Changes in Presynaptic Gene Expression during Homeostatic Compensation at a Central Synapse

Harrell, Evan R.; Pimentel, Diogo; Miesenböck, Gero

doi:10.1523/jneurosci.2979-20.2021

Cited by 15 publications

(11 citation statements)

References 90 publications

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“…Ion channels play important roles for homeostatic E-I balance. Previously, overexpression of Kir2.1 in forebrain excitatory neurons in mature neurons, inhibited the excitability of excitatory neurons (Burrone et al, 2002) induce homeostatic plasticity (Harrell et al, 2021) and network re-stable (Burrone et al, 2002;Okada and Matsuda, 2008). In this study, we showed a reduction in neural activity in forebrain excitatory neurons lead to the reduction of inhibitory transmission in Kir2.1 (+) mice.…”

Section: Discussionmentioning

confidence: 49%

“…Overexpression of Kir2.1 causes hyperpolarization to inhibit neural excitation (Okada and Matsuda, 2008) and network balance control (Paradis et al, 2001). Adult-onset expression of Kir2.1 could induce homeostatic plasticity and presynaptic transcriptional changes in the fruit fly brain (Harrell et al, 2021). Silencing pyramidal neurons with Kir2.1, after synapse formation, causes a homeostatic increase in synaptic inputs to stabilizes network activity (Burrone et al, 2002;Turrigiano, 2011).…”

Section: Introductionmentioning

confidence: 99%

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Forebrain E-I balance controlled in cognition through coordinated inhibition and inhibitory transcriptome mechanism

Tian

Cai²,

Qin³

et al. 2023

Front. Cell. Neurosci.

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IntroductionForebrain neural networks are vital for cognitive functioning, and their excitatory-inhibitory (E-I) balance is governed by neural homeostasis. However, the homeostatic control strategies and transcriptomic mechanisms that maintain forebrain E-I balance and optimal cognition remain unclear.MethodsWe used patch-clamp and RNA sequencing to investigate the patterns of neural network homeostasis with suppressing forebrain excitatory neural activity and spatial training.ResultsWe found that inhibitory transmission and receptor transcription were reduced in tamoxifen-inducible Kir2.1 conditional knock-in mice. In contrast, spatial training increased inhibitory synaptic connections and the transcription of inhibitory receptors.DiscussionOur study provides significant evidence that inhibitory systems play a critical role in the homeostatic control of the E-I balance in the forebrain during cognitive training and E-I rebalance, and we have provided insights into multiple gene candidates for cognition-related homeostasis in the forebrain.

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Section: Discussionmentioning

confidence: 49%

Section: Introductionmentioning

confidence: 99%

Forebrain E-I balance controlled in cognition through coordinated inhibition and inhibitory transcriptome mechanism

Tian

Cai²,

Qin³

et al. 2023

Front. Cell. Neurosci.

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“…Besides, we overexpressed Kir2 . 1 (gene KCNJ2), a rectifying potassium channel that allows more potassium ions to enter the cell [ 57 , 58 ], or tetanous toxin (UAS-TNT) in GB cells [ 59 , 60 ] ( Fig 3I ). All these strategies are directed towards the disruption of synaptic activity in GB cells.…”

Section: Resultsmentioning

confidence: 99%

“…To this aim, we used RNAi against shaker, the structural alpha subunit of a voltage-gated potassium channel [47,48], shakingB, a structural component of the gap junctions at electrical synapses [49][50][51], KCNQ1, a voltage-gated potassium channel [52,53], calcium beta1 subunit, a voltage-gated calcium channel [54] or Acetylcholine alfa 4 or alfa 1 receptor subunits [55,56]. Besides, we overexpressed Kir2.1 (gene KCNJ2), a rectifying potassium channel that allows more potassium ions to enter the cell [57,58], or tetanous toxin (UAS-TNT) in GB cells [59,60] (Fig 3I). All these strategies are directed towards the disruption of synaptic activity in GB cells.…”

