scholarly journals The Antidepressant Sertraline Reduces Synaptic Transmission Efficacy and Synaptogenesis Between Identified Lymnaea Neurons

2020 ◽  
Vol 7 ◽  
Author(s):  
Jennifer Chow ◽  
Andrew J. Thompson ◽  
Fahad Iqbal ◽  
Wali Zaidi ◽  
Naweed I. Syed
Keyword(s):  
Synaptic Transmission ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Synapse Formation ◽  
Lymnaea Stagnalis ◽  
Identified Neurons ◽  
Mammalian Brain ◽  
Short Term ◽  
Brain Functions ◽  
Electrophysiological Recordings ◽  
Term Potentiation

The incidence of depression among humans is growing worldwide, and so is the use of selective serotonin reuptake inhibitors (SSRIs), such as sertraline hydrochloride. Our fundamental understanding regarding the mechanisms by which these antidepressants function and their off-target synaptic effects remain poorly defined, owing to the complexity of the mammalian brain. As all brain functions rely on proper synaptic connections between neurons, we examined the effect of sertraline on synaptic transmission, short-term potentiation underlying synaptic plasticity and synapse formation using identified neurons from the mollusk Lymnaea stagnalis. Through direct electrophysiological recordings, made from soma-soma paired neurons, we demonstrate that whereas sertraline does not affect short-term potentiation, it reduces the efficacy of synaptic transmission at both established and newly formed cholinergic synapses between identified neurons. Furthermore, Lymnaea neurons cultured in the presence of sertraline exhibited a decreased incidence of synaptogenesis. Our study provides the first direct functional evidence that sertraline exerts non-specific effects—outside of its SSRI role—when examined at the resolution of single pre- and post-synaptic neurons.

Sevoflurane Blocks Cholinergic Synaptic Transmission Postsynaptically but Does Not Affect Short-term Potentiation

2005 ◽  
Vol 102 (5) ◽  
pp. 920-928 ◽  
Author(s):  
Hiroaki Naruo ◽  
Shin Onizuka ◽  
David Prince ◽  
Mayumi Takasaki ◽  
Naweed I. Syed
Keyword(s):  
Synaptic Plasticity ◽  
Synaptic Transmission ◽  
Fluorescent Imaging ◽  
Posttetanic Potentiation ◽  
Dependent Manner ◽  
General Anesthetics ◽  
Short Term ◽  
Concentration Dependent Manner ◽  
Cholinergic Synaptic Transmission ◽  
Term Potentiation

Background As compared with their effects on both inhibitory and excitatory synapses, little is known about the mechanisms by which general anesthetics affect synaptic plasticity that forms the basis for learning and memory at the cellular level. To test whether clinically relevant concentrations of sevoflurane affect short-term potentiation involving cholinergic synaptic transmission, the soma-soma synapses between identified, postsynaptic neurons were used. Methods Uniquely identifiable neurons visceral dorsal 4 (presynaptic) and left pedal dorsal 1 (postsynaptic) of the mollusk Lymnaea stagnalis were isolated from the intact ganglion and paired overnight in a soma-soma configuration. Simultaneous intracellular recordings coupled with fluorescent imaging of the FM1-43 dye were made in either the absence or the presence of sevoflurane. Results Cholinergic synapses, similar to those observed in vivo, developed between the neurons, and the synaptic transmission exhibited classic short-term, posttetanic potentiation. Action potential-induced (visceral dorsal 4), 1:1 excitatory postsynaptic potentials were reversibly and significantly suppressed by sevoflurane in a concentration-dependent manner. Fluorescent imaging with the dye FM1-43 revealed that sevoflurane did not affect presynaptic exocytosis or endocytosis; instead, postsynaptic nicotinic acetylcholine receptors were blocked in a concentration-dependent manner. To test the hypothesis that sevoflurane affects short-term potentiation, a posttetanic potentiation paradigm was used, and synaptic transmission was examined in either the presence or the absence of sevoflurane. Although 1.5% sevoflurane significantly reduced synaptic transmission between the paired cells, it did not affect the formation or retention of posttetanic potentiation at this synapse. Conclusions This study demonstrates that sevoflurane blocks cholinergic synaptic transmission postsynaptically but does not affect short-term synaptic plasticity at the visceral dorsal 4-left pedal dorsal 1 synapse.

