Genetic Overexpression of NR2B Subunit Enhances Social Recognition Memory for Different Strains and Species

Jacobs, Stephanie; Tsien, Joseph Zhuo

doi:10.1371/journal.pone.0036387

Cited by 38 publications

(32 citation statements)

References 78 publications

(117 reference statements)

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“…Transgenic mice overexpressing chimeric receptors with the GluN2A amino-terminal domain and the GluN2B carboxyterminal domain showed enhanced cross-strain and cross-species recognition, similar to the GluN2B overexpression mice previously tested (Jacobs and Tsien 2012). Additionally, transgenic mice overexpressing the chimeric subunit with the GluN2B aminoterminal domain and the GluN2A carboxy-terminal domain demonstrated impaired long-term social recognition and olfactory recognition memory, similar to what was previously described in the transgenic GluN2A overexpression mice .…”

Section: Discussionsupporting

confidence: 84%

“…This enhancement is due to the increased GluN2B subunit carboxyterminal domain and intracellular signaling cascades present in these transgenic mice. Similar increases in longterm social memory have been observed in transgenic mice overexpressing the GluN2B subunit in the forebrain regions (Jacobs and Tsien 2012).…”

Section: Discussionsupporting

confidence: 71%

“…Interestingly, a 129P2 inbred strain of mice, in which reduced Csk expression causes an elevated GluN2B subunit expression, was found to have increased social recognition memory as well as increased memory for social food preference (Sinai et al 2012). Directly increasing the GluN2B subunit expression by genetic overexpression also increased the social recognition memory in transgenic GluN2B overexpression mice (Jacobs and Tsien 2012). Conversely, reducing the GluN2B: GluN2A subunit ratio, by genetically overexpressing the GluN2A subunit; decreased the social recognition memory in the transgenic GluN2A overexpression mice .…”

Section: Physiological Studies Of Glun2bmentioning

confidence: 99%

“…Remarkably, many forms of learning and memory including those listed above have been found to be modulated by the GluN2A:GluN2B subunit ratio (Buller et al 1994;Tang et al 1999Tang et al , 2001Philpot et al 2001;White and Youngentob 2004;Walker and Davis 2008;Brigman et al 2010;Cui et al 2011Cui et al , 2013Jacobs and Tsien 2012). This ratio is dynamically regulated with the GluN2B subunit being expressed at birth and decreasing with age; while the GluN2A subunit begins to be expressed after birth and increases with age (Hestrin 1992b;Monyer et al 1994;Sheng et al 1994).…”

mentioning

confidence: 99%

“…Recently, it was demonstrated that the modulation of the GluN2 subunit composition in the NMDA receptor complex also modulated olfactory memory, and social recognition memory (White and Youngentob 2004;Tsien 2012, 2014). Interestingly, genetically increasing the GluN2B:GluN2A subunit ratio increases the ability for the transgenic GluN2B overexpression mice to learn and remember mice of another strain and animals of another rodent species (Jacobs and Tsien 2012). Remarkably, decreasing the GluN2B:GluN2A subunit ratio significantly impairs long-term social recognition memory of conspecifics, females, mice of another strain and rodents of another species .…”

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confidence: 99%

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Importance of the GluN2B carboxy-terminal domain for enhancement of social memories

Jacobs

Wei²,

Wang³

et al. 2015

Learn. Mem.

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The N-methyl-D-aspartate (NMDA) receptor is known to be necessary for many forms of learning and memory, including social recognition memory. Additionally, the GluN2 subunits are known to modulate multiple forms of memory, with a high GluN2A:GluN2B ratio leading to impairments in long-term memory, while a low GluN2A:GluN2B ratio enhances some forms of long-term memory. Here, we investigate the molecular motif responsible for the differences in social recognition memory and olfactory memory in the forebrain-specific transgenic GluN2A overexpression mice and the forebrain-specific transgenic GluN2B overexpression mice by using two transgenic mouse lines that overexpress chimeric GluN2 subunits. The transgenic chimeric GluN2 subunit mice were tested for their ability to learn and remember fruit scents, male juveniles of the same strain, females of the same strain, male juveniles of another strain, and rodents of another species. The data presented here demonstrate that the GluN2B carboxy-terminal domain is necessary for enhanced social recognition memory in GluN2B transgenic overexpression mice. Furthermore, the GluN2A carboxy-terminal domain is responsible for the impaired long-term olfactory and social memory observed in the GluN2A overexpression mice.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionsupporting

confidence: 71%

Section: Physiological Studies Of Glun2bmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Importance of the GluN2B carboxy-terminal domain for enhancement of social memories

Jacobs

Wei²,

Wang³

et al. 2015

Learn. Mem.

