Satellite Glial Cells Drive Homeostatic Synaptic Structural Plasticity in Sympathetic Neurons

Area of Science:

• Neuroscience
• Physiology
• Cell Biology

Background:

• Sympathetic neuronal (SN) activity is crucial for organ function.
• Activity-dependent plasticity may stabilize SN circuits and prevent hyperactivity, a factor in hypertension.
• Understanding these mechanisms is vital for addressing cardiovascular diseases.

Purpose of the Study:

• To investigate how long-term activity changes affect synaptic properties in SNs.
• To determine the role of sympathetic satellite glial cells (SGCs) in this plasticity.
• To examine if these mechanisms are impaired in hypertension models.

Main Methods:

• Utilized chemogenetic and pharmacological manipulations in postnatal SN cultures.
• Examined the impact of enhanced activity in spontaneously hypertensive rat (SHR) neurons.
• Assessed synaptic density and neuronal activity changes.

Main Results:

• Bidirectional changes in SN activity induced homeostatic shifts in synaptic density.
• SGCs are essential for synaptic compensation; their activation decreased synaptic sites and activity.
• Glial inhibition blocked activity-dependent synaptic compensation, highlighting SGCs' regulatory role.
• SGCs downregulated NGF and TNFα in response to cholinergic signaling, stabilizing SN output.
• These plasticity mechanisms were impaired in SHR neurons.

Conclusions:

• Identified a novel homeostatic, activity-dependent plasticity mechanism in the peripheral nervous system.
• Demonstrated a critical role for SGCs in regulating SN synaptic properties and circuit stability.
• Revealed disruptions in these plasticity mechanisms in a model of hypertension, suggesting a potential therapeutic target.