Developmental Switch in Synaptic Mechanisms of Hippocampal Metabotropic Glutamate Receptor-Dependent Long-Term Depression

Nosyreva, E. D.; Huber, Kimberly M.

doi:10.1523/jneurosci.3652-04.2005

Cited by 160 publications

(180 citation statements)

References 63 publications

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“…First, slightly older rats were used (P21-P25) for the hippocampal LTD and mGluR EPSC experiments. Previous work has established that, for DHPGinduced LTD at the CA1 synapse, the requirement for postsynaptic protein synthesis only emerges after approximately P21 (Nosyreva and Huber, 2005). Second, before slice preparation, the rats were deeply anesthetized with halothane and transcardially perfused with ice-cold modified aCSF before decapitation.…”

Section: Methodsmentioning

confidence: 99%

“…This form of LTD, known to require protein synthesis in the postsynaptic cell (in rats that are P21 and older), is also induced by DHPG application (Huber et al, 2000;Nosyreva and Huber, 2005). If intracellular loading of cycloheximide was sufficient to inhibit protein synthesis postsynaptically, then it should also block DHPG-induced LTD in the hippocampus.…”

Section: Striatal Ltd Does Not Require Translation In the Postsynaptimentioning

confidence: 99%

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The Role of Protein Synthesis in Striatal Long-Term Depression

Yin¹,

Davis²,

Ronesi³

et al. 2006

J. Neurosci.

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Long-term depression (LTD) at the corticostriatal synapse is postsynaptically induced but presynaptically expressed, the depression being a result of retrograde endocannabinoid signaling that activates presynaptic cannabinoid CB 1 receptors and reduces the probability of glutamate release. To study the role of protein synthesis in striatal LTD, we used a striatum-only preparation in which the presynaptic cell body is cut off, leaving intact only its axons, whose terminals synapse on medium spiny neurons. LTD (duration Ͼ150 min) was induced in this preparation, thus providing evidence that transcription in the presynaptic cell nucleus is not necessary for this form of plasticity. The maintenance of striatal LTD, however, was blocked by bath application of protein translation inhibitors but not by the same inhibitors loaded into the postsynaptic cell. These results suggest that local translation is critical for the expression of striatal LTD, distinguishing this form of mammalian synaptic plasticity from other forms that require postsynaptic protein synthesis. Possible roles of axonal or glial translation in striatal LTD are considered.

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Section: Methodsmentioning

confidence: 99%

Section: Striatal Ltd Does Not Require Translation In the Postsynaptimentioning

confidence: 99%

The Role of Protein Synthesis in Striatal Long-Term Depression

Yin¹,

Davis²,

Ronesi³

et al. 2006

J. Neurosci.

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“…3F), the time constant of which is inversely related to P r . The decay kinetics were fit by a double exponential, and the fast time-constant of decay (τ f ) compared across groups (26,27). MK-801 blockade led to a slower τ f , implying a lower P r in KO cells [WT: 0.78 ± 0.32, n = 7; KO: 1.86 ± 0.24, n = 7 (stimuli); P < 0.05] (Fig.…”

Section: La Neurons From Ko Mice Exhibit Both Post-and Presynaptic Dementioning

confidence: 99%

Characterization and reversal of synaptic defects in the amygdala in a mouse model of fragile X syndrome

Suvrathan

Hoeffer

Wong

et al. 2010

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

126

108

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Fragile X syndrome (FXS), a common inherited form of mental impairment and autism, is caused by transcriptional silencing of the fragile X mental retardation 1 (FMR1) gene. Earlier studies have identified a role for aberrant synaptic plasticity mediated by the metabotropic glutamate receptors (mGluRs) in FXS. However, many of these observations are derived primarily from studies in the hippocampus. The strong emotional symptoms of FXS, on the other hand, are likely to involve the amygdala. Unfortunately, little is known about how exactly FXS affects synaptic function in the amygdala. Here, using whole-cell recordings in brain slices from adult Fmr1 knockout mice, we find mGluR-dependent long-term potentiation to be impaired at thalamic inputs to principal neurons in the lateral amygdala. Consistent with this long-term potentiation deficit, surface expression of the AMPA receptor subunit, GluR1, is reduced in the lateral amygdala of knockout mice. In addition to these postsynaptic deficits, lower presynaptic release was manifested by a decrease in the frequency of spontaneous miniature excitatory postsynaptic currents (mEPSCs), increased pairedpulse ratio, and slower use-dependent block of NMDA receptor currents. Strikingly, pharmacological inactivation of mGluR5 with 2-methyl-6-phenylethynyl-pyridine (MPEP) fails to rescue either the deficit in long-term potentiation or surface GluR1. However, the same acute MPEP treatment reverses the decrease in mEPSC frequency, a finding of potential therapeutic relevance. Therefore, our results suggest that synaptic defects in the amygdala of knockout mice are still amenable to pharmacological interventions against mGluR5, albeit in a manner not envisioned in the original hippocampal framework.autism | long-term potentiation | synaptic plasticity | metabotropic glutamate receptor

