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https://www.readbyqxmd.com/read/28647593/features-of-emotional-and-social-behavioral-phenotypes-of-calsyntenin2-knockout-mice
#1
S V Ranneva, K S Pavlov, A V Gromova, T G Amstislavskaya, T V Lipina
Calsyntenin-2 (Clstn2) is the synaptic protein that belongs to the super family of cadherins, playing an important role in learning and memory. We recently reported that Clstn2 knockout mice (Clstn2-KO) have a deficit of GABAergic interneurons coupled with hyperactivity and deficient spatial memory. Given, that impaired functioning of GABA receptors is linked to several psychopathologies, including anxiety and autism, we sought to further characterize Clstn2-KO mice with respect to emotional and social behavior...
June 21, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28647082/targeting-neuronal-function-for-cns-drug-discovery
#2
REVIEW
Chris M Hempel, Christopher A Werley, Graham T Dempsey, David J Gerber
There is a pressing need for new and more effective treatments for central nervous system (CNS) disorders. A large body of evidence now suggests that alterations in synaptic transmission and neuronal excitability represent underlying factors for many neurological and psychiatric diseases. However, it has been challenging to target these complex functional domains for therapeutic discovery using traditional neuronal assay methods. Here we review advances in neuronal screening technologies and cellular model systems that enable phenotypic screening of neuronal function as a basis for novel CNS drug discovery approaches...
March 2017: Drug Discovery Today. Technologies
https://www.readbyqxmd.com/read/28642492/segregation-of-glutamatergic-and-cholinergic-transmission-at-the-mixed-motoneuron-renshaw-cell-synapse
#3
Boris Lamotte d'Incamps, Gardave S Bhumbra, Joshua D Foster, Marco Beato, Philippe Ascher
In neonatal mice motoneurons excite Renshaw cells by releasing both acetylcholine (ACh) and glutamate. These two neurotransmitters activate two types of nicotinic receptors (nAChRs) (the homomeric α7 receptors and the heteromeric α*ß* receptors) as well as the two types of glutamate receptors (GluRs) (AMPARs and NMDARs). Using paired recordings, we confirm that a single motoneuron can release both transmitters on a single post-synaptic Renshaw cell. We then show that co-transmission is preserved in adult animals...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28641933/the-role-of-sleep-in-regulating-structural-plasticity-and-synaptic-strength-implications-for-memory-and-cognitive-function
#4
REVIEW
Frank Raven, Eddy A Van der Zee, Peter Meerlo, Robbert Havekes
Dendritic spines are the major sites of synaptic transmission in the central nervous system. Alterations in the strength of synaptic connections directly affect the neuronal communication, which is crucial for brain function as well as the processing and storage of information. Sleep and sleep loss bidirectionally alter structural plasticity, by affecting spine numbers and morphology, which ultimately can affect the functional output of the brain in terms of alertness, cognition, and mood. Experimental data from studies in rodents suggest that sleep deprivation may impact structural plasticity in different ways...
May 18, 2017: Sleep Medicine Reviews
https://www.readbyqxmd.com/read/28641114/a-critical-role-of-presynaptic-cadherin-catenin-p140cap-complexes-in-stabilizing-spines-and-functional-synapses-in-the-neocortex
#5
Min-Yin Li, Wan-Ying Miao, Qiu-Zi Wu, Shun-Ji He, Guoquan Yan, Yanrui Yang, Jia-Jia Liu, M Mark Taketo, Xiang Yu
The formation of functional synapses requires coordinated assembly of presynaptic transmitter release machinery and postsynaptic trafficking of functional receptors and scaffolds. Here, we demonstrate a critical role of presynaptic cadherin/catenin cell adhesion complexes in stabilizing functional synapses and spines in the developing neocortex. Importantly, presynaptic expression of stabilized β-catenin in either layer (L) 4 excitatory neurons or L2/3 pyramidal neurons significantly upregulated excitatory synaptic transmission and dendritic spine density in L2/3 pyramidal neurons, while its sparse postsynaptic expression in L2/3 neurons had no such effects...
