Dual mechanism for presynaptic modulation by axonal metabotropic glutamate receptor at the mouse mossy fibre‐CA3 synapse

Kamiya, Haruyuki; Ozawa, Seiji

doi:10.1111/j.1469-7793.1999.0497p.x

Cited by 79 publications

(104 citation statements)

References 40 publications

(73 reference statements)

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“…These data are consistent with our previous finding that VGCC blockers do not significantly affect the nAChR-induced burst (Sharma and Vijayaraghavan, 2003). DCG-IV has been shown to have a small (ϳ25% reduction) effect on mEPSC frequencies but not amplitudes (Kamiya and Ozawa, 1999). Such changes would not be apparent because of the inherent variation in the nAChR-induced bursts.…”

Section: Resultssupporting

confidence: 81%

Action Potential-Independent and Nicotinic Receptor-Mediated Concerted Release of Multiple Quanta at Hippocampal CA3–Mossy Fiber Synapses

Sharma

Grybko²,

Vijayaraghavan

2008

J. Neurosci.

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Presynaptic action potential-independent transmitter release is a potential means of information transfer across synapses. We show that in the hippocampal mossy fiber boutons, activation of the ␣7-subtype of nicotinic acetylcholine receptors (␣7-nAChRs) results in a large increase in the amplitude of spontaneous events, resulting from concerted release of multiple quanta from the mossy fiber boutons. This amplitude increase is abolished at low temperatures. Activation of ␣7-nAChRs causes a rise in intraterminal calcium at mossy fiber boutons, involving ryanodine receptors. Regulation of concerted release requires the subsequent activation of presynaptic calcium/ calmodulin-dependent protein kinase II (CaMKII). Activation of CaMKII is required to drive presynaptic action potential-independent transmission at the mossy fiber-CA3 pyramidal cell synapse. The effects of ␣7-nAChR activation are mediated by biologically relevant doses of nicotine. Our results demonstrate a novel form of synaptic plasticity mediated by presynaptic ␣7-nAChRs and store calcium that is temporally different and might respond to a different history of synaptic activity than that mediated by incoming action potentials.

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Section: Resultssupporting

confidence: 81%

Action Potential-Independent and Nicotinic Receptor-Mediated Concerted Release of Multiple Quanta at Hippocampal CA3–Mossy Fiber Synapses

Sharma

Grybko²,

Vijayaraghavan

2008

J. Neurosci.

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“…Our results suggest that signaling via inhibitory G␣ subunits is sufficient to account for the actions of mGluR2 in (i) transient suppression of synaptic transmission, (ii) induction of LTD, and (iii) inhibition of LTP. mGluR2 activation also leads to the release of free ␤͞␥ dimers, which regulate several targets, including presynaptic Ca 2ϩ channels (15,16,25). However, the actions of this component of heterotrimeric G protein signaling appear to be dispensable in the presence of G␣ signaling, for the forms of plasticity examined here.…”

Section: Discussionmentioning

confidence: 87%

mGluR2 acts through inhibitory Gα subunits to regulate transmission and long-term plasticity at hippocampal mossy fiber-CA3 synapses

Nicholls¹,

Zhang²,

Bailey

et al. 2006

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

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Presynaptic inhibitory G protein-coupled receptors play a critical role in regulating transmission at a number of synapses in the central and peripheral nervous system. We generated transgenic mice that express a constitutively active form of an inhibitory G␣ subunit to examine the molecular mechanisms underlying the actions of one such receptor, metabotropic glutamate receptor (mGluR) 2, at mossy fiber-CA3 synapses in the hippocampus. mGluR2 participates in at least three types of mossy fiber synaptic plasticity, (i) transient suppression of synaptic transmission, (ii) long-term depression (LTD), and (iii) inhibition of long-term potentiation (LTP), and we find that inhibitory G␣ signaling is sufficient to account for the actions of mGluR2 in each. The fact that constitutively active G␣ i2 occludes the transient suppression of synaptic transmission by mGluR2, while enhancing LTD, suggests further that these two forms of plasticity are expressed via different mechanisms. In addition, the LTP deficit observed in constitutively active G␣ i2-expressing mice suggests that mGluR2 activation may serve as a metaplastic switch to permit the induction of LTD by inhibiting LTP.O ne important mechanism whereby neuronal activity is controlled is through the action of presynaptic inhibitory G protein-coupled receptors (1, 2). One member of this group is the metabotropic glutamate receptor, mGluR2, which is present at mossy fiber-CA3 pyramidal cell synapses. Here, mGluR2s are localized perisynaptically near presynaptic terminals (3, 4), where they are thought to function as autoreceptors to suppress transmission in response to excess glutamate release. Pharmacological and genetic manipulations have shown that mGluR2s participate in at least three types of synaptic plasticity: (i) a transient suppression of synaptic transmission that occurs in response to receptor activation, (ii) a persistent form of synaptic depression requiring both mGluR2 activation and presynaptic calcium influx (long-term depression, LTD), and (iii) mGluR2-mediated inhibition of long-term potentiation (LTP) (5, 6).The relationship among these forms of mossy fiber-CA3 synaptic plasticity and the mechanism of mGluR2 involvement in each is not completely clear. Does the involvement of mGluR2 in both transient and persistent synaptic depression reflect a common mechanism, such that the persistent form merely results from a stabilization of the transient form, or does mGluR2 participate in these two processes via independent mechanisms? Similarly, does the inhibition of LTP by group II mGluR activation reflect opposing actions on a common effector pathway for depression and potentiation, or a permissive role for mGluR2 in inducing LTD by blocking LTP? We have begun to address these questions by exploring the signaling pathway downstream of mGluR2 using transgenic mice that express a constitutively active form of G␣ i2 . We find that the effects of mGluR2 on mossy fiber synaptic plasticity can be accounted for by the actions of inhibitory G␣ subunits. However,...

