RIM1α is required for presynaptic long-term potentiation

Castillo, Pablo E.; Schoch, Susanne; Schmitz, Frank; Südhof, Thomas C.; Malenka, Robert C.

doi:10.1038/415327a

Cited by 375 publications

(404 citation statements)

References 29 publications

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“…PKAdependent forms of presynaptic LTP exist at synaptic contacts between dentate gyrus granule cells and CA3 pyramidal neurons-the so-called mossy fibre terminals [36,37]. Presynaptic mossy fibre LTP requires Rim1a [38] and is regulated by presynaptic kainate receptors [39], thus strongly resembling presynaptic LTP at cortico-LA synapses [28,33]. We thus examined synaptic transmission and plasticity at hippocampal mossy fibre synapses (figure 4a).…”

Section: (D) Lack Of Ophn1 Abolishes Presynaptic Long-term Potentiatimentioning

confidence: 99%

Lack of the presynaptic RhoGAP protein oligophrenin1 leads to cognitive disabilities through dysregulation of the cAMP/PKA signalling pathway

Khelfaoui

Gambino

Houbaert

et al. 2014

Phil. Trans. R. Soc. B

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Loss-of-function mutations in the gene encoding for the RhoGAP protein of oligophrenin-1 (OPHN1) lead to cognitive disabilities (CDs) in humans, yet the underlying mechanisms are not known. Here, we show that in mice constitutive lack of Ophn1 is associated with dysregulation of the cyclic adenosine monophosphate/phosphate kinase A (cAMP/PKA) signalling pathway in a brain-area-specific manner. Consistent with a key role of cAMP/PKA signalling in regulating presynaptic function and plasticity, we found that PKA-dependent presynaptic plasticity was completely abolished in affected brain regions, including hippocampus and amygdala. At the behavioural level, lack of OPHN1 resulted in hippocampus- and amygdala-related learning disabilities which could be fully rescued by the ROCK/PKA kinase inhibitor fasudil. Together, our data identify OPHN1 as a key regulator of presynaptic function and suggest that, in addition to reported postsynaptic deficits, loss of presynaptic plasticity contributes to the pathophysiology of CDs.

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Section: (D) Lack Of Ophn1 Abolishes Presynaptic Long-term Potentiatimentioning

confidence: 99%

Lack of the presynaptic RhoGAP protein oligophrenin1 leads to cognitive disabilities through dysregulation of the cAMP/PKA signalling pathway

Khelfaoui

Gambino

Houbaert

et al. 2014

Phil. Trans. R. Soc. B

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“…Given the present results, cAMP-dependent targets known to be involved in vesicle priming emerge as strong candidates for modulation of synaptic activation state. For instance, active zone proteins of the Rim family are known PKA substrates and are involved in vesicle priming (Lonart, 2002;Calakos et al, 2004) and mossy fiber LTP (Castillo et al, 2002).…”

Section: Possible Downstream Targetsmentioning

confidence: 99%

A Specific Role for Ca²⁺-Dependent Adenylyl Cyclases in Recovery from Adaptive Presynaptic Silencing

Moulder¹,

Jiang²,

Chang³

et al. 2008

J. Neurosci.

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Glutamate generates fast postsynaptic depolarization throughout the CNS. The positive-feedback nature of glutamate signaling likely necessitates flexible adaptive mechanisms that help prevent runaway excitation. We have previously explored presynaptic adaptive silencing, a form of synaptic plasticity produced by ongoing neuronal activity and by strong depolarization. Unsilencing mechanisms that maintain active synapses and restore normal function after adaptation are also important, but mechanisms underlying such presynaptic reactivation remain unexplored. Here we investigate the involvement of the cAMP pathway in the basal balance between silenced and active synapses, as well as the recovery of baseline function after depolarization-induced presynaptic silencing. Activation of the cAMP pathway activates synapses that are silent at rest, and pharmacological inhibition of cAMP signaling silences basally active synapses. Adenylyl cyclase (AC) 1 and AC8, the major Ca 2ϩ -sensitive AC isoforms, are not crucial for the baseline balance between silent and active synapses. In cells from mice doubly deficient in AC1 and AC8, the baseline percentage of active synapses was only modestly reduced compared with wild-type synapses, and forskolin unsilencing was similar in the two genotypes. Nevertheless, after strong presynaptic silencing, recovery of normal function was strongly inhibited in AC1/AC8-deficient synapses. The entire recovery phenotype of the double null was reproduced in AC8-deficient but not AC1-deficient cells. We conclude that, under normal conditions, redundant cyclase activity maintains the balance between presynaptically silent and active synapses, but AC8 plays a particularly important role in rapidly resetting the balance of active to silent synapses after adaptation to strong activity.

