Development of Action Potential Waveform in Hippocampal CA1 Pyramidal Neurons

Abstract

CA1 pyramidal neurons undergo intense morphological and electrophysiological changes from the second to third postnatal weeks in rats throughout a critical period associated with the emergence of exploratory behavior. Using whole cell current-clamp recordings in vitro and neurochemical methods, we studied the development of the somatic action potential (AP) waveform and some of the underlying channels in this critical period. At the third postnatal week, APs showed a more hyperpolarized threshold, higher duration and amplitude. Subthreshold depolarization broadened APs and depolarized their peak overshoots more pronouncedly in immature neurons (2 weeks old). These features were mimicked by pharmacologically blocking the fast-inactivating A-type potassium current (I_A) and matched well with the higher concentrations of K_v4.2 and K_v4.3 and the lower concentrations of BK and K_v1.2 channels detected by Western blotting. Repetitive stimulation with high frequency trains (50 Hz) reproduced AP broadening associated to inactivation of the A-type current in immature cells. Moreover, repetitive firing showed changes in AP amplitude consistent with the inactivation of both sodium and potassium subthreshold currents, which resulted in higher AP amplitudes in the more immature neurons. We propose that maturation of AP waveform and excitability in this critical developmental period could be related to the onset of exploratory behaviors.

Keywords: CA1 pyramidal neurons; action potential; development; neuronal excitability; potassium channels; sodium channels.