The role of γ-secretase in hippocampal synaptic transmission and activity-dependent synaptic plasticity

2013 ◽  
Vol 554 ◽  
pp. 16-21 ◽  
Author(s):  
YuQing Chen ◽  
Thomas Behnisch
Keyword(s):  
Synaptic Plasticity ◽  
Synaptic Transmission ◽  
Activity Dependent

scholarly journals MPTP modulates hippocampal synaptic transmission and activity-dependent synaptic plasticity via dopamine receptors

2012 ◽  
Vol 122 (3) ◽  
pp. 582-593 ◽  
Author(s):  
GuoQi Zhu ◽  
YuYing Huang ◽  
Ying Chen ◽  
YingHan Zhuang ◽  
Thomas Behnisch
Keyword(s):  
Synaptic Plasticity ◽  
Synaptic Transmission ◽  
Dopamine Receptors ◽  
Activity Dependent

Remodeling of astrocytes, a prerequisite for synapse turnover in the adult brain? Insights from the oxytocin system of the hypothalamus

2006 ◽  
Vol 290 (5) ◽  
pp. R1175-R1182 ◽  
Author(s):  
Dionysia T. Theodosis ◽  
Andrei Trailin ◽  
Dominique A. Poulain
Keyword(s):  
Synaptic Plasticity ◽  
Synaptic Transmission ◽  
Neuronal Activity ◽  
Adult Brain ◽  
Synaptic Connectivity ◽  
Excitatory Synapses ◽  
Neuronal Function ◽  
Physiological Conditions ◽  
Baseline Levels ◽  
Activity Dependent

Neurons, including their synapses, are generally ensheathed by fine processes of astrocytes, but this glial coverage can be altered under different physiological conditions that modify neuronal activity. Changes in synaptic connectivity accompany astrocytic transformations so that an increased number of synapses are associated with reduced astrocytic coverage of postsynaptic elements, whereas synaptic numbers are reduced on reestablishment of glial coverage. A system that exemplifies activity-dependent structural synaptic plasticity in the adult brain is the hypothalamo-neurohypophysial system, and in particular, its oxytocin component. Under strong, prolonged activation (parturition, lactation, chronic dehydration), extensive portions of somatic and dendritic surfaces of magnocellular oxytocin neurons are freed of intervening astrocytic processes and become directly juxtaposed. Concurrently, they are contacted by an increased number of inhibitory and excitatory synapses. Once stimulation is over, astrocytic processes again cover oxytocinergic surfaces and synaptic numbers return to baseline levels. Such observations indicate that glial ensheathment of neurons is of consequence to neuronal function, not only directly, for example by modifying synaptic transmission, but indirectly as well, by preparing neuronal surfaces for synapse turnover.

scholarly journals BACE1 Is Necessary for Experience-Dependent Homeostatic Synaptic Plasticity in Visual Cortex

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Emily Petrus ◽  
Hey-Kyoung Lee
Keyword(s):  
Synaptic Plasticity ◽  
Visual Cortex ◽  
Synaptic Transmission ◽  
Sensory Experience ◽  
Synaptic Function ◽  
Excitatory Synaptic Transmission ◽  
Early Gene ◽  
Dependent Manner ◽  
Homeostatic Synaptic Plasticity ◽  
Activity Dependent