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A neuroligin‐1‐derived peptide stimulates phosphorylation of the NMDA receptor NR1 subunit and rescues MK‐801‐induced decrease in long‐term potentiation and memory impairment

Korshunova

Gjørlund

Owczarek

et al. 2015

Pharmacology Res & Perspec

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Neuroligins (NLs) are postsynaptic adhesion molecules, interacting with presynaptic neurexins (NXs), which determine the differential formation of excitatory (glutamatergic, NL1) and inhibitory (GABAergic, NL2) synapses. We have previously demonstrated that treatment with a NL2-derived peptide, neurolide-2, reduces sociability and increase animal aggression. We hypothesized that interfering with NL1 function at the excitatory synapses might regulate synaptic plasticity and learning, and counteract memory deficits induced by N-methyl-d-aspartate (NMDA) receptor inhibition. First, neuronal NMDA receptor phosphorylation after treatment with NL1 or a mimetic peptide, neurolide-1, was quantified by immunoblotting. Subsequently, we investigated effects of neurolide-1 on long-term potentiation (LTP) induction in hippocampal slices compromised by NMDA receptor inhibitor MK-801. Finally, we investigated neurolide-1 effects on short- and long-term social and spatial memory in social recognition, Morris water-maze, and Y-maze tests. We found that subcutaneous neurolide-1 administration, restored hippocampal LTP compromised by NMDA receptor inhibitor MK-801. It counteracted MK-801-induced memory deficit in the water-maze and Y-maze tests after long-term treatment (24 h and 1–2 h before the test), but not after short-term exposure (1–2 h). Long-term exposure to neurolide-1 also facilitated social recognition memory. In addition, neurolide-1-induced phosphorylation of the NMDA receptor NR1 subunit on a site important for synaptic trafficking, potentially favoring synaptic receptor retention. Our findings emphasize the role of NL1–NMDA receptor interaction in cognition, and identify neurolide-1, as a valuable pharmacological tool to examine the in vivo role of postsynaptic NL1 in cognitive behavior in physiological and pathological conditions.

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The effects of an acute challenge with the NMDA receptor antagonists, MK-801, PEAQX, and ifenprodil, on social inhibition in adolescent and adult male rats

Morales

Spear

2013

Psychopharmacology

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Rationale NMDA antagonists consistently produce social inhibition in adult animals, although effects of these manipulations on social behavior of adolescents are relatively unknown. Objectives The aim of this study was to assess potential age differences in the socially inhibitory effects of the non-competitive NMDA antagonist, MK-801, as well as NR2 subunit selective effects, given the regional and developmental differences that exist for the NR2 subunit during ontogeny. Methods In separate experiments, adolescent and adult male Sprague–Dawley rats were treated acutely with MK-801 (0, 0.05, 0.1, 0.2 mg/kg, i.p.), the NR2A antagonist, PEAQX (2.5, 5, 10, 20 mg/kg, s.c.), or the NR2B antagonist, ifenprodil (1.5, 3, 6, 12 mg/kg, i.p.), 10 min prior to a social interaction test. Results Adolescents required higher doses of MK-801 (0.1 and 0.2 mg/kg) to induce social suppression, whereas adults demonstrated reductions in social activity after all doses. Likewise, adolescents required higher doses of ifenprodil (6 and 12 mg/kg) to produce social inhibitory effects relative to adults (all doses). In contrast, adults were less sensitive to PEAQX than adolescents, with adults showing social inhibition after 20 mg/kg whereas adolescents showed this effect following 10 and 20 mg/kg. Although locomotor activity was generally reduced at both ages by all drugs tested, ANCOVAs using locomotor activity as a covariate revealed similar patterns of social inhibitory effects. Conclusions Adolescents are less sensitive than adults to the disruption of social behavior by NMDA and NR2B-selective receptor antagonism, but not by an NR2A antagonist—age differences that may be related to different subunit expression patterns during development.

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Genetic Overexpression of NR2B Subunit Enhances Social Recognition Memory for Different Strains and Species

Cited by 38 publications

References 78 publications

Importance of the GluN2B carboxy-terminal domain for enhancement of social memories

Importance of the GluN2B carboxy-terminal domain for enhancement of social memories

A neuroligin‐1‐derived peptide stimulates phosphorylation of the NMDA receptor NR1 subunit and rescues MK‐801‐induced decrease in long‐term potentiation and memory impairment

The effects of an acute challenge with the NMDA receptor antagonists, MK-801, PEAQX, and ifenprodil, on social inhibition in adolescent and adult male rats

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