Directional Tuning of Phase Precession Properties in the Hippocampus

Abstract

Running direction in the hippocampus is encoded by rate modulations of place field activity but also by spike timing correlations known as theta sequences. Whether directional rate codes and the directionality of place field correlations are related, however, has so far not been explored and therefore the nature of how directional information is encoded in the cornu ammonis remains unresolved. Here, using a previously published dataset that contains the spike activity of rat hippocampal place cells in the CA1, CA2 and CA3 subregions during free foraging of male Long-Evans rats in a 2D environment, we found that rate and spike timing codes are related. Opposite to a place field's preferred firing rate direction spikes are more likely to undergo theta phase precession and, hence, more strongly impact paired correlations. Furthermore, we identified a subset of field pairs whose theta correlations are intrinsic in that they maintain the same firing order when the running direction is reversed. Both effects are associated with differences in theta phase distributions, and are more prominent in CA3 than CA1. We thus hypothesize that intrinsic spiking is most prominent when the directionally modulated sensorymotor drive of hippocampal firing rates is minimal, suggesting that extrinsic and intrinsic sequences contribute to phase precession as two distinct mechanisms.

Distinct roles of dentate gyrus and medial entorhinal cortex inputs for phase precession and temporal correlations in the hippocampal CA3 area

“…These results indicate that it is predominantly the DG input rather than the MEC input to CA3 that is involved in setting the theta phase of CA3 spikes, in particular the precise onset phase within the late phase of the theta cycle. This effect is consistent with the hypothesis that DG inputs are essential for generating intrinsic "look-ahead" spikes in CA3 (Hasselmo et al, 2002;Lisman et al, 2005;Sanders et al, 2015;Yiu et al, 2022).…”

A Theory of Hippocampal Theta Correlations: Extrinsic and Intrinsic Sequences

“…Adding directional sensory input activates extrinsic sequences in the best direction more strongly, and hence, leads to an association between bestangle (worst-angle) pairs and extrinsicity (intrinsicity). These predictions of our model are corroborated by past reports of higher spike phases in the non-preferred arm of a T-maze (Kay et al, 2020) as well as the association of rigid correlations with upward shifts in spike phases and an increase in worst-angle pairs (Yiu et al, 2022).…”

“…Directional sensory input. To, however, fully explain directional properties of theta phase precession and theta spike correlations by a model, also directional modulations of firing rates (Yiu et al, 2022) need to be taken into account.…”

“…Tsodyks' (2015) model is limited (-1.13 radians per field size, see Figure 1F) as compared to the experimental reports (−4.44 radians (Yiu et al, 2022) and −266 degrees (Schmidt et al, 2009) per field size), we introduced short-term synaptic facilitation (STF) to the sensory input (Berretta and Jones, 1996;Thurley et al, 2008) generating temporally asymmetric depolarization as suggested by intracellular recordings in vivo (Harvey et al, 2009) (Figure 2B). STF amplifies the sensory current at the later part of the field, thus creating phase precession with lower phase tail and increasing the steepness of slopes.…”

“…B DG 0 3000 0 4000 Extrinsicity and intrinsicity. We apply quantitative measures for the extrinsic or intrinsic nature of correlations in a pair of place fields following Yiu et al (2022). We the large effect of DG loop, and hence, give an intrinsicity near 1.…”