Space and Time: The Hippocampus as a Sequence Generator

Abstract

Neural computations are often compared to instrument-measured distance or duration, and such relationships are interpreted by a human observer. However, neural circuits do not depend on human-made instruments but perform computations relative to an internally defined rate-of-change. While neuronal correlations with external measures, such as distance or duration, can be observed in spike rates or other measures of neuronal activity, what matters for the brain is how such activity patterns are utilized by downstream neural observers. We suggest that hippocampal operations can be described by the sequential activity of neuronal assemblies and their internally defined rate of change without resorting to the concept of space or time.

Keywords: lateral septum; phase coding; place cells; theta oscillation; time cells.

Figure 1.. Homologous regions of the hippocampus across species.

The ventral quadrant of the rodent hippocampus is disproportionally enlarged in primates to keep up with the increasingly larger share of higher-order neocortex. Only the relatively small tail part of the primate hippocampus communicates with visuospatial areas. This tail is homologous to the rodent dorsal-intermediate hippocampus. The species’ differing connections to and from the segments of the septo-temporal axis are shown. Most recordings and manipulations in the rodent brain have been done in the dorsal hippocampus. Adapted from [29], Image: Debbie Maizels Springer Nature.

Figure 2.. Distance-duration-speed relationships in the hippocampus.

A. Spiking activity of two place cells and local field potential theta rhythm during maze walking. Temporal duration T is the time needed for the rat to run the distance between the peaks of the two place fields (behavioral time scale). τ, time offset between the two neurons within the theta cycle (“theta time scale”). B. Idealized overlapping place fields of three place cells with identical theta oscillation frequency, illustrating the relationship between T and τ. The relationship between distances of place fields and time offsets (τ) shows a linear relationship within the theta time scale (100–160 ms). C. Movement trajectories of a rat through a place field on two trials with different speeds. D. Spikes of one place cell and the corresponding theta rhythm of the same two trials as in C. Horizontal double arrows indicate the time it took for the rat to run through the place field. E. The number of spikes within the neuron’s place field is similar on slow and fast run trials. Trials are sorted by velocity from slowest to fastest. F. In addition to current position, the start and goal positions can be also read out from the theta phase of spike. Left, the decoded probability (high probability: red) of the rat occupying each track position (y-axis) is calculated at each phase of theta (x-axis, white sine wave). In each subplot, the range of the white sine wave demarks the rat’s actual position. Generally, there is a high probability of the rat occupying its actual position. Theta sequencing can be visualized by diagonal streaks of high probability that begin at the START position on the falling phase of theta and finish at the END position at the rising phase. Right, the same data averaged across all positions actually occupied by the rat. Note that theta sequences are bookended by representations of the linear track START and END positions at the falling and rising phases, respectively. G. Place cell assemblies in the hippocampus are organized by theta oscillations (“hippocampus time”). Each row of dots is a trial of the spiking activity of ten place cells (indicated by different colors). Top panel: Trials are shown with reference to distance through the maze. Middle panel: Trials are shown against elapsed time from start. Bottom panel: Trials are shown as phase-locked activity of neurons in successive theta cycles. A-E, after [58]; F, after [128]; G, courtesy of Carina Curto and Eva Pastalkova.

Figure 3.. Internally generated assembly sequences in a memory task.

A. Center: The rat was required to run in a running wheel during the delay between trials while remembering its last choice between the left and right arms of the maze. Dots represent spike occurrences of simultaneously recorded hippocampal neurons. Left: normalized firing rate trajectory of neurons during wheel running, ordered by the latency of their peak firing rates during left trials (each line is a single neuron). Right: normalized firing rates of the same neurons during right trials. The experimenter can easily tell the difference between future left or right choices just looking at the neuronal assembly vector any time during wheel running. B. Mean firing rates, each normalized to their own in- task maximum rate (blue- red = 0–1), of all recorded BF neurons (y- axis) across all phases of the task (x- axis). Green, blue, purple, and red arrows demark, respectively, the light flash, nose- poke, plate- cross and stop/reward phases of the task. C. Same as B, for neurons recorded in posterior parietal cortex. D. Firing patterns of C A1 pyramidal neurons during preferred (first column) and non-preferred (second column) choice trials. Third column shows segments with significantly higher discharge rates in choice-L (red) or choice-R (blue) trials E. Tuning curves of goal-distance cells in the bat hippocampus. Note that task-phase intervals have different, and variable clock durations and organize neurons to internal needs rather than to external (clock) time. A, after [72]; B-E, reproduced from [34,82,83].

Figure 4.. Hippocampal sequencing hypothesis.

Indices that point to cortical, and subcortical, modules for different inputs are sequenced by hippocampal activity patterns, thus preserving the ordinal structure over which experience occurs.

Figure 5.. Rate-independent position-phase correlations of lateral septal neurons.

A. Neuron in the lateral septum shows phase precession relative to CA1 theta phase. Colored dots indicate the occurrence of action potentials from a single lateral septal neuron while a rat traverses a circular track (~3.2 meters; N = 32 trials). Colors map onto C A1 theta oscillation phases. B. Reconstruction of the rat’s position (mean squared error, MSE) from the firing rate (red) or from a spike phase- position relationship (blue) relative to control (shuffled). Reproduced from [118]