NMDA Receptor NR2 Subunit Dependence of the Slow Component of Magnesium Unblock

Clarke, Richard; Johnson, Jon W.

doi:10.1523/jneurosci.0577-06.2006

Cited by 78 publications

(80 citation statements)

References 64 publications

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“…Only when the membrane potential rises above Ϫ60 mV the Mg 2ϩ block is relieved and NMDA receptors are opened upon glutamate binding. The unlocking mechanism consists of a slow and a fast component, which depend on the relative expression of subunits that compose the channel (87,536). Upon reduced extracellular Mg 2ϩ concentrations, less NMDA channels will be blocked, and more NMDA channels can be opened at relatively low membrane potentials (351).…”

Section: A Magnesium In Brainmentioning

confidence: 99%

Magnesium in Man: Implications for Health and Disease

Baaij

Hoenderop

Bindels

2015

Physiological Reviews

1,276

1,299

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Section: A Magnesium In Brainmentioning

confidence: 99%

Magnesium in Man: Implications for Health and Disease

Baaij

Hoenderop

Bindels

2015

Physiological Reviews

1,276

1,299

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“…The greater synaptic charge transfer via NMDAR at immature versus mature synapses could be the result of a change in subunit composition of NMDAR, leading to changes in EPSC decay kinetics and/or differential sensitivity to magnesium block (Ben-Ari et al 1988;Bowe and Nadler 1990;Clarke and Johnson 2006;Monyer et al 1992Monyer et al , 1994Morrisett et al 1990;Muller et al 1989). Previous studies of CNS synapses have demonstrated a subunit switch from NR2B to NR2A containing NMDAR over development Quinlan et al 1999;Ramoa and Prusky 1997;Sheng et al 1994;Williams et al 1993).…”

Section: Changes In Nmdar Subunit Composition Over Developmentmentioning

confidence: 99%

“…However, our observed change in sensitivity of the NMDAR current-voltage relationship to magnesium block over development further supports the presence of NR2C/2D subunits at immature synapses. NMDAR-containing NR2A and NR2B subunits exhibit similar sensitivity to magnesium block, whereas those containing NR2C and NR2D subunits show significantly weaker block by the cation (Clarke and Johnson 2006;Monyer et al 1992Monyer et al , 1994). Thus our data suggest that both NR2B and NR2C/2D subunits contribute to the relatively large and slow inward NMDAR current at the immature retinogeniculate synapses.…”

Section: Properties Of Nmdars Are Significantly Different At Immaturementioning

confidence: 99%

Different Roles for AMPA and NMDA Receptors in Transmission at the Immature Retinogeniculate Synapse

Liu

Chen²

2008

Journal of Neurophysiology

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The relay of information at the retinogeniculate synapse, the connection between retina and visual thalamus, begins days before eye opening and is thought to play an important role in the maturation of neural circuits in the thalamus and visual cortex. Remarkably, during this period of development, the retinogeniculate synapse is immature, with single retinal ganglion cell inputs evoking an average peak excitatory postsynaptic current (EPSC) of only about 40 pA compared with 800 pA in mature synapses. Yet, at the mature synapse, EPSCs Ͼ400 pA are needed to drive relay neuron firing. This raises the question of how smallamplitude EPSCs can drive transmission at the immature retinogeniculate synapse. Here we find that several features of the immature synapse, compared with the mature synapse, contribute to synaptic transmission. First, although the peak amplitude of EPSC is small, the decay time course of both ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) and N-methyl-D-aspartate receptor (NMDAR) currents is significantly slower. The prolonged time course of NMDAR currents is a result of the presence of both NR2B and NR2C/D subunits. In addition, the extended presence of neurotransmitter released prolongs the synaptic current time course. Second, reduced sensitivity to magnesium block results in significantly greater synaptic charge transfer through NMDAR. Third, AMPAR currents contribute to the spike latency, but not to temporal precision, at the immature synapse. Furthermore, intrinsic excitability is greater. These properties enable immature synapses with predominantly NMDARs and little or no AMPARs to contribute to the relay of information from retina to visual cortex.

