scholarly journals Neurotrophin signalling in amygdala-dependent cued fear learning

2020 ◽  
Vol 382 (1) ◽  
pp. 161-172 ◽  
Author(s):  
Susanne Meis ◽  
Thomas Endres ◽  
Volkmar Lessmann
Keyword(s):  
Synaptic Plasticity ◽  
Learning And Memory ◽  
Neurotrophic Factor ◽  
Memory Formation ◽  
Fear Learning ◽  
Mammalian Brain ◽  
Pavlovian Fear Conditioning ◽  
Cortical Afferents ◽  
Trkb Receptors ◽  
Tropomyosin Related Kinase B

Abstract The amygdala is a central hub for fear learning assessed by Pavlovian fear conditioning. Indeed, the prevailing hypothesis that learning and memory are mediated by changes in synaptic strength was shown most convincingly at thalamic and cortical afferents to the lateral amygdala. The neurotrophin brain-derived neurotrophic factor (BDNF) is known to regulate synaptic plasticity and memory formation in many areas of the mammalian brain including the amygdala, where BDNF signalling via tropomyosin-related kinase B (TrkB) receptors is prominently involved in fear learning. This review updates the current understanding of BDNF/TrkB signalling in the amygdala related to fear learning and extinction. In addition, actions of proBDNF/p75NTR and NGF/TrkA as well as NT-3/TrkC signalling in the amygdala are introduced.

Potential role of arteether on N-methyl-D-aspartate (NMDA) receptor expression in experimental cerebral malaria mice and extension of their survival

Parasitology ◽  
2019 ◽  
Vol 146 (12) ◽  
pp. 1571-1577 ◽  
Author(s):  
Sunil Kumar Singh ◽  
Hemlata Dwivedi ◽  
Sarika Gunjan ◽  
Bhavana Singh Chauhan ◽  
Swaroop Kumar Pandey ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Cerebral Malaria ◽  
Learning And Memory ◽  
Neurological Complication ◽  
Receptor Expression ◽  
Extreme Condition ◽  
Mammalian Brain ◽  
Cellular Mechanisms ◽  
Experimental Cerebral Malaria ◽  
Excitatory Neurotransmitter

AbstractCerebral malaria (CM) is the severe neurological complication causing acute non-traumatic encephalopathy in tropical countries. The mechanisms underlying the fatal cerebral complications are still not fully understood. Glutamate, a major excitatory neurotransmitter in the central nervous system of the mammalian brain, plays a key role in the development of neuronal cells, motor function, synaptic plasticity, learning and memory processes under normal physiological conditions. The subtypes of ionotropic glutamate receptor are N-methyl-D-aspartate receptors (NMDARs) which are involved in cellular mechanisms of learning and memory, synaptic plasticity and also mediate excitotoxic neuronal injury. In the present study, we found that glutamate level in synaptosomes, as well as expression of NMDAR, was elevated during the extreme condition of CM in C57BL6 mice. Arteether at 50 mg kg−1× 1, 25 mg kg−1× 2, days decreased the NMDAR expression and increased the overall survival of the experimental CM mice.

Translational control of synaptic plasticity

2010 ◽  
Vol 38 (6) ◽  
pp. 1527-1530 ◽  
Author(s):  
Joel D. Richter
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Synaptic Plasticity ◽  
Synaptic Transmission ◽  
Learning And Memory ◽  
Translational Control ◽  
Synaptic Strength ◽  
Memory Formation ◽  
The Central Nervous System ◽  
Flow Of Information

Synapses, points of contact between axons and dendrites, are conduits for the flow of information in the circuitry of the central nervous system. The strength of synaptic transmission reflects the interconnectedness of the axons and dendrites at synapses; synaptic strength in turn is modified by the frequency with which the synapses are stimulated. This modulation of synaptic strength, or synaptic plasticity, probably forms the cellular basis for learning and memory. RNA metabolism, particularly translational control at or near the synapse, is one process that controls long-lasting synaptic plasticity and, by extension, memory formation and consolidation. In the present paper, I review some salient features of translational control of synaptic plasticity.

Molecular mechanism linking BDNF/TrkB signaling with the NMDA receptor in memory: the role of Girdin in the CNS

2016 ◽  
Vol 27 (5) ◽  
pp. 481-490 ◽  
Author(s):  
Norimichi Itoh ◽  
Atsushi Enomoto ◽  
Taku Nagai ◽  
Masahide Takahashi ◽  
Kiyofumi Yamada
Keyword(s):  
Synaptic Plasticity ◽  
Nmda Receptor ◽  
Learning And Memory ◽  
Molecular Mechanism ◽  
Neuronal Migration ◽  
Neuronal Development ◽  
Long Term Potentiation ◽  
Long Term Memory ◽  
Tropomyosin Related Kinase B

