scholarly journals Glutamatergic synapses are structurally and biochemically complex because of multiple plasticity processes: long-term potentiation, long-term depression, short-term potentiation and scaling

2017 ◽  
Vol 372 (1715) ◽  
pp. 20160260 ◽  
Author(s):  
John Lisman
Keyword(s):  
Primary Dendrite ◽  
Long Term Potentiation ◽  
Synaptic Function ◽  
Homeostatic Plasticity ◽  
Network Activity ◽  
Activity Levels ◽  
Glutamatergic Synapses ◽  
Short Term ◽  
Term Potentiation

Synapses are complex because they perform multiple functions, including at least six mechanistically different forms of plasticity. Here, I comment on recent developments regarding these processes. (i) Short-term potentiation (STP), a Hebbian process that requires small amounts of synaptic input, appears to make strong contributions to some forms of working memory. (ii) The rules for long-term potentiation (LTP) induction in CA3 have been clarified: induction does not depend obligatorily on backpropagating sodium spikes but, rather, on dendritic branch-specific N -methyl- d -aspartate (NMDA) spikes. (iii) Late LTP, a process that requires a dopamine signal (and is therefore neoHebbian), is mediated by trans-synaptic growth of the synapse, a growth that occurs about an hour after LTP induction. (iv) LTD processes are complex and include both homosynaptic and heterosynaptic forms. (v) Synaptic scaling produced by changes in activity levels are not primarily cell-autonomous, but rather depend on network activity. (vi) The evidence for distance-dependent scaling along the primary dendrite is firm, and a plausible structural-based mechanism is suggested. Ideas about the mechanisms of synaptic function need to take into consideration newly emerging data about synaptic structure. Recent super-resolution studies indicate that glutamatergic synapses are modular (module size 70–80 nm), as predicted by theoretical work. Modules are trans-synaptic structures and have high concentrations of postsynaptic density-95 (PSD-95) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor. These modules function as quasi-independent loci of AMPA-mediated transmission and may be independently modifiable, suggesting a new understanding of quantal transmission. This article is part of the themed issue ‘Integrating Hebbian and homeostatic plasticity.’

scholarly journals The AMPA receptor-associated protein Shisa7 regulates hippocampal synaptic function and contextual memory

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Leanne J M Schmitz ◽  
Remco V Klaassen ◽  
Marta Ruiperez-Alonso ◽  
Azra Elia Zamri ◽  
Jasper Stroeder ◽  
...  
Keyword(s):  
Ampa Receptors ◽  
Long Term Potentiation ◽  
Fear Memory ◽  
Synaptic Function ◽  
Glutamatergic Synapses ◽  
Contextual Fear ◽  
Receptor Associated Protein ◽  
Term Potentiation ◽  
Bona Fide

Glutamatergic synapses rely on AMPA receptors (AMPARs) for fast synaptic transmission and plasticity. AMPAR auxiliary proteins regulate receptor trafficking, and modulate receptor mobility and its biophysical properties. The AMPAR auxiliary protein Shisa7 (CKAMP59) has been shown to interact with AMPARs in artificial expression systems, but it is unknown whether Shisa7 has a functional role in glutamatergic synapses. We show that Shisa7 physically interacts with synaptic AMPARs in mouse hippocampus. Shisa7 gene deletion resulted in faster AMPAR currents in CA1 synapses, without affecting its synaptic expression. Shisa7 KO mice showed reduced initiation and maintenance of long-term potentiation of glutamatergic synapses. In line with this, Shisa7 KO mice showed a specific deficit in contextual fear memory, both short-term and long-term after conditioning, whereas auditory fear memory and anxiety-related behavior were normal. Thus, Shisa7 is a bona-fide AMPAR modulatory protein affecting channel kinetics of AMPARs, necessary for synaptic hippocampal plasticity, and memory recall.

scholarly journals GluA2-dependent AMPA receptor endocytosis and the decay of early and late long-term potentiation: possible mechanisms for forgetting of short- and long-term memories

2014 ◽  
Vol 369 (1633) ◽  
pp. 20130141 ◽  
Author(s):  
Oliver Hardt ◽  
Karim Nader ◽  
Yu-Tian Wang
Keyword(s):  
Ampa Receptors ◽  
Long Term Potentiation ◽  
Homeostatic Plasticity ◽  
Molecular Processes ◽  
Short Term ◽  
Receptor Endocytosis ◽  
Term Potentiation ◽  
Short And Long Term ◽  
Activity Dependent

The molecular processes involved in establishing long-term potentiation (LTP) have been characterized well, but the decay of early and late LTP (E-LTP and L-LTP) is poorly understood. We review recent advances in describing the mechanisms involved in maintaining LTP and homeostatic plasticity. We discuss how these phenomena could relate to processes that might underpin the loss of synaptic potentiation over time, and how they might contribute to the forgetting of short-term and long-term memories. We propose that homeostatic downscaling mediates the loss of E-LTP, and that metaplastic parameters determine the decay rate of L-LTP, while both processes require the activity-dependent removal of postsynaptic GluA2-containing AMPA receptors.

scholarly journals Aη-α and Aη-β peptides impair LTP ex vivo within the low nanomolar range and impact neuronal activity in vivo

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Maria Mensch ◽  
Jade Dunot ◽  
Sandy M. Yishan ◽  
Samuel S. Harris ◽  
Aline Blistein ◽  
...  
Keyword(s):  
Neuronal Activity ◽  
Ex Vivo ◽  
Long Term Potentiation ◽  
Network Activity ◽  
Strongly Correlated ◽  
App Processing ◽  
Term Potentiation ◽  
Hippocampal Network

