Thalamus mediates neocortical Down state transition via GABAB-receptor-targeting interneurons

Hay, Y. Audrey; Deperrois, Nicolas; Fuchsberger, Tanja; Quarrell, Thomas Matthew; Koerling, Anna-Lucia; Paulsen, Ole

doi:10.1016/j.neuron.2021.06.030

Cited by 24 publications

(29 citation statements)

References 60 publications

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“…1 and 3). In line with a prominent role of inhibition in the generation of slow waves (Funk et al, 2017; Hay et al, 2021; Lemieux et al, 2015; Niethard et al, 2018; Zucca et al, 2017) microglial TNFα shapes slow waves by controlling transition into down states (fig. 4) and is thereby involved in sleep-dependent memory consolidation (fig.…”

Section: Discussionmentioning

confidence: 74%

“…Such control is likely achieved through a combination of different inhibitory networks. Thalamic drive onto L1 inhibitory neurogliaform cells induces transition into down states (Hay et al, 2021). In addition, SOM-IN firing precedes entry into down states (Niethard et al, 2018) and accordingly their stimulation increases the slope of slow waves and triggers down-states (Funk et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

“…During NREM sleep, slow waves in the delta frequency band (0.1-4Hz), quantified as slow wave activity (SWA), result from the synchronous alternation of active (up) and silent (down) states of cortical neurons. Cortical GABAergic inhibition is a major actor of NREM sleep slow waves (Hay et al, 2021; Lemieux et al, 2015). In particular, the activation of somatostatin positive interneurons, that mainly target L1, triggers down-states (Funk et al, 2017; Niethard et al, 2018).…”

Section: Daily Modulation Of Gabaars In a Sleep- And Microglia-depend...mentioning

confidence: 99%

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Microglial TNFα controls synaptic GABAARs, sleep slow waves and memory consolidation

Pinto

Bizien

Fabre

et al. 2022

Preprint

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Microglia sense the changes in their environment. How microglia actively translate these changes into suitable cues to adapt brain physiology is unknown. We reveal an activity-dependent regulation of cortical inhibitory synapses plasticity by microglia, driven by purinergic signaling acting on P2RX7 and mediated by microglia-derived TNFα. We demonstrate that sleep induces this microglia-dependent inhibitory plasticity by promoting synaptic enrichment of GABAARs. We further show that in turn, microglia-specific depletion of TNFα alters slow waves during NREM sleep and blunts sleep-dependent memory consolidation. Together, our results reveal that microglia orchestrate sleep-intrinsic plasticity of inhibitory synapses, ultimately sculpting sleep slow waves and memory.

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Section: Discussionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Section: Daily Modulation Of Gabaars In a Sleep- And Microglia-depend...mentioning

confidence: 99%

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Microglial TNFα controls synaptic GABAARs, sleep slow waves and memory consolidation

Pinto

Bizien

Fabre

et al. 2022

Preprint

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“…It should be noted that, in addition to the reduction of Ca 2+ transients, PS2 mutations linked to FAD-also reduce ATP levels, compromising the functionality of mitochondria as well as the redox state [ 82 , 90 , 91 ], while toxic Aβ oligomers can cause further metabolic and Ca 2+ dysregulation [ 92 , 93 ]. During slow-wave-sleep, synchronous transitions to DOWN-states are also actively controlled by thalamic sensory inputs via the activation of inhibitory interneurons acting on metabotropic GABA-B receptors [ 94 ], a network known to be altered in AD [ 95 , 96 ]. An important role in UP- and DOWN-state transition is also played by the inward rectifying K + channels (GIRK) dependent on G proteins, in particular those linked to GABA-B receptors at the hippocampal level, as shown in mouse AD models [ 97 ].…”

