Roles of NMDA NR2B Subtype Receptor in Prefrontal Long-Term Potentiation and Contextual Fear Memory

Zhao, Ming; Toyoda, Hiroki; Lee, Yong Seok; Wu, Long Jun; Ko, Shanelle W.; Zhang, Xue Han; Jia, Yongheng; Shum, Fanny; Xu, Hui; Li, Bao Ming; Kaang, Bong Kiun; Zhuo, Min

doi:10.1016/j.neuron.2005.08.014

Cited by 441 publications

(538 citation statements)

References 64 publications

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“…These results are consistent with our previous work, indicating that the induction of ACC LTP is dependent on NMDA receptors (Liauw et al, 2005;Zhao et al, 2005b).…”

Section: L-ltp Within Acc Local Network Of Fmrp Wt Micesupporting

confidence: 94%

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Pharmacological Rescue of Cortical Synaptic and Network Potentiation in a Mouse Model for Fragile X Syndrome

Chen

Song

et al. 2014

Neuropsychopharmacol

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Fragile X syndrome, caused by the mutation of the Fmr1 gene, is characterized by deficits of attention and learning ability. In the hippocampus of Fmr1 knockout mice (KO), long-term depression is enhanced whereas long-term potentiation (LTP) including late-phase LTP (L-LTP) is reduced or unaffected. Here we examined L-LTP in the anterior cingulate cortex (ACC) in Fmr1 KO mice by using a 64-electrode array recording system. In wild-type mice, theta-burst stimulation induced L-LTP that does not occur in all active electrodes/ channels within the cingulate circuit and is typically detected in B75% of active channels. Furthermore, L-LTP recruited new responses from previous inactive channels. Both L-LTP and the recruitment of inactive responses were blocked in the ACC slices of Fmr1 KO mice. Bath application of metabotropic glutamate receptor 5 (mGluR5) antagonist or glycogen synthase kinase-3 (GSK3) inhibitors rescued the L-LTP and network recruitment. Our results demonstrate that loss of FMRP will greatly impair L-LTP and recruitment of cortical network in the ACC that can be rescued by pharmacological inhibition of mGluR5 or GSK3. This study is the first report of the network properties of L-LTP in the ACC, and provides basic mechanisms for future treatment of cortex-related cognitive defects in fragile X patients.

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“…These results are consistent with our previous work, indicating that the induction of ACC LTP is dependent on NMDA receptors (Liauw et al, 2005;Zhao et al, 2005b).…”

Section: L-ltp Within Acc Local Network Of Fmrp Wt Micesupporting

confidence: 94%

“…The mean potentiation for all 139 channels was 102.0±3.7% of the baseline at 3 h after TBS (Figure 3f). Finally, NMDA receptors are known to be important for the induction of LTP in the ACC (Zhao et al, 2005b). To test whether NMDA KO (b) mice.…”

Section: L-ltp Within Acc Local Network Of Fmrp Wt Micementioning

confidence: 99%

Pharmacological Rescue of Cortical Synaptic and Network Potentiation in a Mouse Model for Fragile X Syndrome

Chen

Song

et al. 2014

Neuropsychopharmacol

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“…NMDAR subunit composition confers distinct functional roles to this receptor (Cull-Candy and Leszkiewicz, 2004), with evidence suggesting that the NR2B subunit may be particularly important for NMDAR contributions to synaptic plasticity underlying learning and memory (Wong et al, 2002;Yoshimura et al, 2003;Liu et al, 2004;Kojima et al, 2005;Zhao et al, 2005), apparently more so than NR2A subunits (Barria and Malinow, 2005). For example, overexpression of the NR2B subunit in mice results in enhanced learning and memory in several behavioral tasks, including fear conditioning and fear extinction (Tang et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Acquisition of Fear Extinction Requires Activation of NR2B-Containing NMDA Receptors in the Lateral Amygdala

