scholarly journals Neurexin1α differentially regulates synaptic efficacy within striatal circuits

2020 ◽  
Author(s):  
M. Felicia Davatolhagh ◽  
Marc V. Fuccillo
Keyword(s):  
Motor Control ◽  
Transmitter Release ◽  
Synaptic Strength ◽  
Synaptic Function ◽  
Synaptic Efficacy ◽  
Prior Work ◽  
Indirect Pathway ◽  
Spiny Neurons ◽  
Specific Manner ◽  
Striatal Function

SummaryMutations in genes essential for shared aspects of synaptic function throughout the CNS, such as the presynaptic adhesion molecule Neurexin1α (Nrxn1α), are strongly implicated in neuropsychiatric pathophysiology. As the input nucleus of the basal ganglia, the striatum integrates diverse excitatory projections governing cognitive and motor control, and its functional impairment underlies neuropsychiatric disorders. While prior work has emphasized Neurexins’ contributions to synaptic transmission in hippocampus and brainstem, their function in striatal circuits remains unstudied. As Nrxn1α is highly expressed at striatal inputs, we employed optogenetic-mediated afferent recruitment of dorsal prefrontal cortex-dorsomedial striatal (DMS) connections, uncovering a decrease in net synaptic strength specifically onto indirect pathway spiny neurons in both Nrxn1α+/- and Nrxn1α-/- mice, driven by reductions in transmitter release probability. In contrast, thalamic excitatory inputs to DMS demonstrated relatively normal excitatory synaptic strength. These findings suggest that dysregulation of Nrxn1α modulates striatal function in an input and target-specific manner.

Synapsin Regulates Basal Synaptic Strength, Synaptic Depression, and Serotonin-Induced Facilitation of Sensorimotor Synapses in Aplysia

2007 ◽  
Vol 98 (6) ◽  
pp. 3568-3580 ◽  
Author(s):  
Diasinou Fioravante ◽  
Rong-Yu Liu ◽  
Anne K. Netek ◽  
Leonard J. Cleary ◽  
John H. Byrne
Keyword(s):  
Synaptic Plasticity ◽  
Synaptic Vesicle ◽  
Transmitter Release ◽  
Computational Analysis ◽  
Spontaneous Recovery ◽  
Synaptic Strength ◽  
Short Term ◽  
Homosynaptic Depression ◽  
Heterosynaptic Plasticity

Synapsin is a synaptic vesicle-associated protein implicated in the regulation of vesicle trafficking and transmitter release, but its role in heterosynaptic plasticity remains elusive. Moreover, contradictory results have obscured the contribution of synapsin to homosynaptic plasticity. We previously reported that the neuromodulator serotonin (5-HT) led to the phosphorylation and redistribution of Aplysia synapsin, suggesting that synapsin may be a good candidate for the regulation of vesicle mobilization underlying the short-term synaptic plasticity induced by 5-HT. This study examined the role of synapsin in homosynaptic and heterosynaptic plasticity. Overexpression of synapsin reduced basal transmission and enhanced homosynaptic depression. Although synapsin did not affect spontaneous recovery from depression, it potentiated 5-HT–induced dedepression. Computational analysis showed that the effects of synapsin on plasticity could be adequately simulated by altering the rate of Ca2+-dependent vesicle mobilization, supporting the involvement of synapsin not only in homosynaptic but also in heterosynaptic forms of plasticity by regulating vesicle mobilization.

Characterization of postsynaptic Ca2+ signals at the Drosophila larval NMJ

2011 ◽  
Vol 106 (2) ◽  
pp. 710-721 ◽  
Author(s):  
Sunil A. Desai ◽  
Gregory A. Lnenicka
Keyword(s):  
Transmitter Release ◽  
Postsynaptic Membrane ◽  
Synaptic Activity ◽  
Synaptic Efficacy ◽  
Single Action ◽  
Synaptic Homeostasis ◽  
Multiple Transcripts ◽  
Quantal Size ◽  
Intracellular Ca ◽  
Larval Neuromuscular Junction

