The role of astrocyte structural plasticity in regulating neural circuit function and behavior

Abstract

Brain circuits undergo substantial structural changes during development, driven by the formation, stabilization, and elimination of synapses. Synaptic connections continue to undergo experience‐dependent structural rearrangements throughout life, which are postulated to underlie learning and memory. Astrocytes, a major glial cell type in the brain, are physically in contact with synaptic circuits through their structural ensheathment of synapses. Astrocytes strongly contribute to the remodeling of synaptic structures in healthy and diseased central nervous systems by regulating synaptic connectivity and behaviors. However, whether structural plasticity of astrocytes is involved in their critical functions at the synapse is unknown. This review will discuss the emerging evidence linking astrocytic structural plasticity to synaptic circuit remodeling and regulation of behaviors. Moreover, we will survey possible molecular and cellular mechanisms regulating the structural plasticity of astrocytes and their non‐cell‐autonomous effects on neuronal plasticity. Finally, we will discuss how astrocyte morphological changes in different physiological states and disease conditions contribute to neuronal circuit function and dysfunction.

Aging with TBI vs. Aging: 6-month temporal profiles for neuropathology and astrocyte activation converge in behaviorally relevant thalamocortical circuitry of male and female rats

“…This observation coincided with the appearance of mild neuropathology in shams. Chronic neuropathology and delayed reactive astrogliosis in the thalamus are specifically implicated in sleep disruption, persisting TBI symptoms, accelerating aging, and increasing risk for age-related neurodegenerative diseases, where the role of astrocytes are the least understood, despite their importance in homeostasis, neuroplasticity, neurotoxicity, neurotransmission, and BBB maintenance [76, 77].…”

A genetic tool for the longitudinal study of a subset of post-inflammatory reactive astrocytes

“…Our data showed that one morphological feature of reactivity, increased complexity of distal processes, fails to revert back to baseline levels even 30 days after inflammation, suggesting that some effects of the inflammatory process might be long lasting. Given the emerging relationship between astrocyte morphology and function ( Lawal et al., 2022 ) in the future it will be interesting to investigate how this long-lasting effect on number of distal branches affects astrocyte physiology. In this regard, the Lcn2CreERT2 mouse will be useful to analyze many key functions of astrocytes before, during, and after injury (or in disease progression), such as glutamate uptake and potassium buffering, synaptogenesis and synaptic maintenance, regulation of the brain extracellular space, and cerebrovascular coupling, to name a few.…”

Comparative assessment of the effects of DREADDs and endogenously expressed GPCRs in hippocampal astrocytes on synaptic activity and memory

“…This observation is verified by other investigations of Gq-DREADDs (Chai et al, 2017;Vaidyanathan et al, 2021) and endogenous Gq-GPCRs (Xie et al, 2012;Srinivasan et al, 2015;Oe et al, 2020;10.3389/fncel.202310.3389/fncel. .1159756 Lia et al, 2021Lawal et al, 2022). Interestingly, the specific IP 3 R subtype mediating astrocytic Ca 2+ fluctuations may indicate the subcellular origin of these fluctuations (Sherwood et al, 2021), thereby influencing the impact of astrocytic Ca 2+ elevations on synaptic function and behavior.…”

“…Following this discovery, it was shown that astrocytes are intricately associated with neurons at the synapse, forming what is often termed the “tripartite synapse”: a functional unit consisting of pre- and post-synaptic neurons and peri-synaptic astrocyte processes (PAPs) ( Araque et al, 1999 ; Papouin et al, 2017 ). Although the extent of gliotransmission remains debated ( Bazargani and Attwell, 2016 ; Fiacco and McCarthy, 2018 ; Savtchouk and Volterra, 2018 ; Durkee et al, 2019 ), astrocytes are known to express a plethora of receptors which are also present on neurons, and a multitude of research now illustrates the contribution of astrocytes to synaptic activity and behavior, through dynamic interactions with neurons ( Durkee and Araque, 2019 ; Lawal et al, 2022 ; Lyon and Allen, 2022 ).…”