scholarly journals Autism-associated neuroligin-4 mutation selectively impairs glycinergic synaptic transmission in mouse brainstem synapses

2018 ◽  
Vol 215 (6) ◽  
pp. 1543-1553 ◽  
Author(s):  
Bo Zhang ◽  
Ozgun Gokce ◽  
W. Dylan Hale ◽  
Nils Brose ◽  
Thomas C. Südhof
Keyword(s):  
Synaptic Transmission ◽  
Cell Adhesion Molecule ◽  
Comprehensive Analysis ◽  
Synaptic Function ◽  
Projection Neurons ◽  
Loss Of Function ◽  
Glutamatergic Synaptic Transmission ◽  
Postsynaptic Cell ◽  
Behavioral Impairments ◽  
Low Expression

In human patients, loss-of-function mutations of the postsynaptic cell-adhesion molecule neuroligin-4 were repeatedly identified as monogenetic causes of autism. In mice, neuroligin-4 deletions caused autism-related behavioral impairments and subtle changes in synaptic transmission, and neuroligin-4 was found, at least in part, at glycinergic synapses. However, low expression levels precluded a comprehensive analysis of neuroligin-4 localization, and overexpression of neuroligin-4 puzzlingly impaired excitatory but not inhibitory synaptic function. As a result, the function of neuroligin-4 remains unclear, as does its relation to other neuroligins. To clarify these issues, we systematically examined the function of neuroligin-4, focusing on excitatory and inhibitory inputs to defined projection neurons of the mouse brainstem as central model synapses. We show that loss of neuroligin-4 causes a profound impairment of glycinergic but not glutamatergic synaptic transmission and a decrease in glycinergic synapse numbers. Thus, neuroligin-4 is essential for the organization and/or maintenance of glycinergic synapses.

scholarly journals Parkinson’s disease-linked Parkin mutations impair glutamatergic synaptic transmission and plasticity

2018 ◽  
Author(s):  
Mei Zhu ◽  
Giuseppe P. Cortese ◽  
Clarissa L. Waites
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Synaptic Transmission ◽  
Ampa Receptor ◽  
Hippocampal Neurons ◽  
Receptor Trafficking ◽  
Synaptic Function ◽  
Glutamatergic Synaptic Transmission ◽  
The Impact ◽  
Ampa Receptor Trafficking

AbstractParkinson’s disease (PD)-associated E3 ubiquitin ligase Parkin is enriched at glutamatergic synapses, where it ubiquitinates multiple substrates, suggesting that its mutation/loss-of-function could contribute to the etiology of PD by disrupting excitatory neurotransmission. Here, we evaluate the impact of four common PD-associated Parkin point mutations (T240M, R275W, R334C, G430D) on glutamatergic synaptic function in hippocampal neurons. We find that expression of these point mutants in Parkin-deficient and -null backgrounds alters NMDA and AMPA receptor-mediated currents and cell-surface levels, and prevents the induction of long-term depression. Mechanistically, we demonstrate that Parkin regulates NMDA receptor trafficking through its ubiquitination of GluN1, and that all four mutants are impaired in this ubiquitinating activity. Furthermore, Parkin regulates synaptic AMPA receptor trafficking via its binding and retention of the postsynaptic scaffold Homer1, and all mutants are similarly impaired in this capacity. Our findings demonstrate that pathogenic Parkin mutations disrupt glutamatergic synaptic transmission and plasticity by impeding NMDA and AMPA receptor trafficking, and through these effects likely contribute to the pathophysiology of PD inPARK2patients.

Modulation of synaptic transmission and plasticity by cell adhesion and repulsion molecules

2008 ◽  
Vol 4 (3) ◽  
pp. 197-209 ◽  
Author(s):  
Alexander Dityatev ◽  
Olena Bukalo ◽  
Melitta Schachner
Keyword(s):  
Cell Adhesion ◽  
Synaptic Plasticity ◽  
Synaptic Transmission ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Neuronal Cell ◽  
Long Term Potentiation ◽  
Synaptic Function ◽  
Immunoglobulin Superfamily

Adhesive and repellent molecular cues guide migrating cells and growing neurites during development. They also contribute to synaptic function, learning and memory in adulthood. Here, we review the roles of cell adhesion molecules of the immunoglobulin superfamily (Ig-CAMs) and semaphorins (some of which also contain Ig-like domains) in regulation of synaptic transmission and plasticity. Interestingly, among the seven studied Ig-CAMs, the neuronal cell adhesion molecule proved to be important for all tested forms of hippocampal plasticity, while its associated unusual glycan polysialic acid is necessary and sufficient part for synaptic plasticity only at CA3-CA1 synapses. In contrast, Thy-1 and L1 specifically regulate long-term potentiation (LTP) at synapses formed by entorhinal axons in the dentate gyrus and cornu ammonis, respectively. Contactin-1 is important for long-term depression but not for LTP at CA3-CA1 synapses. Analysis of CHL1-deficient mice illustrates that at intermediate stages of development a deficit in a cell adhesion molecule is compensated but appears as impaired LTP during early and late postnatal development. The emerging mechanisms by which adhesive Ig-CAMs contribute to synaptic plasticity involve regulation of activities of NMDA receptors and L-type Ca2+ channels, signaling via mitogen-activated protein kinase p38, changes in GABAergic inhibition and motility of synaptic elements. Regarding repellent molecules, available data for semaphorins demonstrate their activity-dependent regulation in normal and pathological conditions, synaptic localization of their receptors and their potential to elevate or inhibit synaptic transmission either directly or indirectly.

Postsynaptic neuronal geometry and synaptic effectiveness

1987 ◽  
Vol 45 ◽  
pp. 690-697
Author(s):  
C.J. Wilson
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Synaptic Function ◽  
Postsynaptic Neuron ◽  
Synaptic Inputs ◽  
Partial Analysis ◽  
Postsynaptic Cell ◽  
Neuronal Geometry ◽  
The Relationship ◽  
Complex Scale

Most central nervous system neurons receive synaptic input from hundreds or thousands of other neurons, and the computational function of such neurons results from the interactions of inputs on a large and complex scale. In most situations that have yielded to a partial analysis, the synaptic inputs to a neuron are not alike in function, but rather belong to distinct categories that differ qualitatively in the nature of their effect on the postsynaptic cell, and quantitatively in the strength of their influence. Many factors have been demonstrated to contribute to synaptic function, but one of the simplest and best known of these is the geometry of the postsynaptic neuron. The fundamental nature of the relationship between neuronal shape and synaptic effectiveness was established on theoretical grounds prior to its experimental verification.

Citalopram reduces glutamatergic synaptic transmission in the auditory cortex via activation of 5-HT1A receptors

Neuroreport ◽  
2019 ◽  
Vol 30 (18) ◽  
pp. 1316-1322 ◽  
Author(s):  
Víctor Cervantes-Ramírez ◽  
Martha Canto-Bustos ◽  
Diana Aguilar-Magaña ◽  
Elsy Arlene Pérez-Padilla ◽  
José Luis Góngora-Alfaro ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Auditory Cortex ◽  
Glutamatergic Synaptic Transmission

MODULATION BY P2X RECEPTORS OF THE GLUTAMATERGIC SYNAPTIC TRANSMISSION IN RVLM‐PROJECTING NTS NEURONS OF RATS

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Daniela Accorsi‐Mendonca ◽  
Leni GH Bonagamba ◽  
Ricardo Mauricio Leao ◽  
Benedito H Machado
Keyword(s):  
Synaptic Transmission ◽  
P2x Receptors ◽  
Glutamatergic Synaptic Transmission
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