AbstractIt is well known that synaptic plasticity is the cellular mechanism underlying learning and memory. Activity-dependent synaptic changes in electrical properties and morphology, including synaptogenesis, lead to alterations of synaptic strength, which is associated with long-term potentiation (LTP). Brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) signaling is involved in learning and memory formation by regulating synaptic plasticity. The phosphatidylinositol 3-kinase (PI3-K)/Akt pathway is one of the key signaling cascades downstream BDNF/TrkB and is believed to modulate N-methyl-d-aspartate (NMDA) receptor-mediated synaptic plasticity. However, the molecular mechanism underlying the connection between these two key players in synaptic plasticity remains largely unknown. Girders of actin filament (Girdin), an Akt substrate that directly binds to actin filaments, has been shown to play a role in neuronal migration and neuronal development. Recently, we identified Girdin as a key molecule involved in regulating long-term memory. It was demonstrated that phosphorylation of Girdin by Akt contributed to the maintenance of LTP by linking the BDNF/TrkB signaling pathway with NMDA receptor activity. These findings indicate that Girdin plays a pivotal role in a variety of processes in the CNS. Here, we review recent advances in our understanding about the roles of Girdin in the CNS and focus particularly on neuronal migration and memory.

scholarly journals The HDAC inhibitor CI-994 acts as a molecular memory aid by facilitating synaptic and intra-cellular communication after learning

2021 ◽  
Author(s):  
Allison M Burns ◽  
Mélissa Farinelli-Scharly ◽  
Sandrine Hugues-Ascery ◽  
Jose Vicente Sanchez-Mut ◽  
Giulia Santoni ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Hdac Inhibitor ◽  
Brain Region ◽  
Mode Of Action ◽  
Memory Formation ◽  
Epigenetic Modifications ◽  
Fear Learning ◽  
Cognitive Enhancers ◽  
Hdaci Treatment

AbstractLong-term memory formation relies on synaptic plasticity, activity-dependent transcription and epigenetic modifications. Multiple studies have shown that HDAC inhibitor (HDACi) treatments can enhance individual aspects of these processes, and thereby act as putative cognitive enhancers. However, their mode of action is not fully understood. In particular, it is unclear how systemic application of HDACis, which are devoid of substrate specificity, can target pathways that promote memory formation. In this study, we explore the electrophysiological, transcriptional and epigenetic responses that are induced by CI-994, a class I HDAC inhibitor, combined with contextual fear conditioning (CFC) in mice. We show that CI-994-mediated improvement of memory formation is accompanied by enhanced long-term potentiation in the hippocampus, a brain region recruited by CFC, but not in the striatum, a brain region not primarily implicated in contextual memory formation. Furthermore, using a combination of bulk and single cell RNA sequencing, we find that synaptic plasticity-promoting gene expression cascades are more strongly engaged in the hippocampus than in the striatum, but only when HDACi treatment co-occurred with CFC, and not by either treatment alone. Lastly, using ChIP-sequencing, we show that the combined action of HDACi application and conditioning is required to elicit enhancer histone acetylation in pathways that may underlie improved memory performance. Together, our results indicate that systemic HDACi administration amplifies brain-region specific processes that are naturally induced by learning. These findings shed light onto the mode of action of HDACis as cognitive enhancers.Significance StatementMemory formation relies on a plethora of functions, including epigenetic modifications. Over the past years, multiple studies have indicated the potential of HDAC inhibitors (HDACi) to act as cognitive enhancers, but their mode of action is not fully understood. Here, we tested whether HDACi treatment improves memory formation via “cognitive epigenetic priming”, stipulating that HDACis – without inherent target specificity – specifically enhance plasticity-related processes. We found that combining HDACi with fear learning, but not either treatment alone, enhances synaptic plasticity as well as memory-promoting transcriptional signaling in the hippocampus, a brain area known to be recruited by fear learning, but not in others. These results lend experimental support to the theory of “cognitive epigenetic priming”.

scholarly journals Spatial memory formation requires netrin-1 expression by neurons in the adult mammalian brain.

2018 ◽  
Author(s):  
Edwin Wong ◽  
Stephen D Glasgow ◽  
Lianne J Trigiani ◽  
Daryan Chitsaz ◽  
Vladmir Rymar ◽  
...  
Keyword(s):  
Spatial Memory ◽  
Learning And Memory ◽  
Critical Role ◽  
Long Term Potentiation ◽  
Memory Formation ◽  
Adult Brain ◽  
Mammalian Brain ◽  
Conditional Deletion ◽  
The Impact ◽  
Adult Mammalian Brain

Netrin-1 was initially characterized as an axon guidance molecule that is essential for normal embryonic neural development; however, many types of neurons continue to express netrin-1 in the post-natal and adult mammalian brain. Netrin-1 and the netrin receptor DCC are both enriched at synapses. In the adult hippocampus, activity-dependent secretion of netrin-1 by neurons potentiates glutamatergic synapse function, and is critical for long-term potentiation, an experimental cellular model of learning and memory. Here, we assessed the impact of neuronal expression of netrin-1 in the adult brain on behavior using tests of learning and memory. We show that adult mice exhibit impaired spatial memory following conditional deletion of netrin-1 from glutamatergic neurons in the hippocampus and neocortex. Further, we provide evidence that mice with conditional deletion of netrin-1 do not display aberrant anxiety-like phenotypes and show a reduction in self-grooming behaviour. These findings reveal a critical role for netrin-1 expressed by neurons in the regulation of spatial memory formation.

