a crucial role in gating perseveration.
Loss of astrocyte μ-crystallin disrupts synaptic function and contributes to neuropsychiatric disorder phenotypes.
Targeting astrocyte-neuron interactions offers potential therapeutic strategies for perseveration.