Review
INMED/TINS special issue
Network and intrinsic cellular mechanisms underlying theta phase precession of hippocampal neurons

https://doi.org/10.1016/j.tins.2007.05.002Get rights and content

Hippocampal ‘place cells’ systematically shift their phase of firing in relation to the theta rhythm as an animal traverses the ‘place field’. These dynamics imply that the neural ensemble begins each theta cycle at a point in its state-space that might ‘represent’ the current location of the rat, but that the ensemble ‘looks ahead’ during the rest of the cycle. Phase precession could result from intrinsic cellular dynamics involving interference of two oscillators of different frequencies, or from network interactions, similar to Hebb's ‘phase sequence’ concept, involving asymmetric synaptic connections. Both models have difficulties accounting for all of the available experimental data, however. A hybrid model, in which the look-ahead phenomenon implied by phase precession originates in superficial entorhinal cortex by some form of interference mechanism and is enhanced in the hippocampus proper by asymmetric synaptic plasticity during sequence encoding, seems to be consistent with available data, but as yet there is no fully satisfactory theoretical account of this phenomenon. This review is part of the INMED/TINS special issue Physiogenic and pathogenic oscillations: the beauty and the beast, based on presentations at the annual INMED/TINS symposium (http://inmednet.com).

Introduction

The hippocampus of rodents and many other mammals shows an oscillation of its local field potential in the range of ∼6–8 Hz, while animals are actively locomoting, attending to external stimuli or in REM sleep, and the total spike activity of ensembles of hippocampal principal neurons (pyramidal and granule cells) is phase-locked to this rhythm 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11; however, the behavior of individual neurons is more complex. It is now well established that hippocampal principal cells fire in a manner that is consistent both with a ‘cognitive mapping’ system (e.g. ‘place cells’; [12]), much as originally envisaged by O’Keefe and Nadel [11], and with an episodic memory indexing system (e.g. see Ref. [13]; but the role of the theta rhythm in these (or other) hippocampal functions has been much less clear.

Section snippets

Theta phase precession

Speculation as to the function of the theta rhythm 7, 11, 14, 15, 16, 17, 18 entered a new era with the discovery [19] that hippocampal pyramidal cells, when they show spatially correlated activity, systematically vary their firing phase relative to the theta frequency local field oscillation as a function of spatial location (Figure 1). As an animal enters a ‘place field’ of a given cell, the first spikes occur late in the theta cycle. As the animal leaves the field, they occur near the

Functions of theta phase precession

Since the initial discovery of theta phase precession, it was recognized that a downstream network that can respond to both relative phase and firing rate could generate a more accurate estimate of the location of the animal than firing rate alone 17, 19. The plausibility of this proposal was confirmed [20] using neural ensemble-based reconstruction methods [21] with data from rats running on linear tracks; however, the usefulness of phase information for position encoding during normal

Mechanism of phase precession

As mentioned earlier, phase precession necessarily implies that the burst frequency of the neuron must be somewhat higher than the local field oscillation. O’Keefe and Recce [19] suggested that the mechanism of precession itself might actually be based on interference effects from two oscillators of slightly different frequencies; a slower oscillating input, presumably from the medial septum, which generates the hippocampal theta rhythm, and a slightly faster oscillation that arises from a

Strengths and weaknesses of the two classes of model

Phase precession could be generated by a network mechanism, an intrinsic oscillator mechanism, or possibly by a combination of these. Some recent findings, however, are difficult to reconcile with the intrinsic oscillator model, at least as an explanation for phase precession in CA1. Perhaps the most difficult problem for the intrinsic oscillator model is that CA1 place cells can participate in multiple assemblies within the same theta cycle. For the majority of place fields, phase precession

Hybrid models

The intrinsic oscillation model and the asymmetric connection model both encounter significant difficulties when used to explain phase precession in the hippocampus proper. Skaggs et al. [17] demonstrated that cells in the dentate gyrus also showed phase precession and had their peak firing ∼90° earlier than CA1 pyramidal cells and suggested on this basis that phase precession does not originate in CA1, but rather is inherited from either the dentate gyrus or even the superficial layers of the

Conclusion

The study of the neural mechanisms underlying the spatio-temporal dynamics of the rodent entorhinal–hippocampal system is at an exciting crossroads. It seems clear that there is a deep relationship between the precise ordering of action potentials in relation to the phase of the theta rhythm and the position of the rat in space, and the mechanisms underlying the equally striking, regularly repeating grid fields of neurons in medial entorhinal cortex. Two very different classes of model seem to

Acknowledgements

This work was supported by US PHS Grant NS020331.

