ADVANCE Fellows Award: Theta phases of hippocampal place cell firing in REM sleep and waking

Regents Of The University Of Michigan - Ann Arbor, Ann Arbor MI

Investigators

Abstract

During replayed phase precession of hippocampal CA1 place cells in REM sleep, Poe et al. (Brain Res., 855:176-180, 2000) observed that over a number of days, as the rat became more familiar with the associated track environment, a shift occurred in the mean phase of firing relative to the hippocampal theta rhythm. Specifically, on the first two days the rat was exposed to the track, mean theta phase during REM precession was near the depolarizing peaks of the theta rhythm. Over following days, the mean theta phase shifted to near the hyperpolarizing troughs of the theta cycle during REM precession but remained near the depolarizing peaks during track running. The goal of this project is to investigate the neural mechanisms generating this phase shift that occurs with familiarity during REM precession. The PI, an applied mathematician whose research is in computational neuroscience, will work directly with Prof. Gina Poe, who is currently conducting experiments to record place cell firing in hippocampal region CA1 during active waking and subsequent REM sleep episodes. The collaborators' working hypothesis for the cause of the shift in mean firing phase is that the reported somato-dendritic differential in the theta rhythm drive to CA1 pyramidal cells can differentially modulate the firing phase in response to synaptic inputs at different locations. Specifically, the theta-driven modulation causes proximal dendritic inputs to preferentially generate firing near the depolarizing theta peaks and distal dendritic inputs to preferentially generate firing at the hyperpolarizing theta troughs. The phase shift would result from the potentiation of distal dendritic synaptic inputs, carried by the direct synaptic pathway from the entorhinal cortex, relative to proximal dendritic synaptic inputs carried by the Schaffer collaterals and tri-synaptic loop from the entorhinal cortex. The project tests this hypothesis through simulations of post-synaptic responses in realistic CA1 pyramidal cell models under conditions mimicking track-running and REM sleep, and through analysis of experimental data. It is generally assumed that an ensemble of hippocampal place cells firing in a specific temporal sequence forms the hippocampal representation of a memory of the associated environment for the rat. Replay of place cell firing during sleep episodes following exploration of an environment is thought to contribute to the consolidation of the memory in the hippocampus and to its transfer to neocortical long-term stores. The experimentally observed shift in mean theta phase of place cell firing that occurs during replayed firing in REM sleep as the rat becomes familiar with the associated environment may be an observable indicator of memory transfer and may also suggest a critical function for REM sleep in the hippocampus. As initial steps of the investigation into the neural mechanisms generating this shift, neuronal simulations and data analysis will be conducted whose results will identify constraints on the working hypothesis that the shift is caused by changes in distinct synaptic inputs to the cell. The results will make experimentally-testable predictions and suggest further experiments to investigate this link between REM sleep and memory processing.