Enhanced NR2A Subunit Expression and Decreased NMDA Receptor Decay Time at the Onset of Ocular Dominance Plasticity in the Ferret

Roberts, Elizabeth B.; Ramoa, Ary S.

doi:10.1152/jn.1999.81.5.2587

Cited by 140 publications

(131 citation statements)

References 32 publications

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“…The finding in V1 is in agreement with a recent study that reported that the NMDA current mediated by NR1/NR2B in V1 neurons declined to approximately 30% in postnatal day 60-70 rats (18). Indeed, NR2A normally dominates the subunit composition of NMDARs in adult V1 neurons (19). In addition, as shown in the EPSC traces scaled by peak amplitude (Fig.…”

Section: Higher Proportion Of Nr2b-containing Nmdars At Pfc Recurrentsupporting

confidence: 92%

A specialized NMDA receptor function in layer 5 recurrent microcircuitry of the adult rat prefrontal cortex

Wang

Stradtman

Wang³

et al. 2008

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

194

257

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In the prefrontal cortex, NMDA receptors are important for normal prefrontal functions such as working memory, and their dysfunction plays a key role in the pathological processes of psychiatric disorders such as schizophrenia. Little is known, however, about the synaptic properties of NMDA receptors in the local circuits of recurrent excitation, a leading candidate mechanism underlying working memory. We investigated the NMDA receptor-mediated currents at monosynaptic connections between pairs of layer 5 pyramidal neurons. We found that NMDA receptor-mediated currents at prefrontal synapses in the adult, but not young, rats exhibit a twofold longer decay time-constant and temporally summate a train of stimuli more effectively, compared to those in the primary visual cortex. Experiments with pharmacological, immunocytochemical, and biochemical approaches further suggest that, in the adult animals, neurons express significantly more NR2B subunits in the prefrontal cortex than the visual cortex. The NR2B-rich synapses in the prefrontal circuitry may be critically implicated in online cognitive computations and plasticity in learning, as well as psychiatric disorders.cortical development ͉ persistent activity ͉ working memory ͉ recurrent excitation W hat are the microcircuit properties that enable the prefrontal cortex (PFC) to subserve cognitive functions such as working memory and decision making in contrast to early sensory coding and processing in primary sensory areas? To address this central question, physiologists have focused on a salient feature of PFC, namely self-sustained persistent activity, as a candidate neural mechanism for short-term working memory in primates (1-3) and rodents (4). It has been hypothesized that persistent activity is generated by sufficiently strong recurrent excitation among prefrontal neurons (5). The N-methyl-Daspartate receptors (NMDARs) may be critically involved in persistent activity, as indicated by the findings that NMDAR antagonists impaired performance on delayed response tasks in rat PFC (6, 7). Recently, computational models confirmed that only the slow kinetics of NMDARs could stabilize the active maintenance of memory trace (8-10), and their voltage dependences could enhance the stimulus selectivity of persistent activity (11). Therefore, modeling work suggests that a distinctive feature of PFC is its slow reverberating neural dynamics that depend on the NMDARs in the local recurrent circuits.This raises the question of whether PFC neurons are endowed with a substantially higher number of NMDARs, or with NMDARs that express distinct biophysical properties, compared with those in a sensory area such as the primary visual cortex V1 (10). One anatomical study has reported a higher level of mRNA for NMDARs in PFC than in other cortices in human postmortem brain tissues (12). Physiologically, little is known about the functional properties of NMDARs in the prefrontal local recurrent circuits. Because prefrontal functions mature more slowly than the visual cortex, and thi...

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Section: Higher Proportion Of Nr2b-containing Nmdars At Pfc Recurrentsupporting

confidence: 92%

A specialized NMDA receptor function in layer 5 recurrent microcircuitry of the adult rat prefrontal cortex

Wang

Stradtman

Wang³

et al. 2008

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

194

257

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“…Dark-rearing also extends the critical period for ODP, and the correlation with changes in the NR2B to NR2A switch supports the idea that this mechanism may contribute to the ending of the critical period for ODP. However, another study found that the change in both subtype and kinetics of NMDA receptors coincides with the onset rather than the end of the critical period (Roberts and Ramoa, 1999).…”

Section: Mechanisms Contributing To the Close Of The Critical Periodmentioning

confidence: 98%

Developmental synaptic plasticity at the thalamocortical input to barrel cortex: Mechanisms and roles

