Astrocytes Control Sensory Acuity via Tonic Inhibition in the Thalamus

Kwak, Hankyul; Koh, Won‐Jung; Kim, Sang Woo; Song, Kiyeong; Shin, Jeong-Im; Lee, Jung Moo; Lee, Elliot H.; Bae, Jin Young; Ha, Go Eun; Oh, Joo Hyun; Park, Yongmin Mason; Kim, Sunpil; Feng, Jiguang; Lee, Seung Eun; Choi, Ji Won; Kim, Ki Hun; Kim, Yoo Sung; Woo, Junsung; Lee, Dongsu; Son, Taehwang; Kwon, Soon Woo; Park, Ki Duk; Yoon, Bo-Eun; Lee, Jaeick; Li, Yulong; Lee, Hyunbeom; Bae, Yong Chul; Lee, C. Justin; Cheong, Eunji

doi:10.1016/j.neuron.2020.08.013

Cited by 93 publications

(100 citation statements)

References 61 publications

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“…The antibody against Best1 was validated by the absence of the immunoreactivity in Best1-KO mouse hippocampal sections (Fig. 1C), as previously reported in numerous reports [3,7,8,10,26].…”

Section: Immunohistochemistrysupporting

confidence: 80%

Differential Proximity of Perisynaptic Astrocytic Best1 at the Excitatory and Inhibitory Tripartite Synapses in APP/PS1 and MAOB-KO Mice Revealed by Lattice Structured Illumination Microscopy

Koh

Kang

et al. 2021

Exp Neurobiol

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Bestrophin-1 (Best1) is a Ca 2+ activated Clchannel abundantly expressed in the astrocytes of various brain regions including the hippocampus [1][2][3]. Astrocytes contact multiple synapses through an ultrastructure called microdomain or perisynapse to form tripartite synapses with presynaptic axon terminals and postsynaptic dendritic spines throughout the whole brain [4,5]. The astrocytes actively regulate the homeostasis of the synaptic transmission by either releasing various gliotransmitters such as glutamate, GABA, D-serine, and ATP or removing excessive extracellular transmitters [6]. A series of our previous reports have demonstrated that these gliotransmitters including GABA, glutamate, and D-serine

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“…The antibody against Best1 was validated by the absence of the immunoreactivity in Best1-KO mouse hippocampal sections (Fig. 1C), as previously reported in numerous reports [3,7,8,10,26].…”

Section: Immunohistochemistrysupporting

confidence: 80%

Differential Proximity of Perisynaptic Astrocytic Best1 at the Excitatory and Inhibitory Tripartite Synapses in APP/PS1 and MAOB-KO Mice Revealed by Lattice Structured Illumination Microscopy

Koh

Kang

et al. 2021

Exp Neurobiol

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“…To measure exNMDAR current, a shift in the whole-cell current in response to a treatment of 50 μM (2R)-amino-5-phosphonovaleric acid (APV), the NMDAR blocker, was quantified under voltage-clamping at +40mV in the presence of other inhibitors (20 μM CNQX for AMPAR, 10 μM Bicuculline for GABA A R, 10 μM CGP 55845 for GABA B R, 10 μM Strychnine for GlyR) (Figure 1A). To inhibit astrocytic Ca 2+ signaling, BAPTA, a Ca 2+ chelator, and Alexa Fluor 488, a fluorescent indicator, were loaded into astrocytes through a patch pipette (Figures 1B and S1A), as previously described (Kwak et al, 2020; Serrano et al, 2006; Shigetomi et al, 2008). We observed that exNMDAR current was significantly reduced when astrocytes were loaded with BAPTA (+BAPTA), compared to without BAPTA (-BAPTA) condition (Figures 1C and 1D).…”