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“…MF-principal cell LTP arises via an adenylyl cyclase-cAMP-dependent mechanism involving PKA phosphorylation of Rab3/Rim1a to ultimately strengthen synaptic transmitter release (Castillo et al, 1997(Castillo et al, , 2002Nicoll and Schmitz, 2005) (Fig. 5).…”

Section: Mossy Fiber-inhibitory Interneuron Plasticitymentioning

confidence: 99%

“…1) to follow. Given that the filopodial extensions originate from the large MF terminal, it might be assumed that any change in presynaptic release probability arising from LTP in the large MF bouton would distribute evenly to all synapses, resulting in a potentiation of transmission at both MF-pyramidal cell and interneuron synapses.MF-principal cell LTP arises via an adenylyl cyclase-cAMP-dependent mechanism involving PKA phosphorylation of Rab3/Rim1a to ultimately strengthen synaptic transmitter release (Castillo et al, 1997(Castillo et al, , 2002Nicoll and Schmitz, 2005) (Fig. 5).…”

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confidence: 99%

Chapter 13 Differential mechanisms of transmission and plasticity at mossy fiber synapses

McBain

2008

Progress in Brain Research

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The last few decades have seen the hippocampal formation at front and center in the field of synaptic transmission. However, much of what we know about hippocampal short-and long-term plasticity has been obtained from research at one particular synapse; the Schaffer collateral input onto principal cells of the CA1 subfield. A number of recent studies, however, have demonstrated that there is much to be learned about target-specific mechanisms of synaptic transmission by study of the lesser known synapse made between the granule cells of the dentate gyrus; the so-called mossy fiber synapse, and its targets both within the hilar region and the CA3 hippocampus proper. Indeed investigation of this synapse has provided an embarrassment of riches concerning mechanisms of transmission associated with feedforward excitatory and inhibitory control of the CA3 hippocampus. Importantly, work from a number of labs has revealed that mossy fiber synapses possess unique properties at both the level of their anatomy and physiology, and serve as an outstanding example of a synapse designed for target-specific compartmentalization of synaptic transmission. The purpose of the present review is to highlight several aspects of this synapse as they pertain to a novel mechanism of bidirectional control of synaptic plasticity at mossy fiber synapses made onto hippocampal stratum lucidum interneurons. It is not my intention to pour over all that is known regarding the mossy fiber synapse since many have explored this topic exhaustively in the past and interested readers are directed to other fine reviews (Henze et al., 2000;Urban et al., 2001;Lawrence et al., 2003;Bischofberger et al., 2006;Nicoll and Schmitz, 2005). Keywordshippocampus; local circuit inhibitory interneuron; long-term depression; glutamate receptors; plasticity; mossy fiber; mGluR7 Anatomy of the granule cell mossy fiber axonBefore discussing the physiological properties of the mossy fiber synapse, a short description of the granule cell anatomy and in particular the mossy fiber axon is warranted. The granule cell is the principal cell of the dentate gyrus and releases the neurotransmitter glutamate (Spruston and McBain, 2006). Granule cells typically possess small, ovoid cell bodies with a single apical, and conical dendritic tree, which extends into the molecular layer and terminates close to the hippocampal fissure. Compared to other principal cells of the hippocampal formation the granule cell is relatively small, possessing a somata approximately 10 μm in *Corresponding author. Tel.: +1 301 4024778; Fax: +1 301 4024777; E-mail: E-mail: mcbainc@mail.nih.gov. Uncited references: Castillo et al. (1994), Chicurel and Harris (1992), Henze et al. (2000), Lei and McBain (2002), Urban et al. (2001), Zucker and Regehr (2002). diameter and about 18 μm along its long axis. The number of dendritic branches is highly variable but the total dendritic length is significantly shorter than their CA1 and CA3 pyramidal neuron counterparts. The axon of the granule cell emerges ...

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RIM1α is required for presynaptic long-term potentiation

Cited by 375 publications

References 29 publications

Lack of the presynaptic RhoGAP protein oligophrenin1 leads to cognitive disabilities through dysregulation of the cAMP/PKA signalling pathway

Lack of the presynaptic RhoGAP protein oligophrenin1 leads to cognitive disabilities through dysregulation of the cAMP/PKA signalling pathway

A Specific Role for Ca²⁺-Dependent Adenylyl Cyclases in Recovery from Adaptive Presynaptic Silencing

Chapter 13 Differential mechanisms of transmission and plasticity at mossy fiber synapses

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RIM1α is required for presynaptic long-term potentiation

Cited by 375 publications

References 29 publications

Lack of the presynaptic RhoGAP protein oligophrenin1 leads to cognitive disabilities through dysregulation of the cAMP/PKA signalling pathway

Lack of the presynaptic RhoGAP protein oligophrenin1 leads to cognitive disabilities through dysregulation of the cAMP/PKA signalling pathway

A Specific Role for Ca2+-Dependent Adenylyl Cyclases in Recovery from Adaptive Presynaptic Silencing

Chapter 13 Differential mechanisms of transmission and plasticity at mossy fiber synapses

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A Specific Role for Ca²⁺-Dependent Adenylyl Cyclases in Recovery from Adaptive Presynaptic Silencing