Local Dendritic Activity Sets Release Probability at Hippocampal Synapses

Branco, Tiago; Staras, Kevin; D'Arcy, Kevin; Goda, Yukiko

doi:10.1016/j.neuron.2008.07.006

Cited by 215 publications

(260 citation statements)

References 54 publications

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“…Homeostatic regulation of synaptic strength represents a basic mechanism of neuronal adaptation to constant changes in ongoing activity levels. Strong evidence exists on homeostatic augmentation of Pr and readily releasable pool size in response to prolong inactivity in hippocampal neurons (19,22,(34)(35)(36)(37)(38)(39)(40)(41)(42). These homeostatic adaptations are associated with modulation of presynaptic Ca 2+ flux (29) and remodeling of a large number of proteins in presynaptic cytomatrix (7).…”

Section: Discussionmentioning

confidence: 99%

GABA _B receptor deficiency causes failure of neuronal homeostasis in hippocampal networks

Vertkin

Styr

Slomowitz

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Stabilization of neuronal activity by homeostatic control systems is fundamental for proper functioning of neural circuits. Failure in neuronal homeostasis has been hypothesized to underlie common pathophysiological mechanisms in a variety of brain disorders. However, the key molecules regulating homeostasis in central mammalian neural circuits remain obscure. Here, we show that selective inactivation of GABA B , but not GABA A , receptors impairs firing rate homeostasis by disrupting synaptic homeostatic plasticity in hippocampal networks. Pharmacological GABA B receptor (GABA B R) blockade or genetic deletion of the GB 1a receptor subunit disrupts homeostatic regulation of synaptic vesicle release. GABA B Rs mediate adaptive presynaptic enhancement to neuronal inactivity by two principle mechanisms: First, neuronal silencing promotes syntaxin-1 switch from a closed to an open conformation to accelerate soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex assembly, and second, it boosts spike-evoked presynaptic calcium flux. In both cases, neuronal inactivity removes tonic block imposed by the presynaptic, GB 1a -containing receptors on syntaxin-1 opening and calcium entry to enhance probability of vesicle fusion. We identified the GB 1a intracellular domain essential for the presynaptic homeostatic response by tuning intermolecular interactions among the receptor, syntaxin-1, and the Ca V 2.2 channel. The presynaptic adaptations were accompanied by scaling of excitatory quantal amplitude via the postsynaptic, GB 1b -containing receptors. Thus, GABA B Rs sense chronic perturbations in GABA levels and transduce it to homeostatic changes in synaptic strength. Our results reveal a novel role for GABA B R as a key regulator of population firing stability and propose that disruption of homeostatic synaptic plasticity may underlie seizure's persistence in the absence of functional GABA B Rs.homeostatic plasticity | GABA B receptor | synaptic vesicle release | syntaxin-1 | FRET

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Section: Discussionmentioning

confidence: 99%

GABA _B receptor deficiency causes failure of neuronal homeostasis in hippocampal networks

Vertkin

Styr

Slomowitz

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…This idea is supported by evidence showing that glial cells can serve as general activity sensors and modulate all synapses in an area (17). On the other hand, findings of tight coordination between closely neighboring synapses (18) and of differential regulation of different types of synapses (19) would be compatible with a synapse-based organization.…”

mentioning

confidence: 82%

Postsynaptic GluA1 enables acute retrograde enhancement of presynaptic function to coordinate adaptation to synaptic inactivity

Lindskog

Groth

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Prolonged blockade of AMPA-type glutamate receptors in hippocampal neuron cultures leads to homeostatic enhancements of preand postsynaptic function that appear correlated at individual synapses, suggesting some form of transsynaptic coordination. The respective modifications are important for overall synaptic strength but their interrelationship, dynamics, and molecular underpinnings are unclear. Here we demonstrate that adaptation begins postsynaptically but is ultimately communicated to presynaptic terminals and expressed as an accelerated turnover of synaptic vesicles. Critical postsynaptic modifications occur over hours, but enable retrograde communication within minutes once AMPA receptor (AMPAR) blockade is removed, causing elevation of both spontaneous and evoked vesicle fusion. The retrograde signaling does not require spiking activity and can be interrupted by NBQX, philanthotoxin, postsynaptic BAPTA, or external sequestration of BDNF, consistent with the acute release of retrograde messenger, triggered by postsynaptic Ca 2+ elevation via Ca 2+ -permeable AMPARs.homeostasis | synaptic scaling | calcium signaling | miniature excitatory postsynaptic currents P rolonged perturbations in the level of activity of neuronal circuits initiate major changes in excitatory transmission. Such retuning is generally homeostatic and is proposed to counterbalance other forms of plasticity and to help keep neuronal firing rate within an optimal range for efficient transfer of information (1-3). There is growing agreement about the functional significance of adaptation to inactivity (2, 4), but much uncertainty remains about where and how such adaptation is expressed.The increase in postsynaptic function in response to prolonged inactivity, evident as an increase in the amplitude of unitary synaptic events (miniature excitatory postsynaptic currents, mEPSCs, or minis), is by now well-established (2, 4). The enlargement of mEPSCs is mediated by an accumulation of AMPA receptors (AMPARs) at postsynaptic sites (5-8). Sometimes the increase is attributed to an increase in Ca 2+ -permeable AMPARs that lack GluA2 subunits (7, 9, 10), but in other cases comparable elevations in both GluA1 and GluA2 have been seen (6,8,11,12). Furthermore, adaptation to inactivity induced by postsynaptic blockade may also involve presynaptic changes, reflected by an elevated frequency of mEPSCs and increased vesicular turnover (7,(13)(14)(15)(16).Although evidence is mounting for both pre-and postsynaptic modifications, the fundamental nature of such alterations remains incompletely understood. On one hand, neuronal inactivity causing cellwide changes in transmitter release and receptivity (2) would fit with descriptions of synaptic homeostasis as a global phenomena. This idea is supported by evidence showing that glial cells can serve as general activity sensors and modulate all synapses in an area (17). On the other hand, findings of tight coordination between closely neighboring synapses (18) and of differential regulation of different types...

