scholarly journals MAPK, CREB and zif268 are all required for the consolidation of recognition memory

2003 ◽  
Vol 358 (1432) ◽  
pp. 805-814 ◽  
Author(s):  
Bruno Bozon ◽  
Áine Kelly ◽  
Sheena A. Josselyn ◽  
Alcino J. Silva ◽  
Sabrina Davis ◽  
...  
Keyword(s):  
Recognition Memory ◽  
Molecular Mechanisms ◽  
Long Term Potentiation ◽  
Memory Storage ◽  
Mitogen Activated Protein Kinase ◽  
Early Gene ◽  
Essential Components ◽  
And Storage

There has been nearly a century of interest in the idea that encoding and storage of information in the brain requires changes in the efficacy of synaptic connections between neurons that are activated during learning. Recent research into the molecular mechanisms of long-term potentiation (LTP) has brought about new knowledge that has provided valuable insights into the neural mechanisms of memory storage. The evidence indicates that rapid activation of the genetic machinery can be a key mechanism underlying the enduring modification of neural networks required for the stability of memories. In recent years, a wealth of experimental data has highlighted the importance of mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signalling in the regulation of gene transcription in neurons. Here, we briefly review experiments that have shown MAPK/ERK, cAMP response element-binding protein (CREB) and the immediate early gene (IEG) zif268 are essential components of a signalling cascade required for the expression of late phase LTP and of certain forms of long-term memory. We also present experiments in which we have assessed the role of these three molecules in recognition memory. We show that pharmacological blockade of MAPK/ERK phosphorylation, functional inactivation of CREB in an inducible transgenic mouse and inactivation of zif268 in a mutant mouse result in a similar deficit in long-term recognition memory. In the continuing debate about the role of LTP mechanisms in memory, these findings provide an important complement to the suggestion that synaptic changes brought about by LTP and memory consolidation and storage share, at least in part, common underlying molecular mechanisms.

scholarly journals Chronic Fluoxetine Treatment Induces Brain Region-Specific Upregulation of Genes Associated with BDNF-Induced Long-Term Potentiation

2007 ◽  
Vol 2007 ◽  
pp. 1-9 ◽  
Author(s):  
Maria Nordheim Alme ◽  
Karin Wibrand ◽  
Grethe Dagestad ◽  
Clive R. Bramham
Keyword(s):  
Dentate Gyrus ◽  
Brain Region ◽  
Molecular Mechanisms ◽  
Antidepressant Treatment ◽  
Antidepressant Drugs ◽  
Long Term Potentiation ◽  
Specific Pattern ◽  
Early Gene ◽  
Term Potentiation

Several lines of evidence implicate BDNF in the pathogenesis of stress-induced depression and the delayed efficacy of antidepressant drugs. Antidepressant-induced upregulation of BDNF signaling is thought to promote adaptive neuronal plasticity through effects on gene expression, but the effector genes downstream of BDNF has not been identified. Local infusion of BDNF into the dentate gyrus induces a long-term potentiation (BDNF-LTP) of synaptic transmission that requires upregulation of the immediate early gene Arc. Recently, we identified five genes (neuritin, Narp, TIEG1, Carp, and Arl4d) that are coupregulated with Arc during BDNF-LTP. Here, we examined the expression of these genes in the dentate gyrus, hippocampus proper, and prefrontal cortex after antidepressant treatment. We show that chronic, but not acute, fluoxetine administration leads to upregulation of these BDNF-LTP-associated genes in a brain region-specific pattern. These findings link chronic effects of antidepressant treatment to molecular mechanisms underlying BDNF-induced synaptic plasticity.

Molecular mechanisms of synaptic consolidation during sleep: BDNF function and dendritic protein synthesis

2005 ◽  
Vol 28 (1) ◽  
pp. 65-66
Author(s):  
Clive R. Bramham
Keyword(s):  
Memory Consolidation ◽  
Molecular Mechanisms ◽  
Long Term Potentiation ◽  
Term Potentiation ◽  
Dendritic Protein Synthesis ◽  
Mechanisms Of Memory ◽  
Activity Dependent ◽  
Specific Contribution

Insights into the role of sleep in the molecular mechanisms of memory consolidation may come from studies of activity-dependent synaptic plasticity, such as long-term potentiation (LTP). This commentary posits a specific contribution of sleep to LTP stabilization, in which mRNA transported to dendrites during wakefulness is translated during sleep. Brain-derived neurotrophic factor may drive the translation of newly transported and resident mRNA.

