Three-dimensional structure of dendritic spines, neuronal specializations that impart both stability and flexibility to synaptic function

1993 ◽  
Vol 51 ◽  
pp. 92-93
Author(s):  
Kristen M. Harris
Keyword(s):  
Dendritic Spines ◽  
Three Dimensional ◽  
Synaptic Function ◽  
Dimensional Structure ◽  
Excitatory Synapses ◽  
Concept Of Function ◽  
Section Electron ◽  
High Quality Information ◽  
The Central Nervous System ◽  
Mathematical Analyses

Dendritic spines are the tiny protrusions that stud the surface of many neurons and they are the location of over 90% of all excitatory synapses that occur in the central nervous system. Their small size and variable shapes has in large part made detailed study of their structure refractory to conventional light microscopy and single section electron microscopy (EM). Yet their widespread occurrence and likely involvement in learning and memory has motivated extensive efforts to obtain quantitative descriptions of spines in both steady state and dynamic conditions. Since the seminal mathematical analyses of D’Arcy Thompson, the power of establishing quantitatively key parameters of structure has become recognized as a foundation of successful biological inquiry. For dendritic spines highly precise determinations of structure and its variation are proving themselves as the kingpin for establishing a valid concept of function. The recent conjunction of high quality information about the structure, function, and theoretical implications of dendritic spines has produced a flurry of new considerations of their role in synaptic transmission.

scholarly journals O-GlcNAc transferase regulates excitatory synapse maturity

2017 ◽  
Vol 114 (7) ◽  
pp. 1684-1689 ◽  
Author(s):  
Olof Lagerlöf ◽  
Gerald W. Hart ◽  
Richard L. Huganir
Keyword(s):  
Food Intake ◽  
Dendritic Spines ◽  
Protein Function ◽  
Postsynaptic Density ◽  
Synaptic Function ◽  
Excitatory Synapse ◽  
Excitatory Synapses ◽  
Intracellular Proteins ◽  
Neuronal Stimulation ◽  
Glcnac Transferase

Experience-driven synaptic plasticity is believed to underlie adaptive behavior by rearranging the way neuronal circuits process information. We have previously discovered that O-GlcNAc transferase (OGT), an enzyme that modifies protein function by attaching β–N-acetylglucosamine (GlcNAc) to serine and threonine residues of intracellular proteins (O-GlcNAc), regulates food intake by modulating excitatory synaptic function in neurons in the hypothalamus. However, how OGT regulates excitatory synapse function is largely unknown. Here we demonstrate that OGT is enriched in the postsynaptic density of excitatory synapses. In the postsynaptic density, O-GlcNAcylation on multiple proteins increased upon neuronal stimulation. Knockout of the OGT gene decreased the synaptic expression of the AMPA receptor GluA2 and GluA3 subunits, but not the GluA1 subunit. The number of opposed excitatory presynaptic terminals was sharply reduced upon postsynaptic knockout of OGT. There were also fewer and less mature dendritic spines on OGT knockout neurons. These data identify OGT as a molecular mechanism that regulates synapse maturity.

scholarly journals Astrocytes refine cortical connectivity at dendritic spines

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
W Christopher Risher ◽  
Sagar Patel ◽  
Il Hwan Kim ◽  
Akiyoshi Uezu ◽  
Srishti Bhagat ◽  
...  
Keyword(s):  
Dendritic Spines ◽  
Cortical Neurons ◽  
Three Dimensional ◽  
Early Postnatal Development ◽  
Mouse Cortex ◽  
Section Electron ◽  
Refinement Process ◽  
Serial Section Electron Microscopy ◽  
Cortical Inputs ◽  
The Brain

During cortical synaptic development, thalamic axons must establish synaptic connections despite the presence of the more abundant intracortical projections. How thalamocortical synapses are formed and maintained in this competitive environment is unknown. Here, we show that astrocyte-secreted protein hevin is required for normal thalamocortical synaptic connectivity in the mouse cortex. Absence of hevin results in a profound, long-lasting reduction in thalamocortical synapses accompanied by a transient increase in intracortical excitatory connections. Three-dimensional reconstructions of cortical neurons from serial section electron microscopy (ssEM) revealed that, during early postnatal development, dendritic spines often receive multiple excitatory inputs. Immuno-EM and confocal analyses revealed that majority of the spines with multiple excitatory contacts (SMECs) receive simultaneous thalamic and cortical inputs. Proportion of SMECs diminishes as the brain develops, but SMECs remain abundant in Hevin-null mice. These findings reveal that, through secretion of hevin, astrocytes control an important developmental synaptic refinement process at dendritic spines.