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“…Persistent elevation of network activity decreases the number of readily releasable synaptic vesicles and release-probability (Moulder et al, 2004(Moulder et al, , 2006Branco et al, 2008), whereas chronic suppression of neural activity results in an increased number of docked vesicles, enlarged active zones, and an elevated frequency of mEPSCs (Murthy et al, 2001;Moulder et al, 2006;Han and Stevens, 2009). Recent evidence suggests a direct involvement of proteins involved in synaptic vesicle priming in these processes (Moulder et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

The Presynaptic Active Zone Protein RIM1α Controls Epileptogenesis following Status Epilepticus

Pitsch¹,

Opitz²,

Borm³

et al. 2012

J. Neurosci.

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To ensure operation of synaptic transmission within an appropriate dynamic range, neurons have evolved mechanisms of activitydependent plasticity, including changes in presynaptic efficacy. The multidomain protein RIM1␣ is an integral component of the cytomatrix at the presynaptic active zone and has emerged as key mediator of presynaptically expressed forms of synaptic plasticity. We have therefore addressed the role of RIM1␣ in aberrant cellular plasticity and structural reorganization after an episode of synchronous neuronal activity pharmacologically induced in vivo [status epilepticus (SE)]. Post-SE, all animals developed spontaneous seizure events, but their frequency was dramatically increased in RIM1␣-deficient mice (RIM1␣ Ϫ/Ϫ ). We found that in wild-type mice (RIM1␣ ϩ/ϩ ) SE caused an increase in paired-pulse facilitation in the CA1 region of the hippocampus to the level observed in RIM1␣ Ϫ/Ϫ mice before SE. In contrast, this form of short-term plasticity was not further enhanced in RIM1␣-deficient mice after SE. Intriguingly, RIM1␣ Ϫ/Ϫ mice showed a unique pattern of selective hilar cell loss (i.e., endfolium sclerosis), which so far has not been observed in a genetic epilepsy animal model, as well as less severe astrogliosis and attenuated mossy fiber sprouting. These findings indicate that the decrease in release probability and altered short-and long-term plasticity as present in RIM1␣ Ϫ/Ϫ mice result in the formation of a hyperexcitable network but act in part neuroprotectively with regard to neuropathological alterations associated with epileptogenesis. In summary, our results suggest that presynaptic plasticity and proper function of RIM1␣ play an important part in a neuron's adaptive response to aberrant electrical activity.

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Local Dendritic Activity Sets Release Probability at Hippocampal Synapses

Cited by 215 publications

References 54 publications

GABA _B receptor deficiency causes failure of neuronal homeostasis in hippocampal networks

GABA _B receptor deficiency causes failure of neuronal homeostasis in hippocampal networks

Postsynaptic GluA1 enables acute retrograde enhancement of presynaptic function to coordinate adaptation to synaptic inactivity

The Presynaptic Active Zone Protein RIM1α Controls Epileptogenesis following Status Epilepticus

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Local Dendritic Activity Sets Release Probability at Hippocampal Synapses

Cited by 215 publications

References 54 publications

GABA B receptor deficiency causes failure of neuronal homeostasis in hippocampal networks

GABA B receptor deficiency causes failure of neuronal homeostasis in hippocampal networks

Postsynaptic GluA1 enables acute retrograde enhancement of presynaptic function to coordinate adaptation to synaptic inactivity

The Presynaptic Active Zone Protein RIM1α Controls Epileptogenesis following Status Epilepticus

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GABA _B receptor deficiency causes failure of neuronal homeostasis in hippocampal networks

GABA _B receptor deficiency causes failure of neuronal homeostasis in hippocampal networks