Section: Vesicle Calcium Binding Proteins Are Required For Gb Progres...mentioning

confidence: 99%

Synaptic components are required for glioblastoma progression in Drosophila

et al. 2022

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Glioblastoma (GB) is the most aggressive, lethal and frequent primary brain tumor. It originates from glial cells and is characterized by rapid expansion through infiltration. GB cells interact with the microenvironment and healthy surrounding tissues, mostly neurons and vessels. GB cells project tumor microtubes (TMs) contact with neurons, and exchange signaling molecules related to Wingless/WNT, JNK, Insulin or Neuroligin-3 pathways. This cell to cell communication promotes GB expansion and neurodegeneration. Moreover, healthy neurons form glutamatergic functional synapses with GB cells which facilitate GB expansion and premature death in mouse GB xerograph models. Targeting signaling and synaptic components of GB progression may become a suitable strategy against glioblastoma. In a Drosophila GB model, we have determined the post-synaptic nature of GB cells with respect to neurons, and the contribution of post-synaptic genes expressed in GB cells to tumor progression. In addition, we document the presence of intratumoral synapses between GB cells, and the functional contribution of pre-synaptic genes to GB calcium dependent activity and expansion. Finally, we explore the relevance of synaptic genes in GB cells to the lifespan reduction caused by GB advance. Our results indicate that both presynaptic and postsynaptic proteins play a role in GB progression and lethality.

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“…Notably, the ORN-PN synapse is surprisingly resilient to reduced AZ Ca 2+ channel expression and appears to be able to compensate the drop in release probability by increasing the number of release sites and/or by elevating postsynaptic sensitivity to yield normal eEPSC amplitudes. Homeostatic synaptic plasticity features at the Drosophila NMJ (Davis and Müller, 2015; Goel and Dickman, 2021), mushroom body (Apostolopoulou and Lin, 2020), and also operates in the antennal lobe to match synaptic strength to PN excitability (Harrell et al, 2021; Kazama and Wilson, 2008). Interestingly, Cac RNAi decreases synaptic transmission to a greater extent from ORNs to iLNs than from ORNs to PNs (compare Figures 1B and 5B).…”

Section: Discussionmentioning

confidence: 99%

Homeostatic Synaptic Plasticity Rescues Neural Coding Reliability

Rozenfeld

Ehmann

Manoim

et al. 2021

Preprint

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A key requirement for the repeated identification of a stimulus is a reliable neural representation each time it is encountered. Neural coding is often considered to rely on two major coding schemes: the firing rate of action potentials, known as rate coding, and the precise timing of action potentials, known as temporal coding. Synaptic transmission is the major mechanism of information transfer between neurons. While theoretical studies have examined the effects of neurotransmitter release probability on neural code reliability, it has not yet been addressed how different components of the release machinery affect coding of physiological stimuli in vivo. Here, we use the first synapse of the Drosophila olfactory system to show that the reliability of the neural code is sensitive to perturbations of specific presynaptic proteins controlling distinct stages of neurotransmitter release. Notably, the presynaptic manipulations decreased coding reliability of postsynaptic neurons only at high odor intensity. We further show that while the reduced temporal code reliability arises from monosynaptic effects, the reduced rate code reliability arises from circuit effects, which include the recruitment of inhibitory local neurons. Finally, we find that reducing neural coding reliability decreases behavioral reliability of olfactory stimulus classification.

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Changes in Presynaptic Gene Expression during Homeostatic Compensation at a Central Synapse

Abstract: Changes in presynaptic gene expression during homeostatic compensation at a central synapse Abbreviated title: Trans-synaptic regulation of gene expression

Cited by 15 publications

References 90 publications

Forebrain E-I balance controlled in cognition through coordinated inhibition and inhibitory transcriptome mechanism

Forebrain E-I balance controlled in cognition through coordinated inhibition and inhibitory transcriptome mechanism

Synaptic components are required for glioblastoma progression in Drosophila

Homeostatic Synaptic Plasticity Rescues Neural Coding Reliability

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