The hippocampus is thought to construct a “cognitive map” of experience. How such an abstract map is utilized by other brain regions to guide behavior remains unexplored, leading to an open question in neuroscience: Is the relationship between measured brain activity and an external variable observed by the experimenter actually read out by downstream observer mechanisms in the brain?

In our study, we examined how place cell activity in the hippocampus is utilized by its main output, the lateral septum. We chose this structure because, of all brain regions, it receives the densest hippocampal projections and also has direct projections to the hypothalamus and brainstem, potentially allowing for the selection of action programs. To examine how neuronal firing patterns in the hippocampus are transmitted and transformed, we simultaneously recorded neurons in both structures during a spatial navigation task.

Firing patterns of the lateral septal (LS) neurons did not provide information about the animal’s position. However, when spiking activity was related to the phase of the hippocampal theta oscillations, the preferred theta phase of firing shifted continuously from the beginning to the end of the journey. Thus, we found a firing rate–independent “phase code” for spatial position.

With additional analyses, we identified that the rate-independent phase code is not inherited from the phase or rate information of individual hippocampal place cells; rather, it reflected a computation upon the continuously changing relationship between CA1 and CA3 place cell assemblies. From the perspective of lateral septal neurons, theta sequences of CA3 and CA1 ensembles are the “unit” of information transmission out of the hippocampus.

Overall, our findings demonstrate that transformation of the hippocampal cognitive map depends on higher-order theta sequence structure. Assuming similar transformations in downstream hypothalamic and brainstem circuits, such an “action selector” mechanism may be able to quickly identify the source of information and mediate action from a higher-order map.

—David Tingley, PhD

Read the paper “Transformation of a spatial map across the hippocampal-lateral septal circuit” in Neuron, published June 27, 2018.