Cortical astrocytes modulate dominance behavior in male mice by regulating synaptic excitatory and inhibitory balance

Noh, Kyong Wook; Cho, Woo-Hyun; Lee, Byung Hun; Kim, Dong Wook; Kim, Yoo Sung; Park, Keebum; Hwang, Mun Kyung; Barcelon, Ellane; Cho, Yoon Kyung; Lee, C. Justin; Yoon, Bo-Eun; Choi, Se‐Young; Park, Hye Yoon; Jun, Sang Beom; Lee, Sung Joong

doi:10.1038/s41593-023-01406-4

Cited by 10 publications

(3 citation statements)

References 51 publications

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“…It is possible that the photostimulation of ChR2-expressing astrocytes used in the present study differs from the physiological stimuli that activate astrocytes within the brain. Nonetheless, optogenetic manipulation of astrocytes has been successfully used to study various behavioral responses [ 123 , 124 ]. Our previous study also showed that photostimulation evokes an increase in the intracellular Ca 2+ concentration as well as its sustained oscillation [ 106 ].…”

Section: Discussionmentioning

confidence: 99%

Aberrant activation of hippocampal astrocytes causes neuroinflammation and cognitive decline in mice

Kim,

Michiko,

Choi

et al. 2024

PLoS Biol

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Reactive astrocytes are associated with neuroinflammation and cognitive decline in diverse neuropathologies; however, the underlying mechanisms are unclear. We used optogenetic and chemogenetic tools to identify the crucial roles of the hippocampal CA1 astrocytes in cognitive decline. Our results showed that repeated optogenetic stimulation of the hippocampal CA1 astrocytes induced cognitive impairment in mice and decreased synaptic long-term potentiation (LTP), which was accompanied by the appearance of inflammatory astrocytes. Mechanistic studies conducted using knockout animal models and hippocampal neuronal cultures showed that lipocalin-2 (LCN2), derived from reactive astrocytes, mediated neuroinflammation and induced cognitive impairment by decreasing the LTP through the reduction of neuronal NMDA receptors. Sustained chemogenetic stimulation of hippocampal astrocytes provided similar results. Conversely, these phenomena were attenuated by a metabolic inhibitor of astrocytes. Fiber photometry using GCaMP revealed a high level of hippocampal astrocyte activation in the neuroinflammation model. Our findings suggest that reactive astrocytes in the hippocampus are sufficient and required to induce cognitive decline through LCN2 release and synaptic modulation. This abnormal glial–neuron interaction may contribute to the pathogenesis of cognitive disturbances in neuroinflammation-associated brain conditions.

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Section: Discussionmentioning

confidence: 99%

Aberrant activation of hippocampal astrocytes causes neuroinflammation and cognitive decline in mice

Kim,

Michiko,

Choi

et al. 2024

PLoS Biol

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“…During synaptic transmission, astrocytes absorb glutamate, which releases GABA. The GABA released establishes tonic inhibition depending on the network activity and modulates the E/I balance [57].…”

Section: Gaba Levelsmentioning

confidence: 99%

Disinhibition Is an Essential Network Motif Coordinated by GABA Levels and GABA B Receptors

Villalobos

2024

IJMS

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Network dynamics are crucial for action and sensation. Changes in synaptic physiology lead to the reorganization of local microcircuits. Consequently, the functional state of the network impacts the output signal depending on the firing patterns of its units. Networks exhibit steady states in which neurons show various activities, producing many networks with diverse properties. Transitions between network states determine the output signal generated and its functional results. The temporal dynamics of excitation/inhibition allow a shift between states in an operational network. Therefore, a process capable of modulating the dynamics of excitation/inhibition may be functionally important. This process is known as disinhibition. In this review, we describe the effect of GABA levels and GABAB receptors on tonic inhibition, which causes changes (due to disinhibition) in network dynamics, leading to synchronous functional oscillations.

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“…In the current work, we zero our attention on astrocytes, a prominent type of glial cell within the nervous system. Collective work in the field of astrocyte biology has repeatedly provided evidence on the instrumental role of astrocytes in controlling neuronal functions such as synaptic wiring, synaptic activity, synaptic memory, and neuronal excitability [12][13][14][15][16][17][18][19][20], reflecting the potential of astrocytes to control key computational loci in the brain. However, directly probing the role of astrocytes in brain computation has been virtually impossible at the experimental level due to limited knowledge surrounding their rules of engagement and signaling mechanisms, combined with their non-binary rules of 'excitability', and our inability to specifically target their neuron-bound modulatory functions without affecting their more general 'homeostatic' roles.…”

Section: Introductionmentioning

confidence: 99%

Astrocytes as a mechanism for contextually-guided network dynamics and function

Gong,

Pasqualetti,

Papouin

et al. 2024

PLoS Comput Biol

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Astrocytes are a ubiquitous and enigmatic type of non-neuronal cell and are found in the brain of all vertebrates. While traditionally viewed as being supportive of neurons, it is increasingly recognized that astrocytes play a more direct and active role in brain function and neural computation. On account of their sensitivity to a host of physiological covariates and ability to modulate neuronal activity and connectivity on slower time scales, astrocytes may be particularly well poised to modulate the dynamics of neural circuits in functionally salient ways. In the current paper, we seek to capture these features via actionable abstractions within computational models of neuron-astrocyte interaction. Specifically, we engage how nested feedback loops of neuron-astrocyte interaction, acting over separated time-scales, may endow astrocytes with the capability to enable learning in context-dependent settings, where fluctuations in task parameters may occur much more slowly than within-task requirements. We pose a general model of neuron-synapse-astrocyte interaction and use formal analysis to characterize how astrocytic modulation may constitute a form of meta-plasticity, altering the ways in which synapses and neurons adapt as a function of time. We then embed this model in a bandit-based reinforcement learning task environment, and show how the presence of time-scale separated astrocytic modulation enables learning over multiple fluctuating contexts. Indeed, these networks learn far more reliably compared to dynamically homogeneous networks and conventional non-network-based bandit algorithms. Our results fuel the notion that neuron-astrocyte interactions in the brain benefit learning over different time-scales and the conveyance of task-relevant contextual information onto circuit dynamics.

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Cortical astrocytes modulate dominance behavior in male mice by regulating synaptic excitatory and inhibitory balance

Cited by 10 publications

References 51 publications

Aberrant activation of hippocampal astrocytes causes neuroinflammation and cognitive decline in mice

Aberrant activation of hippocampal astrocytes causes neuroinflammation and cognitive decline in mice

Disinhibition Is an Essential Network Motif Coordinated by GABA Levels and GABA B Receptors

Astrocytes as a mechanism for contextually-guided network dynamics and function

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