BDNF and Control of Synaptic Plasticity in the Adult Brain

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
C. Bramham
Keyword(s):  
Synaptic Plasticity ◽  
Dentate Gyrus ◽  
Antidepressant Drugs ◽  
Long Term Potentiation ◽  
Memory Formation ◽  
Adult Brain ◽  
Early Gene ◽  
Perforant Path ◽  
Mammalian Brain

Experience-dependent changes in synaptic connectivity are thought to play a vital role not only in memory formation, but also in long-term adaptive responses involved in mood regulation, reward behavior, and pain control. The neurotrophin, brain-derived neurotrophic factor (BDNF), which has recently been implicated in memory formation and aspects of major depression, is also an important regulator of long-term synaptic plasticity in the adult mammalian brain. We have investigated BDNF function in the dentate gyrus, a brain region implicated in depression and the action of antidepressant drugs. Local infusion of BDNF into the dentate gyrus generated a long-term potentiation (LTP) of synaptic efficacy at medial perforant path-granule cell synapses. This LTP is associated with expression of the immediate early gene, Arc, in postsynaptic granule cells and transport of Arc mRNA to synaptic regions on dendrites. Using local infusion of antisense oligodeoxynucleotides to block Arc synthesis, we show that Arc is required for the induction and time-dependent consolidation of BDNF-induced LTP. The sustained synthesis of Arc during a critical time-window is required for local expansion of the actin cytoskeletal network in dendritic spines. These results identify Arc as a critical mediator of BDNF in long-term synaptic plasticity in the adult brain. Microarray expression profiling has further revealed a panel of genes that, like Arc, are strongly upregulated following acute BDNF infusion or chronic treatment with the antidepressant fluoxetine.

scholarly journals Hippocampal Regulation of Postsynaptic Density Homer1 by Associative Learning

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Nicholas E. Clifton ◽  
Darren Cameron ◽  
Simon Trent ◽  
Lucy H. Sykes ◽  
Kerrie L. Thomas ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Learning And Memory ◽  
Novelty Detection ◽  
Postsynaptic Density ◽  
Fear Memory ◽  
Contextual Fear Conditioning ◽  
Fear Learning ◽  
Contextual Fear ◽  
Postsynaptic Density Proteins ◽  
Genes Encoding

Genes involved in synaptic plasticity, particularly genes encoding postsynaptic density proteins, have been recurrently linked to psychiatric disorders including schizophrenia and autism. Postsynaptic density Homer1 proteins contribute to synaptic plasticity through the competing actions of short and long isoforms. The activity-induced expression of shortHomer1isoforms,Homer1aandAnia-3, is thought to be related to processes of learning and memory. However, the precise regulation ofHomer1aandAnia-3with different components of learning has not been investigated. Here, we used in situ hybridization to quantify short and longHomer1expression in the hippocampus following consolidation, retrieval, and extinction of associative fear memory, using contextual fear conditioning in rats.Homer1aandAnia-3, but not longHomer1, were regulated by contextual fear learning or novelty detection, although their precise patterns of expression in hippocampal subregions were dependent on the isoform. We also show for the first time that the two short Homer1 isoforms are regulated after the retrieval and extinction of contextual fear memory, albeit with distinct temporal and spatial profiles. These findings support a role of activity-induced Homer1 isoforms in learning and memory processes in discrete hippocampal subregions and suggest that Homer1a and Ania-3 may play separable roles in synaptic plasticity.

scholarly journals The Association of Brain-Derived Neurotrophic Factor with Long-Term Potentiation

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Zahra Salimi ◽  
Farshad Moradpour ◽  
Zahra Rashidi ◽  
Fatemeh Zarei ◽  
Mohammad Rasool Khazaei ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Learning And Memory ◽  
Neurotrophic Factor ◽  
Synapse Formation ◽  
Long Term Potentiation ◽  
Brain Derived Neurotrophic Factor ◽  
Synaptic Efficacy ◽  
Term Potentiation ◽  
The Central Nervous System

: Long-term potentiation (LTP) is one of the most important topics in neuroscience. It refers to a long-lasting increase in synaptic efficacy and is considered as a molecular and cellular mechanism of learning and memory. Neurotrophins play essential roles in different processes in the central nervous system (CNS), such as synaptogenesis, survival of specific populations of neurons, and neuroplasticity. Some evidence suggests that neurotrophins also participate in the synaptic plasticity related to learning and memory formation. Brain-derived neurotrophic factor (BDNF) is an important neurotrophic factor that is extensively expressed in the hippocampus and cerebral cortex, where it promotes neuroprotection, increases synaptogenesis and neurotransmission, and mediates synapse formation and synaptic plasticity. In this review, we first focused on the research investigating the effects of BDNF on synaptic plasticity and LTP induction and then reviewed the neuronal signaling molecules employed by BDNF to promote its effects on these processes.

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