June 21, 2017: Neuron
https://www.readbyqxmd.com/read/28639593/synaptic-roles-of-cyclin-dependent-kinase-5-its-implications-in-epilepsy
#6
REVIEW
Aparna Banerjee Dixit, Jyotirmoy Banerjee, Manjari Tripathi, Chitra Sarkar, P Sarat Chandra
There is an urgent need to understand the molecular mechanisms underlying epilepsy to find novel prognostic/diagnostic biomarkers to prevent epilepsy patients at risk. Cyclin-dependent kinase 5 (CDK5) is involved in multiple neuronal functions and plays a crucial role in maintaining homeostatic synaptic plasticity by regulating intracellular signalling cascades at synapses. CDK5 deregulation is shown to be associated with various neurodegenerative diseases such as Alzheimer's disease. The association between chronic loss of CDK5 and seizures has been reported in animal models of epilepsy...
February 2017: Indian Journal of Medical Research
https://www.readbyqxmd.com/read/28638320/membrane-fusion-involved-in-neurotransmission-glimpse-from-electron-microscope-and-molecular-simulation
#7
REVIEW
Zhiwei Yang, Lu Gou, Shuyu Chen, Na Li, Shengli Zhang, Lei Zhang
Membrane fusion is one of the most fundamental physiological processes in eukaryotes for triggering the fusion of lipid and content, as well as the neurotransmission. However, the architecture features of neurotransmitter release machinery and interdependent mechanism of synaptic membrane fusion have not been extensively studied. This review article expounds the neuronal membrane fusion processes, discusses the fundamental steps in all fusion reactions (membrane aggregation, membrane association, lipid rearrangement and lipid and content mixing) and the probable mechanism coupling to the delivery of neurotransmitters...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28636947/assembly-secretory-pathway-trafficking-and-surface-delivery-of-kainate-receptors-is-regulated-by-neuronal-activity
#8
Ashley J Evans, Sonam Gurung, Kevin A Wilkinson, David J Stephens, Jeremy M Henley
Ionotropic glutamate receptor (iGluR) trafficking and function underpin excitatory synaptic transmission and plasticity and shape neuronal networks. It is well established that the transcription, translation, and endocytosis/recycling of iGluRs are all regulated by neuronal activity, but much less is known about the activity dependence of iGluR transport through the secretory pathway. Here, we use the kainate receptor subunit GluK2 as a model iGluR cargo to show that the assembly, early secretory pathway trafficking, and surface delivery of iGluRs are all controlled by neuronal activity...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28635948/munc13-1-and-munc18-1-together-prevent-nsf-dependent-de-priming-of-synaptic-vesicles
#9
Enqi He, Keimpe Wierda, Rhode van Westen, Jurjen H Broeke, Ruud F Toonen, L Niels Cornelisse, Matthijs Verhage
Synaptic transmission requires a stable pool of release-ready (primed) vesicles. Here we show that two molecules involved in SNARE-complex assembly, Munc13-1 and Munc18-1, together stabilize release-ready vesicles by preventing de-priming. Replacing neuronal Munc18-1 by a non-neuronal isoform Munc18-2 (Munc18-1/2SWAP) supports activity-dependent priming, but primed vesicles fall back into a non-releasable state (de-prime) within seconds. Munc13-1 deficiency produces a similar defect. Inhibitors of N-ethylmaleimide sensitive factor (NSF), N-ethylmaleimide (NEM) or interfering peptides, prevent de-priming in munc18-1/2SWAP or munc13-1 null synapses, but not in CAPS-1/2 null, another priming-deficient mutant...
June 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28635355/aberrant-wnt-signaling-a-special-focus-in-cns-diseases
#10
Mercedes Arnés, Sergio Casas Tintó
Wnt signals regulate cell proliferation, migration and differentiation during development, as well as synaptic transmission and plasticity in the adult brain. Abnormal Wnt signaling is central to a number of brain pathologies. We review here, the significance of this pathway focused in the contribution of the most frequent alterations in receptors, secretable modulators and downstream targets in Alzheimer's disease (AD) and Glioblastoma (GBM). β-catenin and GSK3 levels are pivotal in the neurodegeneration associated to AD contributing to memory deficits, tau phosphorylation, increased β-amyloid production and modulation of Apolipoprotein E in the brain...
