Faculty Opinions recommendation of Glutamatergic synapses are structurally and biochemically complex because of multiple plasticity processes: long-term potentiation, long-term depression, short-term potentiation and scaling.

Long-Term Potentiation (LTP) and Long-Term Depression (LTD) of excitatory synaptic transmission are considered as cellular basis of learning and memory. These two forms of synaptic plasticity have been mainly attributed to global changes in the number of synaptic AMPA-type glutamate receptor (AMPAR) through a regulation of the diffusion/trapping balance at the PSD, exocytosis and endocytosis. While the precise molecular mechanisms at the base of LTP have been intensively investigated, the ones involved in LTD remains elusive. Here we combined super-resolution imaging technique, electrophysiology and modeling to describe the various modifications of AMPAR nanoscale organization and their effect on synaptic transmission in response to two different LTD protocols, based on the activation of either NMDA receptors or P2X receptors. While both type of LTD are associated with a decrease in synaptic AMPAR clustering, only NMDAR-dependent LTD is associated with a reorganization of PSD-95 at the nanoscale. This change increases the pool of diffusive AMPAR improving synaptic short-term facilitation through a post-synaptic mechanism. These results demonstrate that specific dynamic reorganization of synapses at the nanoscale during specific LTD paradigm allows to improve the responsiveness of depressed synapses.

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

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2016.0260 ◽

2017 ◽

Vol 372 (1715) ◽

pp. 20160260 ◽

Cited By ~ 63

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.’

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Faculty Opinions recommendation of Differential roles of NR2A and NR2B-containing NMDA receptors in cortical long-term potentiation and long-term depression.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1010816.250676 ◽

2004 ◽

Author(s):

Paolo Calabresi

Keyword(s):

Nmda Receptors ◽

Long Term Potentiation ◽

Long Term Depression ◽

Term Potentiation

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Faculty Opinions recommendation of Differential roles of NR2A and NR2B-containing NMDA receptors in cortical long-term potentiation and long-term depression.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1010816.240644 ◽

2004 ◽

Author(s):

Marina Picciotto

Keyword(s):

Nmda Receptors ◽

Long Term Potentiation ◽

Long Term Depression ◽

Term Potentiation

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Faculty Opinions recommendation of Distinct roles for Ras-guanine nucleotide-releasing factor 1 (Ras-GRF1) and Ras-GRF2 in the induction of long-term potentiation and long-term depression.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1030887.365605 ◽

2006 ◽

Author(s):

Leonard Maler

Keyword(s):

Long Term Potentiation ◽

Guanine Nucleotide ◽

Long Term Depression ◽

Term Potentiation

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Multiplexed neurochemical transmission emulated using a dual-excitatory synaptic transistor

npj 2D Materials and Applications ◽

10.1038/s41699-021-00205-4 ◽

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.

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