scholarly journals A serotonergic axon-cilium synapse drives nuclear signaling to maintain chromatin accessibility

2021 ◽  
Author(s):  
Shu-Hsien Sheu ◽  
Srigokul Upadhyayula ◽  
Vincent Dupuy ◽  
Song Pang ◽  
Andrew L. Lemire ◽  
...  

Chemical synapses between axons and dendrites mediate much of the brain's intercellular communication. Here we describe a new kind of synapse - the axo-ciliary synapse - between axons and primary cilia. By employing enhanced focused ion beam - scanning electron microscopy on samples with optimally preserved ultrastructure, we discovered synapses between the serotonergic axons arising from the brainstem, and the primary cilia of hippocampal CA1 pyramidal neurons. Functionally, these cilia are enriched in a ciliary-restricted serotonin receptor, 5-hydroxytryptamine receptor 6 (HTR6), whose mutation is associated with learning and memory defects. Using a newly developed cilia-targeted serotonin sensor, we show that optogenetic stimulation of serotonergic axons results in serotonin release onto cilia. Ciliary HTR6 stimulation activates a non-canonical GNAQ/11-RhoA pathway. Ablation of this pathway results in nuclear actin and chromatin accessibility changes in CA1 pyramidal neurons. Axo-ciliary synapses serve as a distinct mechanism for neuromodulators to program neuron transcription through privileged access to the nuclear compartment.

2018 ◽  
Vol 29 (7) ◽  
pp. 2771-2781 ◽  
Author(s):  
Taekyung Kwon ◽  
Angel Merchán-Pérez ◽  
Emiliano M Rial Verde ◽  
José-Rodrigo Rodríguez ◽  
Javier DeFelipe ◽  
...  

Abstract The location of GABAergic synapses on dendrites is likely key for neuronal integration. In particular, inhibitory inputs on dendritic spines could serve to selectively veto or modulate individual excitatory inputs, greatly expanding the computational power of individual neurons. To investigate this, we have undertaken a combined functional, molecular, and ultrastructural mapping of the location of GABAergic inputs onto dendrites of pyramidal neurons from upper layers of juvenile mouse somatosensory cortex. Using two-photon uncaging of GABA, intracellular labeling with gerphyrin intrabodies, and focused ion beam milling with scanning electron microscopy, we find that most (96–98%) spines lack GABAergic synapses, although they still display GABAergic responses, potentially due to extrasynaptic GABA receptors. We conclude that GABAergic inputs, in practice, contact dendritic shafts and likely control clusters of excitatory inputs, defining functional zones on dendrites.


2002 ◽  
Vol 733 ◽  
Author(s):  
Brock McCabe ◽  
Steven Nutt ◽  
Brent Viers ◽  
Tim Haddad

AbstractPolyhedral Oligomeric Silsequioxane molecules have been incorporated into a commercial polyurethane formulation to produce nanocomposite polyurethane foam. This tiny POSS silica molecule has been used successfully to enhance the performance of polymer systems using co-polymerization and blend strategies. In our investigation, we chose a high-temperature MDI Polyurethane resin foam currently used in military development projects. For the nanofiller, or “blend”, Cp7T7(OH)3 POSS was chosen. Structural characterization was accomplished by TEM and SEM to determine POSS dispersion and cell morphology, respectively. Thermal behavior was investigated by TGA. Two methods of TEM sample preparation were employed, Focused Ion Beam and Ultramicrotomy (room temperature).


2002 ◽  
Vol 719 ◽  
Author(s):  
Myoung-Woon Moon ◽  
Kyang-Ryel Lee ◽  
Jin-Won Chung ◽  
Kyu Hwan Oh

AbstractThe role of imperfections on the initiation and propagation of interface delaminations in compressed thin films has been analyzed using experiments with diamond-like carbon (DLC) films deposited onto glass substrates. The surface topologies and interface separations have been characterized by using the Atomic Force Microscope (AFM) and the Focused Ion Beam (FIB) imaging system. The lengths and amplitudes of numerous imperfections have been measured by AFM and the interface separations characterized on cross sections made with the FIB. Chemical analysis of several sites, performed using Auger Electron Spectroscopy (AES), has revealed the origin of the imperfections. The incidence of buckles has been correlated with the imperfection length.


2018 ◽  
Author(s):  
C.S. Bonifacio ◽  
P. Nowakowski ◽  
M.J. Campin ◽  
M.L. Ray ◽  
P.E. Fischione

Abstract Transmission electron microscopy (TEM) specimens are typically prepared using the focused ion beam (FIB) due to its site specificity, and fast and accurate thinning capabilities. However, TEM and high-resolution TEM (HRTEM) analysis may be limited due to the resulting FIB-induced artifacts. This work identifies FIB artifacts and presents the use of argon ion milling for the removal of FIB-induced damage for reproducible TEM specimen preparation of current and future fin field effect transistor (FinFET) technologies. Subsequently, high-quality and electron-transparent TEM specimens of less than 20 nm are obtained.


2018 ◽  
Author(s):  
Sang Hoon Lee ◽  
Jeff Blackwood ◽  
Stacey Stone ◽  
Michael Schmidt ◽  
Mark Williamson ◽  
...  

Abstract The cross-sectional and planar analysis of current generation 3D device structures can be analyzed using a single Focused Ion Beam (FIB) mill. This is achieved using a diagonal milling technique that exposes a multilayer planar surface as well as the cross-section. this provides image data allowing for an efficient method to monitor the fabrication process and find device design errors. This process saves tremendous sample-to-data time, decreasing it from days to hours while still providing precise defect and structure data.


2018 ◽  
Author(s):  
Steve Wang ◽  
Jim McGinn ◽  
Peter Tvarozek ◽  
Amir Weiss

Abstract Secondary electron detector (SED) plays a vital role in a focused ion beam (FIB) system. A successful circuit edit requires a good effective detector. Novel approach is presented in this paper to improve the performance of such a detector, making circuit altering for the most advanced integrated circuit (IC) possible.


Author(s):  
E. Hendarto ◽  
S.L. Toh ◽  
J. Sudijono ◽  
P.K. Tan ◽  
H. Tan ◽  
...  

Abstract The scanning electron microscope (SEM) based nanoprobing technique has established itself as an indispensable failure analysis (FA) technique as technology nodes continue to shrink according to Moore's Law. Although it has its share of disadvantages, SEM-based nanoprobing is often preferred because of its advantages over other FA techniques such as focused ion beam in fault isolation. This paper presents the effectiveness of the nanoprobing technique in isolating nanoscale defects in three different cases in sub-100 nm devices: soft-fail defect caused by asymmetrical nickel silicide (NiSi) formation, hard-fail defect caused by abnormal NiSi formation leading to contact-poly short, and isolation of resistive contact in a large electrical test structure. Results suggest that the SEM based nanoprobing technique is particularly useful in identifying causes of soft-fails and plays a very important role in investigating the cause of hard-fails and improving device yield.


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