scholarly journals Nectin

2002 ◽  
Vol 156 (3) ◽  
pp. 555-565 ◽  
Author(s):  
Akira Mizoguchi ◽  
Hiroyuki Nakanishi ◽  
Kazushi Kimura ◽  
Kaho Matsubara ◽  
Kumi Ozaki-Kuroda ◽  
...  

The nectin–afadin system is a novel cell–cell adhesion system that organizes adherens junctions cooperatively with the cadherin–catenin system in epithelial cells. Nectin is an immunoglobulin-like adhesion molecule, and afadin is an actin filament–binding protein that connects nectin to the actin cytoskeleton. Nectin has four isoforms (-1, -2, -3, and -4). Each nectin forms a homo-cis-dimer followed by formation of a homo-trans-dimer, but nectin-3 furthermore forms a hetero-trans-dimer with nectin-1 or -2, and the formation of each hetero-trans-dimer is stronger than that of each homo-trans-dimer. We show here that at the synapses between the mossy fiber terminals and dendrites of pyramidal cells in the CA3 area of adult mouse hippocampus, the nectin–afadin system colocalizes with the cadherin–catenin system, and nectin-1 and -3 asymmetrically localize at the pre- and postsynaptic sides of puncta adherentia junctions, respectively. During development, nectin-1 and -3 asymmetrically localize not only at puncta adherentia junctions but also at synaptic junctions. Inhibition of the nectin-based adhesion by an inhibitor of nectin-1 in cultured rat hippocampal neurons results in a decrease in synapse size and a concomitant increase in synapse number. These results indicate an important role of the nectin–afadin system in the formation of synapses.

2003 ◽  
Vol 460 (4) ◽  
pp. 514-524 ◽  
Author(s):  
Maiko Inagaki ◽  
Kenji Irie ◽  
Maki Deguchi-Tawarada ◽  
Wataru Ikeda ◽  
Toshihisa Ohtsuka ◽  
...  

1990 ◽  
Vol 64 (3) ◽  
pp. 1000-1008 ◽  
Author(s):  
N. L. Chamberlin ◽  
R. D. Traub ◽  
R. Dingledine

1. Spontaneous discharges that resemble interictal spikes arise in area CA3 b/c of rat hippocampal slices bathed in 8.5 mM [K+]o. Excitatory postsynaptic potentials (EPSPs) also appear at irregular intervals in these cells. The role of local synaptic excitation in burst initiation was examined with intracellular and extracellular recordings from CA3 pyramidal neurons. 2. Most (70%) EPSPs were small (less than 2 mV in amplitude), suggesting that they were the product of quantal release or were evoked by a single presynaptic action potential in another cell. It is unlikely that most EPSPs were evoked by a presynaptic burst of action potentials. Indeed, intrinsic burst firing was not prominent in CA3 b/c pyramidal cells perfused in 8.5 mM [K+]o. 3. The likelihood of occurrence and the amplitude of EPSPs were higher in the 50-ms interval just before the onset of each burst than during a similar interval 250 ms before the burst. This likely reflects increased firing probability of CA3 neurons as they emerge from the afterhyperpolarization (AHP) and conductance shunt associated with the previous burst. 4. Perfusion with 2 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a potent quisqualate receptor antagonist, decreased the frequency of EPSPs in CA3 b/c neurons from 3.6 +/- 0.9 to 0.9 +/- 0.3 (SE) Hz. Likewise, CNQX reversibly reduced the amplitude of evoked EPSPs in CA3 b/c cells. 5. Spontaneous burst firing in 8.5 mM [K+]o was abolished in 11 of 31 slices perfused with 2 microM CNQX.(ABSTRACT TRUNCATED AT 250 WORDS)


2006 ◽  
Vol 96 (4) ◽  
pp. 1829-1837 ◽  
Author(s):  
José V. Negrete-Díaz ◽  
Talvinder S. Sihra ◽  
José M. Delgado-García ◽  
Antonio Rodríguez-Moreno

