mGluR7 Is a Metaplastic Switch Controlling Bidirectional Plasticity of Feedforward Inhibition

Pelkey, Kenneth A.; Lavezzari, Gabriela; Racca, Claudia; Roche, Katherine W.; McBain, Chris J.

doi:10.1016/j.neuron.2005.02.011

Cited by 169 publications

(236 citation statements)

References 53 publications

(3 reference statements)

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“…Two avenues of investigation allowed us to reach this conclusion. First, using overexpression of a myc-tagged mGluR7 in cultured hippocampal neurons, we demonstrated that the same duration application of L-AP4 resulted in a robust internalization of both isoforms of mGluR7a and b (Pelkey et al, 2005). This observation was then extended to immunoelectron microscopy of mossy fiber filopodial terminals.…”

Section: Mglur7 Functions As a Trigger For Bidirectional Plasticity Amentioning

confidence: 81%

“…In marked contrast, the same high-frequency induction protocol that causes LTP at principal cell synapses induces two distinct forms of long-term depression (LTD) at mossy fiber-interneuron synapses (Figs. 4 and 5) (Maccaferri et al, 1998;Lei and McBain, 2004;Pelkey et al, 2005). One can immediately appreciate that this differential, strengthening of synapses onto CA3 pyramidal cells combined with a simultaneous weakening of transmission onto stratum lucidum interneurons will have important consequences for the dynamics of the CA3 circuit.…”

Section: Mossy Fiber-inhibitory Interneuron Plasticitymentioning

confidence: 99%

“…Surprisingly, mGluR7b was largely restricted to the small filopodial and en passant terminals made onto smooth dendrites of inhibitory interneurons and was largely absent at the larger mossy fiber boutons. Given that many mGluRs function as auto-or heterosynaptic receptors to regulate presynaptic release probability we set out to determine whether mGluR7 performed a similar function at the filopodial synapse onto interneurons (Pelkey et al, 2005). Surprisingly, brief application of the Group III agonist, L-AP4, at a concentration capable of activating mGluR7, induced a long-lasting, chemical depression of excitatory transmission at mossy fiber-CP-AMPAR synapses.…”

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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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Section: Mglur7 Functions As a Trigger For Bidirectional Plasticity Amentioning

confidence: 81%

Section: Mossy Fiber-inhibitory Interneuron Plasticitymentioning

confidence: 99%

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confidence: 99%

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

McBain

2008

Progress in Brain Research

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“…For example, it has been recently shown that AMN082 and other mGluRselective agonists facilitate mGluR7 receptor internalization 52,53 in addition to stimulating the receptor. This could induce a functional blockade of mGluR7 subsequent to its activation.…”

Section: Mglur7 Downregulation Blocks Extinction Of Conditioned Fearmentioning

confidence: 99%

mGluR7 facilitates extinction of aversive memories and controls amygdala plasticity

et al. 2007

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Formation and extinction of aversive memories in the mammalian brain are insufficiently understood at the cellular and molecular levels. Using the novel metabotropic glutamate receptor 7 (mGluR7) agonist AMN082, we demonstrate that mGluR7 activation facilitates the extinction of aversive memories in two different amygdala-dependent tasks. Conversely, mGluR7 knockdown using short interfering RNA attenuated the extinction of learned aversion. mGluR7 activation also blocked the acquisition of Pavlovian fear learning and its electrophysiological correlate long-term potentiation in the amygdala. The finding that mGluR7 critically regulates extinction, in addition to acquisition of aversive memories, demonstrates that this receptor may be relevant for the manifestation and treatment of anxiety disorders.

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“…In CA3 pyramidal neurons, highfrequency stimulation (HFS) leads to a large posttetanic potentiation (∼800%) and long-term potentiation (∼200%; [36,68,71,88,89]). In contrast, in stratum lucidum interneurons HFS induces synaptic depression rather than potentiation [50,67]. Likewise, activation of the cAMP pathway by forskolin leads to a large chemical potentiation at mossy fiber-CA3 pyramidal neuron synapses [45,82], but has only minimal effects on monosynaptic transmission at mossy fiber-stratum lucidum interneurons [55].…”

Section: Differential Synaptic Transmission At Mossy Fiber-pyramidal mentioning

confidence: 99%

Timing and efficacy of transmitter release at mossy fiber synapses in the hippocampal network

Bischofberger

Engel

Frotscher

et al. 2006

Pflugers Arch - Eur J Physiol

114

110

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It is widely accepted that the hippocampus plays a major role in learning and memory. The mossy fiber synapse between granule cells in the dentate gyrus and pyramidal neurons in the CA3 region is a key component of the hippocampal trisynaptic circuit. Recent work, partially based on direct presynaptic patch-clamp recordings from hippocampal mossy fiber boutons, sheds light on the mechanisms of synaptic transmission and plasticity at mossy fiber synapses. A high Na + channel density in mossy fiber boutons leads to a large amplitude of the presynaptic action potential. Together with the fast gating of presynaptic Ca 2+ channels, this generates a large and brief presynaptic Ca 2+ influx, which can trigger transmitter release with high efficiency and temporal precision. The large number of release sites, the large size of the releasable pool of vesicles, and the huge extent of presynaptic plasticity confer unique strength to this synapse, suggesting a large impact onto the CA3 pyramidal cell network under specific behavioral conditions. The characteristic properties of the hippocampal mossy fiber synapse may be important for pattern separation and information storage in the dentate gyrus-CA3 cell network.Keywords Presynaptic recording . Mossy fiber boutons . Mossy fiber synapses . Hippocampus . Autoassociative networks . Episodic memory . Synaptic efficacyThe mossy fiber synapse: a key connection in the hippocampal networkThe hippocampal formation consists of three types of principal neurons: granule cells in the dentate gyrus, CA3 pyramidal cells, and CA1 pyramidal neurons. These cells are interconnected by glutamatergic synapses, forming the classical trisynaptic circuit (Fig. 1a,b). Dentate gyrus granule cells receive excitatory glutamatergic input from layer 2 pyramidal cells of the entorhinal cortex and project to CA3 pyramidal cells. CA3 pyramidal cells project to CA1 cells, which in turn project to the subiculum and back to the entorhinal cortex [4]. In addition to this trisynaptic circuit, there is also a direct input from the entorhinal cortex to both CA3 and CA1 pyramidal cells. Furthermore, CA3 pyramidal neurons are extensively connected to each other via recurrent collateral synapses.The nonmyelinated axons of the granule cells, the socalled mossy fibers, show several structural properties that distinguish them from the other synaptic pathways [39]. They project to the CA3 region, mainly traveling within a narrow band termed "stratum lucidum." Several (∼15) large "giant" boutons (∼3-5-μm diameter) emerge from a single mossy fiber axon, either arranged in an en passant manner or attached to the main axon via a short perpendicular axonal branch [1,8,29,31] (Fig. 1c,d). A large mossy fiber bouton typically contacts only a single CA3 pyramidal neuron [21], and a mossy fiber axon contacts a given CA3 pyramidal neuron only once, as boutons are ∼150 μm apart. As the rat hippocampus contains ∼1 million granule cells

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mGluR7 Is a Metaplastic Switch Controlling Bidirectional Plasticity of Feedforward Inhibition

Cited by 169 publications

References 53 publications

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

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

mGluR7 facilitates extinction of aversive memories and controls amygdala plasticity

Timing and efficacy of transmitter release at mossy fiber synapses in the hippocampal network

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