Section: Resultsmentioning

confidence: 99%

Astrocytes render memory flexible

Koh

Park

Chun

et al. 2021

Preprint

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Cognitive flexibility is an essential ability to adapt to changing environment and circumstances. NMDAR has long been implicated in cognitive flexibility, but the precise molecular and cellular mechanism is not well understood. Here, we report that astrocytes regulate NMDAR tone through Best1-mediated glutamate and D-serine release, which is critical for cognitive flexibility. Co-release of D-serine and glutamate is required for not only homosynaptic LTD but also heterosynaptic LTD, which is induced at unstimulated synapses upon release of norepinephrine and activation of astrocytic α1-AR during homosynaptic LTP. Remarkably, heterosynaptic LTD at unstimulated synapses during memory acquisition is required for later repotentiation LTP during reversal learning, laying a foundation for flexible memory and cognitive flexibility. Our study sheds light on the pivotal role of astrocytes in orchestrating multiple synapses during memory formation and determining the fate of consolidated memory to be retained as a flexible memory.

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“…This includes evidence for astrocytes responding in a stimulus dependent manner in somatosensory cortex in vivo (Lines et al, 2020). Astrocytes have also recently been shown to modulate thalamic firing patterns in vitro via GABAergic signalling (Kwak et al, 2020). These findings coincide with advances in our understanding of the fundamental roles microglia play in sculpting synapses in the visual pathway in an activity dependent manner (Cheadle et al, 2020; Tremblay et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Recent findings in the somatosensory (Kwak et al, 2020; Lines et al, 2020) and visual (Cheadle et al, 2020; Tremblay et al, 2010) pathways have shown the essential, active roles glia play in sculpting ongoing neural processing of sensory stimuli. In the auditory pathway, electrical stimulation of cochlea induces activation of both astrocytes and microglia in IC (Rosskothen-Kuhl et al, 2018), suggesting these glia also play essential roles in IC processing.…”

Section: Introductionmentioning

confidence: 99%

Inverse Density of Iba1 and Glutamine Synthetase Expressing Glia in Rat Inferior Colliculus

Orton

2021

Preprint

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Microglia and astrocytes undertake numerous essential roles in nervous systems but we know little of their anatomical distribution within numerous nuclei. In the principal nuclei of the mammalian auditory midbrain, the inferior colliculi (IC), the cellular density and relative distribution of glutamate synthetase (GS) expressing astrocytes and ionized calcium-binding adapter molecule 1 (Iba1) expressing microglia is unknown. To address this, the IC of young adult, male Wistar rats were immunohistochemically labelled for GS and Iba1, using chromogenic methods. Sub-regions of imaged IC sections were demarked and soma density of both cell types determined. GS labelled somata were twice more densely packed as Iba1 labelled somata throughout IC parenchyma and peri-vascular regions. Furthermore, GS labelled somata density was significantly lower in dorsal cortex than external cortex or central nucleus. Iba1 labelled somata density exhibited the opposite trend, revealing an inverse density of these glial cell types between IC sub-regions. GS labelled neuropil was strongest in the cortices with and a gradual transition of lighter labelling towards central nucleus. These data provide the first detailed descriptions of GS labelling in IC and demonstrate sub-regional differences in IC glial cell density. Taken together, these findings suggest neurochemical specialization of glia in IC sub-regions, likely related to local physiological and metabolic demands, with implications for IC function.

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Astrocytes Control Sensory Acuity via Tonic Inhibition in the Thalamus

Cited by 93 publications

References 61 publications

Differential Proximity of Perisynaptic Astrocytic Best1 at the Excitatory and Inhibitory Tripartite Synapses in APP/PS1 and MAOB-KO Mice Revealed by Lattice Structured Illumination Microscopy

Differential Proximity of Perisynaptic Astrocytic Best1 at the Excitatory and Inhibitory Tripartite Synapses in APP/PS1 and MAOB-KO Mice Revealed by Lattice Structured Illumination Microscopy

Astrocytes render memory flexible

Inverse Density of Iba1 and Glutamine Synthetase Expressing Glia in Rat Inferior Colliculus

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