Unlearning: NMDA Receptor-Mediated Metaplasticity in the Anterior Piriform Cortex Following Early Odor Preference Training in Rats

Mukherjee, Bandhan; Morrison, Gillian L.; Fontaine, Christine J.; Hou, Qinlong; Harley, Carolyn W.; Yuan, Qi

doi:10.1523/jneurosci.0128-14.2014

Cited by 16 publications

(24 citation statements)

References 46 publications

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“…This led us to the idea that the regulation of the receptor was not at the protein expression level as seen in other memory models (Baez et al 2013) but rather at the surface expression level. The regulation at the surface expression level has been repeatedly reported in memory and synaptic plasticity experiments (Cammarota et al 2000;Grosshans et al 2002b;Moyano et al 2004;Mukherjee et al 2014).…”

Section: Discussionmentioning

confidence: 78%

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Surface expression of NMDA receptor changes during memory consolidation in the crabNeohelice granulata

et al. 2016

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The aim of the present study was to analyze the surface expression of the NMDA-like receptors during the consolidation of contextual learning in the crab Neohelice granulata. Memory storage is based on alterations in the strength of synaptic connections between neurons. The glutamatergic synapses undergo various forms of N-methyl-D aspartate receptor (NMDAR)-dependent changes in strength, a process that affects the abundance of other receptors at the synapse and underlies some forms of learning and memory. Here we propose a direct regulation of the NMDAR. Changes in NMDAR's functionality might be induced by the modification of the subunit's expression or cellular trafficking. This trafficking does not only include NMDAR's movement between synaptic and extra-synaptic localizations but also the cycling between intracellular compartments and the plasma membrane, a process called surface expression. Consolidation of contextual learning affects the surface expression of the receptor without affecting its general expression. The surface expression of the GluN1 subunit of the NMDAR is down-regulated immediately after training, up-regulated 3 h after training and returns to naïve and control levels 24 h after training. The changes in NMDAR surface expression observed in the central brain are not seen in the thoracic ganglion. A similar increment in surface expression of GluN1 in the central brain is observed 3 h after administration of the competitive GABA A receptor antagonist, bicuculline. These consolidation changes are part of a plasticity event that first, during the down-regulation, stabilizes the trace and later, at 3-h post-training, changes the threshold for synapse activation.

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Section: Discussionmentioning

confidence: 78%

“…We thank Kevin Michael Boergens for language revision of the manuscript. This work was supported with grants from the University of Buenos Aires (UBACyT 2011-2014 20020100200268, UBACyT 2014-2017, from the CONICET (PIP 2011(PIP -2013 and from FonCyT (Grant PICT2010-0391, Grant PICT2013-1657, Grant PICT2013-0412).…”

Section: Acknowledgmentsmentioning

confidence: 99%

Surface expression of NMDA receptor changes during memory consolidation in the crabNeohelice granulata

et al. 2016

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“…In a step-down inhibitory avoidance of a mild foot-electric shock, Cammarota et al [ 46 ] showed that there was an increase of GluN1 in hippocampal synaptosomal fractions (by western blot), without significant changes in GluN2A or in GluN2B 30 minutes after training; 120 minutes after training, NMDAR subunits level was similar to controls. Mukherjee et al [ 47 , 48 ] showed that, in P7 to P10 pups, when the developmental switch from GluN2B to GluN2A did not take place yet [ 12 ], there was a change in NMDAR as the absolute amount of the essential GluN1 decreased three hours after one training session in an odor preference task. This decrease was observed in synaptosomal fractions of the anterior piriform cortex [ 47 ] and in postsynaptic density fractions [ 48 ].…”

Section: Nmdar Expression and Memory Acquisition ( Tablementioning

confidence: 99%

“…Mukherjee et al [ 47 , 48 ] showed that, in P7 to P10 pups, when the developmental switch from GluN2B to GluN2A did not take place yet [ 12 ], there was a change in NMDAR as the absolute amount of the essential GluN1 decreased three hours after one training session in an odor preference task. This decrease was observed in synaptosomal fractions of the anterior piriform cortex [ 47 ] and in postsynaptic density fractions [ 48 ]. However, 24 h after training, GluN1 level was not significantly different compared to controls, indicating that the modification was transient.…”

Section: Nmdar Expression and Memory Acquisition ( Tablementioning

confidence: 99%

NMDA Receptor Subunits Change after Synaptic Plasticity Induction and Learning and Memory Acquisition

