The memory orchestra: the role of astrocytes and oligodendrocytes in parallel to neurons

Abstract

For decades, the study of memory has been neuron-centric, yet neurons do not function in isolation. Today we know that neuronal activity is modulated by the environment within which it occurs, and is subject to modulation by different types of glial cells. In this review we summarize recent findings on the functional roles of astrocytes and oligodendrocytes, two major types of glia cells in the adult brain, in memory formation and its cellular underpinnings across multiple time points. We will discuss the different methods that are being used to investigate the astrocytic and oligodendroglial involvement in memory. We shall focus on chemogenetics and optogenetics, which support genetically specificity and high spatiotemporal resolution, attributes that are particularly well suited to the investigation of the contribution of unique cell types at the different stages of memory formation.

Figure 1. Overview of astrocytic and oligodendroglial contribution to memory formation.

(a) Upper panel: Chemogenetic hippocampal astrocytic activation (orange) induces LTP. Decreasing activity-dependent myelination via OPCs (purple) before acquisition impairs memory acquisition [5,7]. Lower panel: Genetic ablation of mPFC astrocytic GABABRs (GFAP-PFC^∆Gb) reduces the power of low gamma oscillations (30−60 Hz) during forced alteration task and impairs working memory [18^• ]. (b) Upper panel: Both chemogenetic and optogenetic hippocampal astrocytic manipulation (orange) induces LTP and augments the acquisition of recent contextual memory [16^• ,24^• ]. Moreover, the same manipulation during learning enhances memory allocation (green) and short-term memory [16^• ,17^• ]. Astrocytes provide lactate to neurons which is required for LTP and recent memory formation, based on chronic astrocytic manipulation (orange) in transgenic mice before acquisition [,–33]. Lower panel: sustained manipulation of mature OLs (glow grey) before acquisition increases axonal conduction velocity and enhances spatial and contextual memory [40]. (c) Upper panel: Gi-pathway activation of CA1 astrocytes (glow orange) during acquisition disrupts CA1-ACC communication and impairs remote, but not recent, memory [|. Lower panel: Steadman et al. found that cortical inhibition of oligodendrogenesis via manipulation of OPCs (purple) immediately after training blocked hippocampal ripple-cortical spindle coupling and impaired remote memory consolidation [|. Pan et al. [| found that neuronal responses to conditioned context cues evolve over time in the mPFC, but not in animals that cannot form new myelin. (d) Scheme showing the gradual consolidation from acquisition to remote memory. The astrocytic experiment in Section (c) [| suggests that remote memories can stem directly from acquisition, and not only from recent memory as previously thought. Thus, a new path (marked in orange) can be added to the classic scheme from acquisition, through recent to remote memory.