TRPM4 Conductances in Thalamic Reticular Nucleus Neurons Generate Persistent Firing during Slow Oscillations

Area of Science:

• Neuroscience
• Sleep Research
• Cellular Electrophysiology

Background:

• Thalamic reticular nucleus (TRN) neurons exhibit distinct oscillatory activities during sleep.
• Sleep spindles are linked to TRN and sensory relay nuclei circuits, but slow (<1 Hz) thalamic oscillations' mechanisms are unclear.
• Previous studies suggested TRN neurons generate slow oscillations via cell-intrinsic mechanisms involving metabotropic glutamate receptors and specific ion currents.

Purpose of the Study:

• Investigate the mechanisms underlying slow rhythmic activity in TRN neurons and thalamic circuits.
• Identify the ion channels and synaptic interactions involved in generating slow thalamic oscillations.
• Clarify the contribution of thalamic circuits to slow rhythmic activity during sleep.

Main Methods:

• Electrophysiological recordings from adult mouse thalamic slices.
• Stimulation of thalamoreticular inputs and measurement of neuronal activity.
• Pharmacological manipulation to identify ion channel roles (T-type Ca2+ channels, TRPM4).

Main Results:

• Slow rhythmic activity was recorded in TRN neurons, driven by glutamatergic inputs.
• Long-lasting plateau potentials and persistent firing (PF) were observed in TRN neurons.
• These events led to sustained inhibition in ventrobasal thalamus (VB) relay neurons.
• Plateau potentials were mediated by T-type Ca2+ channels and TRPM4 channels.

Conclusions:

• Thalamic circuits, through TRN-VB synaptic interactions, can generate slow oscillatory activity.
• TRN cell-intrinsic mechanisms, involving T-type Ca2+ and TRPM4 channels, control PF and oscillation frequency.
• These findings reveal integrated synaptic and cellular mechanisms for slow thalamic rhythms, important for sleep functions.