Theta Oscillations Coincide with Sustained Hyperpolarization in CA3 Pyramidal Cells, Underlying Decreased Firing

Brain states modulate the membrane potential dynamics of neurons, influencing the functional repertoire of the network. Pyramidal cells (PCs) in the hippocampal CA3 are necessary for rapid memory encoding, which preferentially occurs during exploratory behavior in the high-arousal theta state. However, the relationship between the membrane potential dynamics of CA3 PCs and theta has not been explored. Here we characterize the changes in the membrane potential of PCs in relation to theta using electrophysiological recordings in awake mice. During theta, most PCs behave in a stereotypical manner, consistently hyperpolarizing time-locked to the duration of theta. Additionally, PCs display lower membrane potential variance and a reduced firing rate. In contrast, during large irregular activity, PCs show heterogeneous changes in membrane potential. This suggests coordinated hyperpolarization of PCs during theta, possibly caused by increased inhibition. This could lead to a higher signal-to-noise ratio in the small population of PCs active during theta, as observed in ensemble recordings.