Contribution of persistent Na+ current and muscarine-sensitive K+ current to perithreshold theta resonance in CA1 pyramidal neurons

Abstract

Most neurons from hippocampus and other learning- and memory-related areas have the ability to intrinsically generate subthreshold rhythmic activity at theta frequency (4-10 Hz), which may contribute to the strong theta waves observed during hippocampal-related behaviors like navigation or episodic memory formation. Pyramidal neurons from CA1 area receive theta rhythmic inputs from other brain regions, generating place fields. The way these neurons respond to perithreshold oscillatory stimulation and thus their possibility to translate frequency preference into spiking has been controversial; most evidence favors a non-resonant or integrator-like behavior while other studies suggest a resonant behavior. The ionic currents contributing to perithreshold behavior of pyramidal neurons are the persistent sodium current INaP, a depolarizing fast-activating current that develops above -70 mV and the slower activating, hyperpolarizing muscarine-sensitive K+ current IM, with -60 mV threshold potential. With current- and voltage-clamping we conducted a detailed characterization of perithreshold excitability of CA1 pyramidal neurons under oscillatory stimulation by somatic current injection. These neurons displayed two different perithreshold behaviors: 20% of them expressed resonant behavior and translated theta frequency selectivity into spiking (resonant cells), while the other 80% acted as low-pass filters with no frequency preference in their discharge (non-resonant cells). Measurement of INaP and IM in the same cells revealed that at perithreshold membrane potentials the activation level of IM was generally low, while that of INaP was high enough to depolarize the neurons toward spike threshold overcoming the subtle hyperpolarizing effect of IM.