Homeostatic synaptic plasticity in developing spinal networks driven by excitatory GABAergic currents

Wenner, Peter

doi:10.1016/j.neuropharm.2013.04.058

Cited by 30 publications

(23 citation statements)

References 89 publications

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“…Under chronic suppression of neuronal activity, HSP is expressed via an increase in synaptic expression of AMPARs producing an up-scaling of AMPAR-mediated miniature post-synaptic currents (mEPSCs). While most studies show inactivity-induced synaptic scaling in cultured neurons [2, 46, 50, 55], HSP is also observed in vivo including in the spinal cord [16, 19, 33, 59] and in the visual cortex [11, 17, 31, 34, 38]. AMPARs are heterotetrameric ion channels consisting of different compositions of the four subunits GluA1–4, and the most common of which are GluA1/GluA2 and GluA2/GluA3 combinations [5, 13].…”

Section: Introductionmentioning

confidence: 99%

β-Amyloid triggers aberrant over-scaling of homeostatic synaptic plasticity

Gilbert

Shu

Yang

et al. 2016

acta neuropathol commun

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The over-production of β-amyloid (Aβ) has been strongly correlated to neuronal dysfunction and altered synaptic plasticity in Alzheimer’s disease (AD). Accordingly, it has been proposed that disrupted synaptic transmission and neuronal network instability underlie memory failure that is evident in the early phases of AD. Homeostatic synaptic plasticity (HSP) serves to restrain neuronal activity within a physiological range. Therefore a disruption of this mechanism may lead to destabilization in synaptic and neural circuit function. Here, we report that during HSP by neuronal activity deprivation, application of Aβ results in an aberrant over-response of the up-regulation of AMPA receptor (AMPAR)-mediated synaptic currents and cell-surface AMPAR expression. In the visual cortex, in vivo HSP induced by visual deprivation shows a similar over-response following an Aβ local injection. Aβ increases the expression of GluA2-lacking, calcium permeable AMPARs (CP-AMPARs), which are required for the initiation, but not maintenance of HSP. Both GluA2-lacking and GluA2-containing AMPARs contribute to the Aβ-mediated over-scaling of HSP. We also find that Aβ induces the dissociation of HDAC1 from the miR124 transcription factor EVI1, leading to an up-regulation of miR124 expression and increased amount of CP-AMPARs. Thus, via aberrant stimulation of miR124 expression and biogenesis of CP-AMPARs, Aβ is able to induce an over response in HSP. This Aβ-mediated dysregulation in homeostatic plasticity may play an important role in the pathogenesis of altered neural function and memory deficits in the early stages of AD.Electronic supplementary materialThe online version of this article (doi:10.1186/s40478-016-0398-0) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

β-Amyloid triggers aberrant over-scaling of homeostatic synaptic plasticity

Gilbert

Shu

Yang

et al. 2016

acta neuropathol commun

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“…Although less studied, activity-dependent plasticity also plays a role in more intact embryonic spinal cord preparations in vitro at a time when GABAergic and glycinergic NT evoked currents and are considered depolarizing and excitatory (for reviews see Wenner, 2013; Momose-Sato and Sato, 2013). One of the first experiments to explore the pharmacological details of rSNA, as well as the potential for activity dependent plasticity, was Chub and O’Donovan (1998), who showed that the combined inhibition of glutamatergic and cholinergic NT in the E10–11 chick lumbar spinal cord produced a strengthening of GABAergic and glycinergic NT.…”

Section: Discussionmentioning

confidence: 99%

“…The myriad of potential mechanisms responsible for the self-regulation of embryonic rSNA can be broadly grouped as increases and/or decreases in cellular/network excitability and or alterations in synaptic strength (Lindsly et al, 2014; Gonzalez-Islas et al, 2009; for review see Wenner, 2013). Although we have not determined mechanism by which GABAergic/glycinergic NT is potentiated by the loss of rSNA, we speculate that both the absence of nicotinic-evoked inward currents and the low [K + ] o perturbation increased the strength of GABAergic/glycinergic NT in the following way: we propose that the observed strengthening of Cl − -mediated conductance and depolarization is likely a straightforward result of the prolonged cessation of action potential generation, as others have previously shown in the spinal cord (Lindsly et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…While rSNA is considered a relatively generic multisynaptic depolarization wave synaptically shared by many disparate regions of the embryonic neuraxis, evidence suggests that it is important for proper network construction. For example, both the presence and pattern of rSNA has been shown to influence neuronal migration, axon guidance, expression of individual ion channels, and neurotransmitter phenotypes in the CNS (Borodinsky et al, 2013; Chub and O’Donovan, 1998; Hanson and Landmesser, 2006; Spitzer, 2012; Wenner, 2013; Yoon et al, 2010, 2008). When examining the isolated neuraxis in vitro , rSNA is expressed as periodic episodes of recurrent spike train activity initiated in the hindbrain and or the spinal cord, depending on developmental stage, which then propagates from these initiation zones both rostrally and caudally to the forebrain and the sacral spinal cord, respectively (Hughes et al, 2009; Momose-Sato and Sato, 2014).…”

Section: Introductionmentioning

confidence: 99%

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Activity-dependent plasticity in the isolated embryonic avian brainstem following manipulations of rhythmic spontaneous neural activity

Vincen-Brown

Revill

Pilarski

2016

Respiratory Physiology & Neurobiology

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When rhythmic spontaneous neural activity (rSNA) first appears in the embryonic chick brainstem and cranial nerve motor axons it is principally driven by nicotinic neurotransmission (NT). At this early age, the nicotinic acetylcholine receptor (nAChR) agonist nicotine is known to critically disrupt rSNA at low concentrations (0.1–0.5 µM), which are levels that mimic the blood plasma levels of a fetus following maternal cigarette smoking. Thus, we quantified the effect of persistent exposure to exogenous nicotine on rSNA using an in vitro developmental model. We found that rSNA was eliminated by continuous bath application of exogenous nicotine, but rSNA recovered activity within 6–12 h despite the persistent activation and desensitization of nAChRs. During the recovery period rSNA was critically driven by chloride-mediated membrane depolarization instead of nicotinic NT. To test whether this observed compensation was unique to the antagonism of nicotinic NT or whether the loss of spiking behavior also played a role, we eliminated rSNA by lowering overall excitatory drive with a low [K+]o superfusate. In this context, rSNA again recovered, although the recovery time was much quicker, and exhibited a lower frequency, higher duration, and an increase in the number of bursts per episode when compared to control embryos. Importantly, we show that the main compensatory response to lower overall excitatory drive, similar to nicotinergic block, is a result of potentiated chloride mediated membrane depolarization. These results support increasing evidence that early neural circuits sense spiking behavior to maintain primordial bioelectric rhythms. Understanding the nature of developmental plasticity in the nervous system, especially versions that preserve rhythmic behaviors following clinically meaningful environmental stimuli, both normal and pathological, will require similar studies to determine the consequences of feedback compensation at more mature chronological ages.

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“…This was first described in pioneering theoretical studies and experimental work employing neurons isolated from the stomatogastric nervous system of crustaceans. Such homeostatic plasticity has now been observed and modeled in cell culture, brain slices and in vivo across invertebrates and vertebrates and has led to important concepts such as synaptic scaling (Davis 2006; LeMasson et al 1993; Turrigiano 2007; Wenner 2014). An evolving notion is that intracellular [Ca 2+ ] -- fed by Ca 2+ entry through voltage-gated Ca 2+ channels or Ca 2+ -permeable synaptic channels --serves as an effective signal of neuronal and network activity (Liu et al 1998; Turrigiano 2007).…”

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confidence: 99%