June 21, 2017: Journal of Neurogenetics
https://www.readbyqxmd.com/read/28634303/structural-characterization-of-the-rabphilin-3a-snap25-interaction
#11
Cristina Ferrer-Orta, María Dolores Pérez-Sánchez, Teresa Coronado-Parra, Cristina Silva, David López-Martínez, Jesús Baltanás-Copado, Juan Carmelo Gómez-Fernández, Senena Corbalán-García, Núria Verdaguer
Membrane fusion is essential in a myriad of eukaryotic cell biological processes, including the synaptic transmission. Rabphilin-3A is a membrane trafficking protein involved in the calcium-dependent regulation of secretory vesicle exocytosis in neurons and neuroendocrine cells, but the underlying mechanism remains poorly understood. Here, we report the crystal structures and biochemical analyses of Rabphilin-3A C2B-SNAP25 and C2B-phosphatidylinositol 4,5-bisphosphate (PIP2) complexes, revealing how Rabphilin-3A C2 domains operate in cooperation with PIP2/Ca(2+) and SNAP25 to bind the plasma membrane, adopting a conformation compatible to interact with the complete SNARE complex...
June 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28631873/roles-of-afadin-in-functional-differentiations-of-hippocampal-mossy-fiber-synapse
#12
Xiaoqi Geng, Tomohiko Maruo, Kenji Mandai, Irwan Supriyanto, Muneaki Miyata, Shotaro Sakakibara, Akira Mizoguchi, Yoshimi Takai, Masahiro Mori
A hippocampal mossy fiber synapse has a complex structure and is implicated in learning and memory. In this synapse, the mossy fiber boutons attach to the dendritic shaft by puncta adherentia junctions and wrap around a multiply-branched spine, forming synaptic junctions. We have recently shown using transmission electron microscopy, immunoelectron microscopy and serial block face-scanning electron microscopy that atypical puncta adherentia junctions are formed in the afadin-deficient mossy fiber synapse and that the complexity of postsynaptic spines and mossy fiber boutons, the number of spine heads, the area of postsynaptic densities and the density of synaptic vesicles docked to active zones are decreased in the afadin-deficient synapse...
June 20, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28628388/coordination-of-ampa-receptor-trafficking-by-rab-small-gtpases
#13
Angelika Hausser, Katalin Schlett
Synaptic connections in the brain are continuously weakened or strengthened in response to changes in neuronal activity. This process, known as synaptic plasticity, is the cellular basis for learning and memory, and is thought to be altered in several neuronal disorders. An important aspect of synaptic plasticity is the tightly controlled trafficking and synaptic targeting of the AMPA-type glutamate receptors, which are the major mediators of fast excitatory transmission in the brain. This review addresses the role of Rab GTPases in AMPA receptor trafficking in neurons under basal conditions and during activity-induced synaptic plasticity, especially during long-term potentiation (LTP) and long-term depression (LTD)...
June 19, 2017: Small GTPases
https://www.readbyqxmd.com/read/28627448/opiate-exposure-state-controls-dopamine-d3-receptor-and-cdk5-calcineurin-signaling-in-the-basolateral-amygdala-during-reward-and-withdrawal-aversion-memory-formation
#14
Laura G Rosen, Walter J Rushlow, Steven R Laviolette
The dopamine (DA) D3 receptor (D3R) is highly expressed in the basolateral nucleus of the amygdala (BLA), a neural region critical for processing opiate-related reward and withdrawal aversion-related memories. Functionally, D3R transmission is linked to downstream Cdk5 and calcineurin signaling, both of which regulate D3R activity states and play critical roles in memory-related synaptic plasticity. Previous evidence links D3R transmission to opiate-related memory processing, however little is known regarding how chronic opiate exposure may alter D3R-dependent memory mechanisms...
June 14, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28625718/synaptic-functions-of-endocannabinoid-signaling-in-health-and-disease
#15
REVIEW
Alfonso Araque, Pablo E Castillo, Olivier J Manzoni, Raffaella Tonini
Endocannabinoids (eCBs) are a family of lipid molecules that act as key regulators of synaptic transmission and plasticity. They are synthetized "on demand" following physiological and/or pathological stimuli. Once released from postsynaptic neurons, eCBs typically act as retrograde messengers to activate presynaptic type 1 cannabinoid receptors (CB1) and induce short- or long-term depression of neurotransmitter release. Besides this canonical mechanism of action, recent findings have revealed a number of less conventional mechanisms by which eCBs regulate neural activity and synaptic function, suggesting that eCB-mediated plasticity is mechanistically more diverse than anticipated...
