TRH regulates action potential shape in cerebral cortex pyramidal neurons

• TRH widens and diminishes the amplitude of action potentials in pyramidal cortical neurons.
• Action potential shape varies with dose of TRH, time and cortical neuron location.
• The action of TRH depends on G-protein activity.
• Inhibition of pyroglutamyl peptidase II activity changes action potential shape.
• Pyroglutamyl peptidase II is expressed in cortical glutamatergic and GABAergic neurons.

Thyrotropin releasing hormone (TRH) is a neuropeptide with a wide neural distribution and a variety of functions. It modulates neuronal electrophysiological properties, including resting membrane potential, as well as excitatory postsynaptic potential and spike frequencies. We explored, with whole-cell patch clamp, TRH effect on action potential shape in pyramidal neurons of the sensorimotor cortex. TRH reduced spike and after hyperpolarization amplitudes, and increased spike half-width. The effect varied with dose, time and cortical layer. In layer V, 0.5 µM of TRH induced a small increase in spike half-width, while 1 and 5 µM induced a strong but transient change in spike half-width, and amplitude; after hyperpolarization amplitude was modified at 5 µM of TRH. Cortical layers III and VI neurons responded intensely to 0.5 µM TRH; layer II neurons response was small. The effect of 1 µM TRH on action potential shape in layer V neurons was blocked by G-protein inhibition. Inhibition of the activity of the TRH-degrading enzyme pyroglutamyl peptidase II (PPII) reproduced the effect of TRH, with enhanced spike half-width. Many cortical PPII mRNA+ cells were VGLUT1 mRNA+, and some GAD mRNA+. These data show that TRH regulates action potential shape in pyramidal cortical neurons, and are consistent with the hypothesis that PPII controls its action in this region.