Presynaptic activity regulates Na(+) channel distribution at the axon initial segment

Area of Science:

• Neuroscience
• Cellular Neuroscience
• Auditory Neuroscience

Background:

• Neural circuits exhibit plasticity to restore activity upon afferent input deprivation.
• The axon initial segment (AIS) is crucial for initiating neural signals but lacks known plasticity.
• Homeostatic regulation is essential for maintaining neural function under changing conditions.

Purpose of the Study:

• To investigate whether the AIS undergoes plastic changes in response to sensory deprivation.
• To determine if AIS plasticity contributes to neuronal excitability regulation.
• To explore the role of AIS plasticity in maintaining neural function after hearing loss.

Main Methods:

• Auditory input deprivation in avian brainstem auditory neurons.
• Measurement of AIS length and distribution of voltage-gated Na(+) channels and AIS anchoring proteins.
• Assessment of whole-cell Na(+) current, membrane excitability, and spontaneous firing rates.

Main Results:

• Auditory input deprivation led to a 1.7-fold increase in AIS length within seven days.
• Increased AIS length was associated with enhanced whole-cell Na(+) current and membrane excitability.
• Spontaneous neuronal firing rates also increased following auditory input deprivation.

Conclusions:

• The axon initial segment (AIS) exhibits homeostatic plasticity, lengthening in response to sensory deprivation.
• AIS plasticity augments neuronal excitability, potentially compensating for lost sensory input.
• Plasticity at the spike initiation site offers a mechanism for neural computation refinement during sensory loss.