Daw

Scott

Isaac

2007

Molecular and Cellular Neuroscience

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The thalamocortical (TC) input to layer IV provides the major pathway for ascending sensory information to the mammalian sensory cortex. During development there is a dramatic refinement of this input that underlies the maturation of the topographical map in layer IV. Over the last ten years our understanding of the mechanisms of the developmental and experience-driven changes in synaptic function at TC synapses has been greatly advanced. Here we describe these studies that point to a key role for NMDA receptor-dependent synaptic plasticity, a role for kainate receptors and for a rapid maturation in GABAergic inhibition. The expression mechanisms of some of the forms of neonatal synaptic plasticity are novel and, in combination with other mechanisms, produce a layer IV circuit that exhibits functional properties necessary for mature sensory processing.

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“…The magnitude and the kinetics of the calcium influx through NMDARs affect the functional form of synaptic plasticity in all of the induction protocols we have simulated. Both properties are modifiable, changing during development and as a function of the history of cortical activity (24,36,37,39,40). Therefore, we also examine the consequences of altering NMDAR kinetics.…”

Section: Induction Of Synaptic Plasticity By Varying Spike Timingmentioning

confidence: 99%

A unified model of NMDA receptor-dependent bidirectional synaptic plasticity

Shouval

Bear

Cooper

2002

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

560

834

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Synapses in the brain are bidirectionally modifiable, but the routes of induction are diverse. In various experimental paradigms, N-methyl-D-aspartate receptor-dependent long-term depression and long-term potentiation have been induced selectively by varying the membrane potential of the postsynaptic neurons during presynaptic stimulation of a constant frequency, the rate of presynaptic stimulation, and the timing of pre-and postsynaptic action potentials. In this paper, we present a mathematical embodiment of bidirectional synaptic plasticity that is able to explain diverse induction protocols with a fixed set of parameters. The key assumptions and consequences of the model can be tested experimentally; further, the model provides the foundation for a unified theory of N-methyl-D-aspartate receptordependent synaptic plasticity.S ynapses throughout the brain are bidirectionally modifiable.This property, postulated in almost every theoretical description of synaptic plasticity, has been most clearly demonstrated at the Schaffer collateral-CA1 synapse in the hippocampus. Here, it was shown that a low-frequency tetanus induces long-term depression (LTD), whereas high-frequency stimulation produces long-term potentiation (LTP) of the stimulated synapses, and that LTD and LTP are inversely related (1-4). Similar results have been obtained at excitatory synapses throughout the brain.A considerable body of evidence indicates that the important variable is actually the amount of integrated postsynaptic N-methyl-D-aspartate (NMDA) receptor (NMDAR) activation during conditioning (1, 2, 4-6). Modest NMDAR activation induces LTD, whereas strong activation produces LTP. Because of their voltage dependence, the contribution of NMDARs to synaptic transmission during conditioning stimulation varies with the level of postsynaptic depolarization. Thus, it is possible to induce LTD or LTP with a constant stimulation frequency by clamping the postsynaptic membrane potential at different values (approximately Ϫ50 mV for LTD and Ϫ20 mV for LTP).Recently, it has been demonstrated that synaptic modification also can depend on the precise timing of pre-and postsynaptic action potentials (7-11). If a presynaptic action potential occurs in a window of several tens of milliseconds before a back-propagating postsynaptic action potential, LTP is induced. In contrast, if a presynaptic action potential occurs after the postsynaptic spike, LTD is induced.Ideally, one would like to develop a unified description of bidirectional synaptic plasticity that can account for all routes of induction. One approach is to look beyond the various induction protocols to the critical role of calcium influx through NMDARs. One attractive idea is that modest increases in postsynaptic calcium trigger LTD, whereas large increases trigger . This hypothesis is consistent with the classical rate-based induction protocols if it is assumed that high-frequency stimulation triggers a larger rise in postsynaptic calcium than does low-frequency stimulation. Indeed, recent...

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Enhanced NR2A Subunit Expression and Decreased NMDA Receptor Decay Time at the Onset of Ocular Dominance Plasticity in the Ferret

Cited by 140 publications

References 32 publications

A specialized NMDA receptor function in layer 5 recurrent microcircuitry of the adult rat prefrontal cortex

A specialized NMDA receptor function in layer 5 recurrent microcircuitry of the adult rat prefrontal cortex

Developmental synaptic plasticity at the thalamocortical input to barrel cortex: Mechanisms and roles

A unified model of NMDA receptor-dependent bidirectional synaptic plasticity

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