Astrocytes contribute to remote memory formation by modulating hippocampal–cortical communication during learning

Abstract

The consolidation and retrieval of remote memories depend on the coordinated activity of the hippocampus and frontal cortices. However, the exact time at which these regions are recruited to support memory and the interactions between them are still debated. Astrocytes can sense and modify neuronal activity with great precision, but their role in cognitive function has not been extensively explored. To investigate the role of astrocytes in remote memory we expressed the Gi-coupled receptor hM4Di in CA1 astrocytes, allowing their manipulation by a designer drug. We discovered that astrocytic modulation during learning resulted in a specific impairment in remote, but not recent, memory recall, accompanied by decreased neuronal activity in the anterior cingulate cortex (ACC) during retrieval. We revealed a massive recruitment of ACC-projecting neurons in CA1 during memory acquisition, accompanied by activation of ACC neurons. Astrocytic Gi activation disrupted CA3 to CA1 communication in-vivo, and reduced the downstream response in the ACC. This same manipulation in behaving mice induced a projection-specific inhibition of ACCprojecting CA1 neurons during learning, consequently preventing the recruitment of the ACC. Our findings suggest that the foundation of remote memory is established in the ACC during acquisition, engaging a distinct process from the one supporting consolidation of recent memory. Furthermore, the mechanism underlying remote memory involves projection-specific functions of astrocytes in regulating neuronal activity.

In vitro Characterization of the Regional Binding Distribution of Amyloid PET Tracer Florbetaben and the Glia Tracers Deprenyl and PK11195 in Autopsy Alzheimer’s Brain Tissue

“…Astrocytes play an important role in the brain physiology, as well as in learning and memory formation [ 59 ]. Reactive astrogliosis are dynamic and heterogeneous in their location, subtypes, hypertrophy/proliferation, and upregulation of different markers such as GFAP, vimentin, nestin, MAO-B, and gamma-amino butyric acid [ 60, 61 ].…”

Sedentary Life and Reduced Mastication Impair Spatial Learning and Memory and Differentially Affect Dentate Gyrus Astrocyte Subtypes in the Aged Mice

“…In summary, our data indicate that microanatomical changes may cause learning and spatial memory perturbation, expanding the view that memory formation is not exclusively related to neurons, but also involves glial cells (Azevedo et al, 2009;Kol et al, 2020). No direct correlation related learning and morphology, but suggested different astrocytes profiles.…”

“…No direct correlation related learning and morphology, but suggested different astrocytes profiles. Indeed, astrocytes may contribute to learning and memory as signaling centers, and by giving structural and metabolic support, they regulate synaptic activity and recruit energetic resources for memory consolidation (Zorec et al, 2015;Kol et al, 2020). In particular, it has been demonstrated that hippocampusbased contextual memory process alters the morphology of astrocytes in the dentate gyrus originating a novel cell morphofunctional status, which is different from that of reactive states (Choi et al, 2016).…”

Potential and Realized Impact of Astroglia Ca2 + Dynamics on Circuit Function and Behavior

“…Another finding in ITPR2 −/− mice was increased frequency of sleep spindles during IS sleep, which may cause impaired memory consolidation (Bojarskaite et al, 2020). This finding may provide a mechanistic explanation for impaired remote memory in ITPR2 −/− mice discussed above (Pinto-Duarte et al, 2019) or for impaired remote memory in consequence of manipulation of astroglia Ca 2+ dynamics using the humanized G i protein-coupled muscarinic receptor type 4 DREADD (hM4Di) discussed below (Kol et al, 2020). Bojarskaite et al (2020) also found considerably reduced delta electrocorticogram power during NREM sleep in ITPR2 −/− mice, which indicates reduced sleep pressure, which is consistent with the first study that reported astrocyte control of sleep pressure and the impact of sleep deprivation (Halassa et al, 2009).…”