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“…There is now accumulating evidence that molecular mechanisms of LTP and LTD may differ in young versus adult hippocampus (Zamanillo et al, 1999, Jensen et al, 2003, Lee et al, 2003, Wikstrom et al, 2003, Yasuda et al, 2003, Palmer et al, 2004, Nosyreva and Huber, 2005. In particular, the involvement of GluR1 in LTP has been reported to occur only in adults (Zamanillo et al, 1999, Jensen et al, 2003.…”

Section: Normal Ltp and Ltd In Young "Penta" Phosphomutantsmentioning

confidence: 99%

Identification and characterization of a novel phosphorylation site on the GluR1 subunit of AMPA receptors

Lee

Takamiya

Kameyama³

et al. 2007

Molecular and Cellular Neuroscience

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Phosphorylation of various AMPA receptor subunits can alter synaptic transmission and plasticity at excitatory glutamatergic synapses in the central nervous system. Here, we identified threonine-840 (T840) on the GluR1 subunit of AMPA receptors as a novel phosphorylation site. T840 is phosphorylated by protein kinase C (PKC) in vitro, and is a highly turned-over phosphorylation site in the hippocampus. Interestingly, the high basal phosphorylation of T840 in the hippocampus is maintained by a persistent activity of a protein kinase, which is counter-balanced by a basal protein phosphatase activity. To study the function of T840, we generated a line of mutant mice lacking this phosphorylation site using a gene knock-in technique. The mice generated lacks T840, in addition to two previously identified phosphorylation sites S831 and S845. Using this mouse, we demonstrate that T840 may regulate synaptic plasticity in an age-dependent manner.Many of the brain functions critically depend on plasticity of the glutamatergic excitatory synaptic transmission, which can be accomplished postsynaptically by modulation of glutamate receptors. AMPA-type glutamate receptors mediate the majority of fast excitatory synaptic transmission, and functional changes to these receptors are implicated in synaptic plasticity (Song and Huganir, 2002, Collingridge et al., 2004). One way to alter the function of AMPA receptors is by changing phosphorylation of its subunits. All four subunits of AMPA receptors, GluR1-4, which have several identified phosphorylation sites on their intracellular carboxy-terminus (Song and Huganir, 2002).Among the four subunits, GluR1 has three identified phosphorylation sites, serines 818 (S818) (Boehm et al., 2006), 831 (S831) and 845 (S845) (Roche et al., 1996). S831 is phosphorylated by calcium/calmodulin-dependent protein kinase II (CaMKII) and protein kinase C (PKC), S845 is a cAMP-dependent protein kinase (PKA) substrate (Roche et al., 1996, Barria et al., 1997a, Mammen et al., 1997, while S818 is phosphorylated by PKC (Boehm et al., 2006). Changes in phosphorylation of GluR1 at S845 and S831 affect AMPA receptor mediated currents (Derkach et al., 1999, Banke et al., 2000, and are involved in long-term potentiation (LTP) and long-term depression (LTD) in the hippocampus (Barria et al., 1997b, Kameyama Correspondence to: Hey-Kyoung Lee. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. , Lee et al., 2003. Recent data suggests that S845 and S818 affect the trafficking AMPA receptors to synapses and/or stabilize synaptic AMPA receptors (Esteban et al., 2003,...

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Developmental Switch in Synaptic Mechanisms of Hippocampal Metabotropic Glutamate Receptor-Dependent Long-Term Depression

Cited by 160 publications

References 63 publications

The Role of Protein Synthesis in Striatal Long-Term Depression

The Role of Protein Synthesis in Striatal Long-Term Depression

Characterization and reversal of synaptic defects in the amygdala in a mouse model of fragile X syndrome

Identification and characterization of a novel phosphorylation site on the GluR1 subunit of AMPA receptors

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