Septo-hippocampal dynamics and the encoding of space and time

Abstract

Encoding an event in memory requires neural activity to represent multiple dimensions of behavioral experience in space and time. Recent experiments have explored the influence of neural dynamics regulated by the medial septum on the functional encoding of space and time by neurons in the hippocampus and associated structures. This review addresses these dynamics, focusing on the role of theta rhythm, the differential effects of septal inactivation and activation on the functional coding of space and time by individual neurons, and the influence on phase coding that appears as phase precession. We also discuss data indicating that theta rhythm plays a role in timing the internal dynamics of memory encoding and retrieval, as well as the behavioral influences of these neuronal manipulations with regard to memory function.

Keywords: boundary cells; entorhinal cortex; hippocampus; medial septum; navigation; place cells; retrosplenial cortex; theta rhythm.

Figure 1:. Diagram of the medial septum neural populations and their projections to the hippocampus and entorhinal cortices.

(A) The medial septum contains three primary neuronal subtypes, as illustrated schematically along with their respective percentages in mice: GABAergic neurons (blue), cholinergic neurons (red) and glutamatergic neurons (purple). (B) Sagittal diagram of major connections of the mouse medial septum to hippocampus and entorhinal cortex. The MS and VDB project to both the hippocampus and entorhinal cortex. Abbreviations: cc, corpus callosum; LEC, lateral entorhinal cortex; f, Fornix & Fimbria; HPC, Hippocampus; MEC, medial entorhinal cortex; MS, medial septum; VDB, vertical limb of diagonal band of Broca.

Figure 2. Schematic illustration of theta phase precession and theta rhythmicity.

(A) An animal runs on a trajectory through the firing field of a single place cell. (B) Local field potential (LFP) shows theta rhythm oscillations at about 8 Hz. Cell A illustrates how precession involves spiking that starts out at late phases of theta, but shifts to earlier phases of theta. (C) An autocorrelogram sums up time intervals between individual spikes (gray brackets shown for two example intervals). If mean spike intervals are shorter than the period of the LFP oscillation, autocorrelogram peaks appear at shorter periods (higher frequency) than LFP theta rhythm.

Figure 3. Potential role of theta phases in separating encoding and retrieval during delayed spatial alternation or delayed non-match to position tasks.

(A) With no theta rhythm, the retrieval of a prior left turn response mediated by internal connections (green) can be used to guide a new right turn response. However, if the input of the right turn response (blue) can occur at the same time as retrieval and synaptic modification, this results in synaptic modification (red) strengthening undesired associations between the prior retrieval (green) and the new input (blue), impairing future responses. (B) With theta rhythm separating encoding and retrieval, the retrieval of the prior response (green) occurs on one phase of theta when there is no synaptic modification. Then the encoding of entorhinal input (blue) occurs when synaptic modification is strong (red) resulting in storage of only the new trajectory of the right turn response without interference. This allows effective future retrieval to guide behavior.