scholarly journals Targeting of NF-κB to Dendritic Spines Is Required for Synaptic Signaling and Spine Development

2018 ◽  
Vol 38 (17) ◽  
pp. 4093-4103 ◽  
Author(s):  
Erica C. Dresselhaus ◽  
Matthew C.H. Boersma ◽  
Mollie K. Meffert
Keyword(s):  
Dendritic Spines ◽  
Synaptic Signaling ◽  
Spine Development

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 Targeting of NF-κB to Dendritic Spines is Required for Synaptic Signaling and Spine Development

2018 ◽  
Author(s):  
Erica C. Dresselhaus ◽  
Matthew C.H. Boersma ◽  
Mollie K. Meffert
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Dendritic Spines ◽  
Brain Plasticity ◽  
Spatial Localization ◽  
Synaptic Activity ◽  
Wild Type ◽  
Spine Development ◽  
Response Expression ◽  
Activity Dependent

ABSTRACTLong-term forms of brain plasticity share a requirement for changes in gene expression induced by neuronal activity. Mechanisms that determine how the distinct and overlapping functions of multiple activity-responsive transcription factors, including nuclear factor kappa B (NF-κB), give rise to stimulus-appropriate neuronal responses remain unclear. We report that the p65/RelA subunit of NF-κB confers subcellular enrichment at neuronal dendritic spines and engineer a p65 mutant that lacks spine-enrichment (ΔSEp65) but retains inherent transcriptional activity equivalent to wild-type p65. Wild-type p65 or ΔSEp65 both rescue NF-κB-dependent gene expression in p65-deficient murine hippocampal neurons responding to diffuse (PMA/ionomycin) stimulation. In contrast, neurons lacking spine-enriched NF-κB are selectively impaired in NF-κB-dependent gene expression induced by elevated excitatory synaptic stimulation (bicuculline or glycine). We used the setting of excitatory synaptic activity during development that produces NF-κB-dependent growth of dendritic spines to test physiological function of spine-enriched NF-κB in an activity-dependent response. Expression of wild-type p65, but not ΔSEp65, is capable of rescuing spine density to normal levels in p65-deficient pyramidal neurons. Collectively, these data reveal that spatial localization in dendritic spines contributes unique capacities to the NF-κB transcription factor in synaptic activity-dependent responses.SIGNIFICANCE STATEMENTExtensive research has established a model in which the regulation of neuronal gene expression enables enduring forms of plasticity and learning. However, mechanisms imparting stimulus-specificity to gene regulation, insuring biologically appropriate responses, remain incompletely understood. NF-κB is a potent transcription factor with evolutionarily-conserved functions in learning and the growth of excitatory synaptic contacts. Neuronal NF-κB is localized in both synapse and somatic compartments, but whether the synaptic pool of NF-κB has discrete functions is unknown. This study reveals that NF-κB enriched in dendritic spines (the postsynaptic sites of excitatory contacts) is selectively required for NF-κB activation by synaptic stimulation and normal dendritic spine development. These results support spatial localization at synapses as a key variable mediating selective stimulus-response coupling.

scholarly journals Phosphoinositide-dependent enrichment of actin monomers in dendritic spines regulates synapse development and plasticity

2017 ◽  
Vol 216 (8) ◽  
pp. 2551-2564 ◽  
Author(s):  
Wenliang Lei ◽  
Kenneth R. Myers ◽  
Yanfang Rui ◽  
Siarhei Hladyshau ◽  
Denis Tsygankov ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Dendritic Spines ◽  
Neurological Disorders ◽  
Synaptic Activity ◽  
Excitatory Synapses ◽  
Synapse Development ◽  
Actin Monomer ◽  
Actin Remodeling ◽  
Vertebrate Brain ◽  
Spine Development

Dendritic spines are small postsynaptic compartments of excitatory synapses in the vertebrate brain that are modified during learning, aging, and neurological disorders. The formation and modification of dendritic spines depend on rapid assembly and dynamic remodeling of the actin cytoskeleton in this highly compartmentalized space, but the precise mechanisms remain to be fully elucidated. In this study, we report that spatiotemporal enrichment of actin monomers (G-actin) in dendritic spines regulates spine development and plasticity. We first show that dendritic spines contain a locally enriched pool of G-actin that can be regulated by synaptic activity. We further find that this G-actin pool functions in spine development and its modification during synaptic plasticity. Mechanistically, the relatively immobile G-actin pool in spines depends on the phosphoinositide PI(3,4,5)P3 and involves the actin monomer–binding protein profilin. Together, our results have revealed a novel mechanism by which dynamic enrichment of G-actin in spines regulates the actin remodeling underlying synapse development and plasticity.

