Serotonin receptor 4 regulates hippocampal astrocyte morphology and function

Area of Science:

• Neuroscience
• Cell Biology
• Molecular Biology

Background:

• Astrocytes are key players in synaptic function and neuronal network regulation.
• Rho family GTPases are known regulators of cell morphology, but their specific roles in astrocytes are not fully understood.

Purpose of the Study:

• To investigate the role of serotonin receptor 4 (5-HT₄ R) in hippocampal astrocytes.
• To elucidate the signaling pathway downstream of 5-HT₄ R in astrocytes and its effect on synaptic transmission.

Main Methods:

• Utilized fluorescence microscopy to detect 5-HT₄ R expression and RhoA activity in hippocampal astrocytes.
• Examined astrocyte morphology and filamentous actin assembly upon 5-HT₄ R activation.
• Assessed the impact of 5-HT₄ R signaling on glutamatergic synaptic transmission in mixed cultures and acute brain slices.

Main Results:

• Demonstrated expression of 5-HT₄ R in hippocampal astrocytes.
• Showed that 5-HT₄ R activation leads to RhoA activity via Gα₁₃ signaling, promoting actin assembly and astrocyte morphological changes.
• Found that 5-HT₄ R-RhoA signaling in astrocytes alters glutamatergic synaptic transmission, increasing mEPSC frequency and reducing fEPSP PPR.

Conclusions:

• Astrocytic 5-HT₄ R signaling through Gα₁₃ and RhoA is a novel pathway regulating astrocyte morphology.
• This pathway functionally impacts excitatory synaptic transmission and neuronal network activity.