scholarly journals NMDA Receptor Subunits Change after Synaptic Plasticity Induction and Learning and Memory Acquisition

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
María Verónica Baez ◽  
Magalí Cecilia Cercato ◽  
Diana Alicia Jerusalinsky
Keyword(s):  
Synaptic Plasticity ◽  
Learning And Memory ◽  
De Novo ◽  
Physiological Profile ◽  
Regulatory Subunits ◽  
Neuronal Soma ◽  
Synaptic Changes ◽  
Memory Acquisition ◽  
Activity Dependent ◽  
Neuron Soma

NMDA ionotropic glutamate receptors (NMDARs) are crucial in activity-dependent synaptic changes and in learning and memory. NMDARs are composed of two GluN1 essential subunits and two regulatory subunits which define their pharmacological and physiological profile. In CNS structures involved in cognitive functions as the hippocampus and prefrontal cortex, GluN2A and GluN2B are major regulatory subunits; their expression is dynamic and tightly regulated, but little is known about specific changes after plasticity induction or memory acquisition. Data strongly suggest that following appropriate stimulation, there is a rapid increase in surface GluN2A-NMDAR at the postsynapses, attributed to lateral receptor mobilization from adjacent locations. Whenever synaptic plasticity is induced or memory is consolidated, more GluN2A-NMDARs are assembled likely using GluN2A from a local translation and GluN1 from local ER. Later on, NMDARs are mobilized from other pools, and there are de novo syntheses at the neuron soma. Changes in GluN1 or NMDAR levels induced by synaptic plasticity and by spatial memory formation seem to occur in different waves of NMDAR transport/expression/degradation, with a net increase at the postsynaptic side and a rise in expression at both the spine and neuronal soma. This review aims to put together that information and the proposed hypotheses.

scholarly journals Hebbian activity-dependent plasticity in white matter

2022 ◽  
Author(s):  
Alberto Lazari ◽  
Piergiorgio Salvan ◽  
Michiel Cottaar ◽  
Daniel Papp ◽  
Matthew FS Rushworth ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
White Matter ◽  
Associative Learning ◽  
Fiber Bundle ◽  
Cortical Excitability ◽  
Brain Plasticity ◽  
Cortical Areas ◽  
Hebbian Plasticity ◽  
Synaptic Changes ◽  
Activity Dependent

Synaptic plasticity is required for learning and follows Hebb's Rule, the computational principle underpinning associative learning. In recent years, a complementary type of brain plasticity has been identified in myelinated axons, which make up the majority of brain's white matter. Like synaptic plasticity, myelin plasticity is required for learning, but it is unclear whether it is Hebbian or whether it follows different rules. Here, we provide evidence that white matter plasticity operates following Hebb's Rule in humans. Across two experiments, we find that co-stimulating cortical areas to induce Hebbian plasticity leads to relative increases in cortical excitability and associated increases in a myelin marker within the stimulated fiber bundle. We conclude that Hebbian plasticity extends beyond synaptic changes, and can be observed in human white matter fibers.

scholarly journals Synaptic control of DNA methylation involves activity-dependent degradation of DNMT3A1 in the nucleus

2020 ◽  
Vol 45 (12) ◽  
pp. 2120-2130 ◽  
Author(s):  
Gonca Bayraktar ◽  
PingAn Yuanxiang ◽  
Alessandro D. Confettura ◽  
Guilherme M. Gomes ◽  
Syed A. Raza ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Synaptic Plasticity ◽  
Promoter Methylation ◽  
Dna Methyltransferase ◽  
De Novo ◽  
Memory Formation ◽  
Epigenetic Mark ◽  
Dependent Manner ◽  
Synaptic Control ◽  
Activity Dependent

