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

Abstract

O'Keefe and Recce [ I 9931 Hippocampus 3:317-330 described an interaction between the hippocampal theta rhythm and the spatial firing of pyramidal cells in the CAI region of the rat hippocampus: they found that a cell's spike activity advances to earlier phases of the theta cycle as the rat passes through the cell's place field. The present study makes use of large-scale parallel recordings to clarify and extend this finding in several ways: 1) Most CA1 pyramidal cells show maximal activity at the same phase of the theta cycle. Although individual units exhibit deeper modulation, the depth of modulation of CAI population activity i s about 50%. The peak firing of inhibitory interneurons in CAI occurs about 60" in advance of the peak firing of pyramidal cells, but different interneurons vary widely in their peak phases. 2) The first spikes, as the rat enters a pyramidal cell's place field, come 90"-120" after the phase of maximal pyramidal cell population activity, near the phase where inhibition is least. 3) The phase advance is typically an accelerating, rather than linear, function of position within the place field. 4) These phenomena occur both on linear tracks and in two-dimensional environments where locomotion is not constrained to specific paths. 5) In two-dimensional environments, place-related firing is more spatially specific during the early part of the theta cycle than during the late part. This is also true, to a lesser extent, on a linear track. Thus, spatial selectivity waxes and wanes over the theta cycle. 6 ) Granule cells of the fascia dentata are also modulated by theta. The depth of modulation for the granule cell population approaches 1 OO%, and the peak activity of the granule cell population comes about 90" earlier in the theta cycle than the peak firing of CAI pyramidal cells. 7) Granule cells, like pyramidal cells, show robust phase precession. 8) Cross-correlation analysis shows that portions of the temporal sequence of CA1 pyramidal cell place fields are replicated repeatedly within individual theta cycles, in highly compressed form. The compression ratio can be as much as 1O:l.These findings indicate that phase precession is a very robust effect, distributed across the entire hippocampal population, and that it is likely to be inherited from the fascia dentata or an earlier stage in the hippocampal circuit, rather than generated intrinsically within CA1. It i s hypothesized that the compression of temporal sequences of place fields within individual theta cycles permits the use of long-term potentiation for learning of sequential structure, thereby giving a temporal dimension to hippocampal memory traces.

The hippocampal debate: are we asking the right questions?

“…Non-spatial hippocampal correlates can be explained. Place cell recordings are examining detailed quantitative second-order properties of the tuning curves, including both spatial [39,112,151,174,208] (to list only a few) and non-spatial [11,94,247], and these properties are being modeled at a quantitative level [16,172,196,205]. Detailed explanations of hippocampal roles in both spatial and non-spatial tasks are available [72,173,196,225].…”

“…The role of the hippocampus in retrograde amnesia is still under debate [131,143,180] (see Appendix A). As are the specifics of the hippocampal place field parameters (such as the causes for directionality [21,101,174,200,225] and phase precession [16,151,188,208,227]) and the role of the hippocampus in non-spatial tasks (such as contextual conditioning [52,63,65,66,82]). The twin experiments of H.M.'s surgery and place cells drove two major theories that have driven experiments too numerous to cite here.…”

Timing and efficacy of transmitter release at mossy fiber synapses in the hippocampal network

“…Finally, it is believed that the hippocampus is able to store sequences of places. Experimental support for this hypothesis is the replay of firing sequences during sleep [86] and the phenomenon of phase precession [73]. As an animal moves along a linear track, action potentials shift from late to early time points within a theta cycle, which has been interpreted as a cued and time-compressed recall of previously stored spatial information [53,54].…”

“…In contrast, when the animal is located in a place field center ( Fig. 5a; [44,73]) or during delayed nonmatch-to-sample tasks [84], granule cells will fire at higher frequencies (∼50 and ∼10 Hz, respectively), and the differential synaptic dynamics will lead to conditions in which unitary mossy fiber synaptic events trigger spikes in postsynaptic CA3 pyramidal neurons, as suggested by both in vitro and in vivo experiments [39,40,47,48] (Figs. 4 and 5).…”

Modeling the Nonlinear Dynamic Interactions of Afferent Pathways in the Dentate Gyrus of the Hippocampus

“…The parameter of the Poisson distribution that determines the average firing rate of the RIT was consistent with the known firing rates of the respective hippocampal neurons (2 Hz). 51,57 At the end of RIT stimulation, the system was tested for stationarity by administering a series of I/O curve stimulations. Possible differences in the resulting I/O curves before and after RIT stimulation were taken as indicators of changes in granule cell excitability (non-stationarity of the system).…”