Postsynaptic intracellular Ca2+ concentration ([Ca2+]i) has been proposed to play an important role in both synaptic plasticity and synaptic homeostasis. In particular, postsynaptic Ca2+ signals can alter synaptic efficacy by influencing transmitter release, receptor sensitivity, and protein synthesis. We examined the postsynaptic Ca2+ transients at the Drosophila larval neuromuscular junction (NMJ) by injecting the muscle fibers with Ca2+ indicators rhod-2 and Oregon Green BAPTA-1 (OGB-1) and then monitoring their increased fluorescence during synaptic activity. We observed discrete postsynaptic Ca2+ transients along the NMJ during single action potentials (APs) and quantal Ca2+ transients produced by spontaneous transmitter release. Most of the evoked Ca2+ transients resulted from the release of one or two quanta of transmitter and occurred largely at synaptic boutons. The magnitude of the Ca2+ signals was correlated with synaptic efficacy; the Is terminals, which produce larger excitatory postsynaptic potentials (EPSPs) and have a greater quantal size than Ib terminals, produced a larger Ca2+ signal per terminal length and larger quantal Ca2+ signals than the Ib terminals. During a train of APs, the postsynaptic Ca2+ signal increased but remained localized to the postsynaptic membrane. In addition, we showed that the plasma membrane Ca2+-ATPase (PMCA) played a role in extruding Ca2+ from the postsynaptic region of the muscle. Drosophila melanogaster has a single PMCA gene, predicted to give rise to various isoforms by alternative splicing. Using RT-PCR, we detected the expression of multiple transcripts in muscle and nervous tissues; the physiological significance of the same is yet to be determined.

scholarly journals Sex-specific involvement of indirect-pathway medium spiny neurons in behavioral alteration of 16p11.2 hemi-deletion mouse model

IBRO Reports ◽  
2019 ◽  
Vol 6 ◽  
pp. S494
Author(s):  
Jaekyoon Kim ◽  
Christopher Angelakos ◽  
Joseph Linch ◽  
Sarah Ferri ◽  
Ted Abel
Keyword(s):  
Mouse Model ◽  
Medium Spiny Neurons ◽  
Indirect Pathway ◽  
Behavioral Alteration ◽  
Spiny Neurons

scholarly journals Levodopa-Induced Dyskinesia Is Related to Indirect Pathway Medium Spiny Neuron Excitotoxicity: A Hypothesis Based on an Unexpected Finding

2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Svetlana A. Ivanova ◽  
Anton J. M. Loonen
Keyword(s):  
Oxidative Stress ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Age Of Onset ◽  
Medium Spiny Neuron ◽  
Synaptic Membrane ◽  
Medium Spiny Neurons ◽  
Unexpected Finding ◽  
Indirect Pathway ◽  
Spiny Neurons

A serendipitous pharmacogenetic finding links the vulnerability to developing levodopa-induced dyskinesia to the age of onset of Huntington’s disease. Huntington’s disease is caused by a polyglutamate expansion of the protein huntingtin. Aberrant huntingtin is less capable of binding to a member of membrane-associated guanylate kinase family (MAGUKs): postsynaptic density- (PSD-) 95. This leaves more PSD-95 available to stabilize NR2B subunit carrying NMDA receptors in the synaptic membrane. This results in increased excitotoxicity for which particularly striatal medium spiny neurons from the indirect extrapyramidal pathway are sensitive. In Parkinson’s disease the sensitivity for excitotoxicity is related to increased oxidative stress due to genetically determined abnormal metabolism of dopamine or related products. This probably also increases the sensitivity of medium spiny neurons for exogenous levodopa. Particularly the combination of increased oxidative stress due to aberrant dopamine metabolism, increased vulnerability to NMDA induced excitotoxicity, and the particular sensitivity of indirect pathway medium spiny neurons for this excitotoxicity may explain the observed increased prevalence of levodopa-induced dyskinesia.

scholarly journals Astrocytes in endocannabinoid signalling

2014 ◽  
Vol 369 (1654) ◽  
pp. 20130599 ◽  
Author(s):  
Marta Navarrete ◽  
Adolfo Díez ◽  
Alfonso Araque
Keyword(s):  
Synaptic Transmission ◽  
Cannabinoid Receptors ◽  
Integral Functional ◽  
Synaptic Function ◽  
Synaptic Efficacy ◽  
Brain Pathology ◽  
Dual Effect ◽  
Synaptic Regulation ◽  
Functional Components