Sotres-Bayón

Bush

LeDoux

2007

Neuropsychopharmacol

257

207

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N-methyl-D-aspartate receptors (NMDARs) contribute to synaptic plasticity underlying learning in a variety of brain systems. Fear extinction, which involves learning to suppress the expression of previously learned fear, appears to require NMDAR activation in the amygdala. However, it is unclear whether amygdala NMDARs are required for the acquisition of extinction learning, and it is unknown whether NR2B-containing NMDARs are required in fear extinction. Here, we assessed the effects of selective NR2B blockade with ifenprodil on fear extinction learning, and found that both systemic and intra-amygdala ifenprodil treatment, given before extinction training, impaired the initial acquisition, and subsequent retrieval of fear extinction. These results confirm previous evidence showing that NMDARs in the amygdala are involved in fear extinction, and additionally show that NR2B-containing NMDARs are required. Contrary to the conclusion of previous studies, our findings demonstrate NMDARs are required for the initial acquisition, rather than only the retention, of fear extinction learning. Thus, our results support a previously not known role for NMDA-dependent plasticity in the lateral amygdala during the acquisition of fear extinction.

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“…The dependence of long-term potentiation and depression on the subunit composition of the NMDAR is debated heavily (Liu et al, 2004;Massey et al, 2004), but a number of recent studies indicate that NR2A-and NR2B-containing NMDARs both can contribute to the induction of long-term depression and potentiation (Hendricson et al, 2002;Berberich et al, 2005;Weitlauf et al, 2005;Zhao et al, 2005). An intriguing possibility is that, under certain conditions, an increase in the relative expression of NR2B-containing NMDARs in the adult visual cortex can reinstate some aspects of synaptic plasticity that normally are lost during development.…”

Section: Discussionmentioning

confidence: 99%

Visual Deprivation Modifies Both Presynaptic Glutamate Release and the Composition of Perisynaptic/Extrasynaptic NMDA Receptors in Adult Visual Cortex

Yashiro¹,

Corlew²,

Philpot

2005

J. Neurosci.

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Use-dependent modifications of synapses have been well described in the developing visual cortex, but the ability for experience to modify synapses in the adult visual cortex is poorly understood. We found that 10 d of late-onset visual deprivation modifies both presynaptic and postsynaptic elements at the layer 432/3 connection in the visual cortex of adult mice, and these changes differ from those observed in juveniles. Although visual deprivation in juvenile mice modifies the subunit composition and increases the current duration of synaptic NMDA receptors (NMDARs), no such effect is observed at synapses between layer 4 and layer 2/3 pyramidal neurons in adult mice. Surprisingly, visual deprivation in adult mice enhances the temporal summation of NMDAR-mediated currents induced by bursts of high-frequency stimulation. The enhanced temporal summation of NMDAR-mediated currents in deprived cortex could not be explained by a reduction in the rate of synaptic depression, because our data indicate that late-onset visual deprivation actually increases the rate of synaptic depression. Biochemical and electrophysiological evidence instead suggest that the enhanced temporal summation in adult mice could be accounted for by a change in the molecular composition of NMDARs at perisynaptic/extrasynaptic sites. Our data demonstrate that the experience-dependent modifications observed in the adult visual cortex are different from those observed during development. These differences may help to explain the unique consequences of sensory deprivation on plasticity in the developing versus mature cortex.

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Roles of NMDA NR2B Subtype Receptor in Prefrontal Long-Term Potentiation and Contextual Fear Memory

Cited by 441 publications

References 64 publications

Pharmacological Rescue of Cortical Synaptic and Network Potentiation in a Mouse Model for Fragile X Syndrome

Pharmacological Rescue of Cortical Synaptic and Network Potentiation in a Mouse Model for Fragile X Syndrome

Acquisition of Fear Extinction Requires Activation of NR2B-Containing NMDA Receptors in the Lateral Amygdala

Visual Deprivation Modifies Both Presynaptic Glutamate Release and the Composition of Perisynaptic/Extrasynaptic NMDA Receptors in Adult Visual Cortex

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