Brain-derived neurotrophic factor and control of synaptic consolidation in the adult brain

2006 ◽  
Vol 34 (4) ◽  
pp. 600-604 ◽  
Author(s):  
J. Soulé ◽  
E. Messaoudi ◽  
C.R. Bramham
Keyword(s):  
Gene Expression ◽  
Neurotrophic Factor ◽  
Molecular Mechanisms ◽  
Long Term Potentiation ◽  
Brain Derived Neurotrophic Factor ◽  
Adult Brain ◽  
Memory Storage ◽  
Early Gene ◽  
High Frequency Stimulation ◽  
Activity Dependent

Interest in BDNF (brain-derived neurotrophic factor) as an activity-dependent modulator of neuronal structure and function in the adult brain has intensified in recent years. Localization of BDNF and its receptor tyrosine kinase TrkB (tropomyosin receptor kinase B) to glutamate synapses makes this system attractive as a dynamic, activity-dependent regulator of excitatory transmission and synaptic plasticity in the adult brain. Development of stable LTP (long-term potentiation) in response to high-frequency stimulation requires new gene expression and protein synthesis, a process referred to as synaptic consolidation. Several lines of evidence have implicated endogenous BDNF–TrkB signalling in synaptic consolidation. This mini-review emphasizes new insights into the molecular mechanisms underlying this process. The immediate early gene Arc (activity-regulated cytoskeleton-associated protein) is strongly induced and transported to dendritic processes after LTP induction in the dentate gyrus in live rats. Recent work suggests that sustained synthesis of Arc during a surprisingly protracted time-window is required for hyperphosphorylation of actin-depolymerizing factor/cofilin and local expansion of the actin cytoskeleton in vivo. Moreover, this process of Arc-dependent synaptic consolidation is activated in response to brief infusion of BDNF. Microarray expression profiling has also revealed a panel of BDNF-regulated genes that may co-operate with Arc during LTP maintenance. In addition to regulating gene expression, BDNF signalling modulates the fine localization and biochemical activation of the translation machinery. By modulating the spatial and temporal translation of newly induced (Arc) and constitutively expressed mRNA in neuronal dendrites, BDNF may effectively control the window of synaptic consolidation. These findings have implications for mechanisms of memory storage and mood control.

scholarly journals Integrated Overview of the Memory System

2021 ◽  
Vol 9 (VI) ◽  
pp. 3328-3338
Author(s):  
Ishanee Das Sharma
Keyword(s):  
Molecular Mechanisms ◽  
Short Term Memory ◽  
Long Term Potentiation ◽  
Point Of View ◽  
Memory Storage ◽  
Long Term Memory ◽  
Special Focus ◽  
Term Memory ◽  
Term Potentiation

This review aims to clarify and classify memory from psychological and neuroscientific point of view, delving into the molecular mechanisms taking place as well. The main forms of memory are sensory memory, short term memory and long-term memory. We also try to specify the flow of information through various memory models. The concept of synaptic plasticity and long-term potentiation is highlighted, with special focus on the physiological parts of the brain that are involved in memory storage. Overall, this study will help expand our knowledge on the intrinsic details of memory storage and the functioning of our brain.

scholarly journals The Medial Prefrontal Cortex and Fear Memory: Dynamics, Connectivity, and Engrams

2021 ◽  
Vol 22 (22) ◽  
pp. 12113
Author(s):  
Lucie Dixsaut ◽  
Johannes Gräff
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Memory Formation ◽  
Memory Storage ◽  
Long Term Memory ◽  
Brain Areas ◽  
Long Term Storage ◽  
And Storage

