The hippocampus is perhaps the most well-known brain region among neuroscientists, not only for its beautiful name (Latin for seahorse), but also for its critical role in learning and memory. Decades ago, another landmark discovery showed that hippocampal neurons seem to encode space1. That is, individual hippocampal neurons fire only when an animal moves into a specific spot of its current room. Each neuron may signal a different spot, so together they can tile the entire place. In a sense, they are a map. However, unlike the ordinary maps, which cannot be used outside what they are meant for, the hippocampal maps are reusable: the same cell that responds to one location in one room can represent another spot in a different room. One may say that the hippocampus is a universal map, but even that interpretation is likely incomplete since 1) responses to non-spatial stimuli have been recorded in the hippocampus, and 2) there are many non-spatial forms of memories that are damaged in cases of hippocampal lesions2.
What is the more general role of hippocampus, then? To answer this question, Dmitriy Aronov and coleagues3 in David Tank’s lab designed a task in which a rat has to press a lever to initiate a single-pitch tone. Then, the pitch of the tone rises as the rat continues to hold the lever down, until it reaches a target frequency zone, during which the rat releases the lever to receive a reward. The speed at which the pitch increases differs from trial to trial so rats cannot simply time their lever releases. Instead, rats have to wait for the pitch to reach the internal target zone and release the lever then. Aronov et al’s rats performed really well in this task. Most of them released the lever just after the pitch reached the target frequency, with few undershoots and no overshoots.
Even though there is no exploration of physical space involved in this task, the rat’s hippocampus is far from being idle. In fact, Aronov et al. recorded many neurons that fire specifically in this task. Moreover, they also observed neurons whose firing rate is particularly high in certain part (i.e., pitches) of this task. Different neurons have different preference for what part of the task they respond to, and together these neurons fire in a somewhat reproducible sequential pattern. In navigation tasks, this sequential firing pattern can be understood as the hippocampal place cells adapt to a linear track instead of to a two-dimensional room. Just as place cells fire when animal moves into a spot in a room, they can also fire when the animal moves into a specific segment of the track. Indeed, the sequential firing pattern have been recorded previously as animal travels on a linear track to get to its goal4. In Aronov et al’s experiments, some degree of activeness is required, since little sequential firing is recorded when shifting-pitches were played back to idle rats. So, well, could it be that the firing pattern signifies the progress of a rat actively running on an abstract track of rising pitch? One could imagine.
Aronov et al. found that these sequential firing hippocampal neurons do not just behave like place cells. Some of them are bona fide place cells. It turns out that the place-cell map can not only be reused between different, real rooms, but also be used in abstract spaces as well. Similar findings also apply to a closely linked brain region, the medial entorhinal cortex, where the famous grid cells were found (not going into details here due to space restraints).
I think one of the greatest strength of this paper is the arbitrariness of the task. Pressing a lever to hear shifting tones unlikely bears any significance to non-lab rats. However, the place cells have no trouble adapting their firing pattern to this task. Perhaps, then, the more accurate way of understanding the function of the hippocampus is to say it’s a universal representation of the animal’s behavioral state. In this way, the flexibility of the hippocampus is what allows us to form memory of whatever ongoing events.
1. O’Keefe, J. & Dostrovsky, J. The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely-moving rat. Brain Research 34, (1971).
2. Eichenbaum, H., Dudchenko, P., Wood, E., Shapiro, M. & Tanila, H. The Hippocampus, Memory, and Place Cells: Is It Spatial Memory or a Memory Space? Neuron 23, 209–226 (1999).
3. Aronov, D., Nevers, R. & Tank, D. W. Mapping of a non-spatial dimension by the hippocampal–entorhinal circuit. Nature 543, 719–722 (2017).
4. Diba, K. & Buzsáki, G. Forward and reverse hippocampal place-cell sequences during ripples. Nat. Neurosci. 10, 1241–1242 (2007).