Astrocytes are emerging as integral functional components of synapses, responding to synaptically released neurotransmitters and regulating synaptic transmission and plasticity. Thus, they functionally interact with neurons establishing tripartite synapses: a functional concept that refers to the existence of communication between astrocytes and neurons and its crucial role in synaptic function. Here, we discuss recent evidence showing that astrocytes are involved in the endocannabinoid (ECB) system, responding to exogenous cannabinoids as well as ECBs through activation of type 1 cannabinoid receptors, which increase intracellular calcium and stimulate the release of glutamate that modulates synaptic transmission and plasticity. We also discuss the consequences of ECB signalling in tripartite synapses on the astrocyte-mediated regulation of synaptic function, which reveal novel properties of synaptic regulation by ECBs, such as the spatially controlled dual effect on synaptic strength and the lateral potentiation of synaptic efficacy. Finally, we discuss the potential implications of ECB signalling for astrocytes in brain pathology and animal behaviour.

scholarly journals Equalization of Synaptic Efficacy by Activity- and Timing-Dependent Synaptic Plasticity

2004 ◽  
Vol 91 (5) ◽  
pp. 2273-2280 ◽  
Author(s):  
Clifton C. Rumsey ◽  
L. F. Abbott
Keyword(s):  
Synaptic Plasticity ◽  
Computer Simulations ◽  
Synaptic Strength ◽  
Cooperative Interaction ◽  
Synaptic Potentiation ◽  
Synaptic Efficacy ◽  
Receptor Density ◽  
Vesicle Release ◽  
Local Factors ◽  
Membrane Conductances

In many neurons, synapses increase in strength as a function of distance from the soma in a manner that appears to compensate for dendritic attenuation. This phenomenon requires a cooperative interaction between local factors that control synaptic strength, such as receptor density and vesicle release probability, and global factors that affect synaptic efficacy, such as attenuation and boosting by active membrane conductances. Anti-spiketiming-dependent plasticity, in combination with nonassociative synaptic potentiation, can accomplish this feat even though it acts locally and independently at individual synapses. Analytic computations and computer simulations show that this combination of synaptic plasticity mechanisms equalizes the efficacy of synapses over an extended dendritic cable by adjusting local synaptic strengths to compensate for global attenuation.

scholarly journals Facilitation versus depression in cultured hippocampal neurons determined by targeting of Ca2+ channel Cavβ4 versus Cavβ2 subunits to synaptic terminals

2007 ◽  
Vol 178 (3) ◽  
pp. 489-502 ◽  
Author(s):  
Mian Xie ◽  
Xiang Li ◽  
Jing Han ◽  
Daniel L. Vogt ◽  
Silke Wittemann ◽  
...  
Keyword(s):  
Transmitter Release ◽  
Hippocampal Neurons ◽  
Presynaptic Terminal ◽  
Paired Pulse ◽  
Physiological Properties ◽  
Specific Manner ◽  
A Subunit ◽  
Synaptic Distribution ◽  
Ca2 Channels ◽  
Cultured Hippocampal Neurons

Ca2+ channel β subunits determine the transport and physiological properties of high voltage–activated Ca2+ channel complexes. Our analysis of the distribution of the Cavβ subunit family members in hippocampal neurons correlates their synaptic distribution with their involvement in transmitter release. We find that exogenously expressed Cavβ4b and Cavβ2a subunits distribute in clusters and localize to synapses, whereas Cavβ1b and Cavβ3 are homogenously distributed. According to their localization, Cavβ2a and Cavβ4b subunits modulate the synaptic plasticity of autaptic hippocampal neurons (i.e., Cavβ2a induces depression, whereas Cavβ4b induces paired-pulse facilitation [PPF] followed by synaptic depression during longer stimuli trains). The induction of PPF by Cavβ4b correlates with a reduction in the release probability and cooperativity of the transmitter release. These results suggest that Cavβ subunits determine the gating properties of the presynaptic Ca2+ channels within the presynaptic terminal in a subunit-specific manner and may be involved in organization of the Ca2+ channel relative to the release machinery.

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