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Acta Neurobiologiae Experimentalis 2008The large majority of excitatory synapses are located on dendritic spines which are discrete membrane protrusions present on neuronal dendrites. Interestingly the highly... (Review)
Review
The large majority of excitatory synapses are located on dendritic spines which are discrete membrane protrusions present on neuronal dendrites. Interestingly the highly heterogeneous morphology of dendritic spines is thought to be the morphological basis for synaptic plasticity associated to learning and memory formation. Indeed dendritic spines structure is regulated by molecular mechanisms that are fine tuned and adjusted according to level and direction of synaptic activity, development, specific brain region, and different experimental behavioral conditions. This supports the idea that reciprocal changes between the structure and function of spines impact both local and global integration of signals within dendrites. An increasing number of proteins have been found to be morphogens for dendritic spines and provided new insights into the molecular mechanisms regulating spine formation and morphology. Thus determining the mechanisms that regulate spine formation and morphology is essential for understanding the cellular changes that underlie learning and memory in normal and pathological conditions.
Topics: Animals; Dendrites; Dendritic Spines; Humans; Models, Biological; Neuronal Plasticity; Neurons; RNA, Messenger; Synapses
PubMed: 18511962
DOI: 10.55782/ane-2008-1696 -
Cellular and Molecular Life Sciences :... Dec 2017The nervous system is populated by diverse types of neurons, each of which has dendritic trees with strikingly different morphologies. These neuron-specific morphologies... (Review)
Review
The nervous system is populated by diverse types of neurons, each of which has dendritic trees with strikingly different morphologies. These neuron-specific morphologies determine how dendritic trees integrate thousands of synaptic inputs to generate different firing properties. To ensure proper neuronal function and connectivity, it is necessary that dendrite patterns are precisely controlled and coordinated with synaptic activity. Here, we summarize the molecular and cellular mechanisms that regulate the formation of cell type-specific dendrite patterns during development. We focus on different aspects of vertebrate dendrite patterning that are particularly important in determining the neuronal function; such as the shape, branching, orientation and size of the arbors as well as the development of dendritic spine protrusions that receive excitatory inputs and compartmentalize postsynaptic responses. Additionally, we briefly comment on the implications of aberrant dendritic morphology for nervous system disease.
Topics: Animals; Dendritic Spines; Humans; Nervous System Diseases; Neurons; Synaptic Potentials
PubMed: 28735442
DOI: 10.1007/s00018-017-2588-8 -
Neural Plasticity 2016The asymmetric distribution of various proteins and RNAs is essential for all stages of animal development, and establishment and maintenance of this cellular polarity... (Review)
Review
The asymmetric distribution of various proteins and RNAs is essential for all stages of animal development, and establishment and maintenance of this cellular polarity are regulated by a group of conserved polarity determinants. Studies over the last 10 years highlight important functions for polarity proteins, including apical-basal polarity and planar cell polarity regulators, in dendritic spine development and plasticity. Remarkably, many of the conserved polarity machineries function in similar manners in the context of spine development as they do in epithelial morphogenesis. Interestingly, some polarity proteins also utilize neuronal-specific mechanisms. Although many questions remain unanswered in our understanding of how polarity proteins regulate spine development and plasticity, current and future research will undoubtedly shed more light on how this conserved group of proteins orchestrates different pathways to shape the neuronal circuitry.
Topics: Animals; Cell Polarity; Dendritic Spines; Humans; Neurogenesis; Neuronal Plasticity; Neurons
PubMed: 26839714
DOI: 10.1155/2016/3145019 -
Neuroscience Oct 2013Schizophrenia is a neurodevelopmental disorder whose clinical features include impairments in perception, cognition and motivation. These impairments reflect alterations... (Review)
Review
Schizophrenia is a neurodevelopmental disorder whose clinical features include impairments in perception, cognition and motivation. These impairments reflect alterations in neuronal circuitry within and across multiple brain regions that are due, at least in part, to deficits in dendritic spines, the site of most excitatory synaptic connections. Dendritic spine alterations have been identified in multiple brain regions in schizophrenia, but are best characterized in layer 3 of the neocortex, where pyramidal cell spine density is lower. These spine deficits appear to arise during development, and thus are likely the result of disturbances in the molecular mechanisms that underlie spine formation, pruning, and/or maintenance. Each of these mechanisms may provide insight into novel therapeutic targets for preventing or repairing the alterations in neural circuitry that mediate the debilitating symptoms of schizophrenia.
Topics: Dendritic Spines; Humans; Neocortex; Pyramidal Cells; Schizophrenia
PubMed: 22546337
DOI: 10.1016/j.neuroscience.2012.04.044 -
Neurobiology of Aging Jan 2019Subtle alterations in dendritic spine morphology can induce marked effects on connectivity patterns of neuronal circuits and subsequent cognitive behavior. Past studies...