Abstract DNA methylation is a crucial epigenetic mark for activity-dependent gene expression in neurons. Very little is known about how synaptic signals impact promoter methylation in neuronal nuclei. In this study we show that protein levels of the principal de novo DNA-methyltransferase in neurons, DNMT3A1, are tightly controlled by activation of N-methyl-D-aspartate receptors (NMDAR) containing the GluN2A subunit. Interestingly, synaptic NMDARs drive degradation of the methyltransferase in a neddylation-dependent manner. Inhibition of neddylation, the conjugation of the small ubiquitin-like protein NEDD8 to lysine residues, interrupts degradation of DNMT3A1. This results in deficits in promoter methylation of activity-dependent genes, as well as synaptic plasticity and memory formation. In turn, the underlying molecular pathway is triggered by the induction of synaptic plasticity and in response to object location learning. Collectively, the data show that plasticity-relevant signals from GluN2A-containing NMDARs control activity-dependent DNA-methylation involved in memory formation.

scholarly journals Strong Aversive Conditioning Triggers a Long-Lasting Generalized Aversion

2022 ◽  
Author(s):  
Raul Ramos ◽  
Chi-Hong Wu ◽  
Gina G Turrigiano
Keyword(s):  
Synaptic Plasticity ◽  
Brain Slice ◽  
Aversive Conditioning ◽  
Future Scenarios ◽  
Important Goal ◽  
Neuronal Ensemble ◽  
Deep Layers ◽  
Synaptic Changes ◽  
Activity Dependent ◽  
Hallmark Feature

Generalization is an adaptive mnemonic process in which an animal can leverage past learning experiences to navigate future scenarios, but overgeneralization is a hallmark feature of anxiety disorders. Therefore, understanding the synaptic plasticity mechanisms that govern memory generalization and its persistence is an important goal. Here, we demonstrate that strong CTA conditioning results in a long-lasting generalized aversion that persists for at least two weeks. Using brain slice electrophysiology and activity-dependent labeling of the conditioning-active neuronal ensemble within the gustatory cortex, we find that strong CTA conditioning induces a long-lasting increase in synaptic strengths that occurs uniformly across superficial and deep layers of GC. Repeated exposure to salt, the generalized tastant, causes a rapid attenuation of the generalized aversion that correlates with a reversal of the CTA-induced increases in synaptic strength. Unlike the uniform strengthening that happens across layers, reversal of the generalized aversion results in a more pronounced depression of synaptic strengths in superficial layers. Finally, the generalized aversion and its reversal do not impact the acquisition and maintenance of the aversion to the conditioned tastant (saccharin). The strong correlation between the generalized aversion and synaptic strengthening, and the reversal of both in superficial layers by repeated salt exposure, strongly suggests that the synaptic changes in superficial layers contribute to the formation and reversal of the generalized aversion. In contrast, the persistence of synaptic strengthening in deep layers correlates with the persistence of CTA. Taken together, our data suggest that layer-specific synaptic plasticity mechanisms separately govern the persistence and generalization of CTA memory.

scholarly journals Synaptic control of DNA-methylation involves activity-dependent degradation of DNMT3a1 in the nucleus

2019 ◽  
Author(s):  
Gonca Bayraktar ◽  
PingAn Yuanxiang ◽  
Guilherme M Gomes ◽  
Aessandro D Confettura ◽  
Syed A Raza ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Synaptic Plasticity ◽  
Promoter Methylation ◽  
Dna Methyltransferase ◽  
De Novo ◽  
Memory Formation ◽  
Epigenetic Mark ◽  
Dependent Manner ◽  
Synaptic Control ◽  
Activity Dependent

AbstractDNA-methylation is a crucial epigenetic mark for activity-dependent gene expression in neurons. Very little is known how synaptic signals impact promoter methylation in neuronal nuclei. In this study we show that protein levels of the principal de novo DNA-methyltransferase in neurons, DNMT3a1, are tightly controlled by activation of N-methyl-D-aspartate receptors (NMDAR) containing the GluN2A subunit. Interestingly, synaptic NMDAR drive degradation of the methyltransferase in a neddylation-dependent manner. Inhibition of neddylation, the conjugation of the small ubiquitin-like protein NEDD8 to lysine residues, interrupts degradation of DNMT3a1 and results in deficits of promoter methylation of activity-dependent genes, synaptic plasticity as well as memory formation. In turn, the underlying molecular pathway is triggered by the induction of synaptic plasticity and in response to object location learning. Collectively the data show that GluN2A containing NMDAR control synapse-to-nucleus signaling that links plasticity-relevant signals to activity-dependent DNA-methylation involved in memory formation.

