Activity in the hippocampus and the nearby entorhinal cortex shows truly remarkable correlations to navigational variables, like location, head direction, speed, and proximity to boundaries. Yet, these brain areas are not only involved in spatial navigation. Rather, the hippocampal/entorhinal system is a critical circuit for storing and retrieving memories – a function that attracted the focus of neuroscience to this part of the brain over half a century ago. The relationship between this general function of the circuit and the observed activity patterns is unknown.

How does the hippocampal/entorhinal circuit represent memory-relevant information in the general case (i.e., not just location)? What is the neural signature of the cognitive state of remembering something? How are representations of related memories organized? How are these representations updated when new memories are formed? How do these representations ultimately guide behavior? We focus on these questions by building upon two prior pieces of work:

Rat virtual reality

Retrieval of distinct memories can be triggered by switching an animal between different sensory or behavioral contexts. In the hippocampus, changes of context trigger remapping – a dramatic reorganization of population activity that is thought to be related to distinct memories. Virtual reality (VR) provides a powerful method to achieve this by allowing rapid, closed-loop manipulations of the animal’s context. Because these manipulations are computer-controlled (i.e. the animal is playing a video game), they can be coupled with uninterrupted neural recordings and manipulations.

In a published version of rat VR, we showed that virtual environments engage the full diversity of spatial activity patterns in the hippocampal/entorhinal system, including place cells, grid cells, head direction cells, and border cells. Switching the animal between two distinct virtual environments successfully triggers hippocampal remapping.

 

Top: Rat's view of the virtual environment. Bottom: Schematic of the environment. Blue triangle shows rat location; red dots are (audible) spikes fired by a CA1 place cell.

 

Mapping of a non-spatial dimension

Representations of physical space are highly specialized; yet, memory is a general function that requires processing a variety of other types of information by the hippocampal/entorhinal circuit. A conceptual framework reconciling these views is that spatial representation is one example of a general mechanism for encoding continuous, task-relevant variables. We tested this idea explicitly by training rats to navigate in an acoustic version of a virtual environment. Rats pressed a joystick lever to increase the frequency of a sound and were required to release the joystick in a target range of frequencies to obtain a reward. To uncouple frequency from the amount of elapsed time we varied, on a trial-by-trial basis, the “speed” of traversal through the frequency space. Remarkably, both hippocampal and entorhinal neurons formed discrete firing fields that spanned the entire behavioral task, even though animals were immobile. Some cells formed fields at particular sound frequencies, forming “frequency fields” akin to place and grid fields during spatial navigation. This suggests a more general purpose for the hippocampal and entorhinal firing patterns and implies their role in cognitive processes beyond spatial navigation.

 
Traversal of an acoustic dimension. Animation by Julia Kuhl.

Traversal of an acoustic dimension. Animation by Julia Kuhl.

Left: Simultaneous recording of CA1 neurons in the acoustic task. Sound starts at the joystick press and ends at the joystick release. Right: Recording of the same MEC grid cell during spatial navigation (top) and during the acoustic task (bottom).