TRPM4 Expression During Postnatal Developmental of Mouse CA1 Pyramidal Neurons

Area of Science:

• Neuroscience
• Molecular Biology
• Developmental Biology

Background:

• Transient Receptor Potential Melastatin 4 (TRPM4) is a calcium-activated non-selective cation channel.
• TRPM4 plays a role in neuronal excitability, plasticity, and survival.
• Its developmental expression and subcellular localization in hippocampal CA1 neurons are not well understood.

Purpose of the Study:

• To investigate the subcellular localization and expression pattern of TRPM4 during postnatal development in mouse CA1 pyramidal neurons.
• To characterize the biophysical properties and functional role of TRPM4-like currents in these neurons.

Main Methods:

• Duplex immunofluorescence staining on mouse brain slices at various postnatal ages (P0, P7, P14, P35).
• Whole-cell patch-clamp recordings in CA1 pyramidal neurons.
• Pharmacological inhibition of TRPM4 using 9-phenanthrol (9-Ph).

Main Results:

• TRPM4 expression was initially somatic at P0, extending to apical dendrites by P7 and persisting through P35, while being excluded from the axon initial segment.
• A TRPM4-like current, dependent on intracellular calcium and sensitive to 9-Ph, was detected at resting membrane potential from P0 and increased with development.
• Inhibition of TRPM4 with 9-Ph caused membrane hyperpolarization in mature neurons (P14, P35) but not in younger stages.

Conclusions:

• TRPM4 is expressed in the soma and apical dendrites of CA1 pyramidal neurons during postnatal development.
• A functional TRPM4-like current contributes to neuronal depolarization and its activity is developmentally regulated.
• These findings suggest TRPM4 plays a critical role in controlling membrane potential and action potential firing during hippocampal circuit development.