scholarly journals Phosphorylation of CRMP2 by Cdk5 Regulates Dendritic Spine Development of Cortical Neuron in the Mouse Hippocampus

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Xiaohua Jin ◽  
Kodai Sasamoto ◽  
Jun Nagai ◽  
Yuki Yamazaki ◽  
Kenta Saito ◽  
...  
Keyword(s):  
Mouse Brain ◽  
Dendritic Spines ◽  
Dendritic Spine ◽  
Cortical Neurons ◽  
Hippocampal Neurons ◽  
Molecular Mechanisms ◽  
Brain Functions ◽  
Spine Development ◽  
Mouse Hippocampus

Proper density and morphology of dendritic spines are important for higher brain functions such as learning and memory. However, our knowledge about molecular mechanisms that regulate the　development and maintenance of dendritic spines is limited. We recently reported that cyclin-dependent kinase 5 (Cdk5) is required for the development and maintenance of dendritic spines of cortical neurons in the mouse brain. Previousin vitrostudies have suggested the involvement of Cdk5 substrates in the formation of dendritic spines; however, their role in spine development has not been testedin vivo. Here, we demonstrate that Cdk5 phosphorylates collapsin response mediator protein 2 (CRMP2) in the dendritic spines of cultured hippocampal neurons andin vivoin the mouse brain. When we eliminated CRMP2 phosphorylation inCRMP2KI/KImice, the densities of dendritic spines significantly decreased in hippocampal CA1 pyramidal neurons in the mouse brain. These results indicate that phosphorylation of CRMP2 by Cdk5 is important for dendritic spine development in cortical neurons in the mouse hippocampus.

scholarly journals Csmd2 interacts with Dab1 and is Required in Reelin-Mediated Neuronal Maturation

2020 ◽  
Author(s):  
Mark A Gutierrez ◽  
Brett E Dwyer ◽  
Santos J Franco
Keyword(s):  
Dendritic Spines ◽  
Dendritic Spine ◽  
Neuronal Migration ◽  
Transmembrane Protein ◽  
Adaptor Protein ◽  
Neuronal Maturation ◽  
Mutant Form ◽  
Structural Development ◽  
Signaling Mechanism ◽  
Spine Development

AbstractReelin is a glycoprotein secreted by Cajal-Retzius cells to regulate development of the cerebral cortex. Reelin binding to its receptors on immature neurons initiates a signaling cascade through the downstream adaptor protein, Dab1. Defects in this signaling mechanism result in perturbed neuronal migration, reductions in dendrite complexity, and deficits in synapse development and function. How Reelin controls neuronal migration and brain lamination have been extensively investigated over the years, but the pathways that regulate dendrite and spine development downstream of Reelin and Dab1 have yet to be fully elucidated. Here, we have identified a novel interaction between Dab1 and Csmd2, a synaptic transmembrane protein required for dendrite and dendritic spine development in forebrain excitatory neurons. We demonstrate that Csmd2 contains an NPxY motif on its intracellular region, through which Dab1 interacts with Csmd2. Interestingly, we find that this NPxY consensus motif is not required for Csmd2 to localize at the postsynaptic densities of spiny neurons. Rather, the introduction of an NPxY mutant form of Csmd2 results in a significant overproduction of immature, filopodia-like dendritic spines in maturing neurons. Moreover, we show that knockdown of Csmd2 mRNA expression in immature developing neurons abolishes the ability of Reelin to promote dendrite elaboration and dendritic spine maturation. This suggests that the Csmd2-Dab1 interaction may be a requirement of Reelin/Dab1 signaling to mediate the structural maturation of neurons. Together, these results point toward a role of Csmd2 in the Reelin/Dab1 signaling axis that promotes the development of dendrites and dendritic spines in maturing neurons.Summary StatementHow Reelin controls neuronal maturation remains to be understood. We demonstrate that the synaptic protein Csmd2 interacts with the Reelin-associated adaptor protein Dab1. We also determine that Reelin requires Csmd2 to regulate structural development and maturation of forebrain neurons.

