Genetic Demonstration of a Role for PKA in the Late Phase of LTP and in Hippocampus-Based Long-Term Memory

In the cerebral hypoxia-ischemia rat model, the prophylactic administration of zinc can cause either cytotoxicity or preconditioning effect, whereas the therapeutic administration of selenium decreases the ischemic damage. Herein, we aimed to explore whether supplementation of low doses of prophylactic zinc and therapeutic selenium could protect from a transient hypoxic-ischemic event. We administrated zinc (0.2 mg/kg of body weight; ip) daily for 14 days before a 10 min common carotid artery occlusion (CCAO). After CCAO, we administrated sodium selenite (6 μg/kg of body weight; ip) daily for 7 days. In the temporoparietal cerebral cortex, we determined nitrites by the Griess method and lipid peroxidation by the Gerard-Monnier assay. qPCR was used to measure mRNA of nitric oxide synthases, antioxidant enzymes, chemokines, and their receptors. We measured the enzymatic activity of SOD and GPx and protein levels of chemokines and their receptors by ELISA. We evaluated long-term memory using the Morris-Water maze test. Our results showed that prophylactic administration of zinc caused a preconditioning effect, decreasing nitrosative/oxidative stress and increasing GPx and SOD expression and activity, as well as eNOS expression. The therapeutic administration of selenium maintained this preconditioning effect up to the late phase of hypoxia-ischemia. Ccl2, Ccr2, Cxcl12, and Cxcr4 were upregulated, and long-term memory was improved. Pyknotic cells were decreased suggesting prevention of neuronal cell death. Our results show that the prophylactic zinc and therapeutic selenium administration induces effective neuroprotection in the early and late phases after CCAO.

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Regulation of late-phase LTP and long-term memory in normal and aging hippocampus: role of secreted proteins tPA and BDNF

Ageing Research Reviews ◽

10.1016/j.arr.2004.07.002 ◽

2004 ◽

Vol 3 (4) ◽

pp. 407-430 ◽

Cited By ~ 198

Author(s):

Petti T. Pang ◽

Bai Lu

Keyword(s):

Late Phase ◽

Secreted Proteins ◽

Long Term Memory ◽

Term Memory

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LIMK1 Regulates Long-Term Memory and Synaptic Plasticity via the Transcriptional Factor CREB

Molecular and Cellular Biology ◽

10.1128/mcb.01263-14 ◽

2015 ◽

Vol 35 (8) ◽

pp. 1316-1328 ◽

Cited By ~ 32

Author(s):

Zarko Todorovski ◽

Suhail Asrar ◽

Jackie Liu ◽

Ner Mu Nar Saw ◽

Krutika Joshi ◽

...

Keyword(s):

Synaptic Plasticity ◽

Williams Syndrome ◽

Neurodevelopmental Disorder ◽

Late Phase ◽

Long Term Potentiation ◽

Transcriptional Factor ◽

Adult Brain ◽

Long Term Memory ◽

Term Memory

Deletion of theLIMK1gene is associated with Williams syndrome, a unique neurodevelopmental disorder characterized by severe defects in visuospatial cognition and long-term memory (LTM). However, whether LIMK1 contributes to these deficits remains elusive. Here, we show that LIMK1-knockout (LIMK1−/−) mice are drastically impaired in LTM but not short-term memory (STM). In addition, LIMK1−/−mice are selectively defective in late-phase long-term potentiation (L-LTP), a form of long-lasting synaptic plasticity specifically required for the formation of LTM. Furthermore, we show that LIMK1 interacts and regulates the activity of cyclic AMP response element-binding protein (CREB), an extensively studied transcriptional factor critical for LTM. Importantly, both L-LTP and LTM deficits in LIMK1−/−mice are rescued by increasing the activity of CREB. These results provide strong evidence thatLIMK1deletion is sufficient to lead to an LTM deficit and that this deficit is attributable to CREB hypofunction. Our study has identified a direct gene-phenotype link in mice and provides a potential strategy to restore LTM in patients with Williams syndrome through the enhancement of CREB activity in the adult brain.

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Messengers from the synapses to the nucleus (MSNs) that establish late phase of long-term potentiation (LTP) and long-term memory

Neuroscience Research ◽

10.1016/0168-0102(96)01023-1 ◽

1996 ◽

Vol 25 (1) ◽

pp. 1-6 ◽

Cited By ~ 19

Author(s):

Tatsuo Suzuki

Keyword(s):

Late Phase ◽

Long Term Potentiation ◽

Long Term Memory ◽

Term Memory ◽

Term Potentiation

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Consolidation of Memory for Odor–Reward Association: β-Adrenergic Receptor Involvement in the Late Phase

Learning & Memory ◽

10.1101/lm.6.2.88 ◽

1999 ◽

Vol 6 (2) ◽

pp. 88-96 ◽

Cited By ~ 7

Author(s):

Susan J. Sara ◽

Pascal Roullet ◽

Jean Przybyslawski

Keyword(s):

Temporal Dynamics ◽

Time Window ◽

Food Reinforcement ◽

Late Phase ◽

Critical Time ◽

Current View ◽

Long Term Memory ◽

Term Memory ◽

Noradrenergic Receptors

Experimentally naive rats can learn rapidly to discriminate among three odors to obtain food reinforcement. After three massed trials, they show almost errorless performance. This task has proved to be useful in studying time-dependent postacquisition intracellular processes necessary for long-term memory. The present experiments evaluated the temporal dynamics of the role of β-noradrenergic receptors in long-term consolidation. Rats were implanted with intracerebroventricular cannulae and trained in a single session to find reinforcement in a hole in a sponge impregnated with a particular odor. Injections of the β-receptor antagonist timolol were made at 5 min, 1, 2, or 5 hr after training. Memory and relearning ability were evaluated 48 hr later. Rats treated with timolol 2 hr after training showed a memory deficit at the retention test, but were able to relearn the task normally. Injections at the earlier or later time points were ineffective. The results reinforce previous observations with systemic injections that β-noradrenergic receptors are involved in the late phase of memory consolidation and suggest a critical time window during which they are necessary. The time window is compatible with the current view that long-term memory depends on late involvement of the cAMP cascade leading to new protein synthesis necessary for synaptic reorganization.

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Conceptual short-term memory (CSTM) supports core claims of Christiansen and Chater

Behavioral and Brain Sciences ◽

10.1017/s0140525x15000928 ◽

2016 ◽

Vol 39 ◽

Author(s):

Mary C. Potter

Keyword(s):

Working Memory ◽

Rapid Serial Visual Presentation ◽

Language Comprehension ◽

Short Term Memory ◽

Visual Presentation ◽

Long Term Memory ◽

Short Term ◽

Term Memory ◽

Use Of Knowledge

AbstractRapid serial visual presentation (RSVP) of words or pictured scenes provides evidence for a large-capacity conceptual short-term memory (CSTM) that momentarily provides rich associated material from long-term memory, permitting rapid chunking (Potter 1993; 2009; 2012). In perception of scenes as well as language comprehension, we make use of knowledge that briefly exceeds the supposed limits of working memory.

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