June 15, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28625609/oxidative-stress-induced-by-cumene-hydroperoxide-produces-synaptic-depression-and-transient-hyperexcitability-in-rat-primary-motor-cortex-neurons
#16
R Pardillo-Diaz, L Carrascal, G Barrionuevo, P Nunez-Abades
Pyramidal neurons of the motor cortex are selectively degenerated in Amyotrophic Lateral Sclerosis (ALS). The mechanisms underlying neuronal death in ALS are not well established. In the absence of useful biomarkers, the early increased neuronal excitability seems to be the unique characteristic of ALS. Lipid peroxidation caused by oxidative stress has been postulated as one of the possible mechanisms involved in degeneration motor cortex pyramidal neurons. This paper examines the effect of lipid peroxidation on layer V pyramidal neurons induced by cumene hydroperoxide (CH) in brain slices from wild type rats...
June 15, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28624955/presynaptic-inhibition-of-nociceptive-neurotransmission-by-somatosensory-neuron-secreted-suppressors
#17
REVIEW
Kaicheng Li, Bing Cai, Changlin Li, Xu Zhang
Noxious stimuli cause pain by activating cutaneous nociceptors. The Aδ- and C-fibers of dorsal root ganglion (DRG) neurons convey the nociceptive signals to the laminae I-II of spinal cord. In the dorsal horn of spinal cord, the excitatory afferent synaptic transmission is regulated by the inhibitory neurotransmitter γ-aminobutyric acid and modulators such as opioid peptides released from the spinal interneurons, and by serotonin, norepinepherine and dopamine from the descending inhibitory system. In contrast to the accumulated evidence for these central inhibitors and their neural circuits in the dorsal spinal cord, the knowledge about the endogenous suppressive mechanisms in nociceptive DRG neurons remains very limited...
June 15, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28624587/the-lateral-habenula-and-alcohol-role-of-glutamate-and-m-type-potassium-channels
#18
REVIEW
Avi Shah, Wanhong Zuo, Seungwoo Kang, Jing Li, Rao Fu, Haifeng Zhang, Alex Bekker, Jiang-Hong Ye
Alcohol use disorder (AUD) or alcoholism is a chronic relapsing disorder. Our knowledge of alcoholism hinges on our understanding of its effects on the brain. This review will center on the effects of alcohol in the lateral habenula (LHb), an epithalamic structure that connects the forebrain with the midbrain and encodes aversive signaling. Like many addictive drugs, alcohol has both rewarding and aversive properties. While alcohol's euphoric property is believed to be important for the initiation of drinking, increasing evidence suggests that alcohol's negative affect plays a critical role in excessive drinking and alcohol dependence...
June 14, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28624414/corneal-kindled-c57bl-6-mice-exhibit-saturated-dentate-gyrus-long-term-potentiation-and-associated-memory-deficits-in-the-absence-of-overt-neuron-loss
#19
Gregory J Remigio, Jaycie L Loewen, Sage Heuston, Colin Helgeson, H Steve White, Karen S Wilcox, Peter J West
Memory deficits have a significant impact on the quality of life of patients with epilepsy and currently no effective treatments exist to mitigate this comorbidity. While these cognitive comorbidities can be associated with varying degrees of hippocampal cell death and hippocampal sclerosis, more subtle changes in hippocampal physiology independent of cell loss may underlie memory dysfunction in many epilepsy patients. Accordingly, animal models of epilepsy or epileptic processes exhibiting memory deficits in the absence of cell loss could facilitate novel therapy discovery...
June 15, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28621662/chronic-lithium-treatment-elicits-its-antimanic-effects-via-bdnf-trkb-dependent-synaptic-downscaling
#20
Erinn S Gideons, Pei-Yi Lin, Melissa Mahgoub, Ege T Kavalali, Lisa M Monteggia
Lithium is widely used as a treatment for Bipolar Disorder although the molecular mechanisms that underlie its therapeutic effects are under debate. In this study, we show brain-derived neurotrophic factor (BDNF) is required for the antimanic-like effects of lithium but not the antidepressant-like effects in mice. We performed whole cell patch clamp recordings of hippocampal neurons to determine the impact of lithium on synaptic transmission that may underlie the behavioral effects. Lithium produced a significant decrease in α-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-mediated miniature excitatory postsynaptic current (mEPSC) amplitudes due to postsynaptic homeostatic plasticity that was dependent on BDNF and its receptor tropomyosin receptor kinase B (TrkB)...
June 16, 2017: ELife
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