NMDA enhances a depolarization-activated inward current in subthalamic neurons

Area of Science:

• Neuroscience
• Molecular Biology
• Electrophysiology

Background:

• N-methyl-D-aspartate (NMDA) receptor stimulation is known to induce burst firing in subthalamic nucleus (STN) neurons.
• The underlying ionic mechanisms, particularly the inward currents involved, require further elucidation.

Purpose of the Study:

• To identify and characterize the depolarization-activated inward current (DIC) responsible for NMDA-induced burst firing in STN neurons.
• To investigate the ionic and molecular basis of this DIC.

Main Methods:

• Whole-cell patch-clamp recordings in voltage-clamp mode were performed on rat brain slices.
• NMDA and AMPA receptor agonists were used to evoke currents.
• Ionic substitutions and specific channel blockers (TTX, BAPTA, Ca2+ channel blockers, TRP channel blockers) were employed to dissect the current's properties.

Main Results:

• NMDA superfusion induced a TTX-insensitive, time-dependent DIC at depolarized potentials (-70 to -50 mV), peaking at -60 mV.
• The DIC was dependent on extracellular Ca2+ and Na+, and was blocked by intracellular BAPTA.
• Selective Ca2+ channel blockers did not affect the DIC, but TRP channel blockers (flufenamic acid, SKF96365) significantly reduced it.
• AMPA did not evoke a similar current.

Conclusions:

• NMDA receptor activation enhances a Ca2+-activated non-selective cation current in STN neurons.
• This DIC is likely mediated by a Transient Receptor Potential (TRP) channel family member.
• The identified DIC provides a potential mechanism for NMDA-induced burst firing in STN neurons.