Homeostatic plasticity and excitation-inhibition balance: The good, the bad, and the ugly

Chen, Lu; Li, Xiling; Tjia, Michelle; Thapliyal, Shruti

doi:10.1016/j.conb.2022.102553

Cited by 47 publications

(32 citation statements)

References 77 publications

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“…The exact behavioral impact of altered E/I balance in ASD remains largely unclear. A common view states that network hyperexcitability associated with reduced inhibition and altered inhibitory plasticity impairs neural processing (for recent reviews see Antoine, 2022; Chen et al, 2022; Ferguson and Gao, 2018; Liu et al, 2022), an idea well suited to account for perceptual learning deficits resulting from impairments in sensory discrimination (Goel et al, 2018). Alternatively, it has been proposed that altered excitatory and inhibitory synaptic transmission may not be a primary effect of the ASD phenotype, but rather reflect homeostatic compensations that mitigate other types of dysfunction (Antoine et al, 2019; Domanski et al, 2019; Nelson and Valakh, 2015).…”

Section: Discussionmentioning

confidence: 99%

Daily oscillation of the excitation/inhibition ratio is disrupted in two mouse models of autism

Bridi

Luo

et al. 2021

Preprint

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Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder involving sensory processing abnormalities. Alterations to the balance between excitation and inhibition (E/I ratio) are postulated to underlie behavioral phenotypes in ASD patients and mouse models. However, in primary visual cortex (V1) of wild type mice, the E/I ratio is not a fixed value, but rather oscillates across the 24h day. Therefore, we hypothesized that the E/I oscillation, rather than the overall E/I ratio, may be disrupted in ASD mouse models. To this end, we measured the E/I ratio in Fmr1 KO and BTBR mice, models of syndromic and idiopathic ASD, respectively. We found that the E/I ratio is dysregulated in both models, but in different ways: the oscillation is flattened in Fmr1 KO and phase-shifted in BTBR mice. These phenotypes cannot be explained by altered sleep timing, which was largely normal in both lines. Furthermore, we found that E/I dysregulation occurs due to alterations in both excitatory and inhibitory synaptic transmission in both models. These findings provide a crucial perspective on the E/I ratio in ASD, suggesting that ASD phenotypes may be produced by a mismatch of E/I to the appropriate behavioral state, rather than alterations to overall E/I levels per se.

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Section: Discussionmentioning

confidence: 99%

Daily oscillation of the excitation/inhibition ratio is disrupted in two mouse models of autism

Bridi

Luo

et al. 2021

Preprint

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“…Several studies have provided evidence that multiple pain models involve alterations in the balance of excitatory/inhibitory (E/I) neurotransmission in the medial prefrontal cortex (mPFC) and somatosensory regions [13,14]. Synaptic E/I balance is vital for network stability and information processing [15]; however, the relative role of inhibitory transmission in the ACC in pain states remains largely unexplored.…”

Section: Introductionmentioning

confidence: 99%

Dynamic modulation of synaptic transmission in the mouse ACC by inflammatory pain and dopamine

Darvish-Ghane

Buambach

Martin

2023

Preprint

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Dopamine (DA) inhibits excitatory synaptic transmission in the anterior cingulate cortex (ACC), a brain region involved in the sensory and affective processing of pain. However, DA modulation of inhibitory synaptic transmission in the ACC and its alteration of excitatory/inhibitory (E/I) balance remains relatively understudied. Using patch-clamp recordings, we demonstrate that DA inhibits γ-Aminobutyric acid subtype A (GABAA) receptor-mediated evoked inhibitory currents (eIPSCs) through postsynaptic D2 receptors. Recording excitatory and inhibitory currents from the same neuron yielded a heterogenous response dominated by GABAergic transmission. However, complete Freund’s adjuvant (CFA), a model of inflammatory pain, reduced the percentage of neurons showing synaptic inhibition by DA in the ACC. These results indicate that inflammatory pain induces changes in the interplay between DA signalling and inotropic transmission in the ACC of mice.