Trophic and Contact Conditions Modulate Synapse Formation Between Identified Neurons

1998 ◽  
Vol 79 (6) ◽  
pp. 3279-3283 ◽  
Author(s):  
Neil S. Magoski ◽  
Andrew G. M. Bulloch
Keyword(s):  
Conditioned Medium ◽  
Synapse Formation ◽  
Lymnaea Stagnalis ◽  
Trophic Factors ◽  
Electrical Synapse ◽  
Identified Neurons ◽  
Chemical Synapse ◽  
Contact Conditions ◽  
Cell Pair

Magoski, Neil S. and Andrew G. M. Bulloch. Trophic and contact conditions modulate synapse formation between identified neurons. J. Neurophysiol. 79: 3279–3283, 1998. We tested the ability of an identified interneuron from the mollusk, Lymnaea stagnalis, to reestablish appropriate synapses in vitro. In the CNS, the giant dopaminergic neuron, designated as right pedal dorsal one (RPeD1), makes an excitatory, chemical synapse with a pair of essentially identical postsynaptic cells known as visceral dorsal two and three (VD2/3). When the somata of the pre- and postsynaptic neurons were juxtaposed and cultured in vitro in defined medium, i.e., a soma-soma synapse, only an inappropriate electrical synapse was observed. The postsynaptic cell still responded to applied dopamine, the presynaptic transmitter, indicating that the lack of chemical synapse formation was not due to lack of dopamine receptors. When the somata were cultured apart in conditioned medium (medium previously incubated with Lymnaea CNS, thereby deriving trophic factors), the cells exhibited overlapping neurite outgrowth that resulted in an appropriate excitatory, chemical synapse from RPeD1 to VD2/3. On the other hand, when the cell pair was cultured in a soma-soma configuration, but in conditioned medium, a mixed chemical-electrical synapse was observed. Because conditioned medium could partially overcome the limitations of the soma-soma configuration and initiate chemical synapse formation, this data suggests that conditioned medium contains a factor(s) that supports synaptogenesis.

scholarly journals Specific nanoscale synaptic reshuffling and control of short-term plasticity following NMDAR- and P2XR-dependent Long-Term Depression

2019 ◽  
Author(s):  
Benjamin Compans ◽  
Magalie Martineau ◽  
Remco V. Klaassen ◽  
Thomas M. Bartol ◽  
Corey Butler ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Molecular Mechanisms ◽  
Super Resolution ◽  
Long Term Potentiation ◽  
Global Changes ◽  
Short Term ◽  
Long Term Depression ◽  
Term Potentiation ◽  
And Control

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.

Rapid Development of Synaptic Connections and Plasticity Between Sensory Neurons and Motor Neurons of Aplysia in Cell Culture: Implications for Learning and Regulation of Synaptic Strength

1997 ◽  
Vol 77 (5) ◽  
pp. 2316-2327 ◽  
Author(s):  
Rosalind L. Coulson ◽  
Marc Klein
Keyword(s):  
Cell Culture ◽  
Protein Synthesis ◽  
Synaptic Plasticity ◽  
Synaptic Transmission ◽  
Sensory Neurons ◽  
Motor Neurons ◽  
Synapse Formation ◽  
Rapid Development ◽  
Synaptic Connections ◽  
Short Term

Coulson, Rosalind L. and Marc Klein. Rapid development of synaptic connections and plasticity between sensory neurons and motor neurons of Aplysia in cell culture: implications for learning and regulation of synaptic strength. J. Neurophysiol. 77: 2316–2327, 1997. We describe here the time course of functional synapse formation and of the development of short-term synaptic plasticity at Aplysia sensorimotor synapses in cell culture, as well as the effects of blocking protein synthesis or postsynaptic receptors on the development of synaptic transmission and plasticity. We find that synaptic responses can be elicited in 50% of sensory neuron–motor neuron pairs by 1 h after cell contact and that short-term homosynaptic depression and synaptic augmentation and restoration by the endogenous facilitatory transmitter serotonin are present at the earliest stages of synapse formation. Neither block of protein synthesis with anisomycin nor block of two types of postsynaptic glutamate receptor has any effect on the development of synaptic transmission or synaptic plasticity. The rapidity of synapse formation and maturation and their independence of protein synthesis suggest that changes in the number of functional synapses could contribute to short- and intermediate-term forms of synaptic plasticity and learning.