Subtle alterations in dendritic spine morphology can induce marked effects on connectivity patterns of neuronal circuits and subsequent cognitive behavior. Past studies of rodent and nonhuman primate aging revealed reductions in spine density with concomitant alterations in spine morphology among pyramidal neurons in the prefrontal cortex. In this report, we visualized and digitally reconstructed the three-dimensional morphology of dendritic spines from the dorsolateral prefrontal cortex in cognitively normal individuals aged 40-94 years. Linear models defined relationships between spines and age, Mini-Mental State Examination, apolipoprotein E (APOE) ε4 allele status, and Alzheimer's disease (AD) pathology. Similar to findings in other mammals, spine density correlated negatively with human aging. Reduced spine head diameter associated with higher Mini-Mental State Examination scores. Individuals harboring an APOE ε4 allele displayed greater numbers of dendritic filopodia and structural alterations in thin spines. The presence of AD pathology correlated with increased spine length, reduced thin spine head diameter, and increased filopodia density. Our study reveals how spine morphology in the prefrontal cortex changes in human aging and highlights key structural alterations in selective spine populations that may promote cognitively normal function despite harboring the APOE ε4 allele or AD pathology.
Topics: Adult; Aged; Aging; Alzheimer Disease; Apolipoprotein E4; Cognition; Cognitive Aging; Dendritic Spines; Female; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Neuronal Plasticity; Prefrontal Cortex
PubMed: 30339964
DOI: 10.1016/j.neurobiolaging.2018.09.003 -
ENeuro 2019Dendritic spines are the postsynaptic targets of excitatory synaptic inputs that undergo extensive proliferation and maturation during the first postnatal month in mice....
Dendritic spines are the postsynaptic targets of excitatory synaptic inputs that undergo extensive proliferation and maturation during the first postnatal month in mice. However, our understanding of the molecular mechanisms that regulate spines during this critical period is limited. Previous work has shown that pannexin 1 (Panx1) regulates neurite growth and synaptic plasticity. We therefore investigated the impact of global Panx1 KO on spontaneous cortical neuron activity using Ca imaging and network analysis. Panx1 KO increased both the number and size of spontaneous co-active cortical neuron network ensembles. To understand the basis for these findings, we investigated Panx1 expression in postnatal synaptosome preparations from early postnatal mouse cortex. Between 2 and 4 postnatal weeks, we observed a precipitous drop in cortical synaptosome protein levels of Panx1, suggesting it regulates synapse proliferation and/or maturation. At the same time points, we observed significant enrichment of the excitatory postsynaptic density proteins PSD-95, GluA1, and GluN2a in cortical synaptosomes from global Panx1 knock-out mice. analysis of pyramidal neuron structure in somatosensory cortex revealed a consistent increase in dendritic spine densities in both male and female Panx1 KO mice. Similar findings were observed in an excitatory neuron-specific Panx1 KO line (Emx1-Cre driven; Panx1 cKO) and in primary Panx1 KO cortical neurons cultured Altogether, our study suggests that Panx1 negatively regulates cortical dendritic spine development.
Topics: Animals; Calcium Signaling; Cerebral Cortex; Connexins; Dendritic Spines; Disks Large Homolog 4 Protein; Female; Male; Mice, Inbred C57BL; Mice, Knockout; Nerve Tissue Proteins; Neural Pathways; Optical Imaging; Synaptosomes
PubMed: 31118206
DOI: 10.1523/ENEURO.0503-18.2019 -
Journal of Neurophysiology Oct 2014Glutamatergic synapses on pyramidal neurons are formed on dendritic spines where glutamate activates ionotropic receptors, and calcium influx via N-methyl-d-aspartate...
Glutamatergic synapses on pyramidal neurons are formed on dendritic spines where glutamate activates ionotropic receptors, and calcium influx via N-methyl-d-aspartate receptors leads to a localized rise in spine calcium that is critical for the induction of synaptic plasticity. In the basolateral amygdala, activation of metabotropic receptors is also required for synaptic plasticity and amygdala-dependent learning. Here, using acute brain slices from rats, we show that, in basolateral amygdala principal neurons, high-frequency synaptic stimulation activates metabotropic glutamate receptors and raises spine calcium by releasing calcium from inositol trisphosphate-sensitive calcium stores. This spine calcium release is unevenly distributed, being present in proximal spines, but largely absent in more distal spines. Activation of metabotropic receptors also generated calcium waves that differentially invaded spines as they propagated toward the soma. Dendritic wave invasion was dependent on diffusional coupling between the spine and parent dendrite which was determined by spine neck length, with waves preferentially invading spines with short necks. Spine calcium is a critical trigger for the induction of synaptic plasticity, and our findings suggest that calcium release from inositol trisphosphate-sensitive calcium stores may modulate homosynaptic plasticity through store-release in the spine head, and heterosynaptic plasticity of unstimulated inputs via dendritic calcium wave invasion of the spine head.
Topics: Animals; Basolateral Nuclear Complex; Calcium Signaling; Dendritic Spines; Female; Inositol Phosphates; Male; Neurons; Rats; Rats, Wistar; Receptors, Metabotropic Glutamate
PubMed: 24944224
DOI: 10.1152/jn.00770.2013 -
Nature Communications Jan 2018Modeling studies suggest that clustered structural plasticity of dendritic spines is an efficient mechanism of information storage in cortical circuits. However, why new...
