Hippocampal astrocytes induce sex-dimorphic effects on memory

Area of Science:

• Neuroscience
• Cell Biology
• Cognitive Science

Background:

• Astrocytic receptors are crucial for cognitive functions.
• The influence of biological sex on astrocytic receptor function in cognition is largely unknown.
• Astrocytes play a significant role in brain function and disease pathology.

Purpose of the Study:

• To investigate the sex-dependent roles of astrocytic receptors in spatial memory.
• To examine how manipulating metabotropic glutamate receptor 3 (mGluR3) in astrocytes affects cognitive processes.
• To determine the impact of astrocytic receptor signaling pathways (G_i/o and G_s) on memory in a sex-specific manner.

Main Methods:

• Utilized in vivo gene editing techniques to modify astrocytic receptor expression.
• Employed chemogenetics to selectively activate or inhibit specific astrocytic receptor pathways.
• Assessed spatial memory performance and spatial search strategies in male and female subjects.

Main Results:

• Reduced astrocytic metabotropic glutamate receptor 3 (mGluR3) impaired memory in females but enhanced it in males.
• Increased astrocytic mGluR3 levels showed sex-dependent effects, enhancing memory in females.
• Chemogenetic stimulation of G_i/o- and G_s-coupled receptors in astrocytes produced bidirectional and sex-dimorphic effects on memory.

Conclusions:

• Astrocytes act as sex-dependent modulators of cognitive function, particularly spatial memory.
• Sex differences in astrocyte signaling contribute to variations in cognitive performance.
• These findings suggest astrocytes may play a role in sex differences observed in aging and neurological diseases.