EFFECT OF TWO NEW TRIPEPTIDES ON THE HIPPOCAMPUS IN RATS

2021 ◽  
Vol 55 (4) ◽  
pp. 73-77
Author(s):  
Vik.V. Yasnetsov ◽  
◽  
Yu.V. Ivanov ◽  
S.K. Karsanova ◽  
V.V. Yasnetsov ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Nmda Receptors ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
The Other ◽  
Short Term ◽  
Population Responses ◽  
Schaffer Collaterals ◽  
Term Potentiation ◽  
Field Ca1

Experiments on hippocampal slices in rats showed that, in contrast to piracetam (100 µM to 10 mM), two new tripeptides, i.e. H-asparagil-glutamyl-proline-OH and H-asparagil-glutamyl-arginin-OH (concentrations 500 µM, 1 and 2.5 mM respectively), strengthened the orthodrome population responses in field СА1. In all three concentrations the effect of H-asparagil-glutamyl-proline-OH was stronger than of the other tripeptide. That is both tripeptides facilitate synaptic transmission within the Schaffer collaterals-pyramidal neurons system in hippocumpal field CA1. Similarly to piracetam (100 µM, within 15 minutes) these tripeptides supported short-term potentiation of the hippocampal synaptic transfer by N-methyl-D-aspartate (NMDA). Specific NMDA-receptors antagonist D-AP5 cancelled the NMDA effect fully which infers that the observed effect is achieved through activation of NMDA-receptors. Effect from H-asparagil-glutamyl-proline-OH excelled equally piracetam and H-asparagil-glutamyl-arginin-OH; H-asparagil-glutamyl-arginin-OH excelled piracetam only.

Neuroligin-2 as a central organizer of inhibitory synapses in health and disease

2020 ◽  
Vol 13 (663) ◽  
pp. eabd8379
Author(s):  
Heba Ali ◽  
Lena Marth ◽  
Dilja Krueger-Burg
Keyword(s):  
Synaptic Transmission ◽  
Synapse Formation ◽  
Current Knowledge ◽  
Protein Complexes ◽  
Inhibitory Synapses ◽  
Molecular Architecture ◽  
Cellular Functions ◽  
Altered Expression ◽  
Health And Disease ◽  
Flow Of Information

Postsynaptic organizational protein complexes play central roles both in orchestrating synapse formation and in defining the functional properties of synaptic transmission that together shape the flow of information through neuronal networks. A key component of these organizational protein complexes is the family of synaptic adhesion proteins called neuroligins. Neuroligins form transsynaptic bridges with presynaptic neurexins to regulate various aspects of excitatory and inhibitory synaptic transmission. Neuroligin-2 (NLGN2) is the only member that acts exclusively at GABAergic inhibitory synapses. Altered expression and mutations in NLGN2 and several of its interacting partners are linked to cognitive and psychiatric disorders, including schizophrenia, autism, and anxiety. Research on NLGN2 has fundamentally shaped our understanding of the molecular architecture of inhibitory synapses. Here, we discuss the current knowledge on the molecular and cellular functions of mammalian NLGN2 and its role in the neuronal circuitry that regulates behavior in rodents and humans.

scholarly journals Long- and Short-Term Conductance Control of Artificial Polymer Wire Synapses

Polymers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 312
Author(s):  
Naruki Hagiwara ◽  
Shoma Sekizaki ◽  
Yuji Kuwahara ◽  
Tetsuya Asai ◽  
Megumi Akai-Kasaya
Keyword(s):  
Artificial Intelligence ◽  
Human Brain ◽  
High Speed ◽  
Conductive Polymer ◽  
Long Term Potentiation ◽  
Short Term ◽  
Synaptic Functions ◽  
Term Potentiation ◽  
Artificial Brain ◽  
External Stimuli

Networks in the human brain are extremely complex and sophisticated. The abstract model of the human brain has been used in software development, specifically in artificial intelligence. Despite the remarkable outcomes achieved using artificial intelligence, the approach consumes a huge amount of computational resources. A possible solution to this issue is the development of processing circuits that physically resemble an artificial brain, which can offer low-energy loss and high-speed processing. This study demonstrated the synaptic functions of conductive polymer wires linking arbitrary electrodes in solution. By controlling the conductance of the wires, synaptic functions such as long-term potentiation and short-term plasticity were achieved, which are similar to the manner in which a synapse changes the strength of its connections. This novel organic artificial synapse can be used to construct information-processing circuits by wiring from scratch and learning efficiently in response to external stimuli.

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.

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