Linking temporal coordination of hippocampal activity to memory function

Front Cell Neurosci. 2023 Aug 31:17:1233849. doi: 10.3389/fncel.2023.1233849. eCollection 2023.


Oscillations in neural activity are widespread throughout the brain and can be observed at the population level through the local field potential. These rhythmic patterns are associated with cycles of excitability and are thought to coordinate networks of neurons, in turn facilitating effective communication both within local circuits and across brain regions. In the hippocampus, theta rhythms (4-12 Hz) could contribute to several key physiological mechanisms including long-range synchrony, plasticity, and at the behavioral scale, support memory encoding and retrieval. While neurons in the hippocampus appear to be temporally coordinated by theta oscillations, they also tend to fire in sequences that are developmentally preconfigured. Although loss of theta rhythmicity impairs memory, these sequences of spatiotemporal representations persist in conditions of altered hippocampal oscillations. The focus of this review is to disentangle the relative contribution of hippocampal oscillations from single-neuron activity in learning and memory. We first review cellular, anatomical, and physiological mechanisms underlying the generation and maintenance of hippocampal rhythms and how they contribute to memory function. We propose candidate hypotheses for how septohippocampal oscillations could support memory function while not contributing directly to hippocampal sequences. In particular, we explore how theta rhythms could coordinate the integration of upstream signals in the hippocampus to form future decisions, the relevance of such integration to downstream regions, as well as setting the stage for behavioral timescale synaptic plasticity. Finally, we leverage stimulation-based treatment in Alzheimer's disease conditions as an opportunity to assess the sufficiency of hippocampal oscillations for memory function.

Keywords: hippocampus; medial septum; memory; phase-precession; plasticity; theta rhythms.

Publication types

  • Review

Grants and funding

This work was supported by funding from the Canadian Institutes for Health Research (CIHR) Foundation Program FDN-148478, the Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant RGPIN-2020-06717, and a Tier 1 Canada Research Chair to SW. JC was supported by an Alzheimer's Association Grant (AARF-22-928742) and by the Canada Brain Research Fund (CBRF), an innovative arrangement between the Government of Canada (through Health Canada), the Brain Canada Foundation, and the Alzheimer's Association.