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“…All experiments were performed according to the guidelines for the care and use of laboratory animals of Kobe University and Hokkaido University School of Medicine. Simultaneous recordings of field EPSPs and presynaptic Ca 2ϩ transients in hippocampal slices were carried out as described before (29). Briefly, transverse hippocampal slices were prepared from C57BL/6J mice (14 -21 days old).…”

Section: Methodsmentioning

confidence: 99%

“…Furthermore we optically monitored presynaptic Ca 2ϩ dynamics by selective loading of the mossy fibers with the fluorescent Ca 2ϩ indicator in hippocampal slices (29). Background fluorescence (F) was significantly increased by caffeine (to 111 Ϯ 2% of control; Fig.…”

Section: Presynaptic Effects Of Caffeine At the Mossy Fiber-ca3 Synapsementioning

confidence: 99%

Use-dependent amplification of presynaptic Ca ²⁺ signaling by axonal ryanodine receptors at the hippocampal mossy fiber synapse

Shimizu¹,

Fukaya²,

Yamasaki³

et al. 2008

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

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Presynaptic Ca 2؉ stores have been suggested to regulate Ca 2؉ dynamics within the nerve terminals at certain types of the synapse. However, little is known about their mode of activation, molecular identity, and detailed subcellular localization. Here, we show that the ryanodine-sensitive stores exist in axons and amplify presynaptic Ca 2؉ accumulation at the hippocampal mossy fiber synapses, which display robust presynaptic forms of plasticity. Caffeine, a potent drug inducing Ca 2؉ release from ryanodinesensitive stores, causes elevation of presynaptic Ca 2؉ levels and enhancement of transmitter release from the mossy fiber terminals. The blockers of ryanodine receptors, TMB-8 or ryanodine, reduce presynaptic Ca 2؉ transients elicited by repetitive stimuli of mossy fibers but do not affect those evoked by single shocks, suggesting that ryanodine receptors amplify presynaptic Ca 2؉ dynamics in an activity dependent manner. Furthermore, we generated the specific antibody against the type 2 ryanodine receptor (RyR2; originally referred to as the cardiac type) and examined the cellular and subcellular localization using immunohistochemistry. RyR2 is highly expressed in the stratum lucidum of the CA3 region and mostly colocalizes with axonal marker NF160 but not with terminal marker VGLUT1. Immunoelectron microscopy revealed that RyR2 is distributed around smooth ER within the mossy fibers but is almost excluded from their terminal portions. These results suggest that axonal localization of RyR2 at sites distant from the active zones enables use dependent Ca 2؉ release from intracellular stores within the mossy fibers and thereby facilitates robust presynaptic forms of plasticity at the mossy fiber-CA3 synapse.calcium store ͉ hippocampus ͉ axon ͉ plasticity

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Dual mechanism for presynaptic modulation by axonal metabotropic glutamate receptor at the mouse mossy fibre‐CA3 synapse

Cited by 79 publications

References 40 publications

Action Potential-Independent and Nicotinic Receptor-Mediated Concerted Release of Multiple Quanta at Hippocampal CA3–Mossy Fiber Synapses

Action Potential-Independent and Nicotinic Receptor-Mediated Concerted Release of Multiple Quanta at Hippocampal CA3–Mossy Fiber Synapses

mGluR2 acts through inhibitory Gα subunits to regulate transmission and long-term plasticity at hippocampal mossy fiber-CA3 synapses

Use-dependent amplification of presynaptic Ca ²⁺ signaling by axonal ryanodine receptors at the hippocampal mossy fiber synapse

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Dual mechanism for presynaptic modulation by axonal metabotropic glutamate receptor at the mouse mossy fibre‐CA3 synapse

Cited by 79 publications

References 40 publications

Action Potential-Independent and Nicotinic Receptor-Mediated Concerted Release of Multiple Quanta at Hippocampal CA3–Mossy Fiber Synapses

Action Potential-Independent and Nicotinic Receptor-Mediated Concerted Release of Multiple Quanta at Hippocampal CA3–Mossy Fiber Synapses

mGluR2 acts through inhibitory Gα subunits to regulate transmission and long-term plasticity at hippocampal mossy fiber-CA3 synapses

Use-dependent amplification of presynaptic Ca 2+ signaling by axonal ryanodine receptors at the hippocampal mossy fiber synapse

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Use-dependent amplification of presynaptic Ca ²⁺ signaling by axonal ryanodine receptors at the hippocampal mossy fiber synapse