Section: Discussionmentioning

confidence: 99%

Accelerated Aging Characterizes the Early Stage of Alzheimer’s Disease

Leparulo

Bisio

Redolfi

et al. 2022

Cells

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For Alzheimer’s disease (AD), aging is the main risk factor, but whether cognitive impairments due to aging resemble early AD deficits is not yet defined. When working with mouse models of AD, the situation is just as complicated, because only a few studies track the progression of the disease at different ages, and most ignore how the aging process affects control mice. In this work, we addressed this problem by comparing the aging process of PS2APP (AD) and wild-type (WT) mice at the level of spontaneous brain electrical activity under anesthesia. Using local field potential recordings, obtained with a linear probe that traverses the posterior parietal cortex and the entire hippocampus, we analyzed how multiple electrical parameters are modified by aging in AD and WT mice. With this approach, we highlighted AD specific features that appear in young AD mice prior to plaque deposition or that are delayed at 12 and 16 months of age. Furthermore, we identified aging characteristics present in WT mice but also occurring prematurely in young AD mice. In short, we found that reduction in the relative power of slow oscillations (SO) and Low/High power imbalance are linked to an AD phenotype at its onset. The loss of SO connectivity and cortico-hippocampal coupling between SO and higher frequencies as well as the increase in UP-state and burst durations are found in young AD and old WT mice. We show evidence that the aging process is accelerated by the mutant PS2 itself and discuss such changes in relation to amyloidosis and gliosis.

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“…The brain-internal interactions that generate this large state-space are still largely unknown. LC neurons were classically thought to modulate cortical and thalamic neuronal excitability level using noradrenergic "tone" (4-7), whereas the neuronal interactions that produce the cortical state are contained within the cortex and thalamus (36,37).…”

Section: Nuanced Activation Patterns Of Diverse Lc Ensembles Enable Greater Diversity In Neuromodulatory Functionsmentioning

confidence: 99%

Distinct ensembles in the noradrenergic locus coeruleus evoke diverse cortical states

Noei

Zouridis

Logothetis

et al. 2020

Preprint

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13Identifying the neurons that control global brain state has been a fundamental topic of research 14 that has largely focused on diffusely-projecting neuromodulatory centers, such as the locus 15 coeruleus (LC). This noradrenergic brain stem nucleus, which projects throughout the forebrain, 16 is thought to act as an "undifferentiated state controller" across all forebrain targets because LC 17 neurons spike synchronously. However, recent work demonstrated ensembles in the LC and 18 therefore made targeted neuromodulation a possibility. In order to demonstrate that LC 19 ensembles cause targeted neuromodulation, it is necessary to resolve LC ensemble dynamics 20 over time in relation to ongoing cortical states. Here, we used non-negative matrix factorization 21 on LC single unit recordings to investigate the spatial and temporal properties of ensemble 22 activation patterns. We assessed the potential for targeted neuromodulation of the prefrontal 23 cortex (PFC) using LC ensemble activity-triggered local field potential (LFP) power spectrograms. 24We analyzed 285 single units recorded from 15 urethane-anesthetized rats (range of 5 to 34 25 simultaneously recorded units). LC ensembles became active at different times. Analysis of auto-26 correlograms and ensemble-pair cross-correlograms demonstrated that self-and lateral-inhibition 27 of activity is a property of LC ensembles, which may contribute to their sparse activity. 28Neuromodulatory effects on cortical state were diverse across ensembles. We observed four 29 types of ensemble-triggered LFP spectrograms in the PFC. These results demonstrate that the 30 LC is capable of differentiated neuromodulation of its forebrain targets by dynamic firing patterns 31 across subsets of LC neurons. 34Internal, spontaneously occurring brain states are associated with changes in wakefulness, 35perceptual ability, and reaction times (1-3). Behavioral transitions, such as waking from sleep or 36 reacting more quickly to stimuli during stress, involve changes in global brain state. It remains 37 unclear exactly which neurons could control brain state globally. 38Brainstem neuromodulatory centers, such as the noradrenergic locus coeruleus (LC), are a likely 39 global state-controller (1, 2, 4). The LC projects globally throughout the central nervous system 40 and releases norepinephrine to modulate neuronal excitability (5-11). Global noradrenergic 41 neuromodulation can result in behavioral transitions, such as: awakening from sleep or 42 anesthesia, altering locomotion patterns (increased generalized movements and decreased 43 reaction times), and improving perceptual sensitivity and attentional focus (12-24). The brain 44 state change that occurs spontaneously during behavioral transitions, such as awakening, also 45 resembles the brain state evoked by stimulation of the LC in awake or anesthetized animals (9, 46 16, 24, 25). Thus, the LC is thought to be at least one group of neurons that can alter global brain 47 states associated with behavioral state transitions. 48 LC n...

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Thalamus mediates neocortical Down state transition via GABAB-receptor-targeting interneurons

Cited by 24 publications

References 60 publications

Microglial TNFα controls synaptic GABAARs, sleep slow waves and memory consolidation

Microglial TNFα controls synaptic GABAARs, sleep slow waves and memory consolidation

Accelerated Aging Characterizes the Early Stage of Alzheimer’s Disease

Distinct ensembles in the noradrenergic locus coeruleus evoke diverse cortical states

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