Intrinsic adaptive plasticity in mouse and human sensory neurons

Area of Science:

• Neuroscience
• Cellular Neuroscience
• Peripheral Nervous System Research

Background:

• Neurons in the central nervous system employ homeostatic plasticity to maintain network function amid changing synaptic strengths.
• This plasticity involves synaptic scaling and intrinsic excitability regulation.
• Increased sensory neuron excitability is linked to chronic pain, but its presence in the peripheral nervous system (PNS) is unclear.

Purpose of the Study:

• To investigate whether homeostatic plasticity mechanisms are active in peripheral sensory neurons.
• To determine how sensory neurons respond to sustained depolarization and altered activity levels.

Main Methods:

• Sustained depolarization of mouse and human sensory neurons using high KCl concentration (30 mM for 24 h).
• Voltage-clamp recordings to assess changes in ion currents, specifically voltage-gated sodium and potassium currents.
• Optogenetic stimulation to induce sustained action potential firing (1 Hz for 24 h) for comparison.

Main Results:

• Sustained depolarization induced a compensatory decrease in sensory neuron excitability.
• This decrease was associated with a significant reduction in voltage-gated sodium currents, not potassium currents.
• The adaptive changes were reversible after a 24-h recovery period.
• Sustained action potential firing did not induce similar adaptive changes, highlighting the role of prolonged depolarization.

Conclusions:

• Mouse and human sensory neurons possess homeostatic plasticity mechanisms to regulate intrinsic excitability.
• These adaptive responses to sustained depolarization are similar to those found in the central nervous system.
• This finding has implications for understanding sensory neuron function and dysfunction in conditions like chronic pain.