It is becoming increasingly apparent that long-term memory formation relies on a distributed network of brain areas. While the hippocampus has been at the center of attention for decades, it is now clear that other regions, in particular the medial prefrontal cortex (mPFC), are taking an active part as well. Recent evidence suggests that the mPFC—traditionally implicated in the long-term storage of memories—is already critical for the early phases of memory formation such as encoding. In this review, we summarize these findings, relate them to the functional importance of the mPFC connectivity, and discuss the role of the mPFC during memory consolidation with respect to the different theories of memory storage. Owing to its high functional connectivity to other brain areas subserving memory formation and storage, the mPFC emerges as a central hub across the lifetime of a memory, although much still remains to be discovered.

scholarly journals Corticosteroid Regulation of Synaptic Plasticity in the Hippocampus

2010 ◽  
Vol 10 ◽  
pp. 462-469 ◽  
Author(s):  
Nicola Maggio ◽  
Menahem Segal
Keyword(s):  
Synaptic Plasticity ◽  
Stress Level ◽  
Cognitive Functions ◽  
Molecular Mechanisms ◽  
High Stress ◽  
Long Term Potentiation ◽  
Cellular Functions ◽  
Effects Of Stress

Stress, via release of steroid hormones, has been shown to affect several cellular functions in the brain, including synaptic receptors and ion channels. As such, corticosteroids were reported to modulate plasticity, expressed as long-term changes in reactivity to afferent stimulation. The classical view of the effects of stress on synaptic plasticity and cognitive functions assumes an inverted U-shape curve, such that a low stress level facilitates and a high stress level (i.e., corticosterone levels) impairs cognitive functions. This universal view has been challenged recently in a series of studies that show that stress and corticosterone have immediate and opposite effects on the ability to express long-term potentiation (LTP) in the dorsal and ventral sectors of the hippocampus. This differential role of stress may be related to the different functions associated with these sectors of the hippocampus. Herein, we review the known effects of stress hormones on cellular functions and outline the role of molecular mechanisms in stress-related global functions of the hippocampus.

scholarly journals The immediate early gene Arc is not required for hippocampal long-term potentiation

2020 ◽  
Author(s):  
M. Kyrke-Smith ◽  
L.J. Volk ◽  
S.F. Cooke ◽  
M.F. Bear ◽  
R.L. Huganir ◽  
...  
Keyword(s):  
Immediate Early Gene ◽  
Long Term Potentiation ◽  
Memory Storage ◽  
Early Gene ◽  
Immediate Early ◽  
Long Term Memory ◽  
Memory Encoding ◽  
Term Potentiation ◽  
Mrna And Protein Expression

ABSTRACTThe immediate early gene Arc is critical for maintenance of long-term memory. How Arc mediates this process remains unclear, but it has been proposed to sustain Hebbian synaptic potentiation, which is a key component of memory encoding. This form of plasticity is modelled experimentally by induction of long-term potentiation (LTP), which increases Arc mRNA and protein expression. However, mechanistic data implicates Arc in the endocytosis of AMPA-type glutamate receptors and the weakening of synapses. Here, we took a comprehensive approach to determine if Arc is necessary for hippocampal LTP. We find that Arc is not required for LTP maintenance and must regulate memory storage through alternative mechanisms.

scholarly journals The Importance of Ventral Hippocampal Dopamine and Norepinephrine in Recognition Memory

2021 ◽  
Vol 15 ◽  
Author(s):  
Joep Titulaer ◽  
Carl Björkholm ◽  
Kristin Feltmann ◽  
Torun Malmlöf ◽  
Devesh Mishra ◽  
...  
Keyword(s):  
Recognition Memory ◽  
Familiar Object ◽  
Long Term Potentiation ◽  
Ventral Hippocampus ◽  
Memory Storage ◽  
Object Recognition Test ◽  
Novel Object ◽  
Object A ◽  
Long Term Storage