The mechanisms involved in the inhibition of glutamate release mediated by the activation of presynaptic kainate receptors (KARs) at the hippocampal mossy fiber–CA3 synapse are not well understood. We have observed a long-lasting inhibition of CA3 evoked excitatory postsynaptic currents (eEPSCs) after a brief application of kainate (KA) at concentrations ranging from 0.3 to 10 μM. The inhibition outlasted the change in holding current caused by the activation of ionotropic KARs in CA3 pyramidal cells, indicating that this action is not contingent on the opening of the receptor channels. The inhibition of the eEPSCs by KA was prevented by G protein and protein kinase A (PKA) inhibitors and was enhanced after stimulation of the adenylyl cyclase (AC) with forskolin. We conclude that KARs present at mossy fiber terminals mediate the inhibition of glutamate release through a metabotropic mechanism that involves the activation of an AC-second messenger cAMP-PKA signaling cascade.


1997 ◽  
Vol 78 (2) ◽  
pp. 703-720 ◽  
Author(s):  
Nicholas T. Carnevale ◽  
Kenneth Y. Tsai ◽  
Brenda J. Claiborne ◽  
Thomas H. Brown

Carnevale, Nicholas T., Kenneth Y. Tsai, Brenda J. Claiborne, and Thomas H. Brown. Comparative electrotonic analysis of three classes of rat hippocampal neurons. J. Neurophysiol. 78: 703–720, 1997. We present a comparative analysis of electrotonus in the three classes of principal neurons in rat hippocampus: pyramidal cells of the CA1 and CA3c fields of the hippocampus proper, and granule cells of the dentate gyrus. This analysis used the electrotonic transform, which combines anatomic and biophysical data to map neuronal anatomy into electrotonic space, where physical distance between points is replaced by the logarithm of voltage attenuation (log A). The transforms were rendered as “neuromorphic figures” by redrawing the cell with branch lengths proportional to log A along each branch. We also used plots of log A versus anatomic distance from the soma; these reveal features that are otherwise less apparent and facilitate comparisons between dendritic fields of different cells. Transforms were always larger for voltage spreading toward the soma ( V in) than away from it ( V out). Most of the electrotonic length in V out transforms was along proximal large diameter branches where signal loss for somatofugal voltage spread is greatest. In V in transforms, more of the length was in thin distal branches, indicating a steep voltage gradient for signals propagating toward the soma. All transforms lengthened substantially with increasing frequency. CA1 neurons were electrotonically significantly larger than CA3c neurons. Their V out transforms displayed one primary apical dendrite, which bifurcated in some cases, whereas CA3c cell transforms exhibited multiple apical branches. In both cell classes, basilar dendrite V out transforms were small, indicating that somatic potentials reached their distal ends with little attenuation. However, for somatopetal voltage spread, attenuation along the basilar and apical dendrites was comparable, so the V in transforms of these dendritic fields were nearly equal in extent. Granule cells were physically and electrotonically most compact. Their V out transforms at 0 Hz were very small, indicating near isopotentiality at DC and low frequencies. These transforms resembled those of the basilar dendrites of CA1 and CA3c pyramidal cells. This raises the possibility of similar functional or computational roles for these dendritic fields. Interpreting the anatomic distribution of thorny excrescences on CA3 pyramidal neurons with this approach indicates that synaptic currents generated by some mossy fiber inputs may be recorded accurately by a somatic patch clamp, providing that strict criteria on their time course are satisfied. Similar accuracy may not be achievable in somatic recordings of Schaffer collateral synapses onto CA1 pyramidal cells in light of the anatomic and biophysical properties of these neurons and the spatial distribution of synapses.


2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Shan Liu ◽  
Xing Wang ◽  
Yun Li ◽  
Lei Xu ◽  
Xiaoliang Yu ◽  
...  