Alzheimer’s disease (AD) is the most common form of age-related dementia, which is thought to result from overproduction and/or reduced clearance of amyloid-beta (Aβ) peptides. Studies over the past few decades suggest that Aβis produced in an activity-dependent manner and has physiological relevance to normal brain functions. Similarly, physiological functions forβ- andγ-secretases, the two key enzymes that produce Aβby sequentially processing the amyloid precursor protein (APP), have been discovered over recent years. In particular, activity-dependent production of Aβhas been suggested to play a role in homeostatic regulation of excitatory synaptic function. There is accumulating evidence that activity-dependent immediate early gene Arc is an activity “sensor,” which acts upstream of Aβproduction and triggers AMPA receptor endocytosis to homeostatically downregulate the strength of excitatory synaptic transmission. We previously reported that Arc is critical for sensory experience-dependent homeostatic reduction of excitatory synaptic transmission in the superficial layers of visual cortex. Here we demonstrate that mice lacking the major neuronalβ-secretase, BACE1, exhibit a similar phenotype: stronger basal excitatory synaptic transmission and failure to adapt to changes in visual experience. Our results indicate that BACE1 plays an essential role in sensory experience-dependent homeostatic synaptic plasticity in the neocortex.

scholarly journals Postsynaptic regulation of synaptic plasticity by synaptotagmin 4 requires both C2 domains

2009 ◽  
Vol 187 (2) ◽  
pp. 295-310 ◽  
Author(s):  
Cynthia F. Barber ◽  
Ramon A. Jorquera ◽  
Jan E. Melom ◽  
J. Troy Littleton
Keyword(s):  
Synaptic Plasticity ◽  
Messenger Rna ◽  
Molecular Mechanisms ◽  
Neuromuscular Junctions ◽  
Vesicle Fusion ◽  
Synaptic Growth ◽  
Synaptotagmin 1 ◽  
Presynaptic Vesicle ◽  
Activity Dependent

Ca2+ influx into synaptic compartments during activity is a key mediator of neuronal plasticity. Although the role of presynaptic Ca2+ in triggering vesicle fusion though the Ca2+ sensor synaptotagmin 1 (Syt 1) is established, molecular mechanisms that underlie responses to postsynaptic Ca2+ influx remain unclear. In this study, we demonstrate that fusion-competent Syt 4 vesicles localize postsynaptically at both neuromuscular junctions (NMJs) and central nervous system synapses in Drosophila melanogaster. Syt 4 messenger RNA and protein expression are strongly regulated by neuronal activity, whereas altered levels of postsynaptic Syt 4 modify synaptic growth and presynaptic release properties. Syt 4 is required for known forms of activity-dependent structural plasticity at NMJs. Synaptic proliferation and retrograde signaling mediated by Syt 4 requires functional C2A and C2B Ca2+–binding sites, as well as serine 284, an evolutionarily conserved substitution for a key Ca2+-binding aspartic acid found in other synaptotagmins. These data suggest that Syt 4 regulates activity-dependent release of postsynaptic retrograde signals that promote synaptic plasticity, similar to the role of Syt 1 as a Ca2+ sensor for presynaptic vesicle fusion.

scholarly journals Molekulare Regulation der neuronalen Plastizität und Lernprozesse

BIOspektrum ◽  
2020 ◽  
Vol 26 (6) ◽  
pp. 600-602
Author(s):  
Marta Zagrebelsky
Keyword(s):  
Synaptic Plasticity ◽  
Synaptic Transmission ◽  
Neuronal Plasticity ◽  
Neuronal Networks ◽  
Inhibitory Synaptic Transmission ◽  
Memory Traces ◽  
Brain Circuitry ◽  
Plastic Changes ◽  
Activity Dependent ◽  
The Brain

Abstract Activity-dependent plastic changes at synapses are essential for learning, but maintaining memory traces requires stable neuronal networks. The balance between plasticity and stability of the brain circuitry is tightly regulated. Among the mechanisms involved in regulating neuronal plasticity is the modulation of excitation and inhibition. Nogo-A was recently described for its ability to limit synaptic plasticity and to reciprocally regulate excitatory and inhibitory synaptic transmission.

scholarly journals Elements of a neurobiological theory of the hippocampus: the role of activity-dependent synaptic plasticity in memory