scholarly journals Dendritic Spines and Development: Towards a Unifying Model of Spinogenesis—A Present Day Review of Cajal's Histological Slides and Drawings

2010 ◽  
Vol 2010 ◽  
pp. 1-29 ◽  
Author(s):  
Pablo García-López ◽  
Virginia García-Marín ◽  
Miguel Freire
Keyword(s):  
Central Nervous System ◽  
Dendritic Spines ◽  
Neural Activity ◽  
Molecular Mechanisms ◽  
Three Dimensional ◽  
Practical Interest ◽  
High Quality ◽  
Spine Development ◽  
Dimensional Reconstruction ◽  
The Central Nervous System

Dendritic spines receive the majority of excitatory connections in the central nervous system, and, thus, they are key structures in the regulation of neural activity. Hence, the cellular and molecular mechanisms underlying their generation and plasticity, both during development and in adulthood, are a matter of fundamental and practical interest. Indeed, a better understanding of these mechanisms should provide clues to the development of novel clinical therapies. Here, we present original results obtained from high-quality images of Cajal's histological preparations, stored at the Cajal Museum (Instituto Cajal, CSIC), obtained using extended focus imaging, three-dimensional reconstruction, and rendering. Based on the data available in the literature regarding the formation of dendritic spines during development and our results, we propose a unifying model for dendritic spine development.

scholarly journals Neuronal hibernation following hippocampal demyelination

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Selva Baltan ◽  
Safdar S. Jawaid ◽  
Anthony M. Chomyk ◽  
Grahame J. Kidd ◽  
Jacqueline Chen ◽  
...  
Keyword(s):  
Dendritic Spines ◽  
Hippocampal Neurons ◽  
Molecular Mechanisms ◽  
Three Dimensional ◽  
Long Term Potentiation ◽  
Synaptic Function ◽  
Mammalian Brain ◽  
Gene Transcript ◽  
Ca1 Neurons

AbstractCognitive dysfunction occurs in greater than 50% of individuals with multiple sclerosis (MS). Hippocampal demyelination is a prominent feature of postmortem MS brains and hippocampal atrophy correlates with cognitive decline in MS patients. Cellular and molecular mechanisms responsible for neuronal dysfunction in demyelinated hippocampi are not fully understood. Here we investigate a mouse model of hippocampal demyelination where twelve weeks of treatment with the oligodendrocyte toxin, cuprizone, demyelinates over 90% of the hippocampus and causes decreased memory/learning. Long-term potentiation (LTP) of hippocampal CA1 pyramidal neurons is considered to be a major cellular readout of learning and memory in the mammalian brain. In acute slices, we establish that hippocampal demyelination abolishes LTP and excitatory post-synaptic potentials of CA1 neurons, while pre-synaptic function of Schaeffer collateral fibers is preserved. Demyelination also reduced Ca2+-mediated firing of hippocampal neurons in vivo. Using three-dimensional electron microscopy, we investigated the number, shape (mushroom, stubby, thin), and post-synaptic densities (PSDs) of dendritic spines that facilitate LTP. Hippocampal demyelination did not alter the number of dendritic spines. Surprisingly, dendritic spines appeared to be more mature in demyelinated hippocampi, with a significant increase in mushroom-shaped spines, more perforated PSDs, and more astrocyte participation in the tripartite synapse. RNA sequencing experiments identified 400 altered transcripts in demyelinated hippocampi. Gene transcripts that regulate myelination, synaptic signaling, astrocyte function, and innate immunity were altered in demyelinated hippocampi. Hippocampal remyelination rescued synaptic transmission, LTP, and the majority of gene transcript changes. We establish that CA1 neurons projecting demyelinated axons silence their dendritic spines and hibernate in a state that may protect the demyelinated axon and facilitates functional recovery following remyelination.

scholarly journals Random mutagenesis of human serine racemase reveals residues important for the enzymatic activity

2010 ◽  
Vol 75 (1) ◽  
pp. 59-79 ◽  
Author(s):  
Hillary E. Hoffman ◽  
Jana Jirásková ◽  
Marketa Zvelebil ◽  
Jan Konvalinka
Keyword(s):  
Enzymatic Activity ◽  
Three Dimensional ◽  
Random Mutagenesis ◽  
Serine Racemase ◽  
Dimensional Structure ◽  
Aspartate Receptor ◽  
Overall Stability ◽  
The Central Nervous System ◽  
Lateral Sclerosis ◽  
Specific Inhibitors