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“…Theoretical and experimental studies have confirmed the existence of a dynamically regulated balance of excitation and inhibition in local cortical networks at multiple states of wakefulness and sleep [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]. It has been hypothesized that balance of excitation and inhibition is essential for controlling network-level information transmission [19,20], efficient, high-precision, and high-dimensional representations and processing of sensory information [5,11,13], enabling cortical computations by enhancing the range of network sensitivity to sensory inputs [8], selective amplification of specific activity patterns in unstructured inputs [21], maintaining information in working memory [22], and, importantly, preserving network stability [10,23]. Pathological conditions resulting in deviations from normal levels of excitationinhibition balance, hence hypo-or hyper-excitation in cortical networks, have been associated with several neurological disorders, such as Autism Spectrum Disorders, schizophrenia, mood disorders, Alzheimer's disease, Rett Syndrome, and epilepsy [7,9,19,[23][24][25][26][27].…”

Section: Introductionmentioning

confidence: 99%

“…Despite the importance of excitation-inhibition balance in cortical functionality, and numerous homeostatic mechanisms that have been proposed as possible regulatory processes involved in maintaining this balance [8,10,19,23,[28][29][30][31][32][33], little is known about how balance of excitation and inhibition is established in cortical networks, what cellular and network properties are homeostatically adjusted to maintain it, and how it can be accurately and meaningfully measured [16,28,34]. However, it can be conceived that the balance is most likely established and regulated locally, that means through internal recurrent interactions within a local cortical network, since global interactions between different regions of the cortex is predominantly excitatory and cannot be effectively balanced at a global scale by short-range activity of inhibitory neurons [2,7,11,18,35].…”

Section: Introductionmentioning

confidence: 99%

On the physiological and structural contributors to the overall balance of excitation and inhibition in local cortical networks

Shirani

Choi

2023

Preprint

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Overall balance of excitation and inhibition in cortical networks is central to their functionality and normal operation. Such orchestrated temporal co-evolution of excitation and inhibition is established through local connections, and is homeostatically regulated to keep the networks in a vigilant state, so that they readily respond to their inputs and rapidly transition between different states without losing their stability. Several homeostatic plasticity mechanisms have been identified that adjust the strength and kinetics of synaptic activity in cortical networks to restore their balance when it is perturbed from a normal level. However, it is not yet well-understood how a balanced state is established, how it is dynamically regulated, and how it can accurately be measured, partially due to lack of a universally accepted definition of excitation-inhibition balance. Here, we use biologically plausible mathematical models to demonstrate how some of the key physiological factors that control the kinetics of synapses and structural factors that determine the overall topology of a cortical network contribute to establishment of an overall balance of excitation and inhibition throughout the network. We characterize a network's baseline balanced state by a set of functional properties, and show that deviations from this reference state can be continuously quantified by measuring the ratio between mean excitatory and mean inhibitory synaptic conductances in the network. We show how variations in physiological and structural parameters of a network dynamically change the level of excitation-inhibition balance and result in transitions in the spontaneous activity of the network to high-amplitude slow oscillatory regimes. Our results particularly show that the commonly observed ratio between the number of inhibitory and excitatory neurons in local cortical networks is nearly optimal, and the values of inhibitory synaptic decay time constants and the density of inhibitory-to-inhibitory connectivity are critical to network balance and stability.

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Homeostatic plasticity and excitation-inhibition balance: The good, the bad, and the ugly

Cited by 47 publications

References 77 publications

Daily oscillation of the excitation/inhibition ratio is disrupted in two mouse models of autism

Daily oscillation of the excitation/inhibition ratio is disrupted in two mouse models of autism

Dynamic modulation of synaptic transmission in the mouse ACC by inflammatory pain and dopamine

On the physiological and structural contributors to the overall balance of excitation and inhibition in local cortical networks

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