2018

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NMDA ionotropic glutamate receptors (NMDARs) are crucial in activity-dependent synaptic changes and in learning and memory. NMDARs are composed of two GluN1 essential subunits and two regulatory subunits which define their pharmacological and physiological profile. In CNS structures involved in cognitive functions as the hippocampus and prefrontal cortex, GluN2A and GluN2B are major regulatory subunits; their expression is dynamic and tightly regulated, but little is known about specific changes after plasticity induction or memory acquisition. Data strongly suggest that following appropriate stimulation, there is a rapid increase in surface GluN2A-NMDAR at the postsynapses, attributed to lateral receptor mobilization from adjacent locations. Whenever synaptic plasticity is induced or memory is consolidated, more GluN2A-NMDARs are assembled likely using GluN2A from a local translation and GluN1 from local ER. Later on, NMDARs are mobilized from other pools, and there are de novo syntheses at the neuron soma. Changes in GluN1 or NMDAR levels induced by synaptic plasticity and by spatial memory formation seem to occur in different waves of NMDAR transport/expression/degradation, with a net increase at the postsynaptic side and a rise in expression at both the spine and neuronal soma. This review aims to put together that information and the proposed hypotheses.

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“…Since then evidence has been obtained for a major role of NMDA receptors in synaptic transmission and plasticity including learning and memory and other aspects of cognition (Tsien et al ; Cammarota et al ; Bartlett et al ; Berberich et al ; Zorumski and Izumi ; Paoletti et al ; Mukherjee et al ). Since maintained or excessive activation of NMDA receptors causes cellular calcium overload, quinolinic acid can produce excitotoxicity and neurodegeneration (Stone and Addae ; Kalia et al ; Hardingham ; Hardingham and Bading ; Danysz and Parsons, ; Guillemin, ; Stone et al ,b; Lovelace et al ), again balanced or prevented by endogenous levels of kynurenic acid (Harris et al ; Sapko et al ; Stone and Darlington ).…”

Section: Introduction: the Kynurenine Pathway And Receptorsmentioning

confidence: 99%

Does kynurenic acid act on nicotinic receptors? An assessment of the evidence

Stone

2019

Journal of Neurochemistry

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As a major metabolite of kynurenine in the oxidative metabolism of tryptophan, kynurenic acid is of considerable biological and clinical importance as an endogenous antagonist of glutamate in the central nervous system. It is most active as an antagonist at receptors sensitive to N‐methyl‐D‐aspartate (NMDA) which regulate neuronal excitability and plasticity, brain development and behaviour. It is also thought to play a causative role in hypo‐glutamatergic conditions such as schizophrenia, and a protective role in several neurodegenerative disorders, notably Huntington’s disease. An additional hypothesis, that kynurenic acid could block nicotinic receptors for acetylcholine in the central nervous system has been proposed as an alternative mechanism of action of kynurenate. However, the evidence for this alternative mechanism is highly controversial, partly because at least eight earlier studies concluded that kynurenic acid blocked NMDA receptors but not nicotinic receptors and five subsequent, independent studies designed to repeat the results have failed to do so. Many studies considered to support the alternative ‘nicotinic’ hypothesis have been based on the use of analogs of kynurenate such as 7‐chloro‐kynurenic acid, or putatively nicotinic modulators such as galantamine, but a detailed analysis of the pharmacology of these compounds suggests that the results have often been misinterpreted, especially since the pharmacology of galantamine itself has been disputed. This review examines the evidence in detail, with the conclusion that there is no confirmed, reliable evidence for an antagonist activity of kynurenic acid at nicotinic receptors. Therefore, since there is overwhelming evidence for kynurenate acting at ionotropic glutamate receptors, especially NMDAR glutamate and glycine sites, with some activity at GPR35 sites and Aryl Hydrocarbon Receptors, results with kynurenic acid should be interpreted only in terms of these confirmed sites of action.

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Unlearning: NMDA Receptor-Mediated Metaplasticity in the Anterior Piriform Cortex Following Early Odor Preference Training in Rats

Cited by 16 publications

References 46 publications

Surface expression of NMDA receptor changes during memory consolidation in the crabNeohelice granulata

Surface expression of NMDA receptor changes during memory consolidation in the crabNeohelice granulata

NMDA Receptor Subunits Change after Synaptic Plasticity Induction and Learning and Memory Acquisition

Does kynurenic acid act on nicotinic receptors? An assessment of the evidence

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