Tumor necrosis factor-α(TNF-α) is a critical proinflammatory cytokine regulating neuroinflammation. Elevated levels of TNF-αhave been associated with various neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. However, the signaling events that lead to TNF-α-initiated neurotoxicity are still unclear. Here, we report that RIP3-mediated necroptosis, a form of regulated necrosis, is activated in the mouse hippocampus after intracerebroventricular injection of TNF-α. RIP3 deficiency attenuates TNF-α-initiated loss of hippocampal neurons. Furthermore, we characterized the molecular mechanism of TNF-α-induced neurotoxicity in HT-22 hippocampal neuronal cells. HT-22 cells are sensitive to TNF-αonly upon caspase blockage and subsequently undergo necrosis. The cell death is suppressed by knockdown of CYLD or RIP1 or RIP3 or MLKL, suggesting that this necrosis is necroptosis and mediated by CYLD-RIP1-RIP3-MLKL signaling pathway. TNF-α-induced necroptosis of HT-22 cells is largely independent of both ROS accumulation and calcium influx although these events have been shown to be critical for necroptosis in certain cell lines. Taken together, these data not only provide the firstin vivoevidence for a role of RIP3 in TNF-α-induced toxicity of hippocampal neurons, but also demonstrate that TNF-αpromotes CYLD-RIP1-RIP3-MLKL-mediated necroptosis of hippocampal neurons largely bypassing ROS accumulation and calcium influx.


2017 ◽  
Author(s):  
Daria Merkurjev ◽  
Wan-Ting Hong ◽  
Kei lida ◽  
Belinda J Goldie ◽  
Hitoshi Yamaguti ◽  
...  

AbstractA localized transcriptome at the synapse facilitates synapse-, stimulus-, and transcript-specific synthesis of the local proteome in response to neuronal activity. While enzyme-mediated mRNA modifications have been shown to regulate cellular mRNA turnover and translation, the role of these modifications in regulating synaptic RNA has not been studied. We established low-input m6A-seq of synaptosomal RNA to determine the chemically modified local transcriptome in healthy adult mouse forebrain and identified 4,329 selectively enriched m6A RNA peaks in 2,987 genes, which we refer to as the synaptic m6A epitranscriptome (SME). SME is functionally enriched in synthesis and modulation of tripartite synapses, and in pathways implicated in neurodevelopmental and neuropsychiatric diseases. Interrupting m6A-mediated regulation via knockdown of reader YTHDF1 in hippocampal neurons alters expression of SME member Apc, and causes synaptic malfunctions manifesting immature spine morphology and dampened excitatory synaptic transmission concomitant with decreased PSD-95 clustering and GluA1 surface expression. Our findings indicate that chemical modifications of synaptic mRNAs critically contribute to synaptic function.


Author(s):  
Wei-Wei Zhang ◽  
Rong-Rong Li ◽  
Jie Zhang ◽  
Jie Yan ◽  
Qian-Hui Zhang ◽  
...  

AbstractWhile the hippocampus has been implicated in supporting the association among time-separated events, the underlying cellular mechanisms have not been fully clarified. Here, we combined in vivo multi-channel recording and optogenetics to investigate the activity of hippocampal interneurons in freely-moving mice performing a trace eyeblink conditioning (tEBC) task. We found that the hippocampal interneurons exhibited conditioned stimulus (CS)-evoked sustained activity, which predicted the performance of conditioned eyeblink responses (CRs) in the early acquisition of the tEBC. Consistent with this, greater proportions of hippocampal pyramidal cells showed CS-evoked decreased activity in the early acquisition of the tEBC. Moreover, optogenetic suppression of the sustained activity in hippocampal interneurons severely impaired acquisition of the tEBC. In contrast, suppression of the sustained activity of hippocampal interneurons had no effect on the performance of well-learned CRs. Our findings highlight the role of hippocampal interneurons in the tEBC, and point to a potential cellular mechanism subserving associative learning.


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