Theta oscillations coincide with sustained hyperpolarization in CA3 pyramidal cells, underlying decreased firing

Brain-state fluctuations modulate membrane potential dynamics of neurons, influencing the functional repertoire of the network. Pyramidal cells (PCs) in hippocampal CA3 are necessary for rapid memory encoding, preferentially occurring 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 reduced firing rate. In contrast, during large irregular activity, a low-arousal state, PCs show heterogeneous changes in membrane potential. This suggests coordinated hyperpolarization of PCs during theta, possibly caused by increased inhibition. This could lead to higher signal-to-noise ratio in the small population of PCs active during theta as observed in ensemble recordings.

Methods
To investigate the intracellular dynamics of hippocampal CA3 pyramidal cells (PCs) in vivo across brain states, we performed simultaneous whole-cell and local field potential (LFP) recordings in awake head-fixed mice free to run on a wheel. An LFP electrode was first positioned in the stratum pyramidale of dorsal CA3 before lowering the patch-clamp electrode for whole-cell recordings in the vicinity of the LFP electrode.  To monitor the level of arousal, we measured both pupil diameter and locomotor activity on the wheel. We recorded a total of 33 CA3 PCs in 21 mice.

For details about how these raw data were processed to produce the provided dataset, please see https://github.com/Ashkees/Malezieux_CellRep_2020

For more information about data collection and processing, please see the corresponding paper.