Hippocampal receptor complexes paralleling LTP reinforcement in the spatial memory holeboard test in the rat

Subramaniyan, Saraswathi; Hajali, Vahid; Scherf, Thomas; Sase, Sunetra; Sialana, Fernando J.; Gröger, Marion; Bennett, Keiryn L.; Pollak, Arnold; Li, Lin; Korz, Volker; Lubec, Gert

doi:10.1016/j.bbr.2015.01.036

Cited by 11 publications

(9 citation statements)

References 97 publications

(109 reference statements)

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“…It was also shown that synaptic NMDAR are increased 6 h after the last of 10 day training in a radial maze (Shanmugasundaram et al, 2015) or after 3 days training in the holeboard (Subramaniyan et al, 2015). …”

Section: Discussionmentioning

confidence: 99%

“…Therefore, we could not discard that similar changes could happen in other central structures and/or in other time intervals. More recently, it has been reported that 6 h after training rats in the radial maze (Shanmugasundaram et al, 2015) or in a hole-board (Subramaniyan et al, 2015), there was an increase in GluN1 and GluN2A in the hippocampal synaptosomal fraction. After training in the hole-board, GluN2B was unchanged, but it was increased in PFC synaptosomal fraction following training in the radial maze task.…”

Section: Discussionmentioning

confidence: 99%

“…Subramaniyan et al (2015) showed that there was an increase in GluN1 and GluN2A complexes in dorsal hippocampus synaptosomal fraction 6 h after training in a holeboard (along 3 days) and stimulated (before the third session) with a weak tetanizing stimulus (which per se was not able to lead to L-LTP). However, they have also shown that there was an increase in GluN1 and GluN2B hippocampal complexes in synapstosomal fraction extracted 6 h after 10 days training in a radial maze, without electric stimulation (Shanmugasundaram et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

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GluN1 and GluN2A NMDA Receptor Subunits Increase in the Hippocampus during Memory Consolidation in the Rat

Cercato

Vázquez

Kornisiuk

et al. 2017

Front. Behav. Neurosci.

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It is widely accepted that NMDA receptors (NMDAR) are required for learning and memory formation, and for synaptic plasticity induction. We have previously shown that hippocampal GluN1 and GluN2A NMDAR subunits significantly increased following habituation of rats to an open field (OF), while GluN2B remained unchanged. Similar results were obtained after CA1-long-term potentiation (LTP) induction in rat hippocampal slices. Other studies have also shown NMDAR up regulation at earlier and later time points after LTP induction or learning acquisition. In this work, we have studied NMDAR subunits levels in the hippocampus and prefrontal cortex (PFC) after OF habituation and after object recognition (OR), to find out whether rising of NMDAR subunits is a general and structure-specific feature during memory formation. In 1, 2 and 3 month old rats there was an increase in hippocampal GluN1 and GluN2A, but not in GluN2B levels 70 min after OF habituation. This rise overlaps with early phase of memory consolidation, suggesting a putative relationship between them. The increases fell down to control levels 90 min after training. Similar results were obtained in the hippocampus of adult rats 70 min after OR training, without changes in PFC. Following OF test or OR discrimination phase, NMDAR subunits remained unchanged. Hence, rising of hippocampal GluN1 and GluN2A appears to be a general feature after novel “spatial/discrimination” memory acquisition. To start investigating the dynamics and possible mechanisms of these changes, we have studied hippocampal neuron cultures stimulated by KCl to induce plasticity. GluN1 and GluN2A increased both in dendrites and neuronal bodies, reaching a maximum 75 min later and returning to control levels at 90 min. Translation and/or transcription and mobilization differentially contribute to this rise in subunits in bodies and dendrites. Our results showed that the NMDAR subunits increase follows a similar time course both in vitro and in vivo. These changes happen in the hippocampus where a spatial representation of the environment is being formed making possible short term and long term memories (STM and LTM); appear to be structure-specific; are preserved along life; and could be related to synaptic tagging and/or to memory consolidation of new spatial/discrimination information.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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GluN1 and GluN2A NMDA Receptor Subunits Increase in the Hippocampus during Memory Consolidation in the Rat

Cercato

Vázquez

Kornisiuk

et al. 2017

Front. Behav. Neurosci.

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“…Saroja et al ( 2014 ) conclude that individual monoamine receptors are linked to spatial memory retrieval and are modulated by age. This same group (Subramaniyan et al, 2015 ) reports that the receptor complex levels containing hippocampal GluN1 and GluN2A of NMDARs, GluA1 and GluA2 of AMPA receptors, nAch7 and the D1A dopamine receptors were elevated during spatial learning, whilst levels of GluA3 and 5-HT 1A receptor containing complexes were reduced. Thus, supporting that 5-HT 1A receptor is useful neurobiological marker of memory.…”

Section: Memory Tasks and Molecular Changesmentioning

confidence: 89%

Serotonin, neural markers, and memory

Meneses¹

2015

Front. Pharmacol.

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Diverse neuropsychiatric disorders present dysfunctional memory and no effective treatment exits for them; likely as result of the absence of neural markers associated to memory. Neurotransmitter systems and signaling pathways have been implicated in memory and dysfunctional memory; however, their role is poorly understood. Hence, neural markers and cerebral functions and dysfunctions are revised. To our knowledge no previous systematic works have been published addressing these issues. The interactions among behavioral tasks, control groups and molecular changes and/or pharmacological effects are mentioned. Neurotransmitter receptors and signaling pathways, during normal and abnormally functioning memory with an emphasis on the behavioral aspects of memory are revised. With focus on serotonin, since as it is a well characterized neurotransmitter, with multiple pharmacological tools, and well characterized downstream signaling in mammals' species. 5-HT1A, 5-HT4, 5-HT5, 5-HT6, and 5-HT7 receptors as well as SERT (serotonin transporter) seem to be useful neural markers and/or therapeutic targets. Certainly, if the mentioned evidence is replicated, then the translatability from preclinical and clinical studies to neural changes might be confirmed. Hypothesis and theories might provide appropriate limits and perspectives of evidence.

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“…17 In the rat hippocampus, the transition from early into late LTP is accompanied by an increase in expression of the AMPA receptor (AMPAr) subunits GluA1 and GluA2 in the membrane fraction. 18 The activation of mTOR results in phosphorylation of the downstream target p70S6K, which regulates protein translation by phosphorylating proteins that bind to eukaryotic initiation factor-4E (eIF4E), these proteins are known as eIF4Ebinding proteins (4EBPs). 19 Previous studies using genetic mutations and pharmacological agents have reported increased phosphorylation of 4EBP and eIF4E occurs during LTP and memory formation.…”

Section: Introductionmentioning

confidence: 99%

Akt3 deletion in mice impairs spatial cognition and hippocampal CA1 long long‐term potentiation through downregulation of mTOR

et al. 2018

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Hippocampal receptor complexes paralleling LTP reinforcement in the spatial memory holeboard test in the rat

Cited by 11 publications

References 97 publications

GluN1 and GluN2A NMDA Receptor Subunits Increase in the Hippocampus during Memory Consolidation in the Rat

GluN1 and GluN2A NMDA Receptor Subunits Increase in the Hippocampus during Memory Consolidation in the Rat

Serotonin, neural markers, and memory

Akt3 deletion in mice impairs spatial cognition and hippocampal CA1 long long‐term potentiation through downregulation of mTOR

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