2003 ◽  
Vol 358 (1432) ◽  
pp. 773-786 ◽  
Author(s):  
R. G. M. Morris ◽  
E. I. Moser ◽  
G. Riedel ◽  
S. J. Martin ◽  
J. Sandin ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Long Term Potentiation ◽  
Cellular Mechanisms ◽  
Memory Processing ◽  
Functional Studies ◽  
Term Potentiation ◽  
Intermediate Storage ◽  
Activity Dependent

The hypothesis that synaptic plasticity is a critical component of the neural mechanisms underlying learning and memory is now widely accepted. In this article, we begin by outlining four criteria for evaluating the ‘synaptic plasticity and memory (SPM)’ hypothesis. We then attempt to lay the foundations for a specific neurobiological theory of hippocampal (HPC) function in which activity-dependent synaptic plasticity, such as long-term potentiation (LTP), plays a key part in the forms of memory mediated by this brain structure. HPC memory can, like other forms of memory, be divided into four processes: encoding, storage, consolidation and retrieval. We argue that synaptic plasticity is critical for the encoding and intermediate storage of memory traces that are automatically recorded in the hippocampus. These traces decay, but are sometimes retained by a process of cellular consolidation. However, we also argue that HPC synaptic plasticity is not involved in memory retrieval, and is unlikely to be involved in systems-level consolidation that depends on HPC-neocortical interactions, although neocortical synaptic plasticity does play a part. The information that has emerged from the worldwide focus on the mechanisms of induction and expression of plasticity at individual synapses has been very valuable in functional studies. Progress towards a comprehensive understanding of memory processing will also depend on the analysis of these synaptic changes within the context of a wider range of systems-level and cellular mechanisms of neuronal transmission and plasticity.

scholarly journals Calcineurin mediates homeostatic synaptic plasticity by regulating retinoic acid synthesis

2015 ◽  
Vol 112 (42) ◽  
pp. E5744-E5752 ◽  
Author(s):  
Kristin L. Arendt ◽  
Zhenjie Zhang ◽  
Subhashree Ganesan ◽  
Maik Hintze ◽  
Maggie M. Shin ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Synaptic Plasticity ◽  
Synaptic Transmission ◽  
Critical Role ◽  
Signal Transduction Pathway ◽  
Acid Synthesis ◽  
Synaptic Activity ◽  
Homeostatic Synaptic Plasticity ◽  
Dependent Protein

Homeostatic synaptic plasticity is a form of non-Hebbian plasticity that maintains stability of the network and fidelity for information processing in response to prolonged perturbation of network and synaptic activity. Prolonged blockade of synaptic activity decreases resting Ca2+ levels in neurons, thereby inducing retinoic acid (RA) synthesis and RA-dependent homeostatic synaptic plasticity; however, the signal transduction pathway that links reduced Ca2+-levels to RA synthesis remains unknown. Here we identify the Ca2+-dependent protein phosphatase calcineurin (CaN) as a key regulator for RA synthesis and homeostatic synaptic plasticity. Prolonged inhibition of CaN activity promotes RA synthesis in neurons, and leads to increased excitatory and decreased inhibitory synaptic transmission. These effects of CaN inhibitors on synaptic transmission are blocked by pharmacological inhibitors of RA synthesis or acute genetic deletion of the RA receptor RARα. Thus, CaN, acting upstream of RA, plays a critical role in gating RA signaling pathway in response to synaptic activity. Moreover, activity blockade-induced homeostatic synaptic plasticity is absent in CaN knockout neurons, demonstrating the essential role of CaN in RA-dependent homeostatic synaptic plasticity. Interestingly, in GluA1 S831A and S845A knockin mice, CaN inhibitor- and RA-induced regulation of synaptic transmission is intact, suggesting that phosphorylation of GluA1 C-terminal serine residues S831 and S845 is not required for CaN inhibitor- or RA-induced homeostatic synaptic plasticity. Thus, our study uncovers an unforeseen role of CaN in postsynaptic signaling, and defines CaN as the Ca2+-sensing signaling molecule that mediates RA-dependent homeostatic synaptic plasticity.

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