Modeling studies suggest that clustered structural plasticity of dendritic spines is an efficient mechanism of information storage in cortical circuits. However, why new clustered spines occur in specific locations and how their formation relates to learning and memory (L&M) remain unclear. Using in vivo two-photon microscopy, we track spine dynamics in retrosplenial cortex before, during, and after two forms of episodic-like learning and find that spine turnover before learning predicts future L&M performance, as well as the localization and rates of spine clustering. Consistent with the idea that these measures are causally related, a genetic manipulation that enhances spine turnover also enhances both L&M and spine clustering. Biophysically inspired modeling suggests turnover increases clustering, network sparsity, and memory capacity. These results support a hotspot model where spine turnover is the driver for localization of clustered spine formation, which serves to modulate network function, thus influencing storage capacity and L&M.
Topics: Animals; Cerebral Cortex; Conditioning, Psychological; Dendritic Spines; Fear; Female; Intravital Microscopy; Learning; Male; Memory; Mice; Neuronal Plasticity; Spatial Memory
PubMed: 29379017
DOI: 10.1038/s41467-017-02751-2 -
Biomolecules Nov 2021Compartmentalization of the membrane is essential for cells to perform highly specific tasks and spatially constrained biochemical functions in topographically defined... (Review)
Review
Compartmentalization of the membrane is essential for cells to perform highly specific tasks and spatially constrained biochemical functions in topographically defined areas. These membrane lateral heterogeneities range from nanoscopic dimensions, often involving only a few molecular constituents, to micron-sized mesoscopic domains resulting from the coalescence of nanodomains. Short-lived domains lasting for a few milliseconds coexist with more stable platforms lasting from minutes to days. This panoply of lateral domains subserves the great variety of demands of cell physiology, particularly high for those implicated in signaling. The dendritic spine, a subcellular structure of neurons at the receiving (postsynaptic) end of central nervous system excitatory synapses, exploits this compartmentalization principle. In its most frequent adult morphology, the mushroom-shaped spine harbors neurotransmitter receptors, enzymes, and scaffolding proteins tightly packed in a volume of a few femtoliters. In addition to constituting a mesoscopic lateral heterogeneity of the dendritic arborization, the dendritic spine postsynaptic membrane is further compartmentalized into spatially delimited nanodomains that execute separate functions in the synapse. This review discusses the functional relevance of compartmentalization and nanodomain organization in synaptic transmission and plasticity and exemplifies the importance of this parcelization in various neurotransmitter signaling systems operating at dendritic spines, using two fast ligand-gated ionotropic receptors, the nicotinic acetylcholine receptor and the glutamatergic receptor, and a second-messenger G-protein coupled receptor, the cannabinoid receptor, as paradigmatic examples.
Topics: Dendritic Spines; Neurons; Synapses; Synaptic Transmission
PubMed: 34827695
DOI: 10.3390/biom11111697 -
Behavioural Brain Research May 2021In this study, apical dendritic spine density of neurons in hippocampal, amygdalar and prefrontal cortical areas was compared in rats that were repeatedly winning or...
In this study, apical dendritic spine density of neurons in hippocampal, amygdalar and prefrontal cortical areas was compared in rats that were repeatedly winning or losing social conflicts. Territorial male wild-type Groningen (WTG) rats were allowed multiple daily attacks (>20 times) on intruder males in the resident-intruder paradigm. Frequent winning experiences are known to facilitate uncontrolled aggressive behavior reflected in aggressive attacks on anesthetized males which was also observed in the winners in this study. Both winners and losers were socially housed during the experiments; winners with females to stimulate territorial behavior, and losers with two other losing male rats. Twenty-four hours after the last social encounter, brains from experienced residential winners and repeatedly defeated intruder rats were collected and neuronal morphology in selected brain regions was studied via Golgi-Cox staining. Results indicate that spine density in the apical dendrites of the hippocampal CA1 reduced similarly in both winners and losers. In addition, winners showed increased spine densities at the proximal segments (20-30 μm) of the basolateral amygdala neurons and losers tended to show a decreased spine density at the more proximal segments of the infralimbic region of prefrontal cortex neurons. No effect of winning and losing was observed in the medial amygdala. The atrophic effect of repeated defeats in hippocampal and prefrontal regions was anticipated despite the fact that social housing of the repeatedly losing intruder males may have played a protective role. The reduction of hippocampal spine density in the winners seems surprising but supports previous findings in hierarchical dominant males in rat colonies. The dominants showed even greater shrinkage of the apical dendritic arbors of hippocampal CA3 pyramidal neurons compared to the stressed subordinates.
Topics: Animals; Basolateral Nuclear Complex; Behavior, Animal; CA1 Region, Hippocampal; Competitive Behavior; Dendritic Spines; Male; Neuronal Plasticity; Prefrontal Cortex; Pyramidal Cells; Rats; Social Dominance
PubMed: 33727049
DOI: 10.1016/j.bbr.2021.113243