Dopaminergic neurons originating from the ventral tegmental area (VTA) and the locus coeruleus are innervating the ventral hippocampus and are thought to play an essential role for efficient cognitive function. Moreover, these VTA projections are hypothesized to be part of a functional loop, in which dopamine regulates memory storage. It is hypothesized that when a novel stimulus is encountered and recognized as novel, increased dopamine activity in the hippocampus induces long-term potentiation and long-term storage of memories. We here demonstrate the importance of increased release of dopamine and norepinephrinein the rat ventral hippocampus on recognition memory, using microdialysis combined to a modified novel object recognition test. We found that presenting rats to a novel object significantly increased dopamine and norepinephrine output in the ventral hippocampus. Two hours after introducing the first object, a second object (either novel or familiar) was placed in the same position as the first object. Presenting the animals to a second novel object significantly increased dopamine and norepinephrine release in the ventral hippocampus, compared to a familiar object. In conclusion, this study suggests that dopamine and norepinephrine output in the ventral hippocampus has a crucial role in recognition memory and signals novelty.

The role of PKMζ in the maintenance of long-term memory: a review

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Hamish Patel ◽  
Reza Zamani
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Long Term Potentiation ◽  
Global Memory ◽  
Long Term Memory ◽  
Compensatory Mechanism ◽  
Term Memory ◽  
Kinase C

Abstract Long-term memories are thought to be stored in neurones and synapses that undergo physical changes, such as long-term potentiation (LTP), and these changes can be maintained for long periods of time. A candidate enzyme for the maintenance of LTP is protein kinase M zeta (PKMζ), a constitutively active protein kinase C isoform that is elevated during LTP and long-term memory maintenance. This paper reviews the evidence and controversies surrounding the role of PKMζ in the maintenance of long-term memory. PKMζ maintains synaptic potentiation by preventing AMPA receptor endocytosis and promoting stabilisation of dendritic spine growth. Inhibition of PKMζ, with zeta-inhibitory peptide (ZIP), can reverse LTP and impair established long-term memories. However, a deficit of memory retrieval cannot be ruled out. Furthermore, ZIP, and in high enough doses the control peptide scrambled ZIP, was recently shown to be neurotoxic, which may explain some of the effects of ZIP on memory impairment. PKMζ knockout mice show normal learning and memory. However, this is likely due to compensation by protein-kinase C iota/lambda (PKCι/λ), which is normally responsible for induction of LTP. It is not clear how, or if, this compensatory mechanism is activated under normal conditions. Future research should utilise inducible PKMζ knockdown in adult rodents to investigate whether PKMζ maintains memory in specific parts of the brain, or if it represents a global memory maintenance molecule. These insights may inform future therapeutic targets for disorders of memory loss.

scholarly journals Chondroitin 6-sulphate is required for neuroplasticity and memory in ageing

2021 ◽  
Author(s):  
Sujeong Yang ◽  
Sylvain Gigout ◽  
Angelo Molinaro ◽  
Yuko Naito-Matsui ◽  
Sam Hilton ◽  
...  
Keyword(s):  
Chondroitin Sulphate ◽  
Memory Loss ◽  
Memory Deficits ◽  
Long Term Potentiation ◽  
Aged Mice ◽  
Age Related ◽  
Term Potentiation ◽  
Early Memory

AbstractPerineuronal nets (PNNs) are chondroitin sulphate proteoglycan-containing structures on the neuronal surface that have been implicated in the control of neuroplasticity and memory. Age-related reduction of chondroitin 6-sulphates (C6S) leads to PNNs becoming more inhibitory. Here, we investigated whether manipulation of the chondroitin sulphate (CS) composition of the PNNs could restore neuroplasticity and alleviate memory deficits in aged mice. We first confirmed that aged mice (20-months) showed memory and plasticity deficits. They were able to retain or regain their cognitive ability when CSs were digested or PNNs were attenuated. We then explored the role of C6S in memory and neuroplasticity. Transgenic deletion of chondroitin 6-sulfotransferase (chst3) led to a reduction of permissive C6S, simulating aged brains. These animals showed very early memory loss at 11 weeks old. Importantly, restoring C6S levels in aged animals rescued the memory deficits and restored cortical long-term potentiation, suggesting a strategy to improve age-related memory impairment.

Sign in / Sign up

Export Citation Format

Share Document