Development of prefrontal layer III pyramidal neurons in infants with Down syndrome

2011 ◽  
Vol 2 (3) ◽  
Author(s):  
Mario Vukšić ◽  
Zdravko Petanjek ◽  
Ivica Kostović
Keyword(s):  
Down Syndrome ◽  
Dendritic Spines ◽  
Dendritic Spine ◽  
Pyramidal Neurons ◽  
Perinatal Period ◽  
Spine Morphology ◽  
Biological Potential ◽  
Spine Development ◽  
Intensive Formation ◽  
Limited Period

AbstractWe quantitatively analyzed the dendritic and dendritic spine development on basal and oblique dendrites of large layer IIIc pyramidal neurons of the prospective prefrontal area 9 in the brains of three infants with Down syndrome (DS) and five age-matched-controls over the period from 32 weeks postconception to the 7th postnatal month. By using Neurolucida 3.1 software on rapid Golgi impregnated slices, 9–10 neurons were three-dimensionally reconstructed. There were no significant differences in the pattern of the dendritic and spine development between the basal and apical oblique dendrites. The DS subjects did not depart significantly from the developmental curve of the control subjects. Our data showed that large and significant segment outgrowth, in parallel with dendritic elongation occurred during a limited period of time, between 36 weeks postconception and the first postnatal month. Dendritic spines appeared at the time of birth and their density continued to increase up to the age of 7 months. During the first postnatal month long thin spines and filopodia-like protrusions predominated, but the spines later changed their morphology to a more mature form. No differences in the spine morphology were qualitatively observed between the DS infants and the age matched controls. This data suggests that intensive formation of cortical circuitry occurs on large layer IIIc pyramidal neurons during perinatal period and is not disturbed in DS infants. Consequently, this could be a biological potential to mitigate psychomotor impairment in DS patient.

scholarly journals Multiple EphB receptor tyrosine kinases shape dendritic spines in the hippocampus

2003 ◽  
Vol 163 (6) ◽  
pp. 1313-1326 ◽  
Author(s):  
Mark Henkemeyer ◽  
Olga S. Itkis ◽  
Michelle Ngo ◽  
Peter W. Hickmott ◽  
Iryna M. Ethell
Keyword(s):  
Dendritic Spines ◽  
Dendritic Spine ◽  
Tyrosine Kinases ◽  
Hippocampal Neurons ◽  
Receptor Tyrosine Kinases ◽  
Triple Mutant ◽  
Spine Formation ◽  
Truncating Mutation ◽  
Ephb Receptor ◽  
Spine Development

Here, using a genetic approach, we dissect the roles of EphB receptor tyrosine kinases in dendritic spine development. Analysis of EphB1, EphB2, and EphB3 double and triple mutant mice lacking these receptors in different combinations indicates that all three, although to varying degrees, are involved in dendritic spine morphogenesis and synapse formation in the hippocampus. Hippocampal neurons lacking EphB expression fail to form dendritic spines in vitro and they develop abnormal spines in vivo. Defective spine formation in the mutants is associated with a drastic reduction in excitatory glutamatergic synapses and the clustering of NMDA and AMPA receptors. We show further that a kinase-defective, truncating mutation in EphB2 also results in abnormal spine development and that ephrin-B2–mediated activation of the EphB receptors accelerates dendritic spine development. These results indicate EphB receptor cell autonomous forward signaling is responsible for dendritic spine formation and synaptic maturation in hippocampal neurons.

Synaptic organization of the gustatory NST

1994 ◽  
Vol 52 ◽  
pp. 150-151
Author(s):  
M. C. Whitehead
Keyword(s):  
Central Nervous System ◽  
Dendritic Spines ◽  
Fundamental Problem ◽  
Cell Types ◽  
Brain Regions ◽  
Excitatory Synapses ◽  
Solitary Tract ◽  
Synaptic Organization ◽  
Synaptic Junctions ◽  
Afferent Terminals

A fundamental problem in taste research is to determine how gustatory signals are processed and disseminated in the mammalian central nervous system. An important first step toward understanding information processing is the identification of cell types in the nucleus of the solitary tract (NST) and their synaptic relationships with oral primary afferent terminals. Facial and glossopharyngeal (LIX) terminals in the hamster were labelled with HRP, examined with EM, and characterized as containing moderate concentrations of medium-sized round vesicles, and engaging in asymmetrical synaptic junctions. Ultrastructurally the endings resemble excitatory synapses in other brain regions.Labelled facial afferent endings in the RC subdivision synapse almost exclusively with distal dendrites and dendritic spines of NST cells. Most synaptic relationships between the facial synapses and the dendrites are simple. However, 40% of facial endings engage in complex synaptic relationships within glomeruli containing unlabelled axon endings particularly ones termed "SP" endings. SP endings are densely packed with small, pleomorphic vesicles and synapse with both the facial endings and their postsynaptic dendrites by means of nearly symmetrical junctions.

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.

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