References (66)

  • A.D. Ekstrom

    NMDA receptor antagonism blocks experience-dependent expansion of hippocampal ‘place fields’

    Neuron

    (2001)
  • E.I. Moser

    A test of the reverberatory activity hypothesis for hippocampal ‘place’ cells

    Neuroscience

    (2005)
  • N. Burgess

    A model of hippocampal function

    Neural Networks

    (1994)
  • R. Jung et al.

    Eine methodic der Ableitung lokalisierter Potentialschwankungen aus Hirngebieten

    Arch. Pschiat. Nervenkr.

    (1938)
  • J.D. Green et al.

    Hippocampal electrical activity in arousal

    J. Neurophysiol.

    (1954)
  • L. Pickenhain et al.

    Behavioral and electrophysiological changes during avoidance conditioning to light flashes in the rat

    Electroenceph. Clin. Neurophysiol.

    (1965)
  • W.R. Adey

    Hippocampal slow waves: distribution and phase relationships in the course of approach learning

    Arch. Neurol.

    (1966)
  • W.L. McFarland

    Relationship between hippocampal theta activity and running speed in the rat

    J. Comp. Physiol. Psychol.

    (1975)
  • J. O’Keefe et al.

    The Hippocampus as a Cognitive Map

    (1978)
  • S. Leutgeb

    Independent codes for spatial and episodic memory in hippocampal neuronal ensembles

    Science

    (2005)
  • P.W. Landfield

    Theta rhythm: a temporal correlate of memory storage processes in the rat

    Science

    (1972)
  • J.A. Gray

    The Neuropsychology of Anxiety: An Enquiry into the Functions of the Spot-Hippocampal System

    (1982)
  • W.E. Skaggs

    Theta phase precession in hippocampal neuronal populations and the compression of temporal sequences

    Hippocampus

    (1996)
  • G. Buzsaki

    Theta rhythm of navigation: link between path integration and landmark navigation, episodic and semantic memory

    Hippocampus

    (2005)
  • J. O’Keefe et al.

    Phase relationship between hippocampal place units and the EEG theta rhythm

    Hippocampus

    (1993)
  • O. Jensen et al.

    Position reconstruction from an ensemble of hippocampal place cells: contribution of theta phase coding

    J. Neurophysiol.

    (2000)
  • M.A. Wilson et al.

    Dynamics of the hippocampal ensemble code for space

    Science

    (1993)
  • D.O. Hebb

    The Organization of Behavior

    (1949)
  • M.V. Tsodyks

    Population dynamics and theta rhythm phase precession of hippocampal place cell firing: a spiking neuron model

    Hippocampus

    (1996)
  • O. Jensen et al.

    Hippocampal CA3 region predicts memory sequences: accounting for the phase precession of place cells

    Learn Mem.

    (1996)
  • W.R. Holmes et al.

    Insights into associative long-term potentiation from computational models of NMDA receptor–mediated calcium influx and intracellular calcium concentration changes

    J. Neurophysiol.

    (1990)
  • L.F. Abbott et al.

    Functional significance of long-term potentiation for sequence learning and prediction

    Cereb. Cortex.

    (1996)
  • A. Kamondi

    Theta oscillations in somata and dendrites of hippocampal pyramidal cells in vivo: activity-dependent phase–precession of action potentials

    Hippocampus

    (1998)
  • Cited by (83)

    • Neural computations underlying contextual processing in humans

      2022, Cell Reports
      Citation Excerpt :

      Also, a population-level phase shift is compatible with the theta-gamma PAC when the phase-shift is accompanied by phase-dependent activity modulation. Theta-gamma phase shift in the present study shows multiple similarities with theta phase precession (Maurer and McNaughton, 2007; O'Keefe and Recce, 1993), especially in the non-spatial context (Pastalkova et al., 2008; Qasim et al., 2021; Robinson et al., 2017; Takahashi et al., 2014; Terada et al., 2017). This includes the negative circular-linear correlation between the gamma activity and theta phase across the task stages (Figure 4) as well as the decodability of current and future states based on the HGA during different theta phases (Figure 5).

    • Hippocampal Theta-Gamma Coupling Reflects State-Dependent Information Processing in Decision Making

      2018, Cell Reports
      Citation Excerpt :

      During attentive behaviors, the local field potential shows a 6–12 Hz theta rhythm (O’Keefe and Nadel, 1978; Vanderwolf, 1971). During each cycle of theta, the hippocampal place cells fire in order of their place fields along the path of the rat in the direction of travel (Foster and Wilson, 2007; Maurer and McNaughton, 2007). These two descriptions are duals of each other: when rats are planning paths to a goal, the sequence goes farther to the goal and the place fields begin earlier in the journey (Wikenheiser and Redish, 2015).

    • Goal-directed sequences in the hippocampus

      2018, Goal-Directed Decision Making: Computations and Neural Circuits
    View all citing articles on Scopus
    View full text