Abstract Background Amyloid precursor protein (APP) processing is central to Alzheimer’s disease (AD) etiology. As early cognitive alterations in AD are strongly correlated to abnormal information processing due to increasing synaptic impairment, it is crucial to characterize how peptides generated through APP cleavage modulate synapse function. We previously described a novel APP processing pathway producing η-secretase-derived peptides (Aη) and revealed that Aη–α, the longest form of Aη produced by η-secretase and α-secretase cleavage, impaired hippocampal long-term potentiation (LTP) ex vivo and neuronal activity in vivo. Methods With the intention of going beyond this initial observation, we performed a comprehensive analysis to further characterize the effects of both Aη-α and the shorter Aη-β peptide on hippocampus function using ex vivo field electrophysiology, in vivo multiphoton calcium imaging, and in vivo electrophysiology. Results We demonstrate that both synthetic peptides acutely impair LTP at low nanomolar concentrations ex vivo and reveal the N-terminus to be a primary site of activity. We further show that Aη-β, like Aη–α, inhibits neuronal activity in vivo and provide confirmation of LTP impairment by Aη–α in vivo. Conclusions These results provide novel insights into the functional role of the recently discovered η-secretase-derived products and suggest that Aη peptides represent important, pathophysiologically relevant, modulators of hippocampal network activity, with profound implications for APP-targeting therapeutic strategies in AD.

scholarly journals Multiplexed neurochemical transmission emulated using a dual-excitatory synaptic transistor

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Mingxue Ma ◽  
Yao Ni ◽  
Zirong Chi ◽  
Wanqing Meng ◽  
Haiyang Yu ◽  
...  
Keyword(s):  
Neural Network ◽  
Central Nervous System ◽  
Nervous System ◽  
Long Term Potentiation ◽  
Short Term ◽  
Term Potentiation ◽  
Binary Neural Network ◽  
Neuromorphic Systems ◽  
Human Brains

AbstractThe ability to emulate multiplexed neurochemical transmission is an important step toward mimicking complex brain activities. Glutamate and dopamine are neurotransmitters that regulate thinking and impulse signals independently or synergistically. However, emulation of such simultaneous neurotransmission is still challenging. Here we report design and fabrication of synaptic transistor that emulates multiplexed neurochemical transmission of glutamate and dopamine. The device can perform glutamate-induced long-term potentiation, dopamine-induced short-term potentiation, or co-release-induced depression under particular stimulus patterns. More importantly, a balanced ternary system that uses our ambipolar synaptic device backtrack input ‘true’, ‘false’ and ‘unknown’ logic signals; this process is more similar to the information processing in human brains than a traditional binary neural network. This work provides new insight for neuromorphic systems to establish new principles to reproduce the complexity of a mammalian central nervous system from simple basic units.

scholarly journals Differential modulation of short-term synaptic dynamics by long-term potentiation at mouse hippocampal mossy fibre synapses

2007 ◽  
Vol 585 (3) ◽  
pp. 853-865 ◽  
Author(s):  
Anja Gundlfinger ◽  
Christian Leibold ◽  
Katja Gebert ◽  
Marion Moisel ◽  
Dietmar Schmitz ◽  
...  
Keyword(s):  
Long Term Potentiation ◽  
Mossy Fibre ◽  
Differential Modulation ◽  
Short Term ◽  
Term Potentiation ◽  
Synaptic Dynamics

scholarly journals GPR68 deletion impairs hippocampal long-term potentiation and passive avoidance behavior

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Yuanyuan Xu ◽  
Mike T. Lin ◽  
Xiang-ming Zha
Keyword(s):  
Passive Avoidance ◽  
Pyramidal Neurons ◽  
Granule Cells ◽  
Hippocampal Slices ◽  
Synaptic Cleft ◽  
Long Term Potentiation ◽  
Synaptic Function ◽  
Metabotropic Receptor ◽  
Term Potentiation

Abstract Increased neural activities reduced pH at the synaptic cleft and interstitial spaces. Recent studies have shown that protons function as a neurotransmitter. However, it remains unclear whether protons signal through a metabotropic receptor to regulate synaptic function. Here, we showed that GPR68, a proton-sensitive GPCR, exhibited wide expression in the hippocampus, with higher expression observed in CA3 pyramidal neurons and dentate granule cells. In organotypic hippocampal slice neurons, ectopically expressed GPR68-GFP was present in dendrites, dendritic spines, and axons. Recordings in hippocampal slices isolated from GPR68−/− mice showed a reduced fiber volley at the Schaffer collateral-CA1 synapses, a reduced long-term potentiation (LTP), but unaltered paired-pulse ratio. In a step-through passive avoidance test, GPR68−/− mice exhibited reduced avoidance to the dark chamber. These findings showed that GPR68 contributes to hippocampal LTP and aversive fear memory.

Remodeling the Plasticity Debate: The Presynaptic Locus Revisited

Physiology ◽  
2006 ◽  
Vol 21 (5) ◽  
pp. 346-351 ◽  
Author(s):  
Stefan Krueger ◽  
Reiko Maki Fitzsimonds
Keyword(s):  
Long Term Potentiation ◽  
Glutamatergic Synapses ◽  
Cellular Mechanisms ◽  
Present Evidence ◽  
Term Potentiation

The cellular mechanisms contributing to long-term potentiation and activity-induced formation of glutamatergic synapses have been intensely debated. Recent studies have sparked renewed interest in the role of presynaptic components in these processes. Based on the present evidence, it appears likely that long-term plasticity utilizes both pre- and postsynaptic expression mechanisms.

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