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“…In particular, receptors containing NR1/2C and NR1/2D receptor subunits show a more rapid response to fast depolarizations (Clarke and Johnson, 2006) making them less effective as coincidence detectors, and they are less sensitive to blockade by magnesium ions (Momiyama et al, 1996) allowing for stronger activity at relatively negative membrane potentials. Moreover, the presence of NR2D confers a greater affinity for glutamate (Kuppenbender et al, 2000).…”

mentioning

confidence: 99%

Cholinergic neurons of the adult rat striatum are immunoreactive for glutamatergic N-methyl-d-aspartate 2D but not N-methyl-d-aspartate 2C receptor subunits

et al. 2007

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Cholinergic neurons of the striatum play a crucial role in controlling output from this region. Their firing is under the control of a relatively limited glutamatergic input, deriving principally from the thalamus. Glutamate transmission is effected via three major subtypes of receptors, including those with affinity for N-methyl-D-aspartate (NMDA) and the properties of individual receptors reflect their precise subunit composition. We examined the distribution of NMDA2C and NMDA2D subunits in the rat striatum using immunocytochemistry and show that a population of large neurons is strongly immunoreactive for NMDA2D subunits. From their morphology and ultrastructure, these neurons were presumed to be cholinergic and this was confirmed with double immunofluorescence. We also show that NMDA2C is present in a small number of septal and olfactory cortical neurons but absent from the striatum.Receptors that include NMDA2D subunits are relatively insensitive to magnesium ion block making neurons more likely to fire at more negative membrane potentials. Their localization to cholinergic neurons may enable very precise regulation of firing of these neurons by relatively small glutamatergic inputs. Keywordsinterneuron; ultrastructure; synapse; endoplasmic reticulumThe cholinergic neurons of the striatum play an important role in basal ganglia control of voluntary movement. They represent only 1-2% of striatal neurons but their extensive local axon collateral system, innervating both medium-sized densely spiny neurons (MSN) (Izzo and Bolam, 1988) and other local circuit neurons (Koos and Tepper, 2002) is consistent with a primary role in determining the final activity of striatal output neurons (Calabresi et al., 2000). While the majority of glutamatergic input to MSN originates in the cortical regions, excitatory input to these tonically active, cholinergic striatal neurons comes almost exclusively from the parafascicular thalamic nucleus (Lapper and Bolam, 1992;Zhou et al., 2002) and possibly from the cortex (Thomas et al., 2000), and principally from the midline/intralaminar thalamic nuclei to the ventral striatum (Meredith and Wouterlood, 1990 The firing of cholinergic neurons is under the control of a relatively few inputs and interactions are subserved by a number of different glutamate receptor subtypes. Although no AMPA subunits have been reported (Chen et al., 1996;Fujiyama et al., 2004), cholinergic neurons express kainate GluR5, 6 and 7 subunits (Chen et al., 1996). Moreover, stimulation of metabotropic receptor subunits, mGluR1-3, 5 and 7 (Bell et al., 2002) exerts a profound effect on cell excitability (Di Chiara et al., 1994). In addition, N-methyl-D-aspartate (NMDA) agonists potentiate striatal acetylcholine release (Giovannini et al., 1995) while direct stimulation of the thalamostriatal pathway increases acetylcholine release, via action on N-methyl-D-aspartate receptors (NR) (Consolo et al., 1996). Double labeling studies combining in situ hybridization for subunit mRNA with immunolabeling with a...

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NMDA Receptor NR2 Subunit Dependence of the Slow Component of Magnesium Unblock

Cited by 78 publications

References 64 publications

Magnesium in Man: Implications for Health and Disease

Magnesium in Man: Implications for Health and Disease

Different Roles for AMPA and NMDA Receptors in Transmission at the Immature Retinogeniculate Synapse

Cholinergic neurons of the adult rat striatum are immunoreactive for glutamatergic N-methyl-d-aspartate 2D but not N-methyl-d-aspartate 2C receptor subunits

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