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.