Human serine racemase (hSR) is a cytosolic pyridoxal-5′-phosphate dependent enzyme responsible for production of D-serine in the central nervous system. D-Serine acts as an endogenous coagonist of N-methyl-D-aspartate receptor ion channels. Increased levels of D-serine have been linked to amyotrophic lateral sclerosis and Alzheimer’s disease, indicating that SR inhibitors might be useful tools for investigation or treatment of neurodegenerative diseases. However, despite hSR’s promise as a therapeutic target, relatively few specific inhibitors have been identified, which is due in part to the lack of a three-dimensional structure of the enzyme. Here, we present a strategy for the generation and screening of random hSR mutants. From a library of randomly mutated hSR variants, twenty-seven soluble mutants were selected, expressed, and evaluated for enzymatic activity. Taking three carefully characterized mutants as an example, we show how this strategy can be used to pinpoint structurally and functionally important residues. In particular, we identify S84 and P111 as residues crucial for hSR activity and C217 and K221 as residues important for binding of the Mg2+ cofactor as well as for overall stability of the enzyme.

scholarly journals Hippocampal Dendritic Spines Modifications Induced by Perinatal Asphyxia

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
G. E. Saraceno ◽  
R. Castilla ◽  
G. E. Barreto ◽  
J. Gonzalez ◽  
R. A. Kölliker-Frers ◽  
...  
Keyword(s):  
Actin Cytoskeleton ◽  
Dendritic Spines ◽  
Perinatal Asphyxia ◽  
Synaptic Function ◽  
Protein Accumulation ◽  
Morphological Organization ◽  
The Central Nervous System ◽  
Old Rats ◽  
The Difference

Perinatal asphyxia (PA) affects the synaptic function and morphological organization. In previous works, we have shown neuronal and synaptic changes in rat neostriatum subjected to hypoxia leading to long-term ubi-protein accumulation. Since F-actin is highly concentrated in dendritic spines, modifications in its organization could be related with alterations induced by hypoxia in the central nervous system (CNS). In the present study, we investigate the effects of PA on the actin cytoskeleton of hippocampal postsynaptic densities (PSD) in 4-month-old rats. PSD showed an increment in their thickness and in the level of ubiquitination. Correlative fluorescence-electron microscopy photooxidation showed a decrease in the number of F-actin-stained spines in hippocampal excitatory synapses subjected to PA. Although Western Blot analysis also showed a slight decrease inβ-actin in PSD in PA animals, the difference was not significant. Taken together, this data suggests that long-term actin cytoskeleton might have role in PSD alterations which would be a spread phenomenon induced by PA.

Comparison of IVEM and quick-freeze, deep-etch, rotary shadow images of the cell cytoplasm

1993 ◽  
Vol 51 ◽  
pp. 66-67
Author(s):  
Carolyn A. Larabell
Keyword(s):  
Electron Microscopy ◽  
Three Dimensional ◽  
Freeze Fracture ◽  
Dimensional Structure ◽  
Whole Mount ◽  
Thin Section Electron Microscopy ◽  
Section Electron ◽  
Excellent Method ◽  
Fine Structures ◽  
The Individual

The techniques of freeze-fracture and quick-freeze, deep-etch, rotary-shadow electron microscopy have provided information about cellular structures that cannot be obtained from thin section electron microscopy. Freeze-fracture replicas provide extensive views of membranes and the arrangement of integral membrane proteins, but filamentous structures such as the cytoskeleton and extracellular matrix are not visualized because they are embedded in ice. In order to visualize such fine structures, it is necessary to deeply etch (or freeze-dry) cells that have been rapidly frozen, thus revealing about 0.1 to 0.3 μm of three dimensional structure. Replicas of cells prepared in this fashion provide excellent high magnification views of the individual filaments and their interactions with the plasma membrane as well as with membrane-bounded organelles. Another excellent method for visualization of cytoskeletal structures is whole mount electron microscopy. In this paper, I describe views of the egg cytoskeleton obtained from visualization of the isolated egg cortex prepared as a whole mount at 400 kV and compare these results with those obtained from replicas of cells that have been rapidly frozen men fractured and deeply etched.

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