Inhibitory Receptor Diffusion Dynamics

Maynard, Stephanie A.; Triller, Antoine

doi:10.3389/fnmol.2019.00313

Cited by 22 publications

(15 citation statements)

References 98 publications

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“…Increases or decreases in channel function can occur as a result of GABA A R phosphorylation by multiple kinases, including, CaMKII, PKC, PKA and Src (Vithlani et al., 2011). GABA A Rs are further controlled by constitutive cycling, regulating insertion and removal, as well as lateral diffusion at the synaptic membrane surface (Luscher et al., 2011; Maynard & Triller, 2019; Pizzarelli et al., 2019; Tomita, 2019; Vithlani et al., 2011). The number of GABA A Rs at the cell surface is regulated by endocytosis and exocytosis.…”

Section: Postsynaptic Forms Of Ispmentioning

confidence: 99%

The ins and outs of inhibitory synaptic plasticity: Neuron types, molecular mechanisms and functional roles

Capogna

Castillo

Maffei

2020

Eur J of Neuroscience

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GABAergic interneurons are highly diverse, and their synaptic outputs express various forms of plasticity. Compelling evidence indicates that activity-dependent changes of inhibitory synaptic transmission play a significant role in regulating neural circuits critically involved in learning and memory and circuit refinement. Here, we provide an updated overview of inhibitory synaptic plasticity with a focus on the hippocampus and neocortex. To illustrate the diversity of inhibitory interneurons, we discuss the case of two highly divergent interneuron types, parvalbumin-expressing basket cells and neurogliaform cells, which support unique roles on circuit dynamics. We also present recent progress on the molecular mechanisms underlying longterm, activity-dependent plasticity of fast inhibitory transmission. Lastly, we discuss the role of inhibitory synaptic plasticity in neuronal circuits' function. The emerging picture is that inhibitory synaptic transmission in the CNS is extremely diverse, undergoes various mechanistically distinct forms of plasticity and contributes to a much more refined computational role than initially thought. Both the remarkable diversity of inhibitory interneurons and the various forms of plasticity expressed by GABAergic synapses provide an amazingly rich inhibitory repertoire that is central to a variety of complex neural circuit functions, including memory.

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Section: Postsynaptic Forms Of Ispmentioning

confidence: 99%

The ins and outs of inhibitory synaptic plasticity: Neuron types, molecular mechanisms and functional roles

Capogna

Castillo

Maffei

2020

Eur J of Neuroscience

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“…That the sIPSCs amplitudes and densities were decreased in the aged tg‐APPSwe mice relative to the aged wild‐type littermates, implies a general decrease in the number of postsynaptic GABA A receptors in the DG granule cells in the aged tg‐APPSwe animals or, alternatively, decreased release of GABA from the presynaptic terminals. It is possible that the increased tonic current that was normalized by insulin is related, in part, to the synaptic‐type receptors remaining outside of synapses in the aged tg‐APPSwe mice but then, are rescued by insulin, resulting in normalized and increased synaptic and decreased extrasynaptic current densities 72‐74 . Notably, the DG granule cells are clearly not insulin resistant in the presence of amyloid pathology.…”

Section: Discussionmentioning

confidence: 99%

Insulin differentially modulates GABA signalling in hippocampal neurons and, in an age‐dependent manner, normalizes GABA‐activated currents in the tg‐APPSwe mouse model of Alzheimer’s disease

et al. 2021

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Aim We examined if tonic γ‐aminobutyric acid (GABA)‐activated currents in primary hippocampal neurons were modulated by insulin in wild‐type and tg‐APPSwe mice, an Alzheimer's disease (AD) model. Methods GABA‐activated currents were recorded in dentate gyrus (DG) granule cells and CA3 pyramidal neurons in hippocampal brain slices, from 8 to 10 weeks old (young) wild‐type mice and in dorsal DG granule cells in adult, 5‐6 and 10‐12 (aged) months old wild‐type and tg‐APPSwe mice, in the absence or presence of insulin, by whole‐cell patch‐clamp electrophysiology. Results In young mice, insulin (1 nmol/L) enhanced the total spontaneous inhibitory postsynaptic current (sIPSCT) density in both dorsal and ventral DG granule cells. The extrasynaptic current density was only increased by insulin in dorsal CA3 pyramidal neurons. In absence of action potentials, insulin enhanced DG granule cells and dorsal CA3 pyramidal neurons miniature IPSC (mIPSC) frequency, consistent with insulin regulation of presynaptic GABA release. sIPSCT densities in DG granule cells were similar in wild‐type and tg‐APPSwe mice at 5‐6 months but significantly decreased in aged tg‐APPSwe mice where insulin normalized currents to wild‐type levels. The extrasynaptic current density was increased in tg‐APPSwe mice relative to wild‐type littermates but, only in aged tg‐APPSwe mice did insulin decrease and normalize the current. Conclusion Insulin effects on GABA signalling in hippocampal neurons are selective while multifaceted and context‐based. Not only is the response to insulin related to cell‐type, hippocampal axis‐location, age of animals and disease but also to the subtype of neuronal inhibition involved, synaptic or extrasynaptic GABAA receptors‐activated currents.

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“…This process is regulated by scaffolding proteins, but also by the exocytosis of de novo synthetized GABA A Rs or the endocytosis of recycled ones [ 15 ]. In addition, several lines of evidence point that a much faster turnover can occur through the lateral diffusion of membrane GABA A Rs [ 16 ]. The distribution and stability of postsynaptic GABA A Rs are regulated by intracellular signaling pathways following G-protein-coupled receptor (GPCRs) activation.…”

Section: Introductionmentioning

confidence: 99%

Characterization of the Functional Cross-Talk between Surface GABAA and Dopamine D5 Receptors

Maingret

Groc

2021

IJMS

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The γ-aminobutyric acid type A receptor (GABAAR) plays a major role in fast inhibitory synaptic transmission and is highly regulated by the neuromodulator dopamine. In this aspect, most of the attention has been focused on the classical intracellular signaling cascades following dopamine G-protein-coupled receptor activation. Interestingly, the GABAAR and dopamine D5 receptor (D5R) have been shown to physically interact in the hippocampus, but whether a functional cross-talk occurs is still debated. In the present study, we use a combination of imaging and single nanoparticle tracking in live hippocampal neurons to provide evidence that GABAARs and D5Rs form dynamic surface clusters. Disrupting the GABAAR–D5R interaction with a competing peptide leads to an increase in the diffusion coefficient and the explored area of both receptors, and a drop in immobile synaptic GABAARs. By means of patch-clamp recordings, we show that this fast lateral redistribution of surface GABAARs correlates with a robust depression in the evoked GABAergic currents. Strikingly, it also shifts in time the expression of long-term potentiation at glutamatergic synapses. Together, our data both set the plasma membrane as the primary stage of a functional interplay between GABAAR and D5R, and uncover a non-canonical role in regulating synaptic transmission.

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Inhibitory Receptor Diffusion Dynamics

Cited by 22 publications

References 98 publications

The ins and outs of inhibitory synaptic plasticity: Neuron types, molecular mechanisms and functional roles

The ins and outs of inhibitory synaptic plasticity: Neuron types, molecular mechanisms and functional roles

Insulin differentially modulates GABA signalling in hippocampal neurons and, in an age‐dependent manner, normalizes GABA‐activated currents in the tg‐APPSwe mouse model of Alzheimer’s disease

Characterization of the Functional Cross-Talk between Surface GABAA and Dopamine D5 Receptors

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