scholarly journals Synaptic GluN2A-Containing NMDA Receptors: From Physiology to Pathological Synaptic Plasticity

2020 ◽  
Vol 21 (4) ◽  
pp. 1538 ◽  
Author(s):  
Luca Franchini ◽  
Nicolò Carrano ◽  
Monica Di Luca ◽  
Fabrizio Gardoni
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Synaptic Plasticity ◽  
Receptor Subtypes ◽  
Interacting Proteins ◽  
Regulatory Subunits ◽  
Different Types ◽  
The Central Nervous System ◽  
Nmdar Subunit ◽  
Activity Dependent

N-Methyl-d-Aspartate Receptors (NMDARs) are ionotropic glutamate-gated receptors. NMDARs are tetramers composed by several homologous subunits of GluN1-, GluN2-, or GluN3-type, leading to the existence in the central nervous system of a high variety of receptor subtypes with different pharmacological and signaling properties. NMDAR subunit composition is strictly regulated during development and by activity-dependent synaptic plasticity. Given the differences between GluN2 regulatory subunits of NMDAR in several functions, here we will focus on the synaptic pool of NMDARs containing the GluN2A subunit, addressing its role in both physiology and pathological synaptic plasticity as well as the contribution in these events of different types of GluN2A-interacting proteins.

Activity-dependent morphological synaptic plasticity in an adult neurosecretory system: magnocellular oxytocin neurons of the hypothalamus

2000 ◽  
Vol 78 (3) ◽  
pp. 317-327 ◽  
Author(s):  
Mohammed El Majdoubi ◽  
Dominique A Poulain ◽  
Dionysia T Theodosis
Keyword(s):  
Synaptic Plasticity ◽  
General Circulation ◽  
Neurosecretory System ◽  
Cellular Mechanisms ◽  
Paraventricular Nuclei ◽  
Quantitative Analyses ◽  
Synaptic Changes ◽  
Afferent Inputs ◽  
Vasopressin Neurons ◽  
Activity Dependent

Oxytocin and vasopressin neurons, located in the supraoptic and paraventricular nuclei of the hypothalamus, send their axons to the neurohypophysis where the neurohormones are released directly into the general circulation. Hormone release depends on the electrical activity of the neurons, which in turn is regulated by different afferent inputs. During conditions that enhance oxytocin secretion (parturition, lactation, and dehydration), these afferents undergo morphological remodelling which results in an increased number of synapses contacting oxytocin neurons. The synaptic changes are reversible with cessation of stimulation. Using quantitative analyses on immunolabelled preparations, we have established that this morphological synaptic plasticity affects both inhibitory and excitatory afferent inputs to oxytocin neurons. This review describes such synaptic modifications, their functional significance, and the cellular mechanisms that may be responsible.Key words: oxytocin, vasopressin, GABA, glutamate, noradrenaline, hypothalamo-neurohypophysial system, lactation.

scholarly journals SYNPLA, a method to identify synapses displaying plasticity after learning

2020 ◽  
Vol 117 (6) ◽  
pp. 3214-3219 ◽  
Author(s):  
Kim Dore ◽  
Yvonne Pao ◽  
Jose Soria Lopez ◽  
Sage Aronson ◽  
Huiqing Zhan ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Learning And Memory ◽  
High Throughput ◽  
Neural Circuits ◽  
Synaptic Strength ◽  
Proximity Ligation Assay ◽  
Neural Pathways ◽  
Proximity Ligation ◽  
Synaptic Changes ◽  
Specific Learning

Which neural circuits undergo synaptic changes when an animal learns? Although it is widely accepted that changes in synaptic strength underlie many forms of learning and memory, it remains challenging to connect changes in synaptic strength at specific neural pathways to specific behaviors and memories. Here we introduce SYNPLA (synaptic proximity ligation assay), a synapse-specific, high-throughput, and potentially brain-wide method capable of detecting circuit-specific learning-induced synaptic plasticity.

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