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The Journal of Physiology Jan 2010In the central nervous system, most excitatory synapses occur on dendritic spines, which are small protrusions from the dendritic tree. In the mature cortex and... (Review)
Review
In the central nervous system, most excitatory synapses occur on dendritic spines, which are small protrusions from the dendritic tree. In the mature cortex and hippocampus, dendritic spines are heterogeneous in shape. It has been shown that the shapes of the spine can affect synapse stability and synaptic function. Dendritic spines are highly motile structures that can undergo actin-dependent shape changes, which occur over a time scale ranging from seconds to tens of minutes or even days. The formation, remodelling and elimination of excitatory synapses on dendritic spines represent ways of refining the microcircuitry in the brain. Here I review the current knowledge on the effects of modulation of AMPA and NMDA ionotropic glutamate receptors on dendritic spine formation, motility and remodelling.
Topics: Animals; Brain; Dendritic Spines; Excitatory Amino Acids; Excitatory Postsynaptic Potentials; Humans; Neuronal Plasticity; Receptors, AMPA; Receptors, N-Methyl-D-Aspartate
PubMed: 19933758
DOI: 10.1113/jphysiol.2009.178905 -
ACS Chemical Neuroscience May 2023Quantitative methods for assessing neural anatomy have rapidly evolved in neuroscience and provide important insights into brain health and function. However, as new... (Review)
Review
Quantitative methods for assessing neural anatomy have rapidly evolved in neuroscience and provide important insights into brain health and function. However, as new techniques develop, it is not always clear when and how each may be used to answer specific scientific questions posed. Dendritic spines, which are often indicative of synapse formation and neural plasticity, have been implicated across many brain regions in neurodevelopmental disorders as a marker for neural changes reflecting neural dysfunction or alterations. In this Perspective we highlight several techniques for staining, imaging, and quantifying dendritic spines as well as provide a framework for avoiding potential issues related to pseudoreplication. This framework illustrates how others may apply the most rigorous approaches. We consider the cost-benefit analysis of the varied techniques, recognizing that the most sophisticated equipment may not always be necessary for answering some research questions. Together, we hope this piece will help researchers determine the best strategy toward using the ever-growing number of techniques available to determine neural changes underlying dendritic spine morphology in health and neurodevelopmental disorders.
Topics: Humans; Dendritic Spines; Neurodevelopmental Disorders; Neuronal Plasticity; Brain
PubMed: 37070364
DOI: 10.1021/acschemneuro.3c00062 -
The Journal of Neuroscience : the... Jul 2014Synaptic rearrangements during critical periods of postnatal brain development rely on the correct formation, strengthening, and elimination of synapses and associated...
Synaptic rearrangements during critical periods of postnatal brain development rely on the correct formation, strengthening, and elimination of synapses and associated dendritic spines to form functional networks. The correct balance of these processes is thought to be regulated by synapse-specific changes in the subunit composition of NMDA-type glutamate receptors (NMDARs). Among these, the nonconventional NMDAR subunit GluN3A has been suggested to play a role as a molecular brake in synaptic maturation. We tested here this hypothesis using confocal time-lapse imaging in rat hippocampal organotypic slices and assessed the role of GluN3A-containing NMDARs on spine dynamics. We found that overexpressing GluN3A reduced spine density over time, increased spine elimination, and decreased spine stability. The effect of GluN3A overexpression could be further enhanced by using an endocytosis-deficient GluN3A mutant and reproduced by silencing the adaptor protein PACSIN1, which prevents the endocytosis of endogenous GluN3A. Conversely, silencing of GluN3A reduced spine elimination and favored spine stability. Moreover, reexpression of GluN3A in more mature tissue reinstated an increased spine pruning and a low spine stability. Mechanistically, the decreased stability in GluN3A overexpressing neurons could be linked to a failure of plasticity-inducing protocols to selectively stabilize spines and was dependent on the ability of GluN3A to bind the postsynaptic scaffold GIT1. Together, these data provide strong evidence that GluN3A prevents the activity-dependent stabilization of synapses thereby promoting spine pruning, and suggest that GluN3A expression operates as a molecular signal for controlling the extent and timing of synapse maturation.
Topics: Action Potentials; Aging; Animals; Animals, Newborn; Cells, Cultured; Dendritic Spines; Female; Hippocampus; Male; Membrane Glycoproteins; Neuronal Plasticity; Rats; Synaptic Transmission
PubMed: 25009255
DOI: 10.1523/JNEUROSCI.5183-13.2014 -
Molecular Autism May 2020Autism spectrum disorder (ASD) is a brain disorder that involves changes in neuronal connections. Abnormal morphology of dendritic spines on postsynaptic neurons has... (Review)
Review
Autism spectrum disorder (ASD) is a brain disorder that involves changes in neuronal connections. Abnormal morphology of dendritic spines on postsynaptic neurons has been observed in ASD patients and transgenic mice that model different monogenetic causes of ASD. A number of ASD-associated genetic variants are known to disrupt dendritic local protein synthesis, which is essential for spine morphogenesis, synaptic transmission, and plasticity. Most of our understanding on the molecular mechanism underlying ASD depends on studies using rodents. However, recent advance in human pluripotent stem cells and their neural differentiation provides a powerful alternative tool to understand the cellular aspects of human neurological disorders. In this review, we summarize recent progress on studying mRNA targeting and local protein synthesis in stem cell-derived neurons, and discuss how perturbation of these processes may impact synapse development and functions that are relevant to cognitive deficits in ASD.
Topics: Animals; Autism Spectrum Disorder; Biomarkers; Cell Differentiation; Dendritic Spines; Disease Susceptibility; Gene Expression Regulation; Humans; Morphogenesis; Mutation; Neurons; Pluripotent Stem Cells; Protein Biosynthesis; RNA, Messenger
PubMed: 32460854
DOI: 10.1186/s13229-020-00349-y -
Current Opinion in Neurobiology Jun 2012Dendritic spines are small mushroom-like protrusions arising from neurons where most excitatory synapses reside. Their peculiar shape suggests that spines can serve as... (Review)
Review
Dendritic spines are small mushroom-like protrusions arising from neurons where most excitatory synapses reside. Their peculiar shape suggests that spines can serve as an autonomous postsynaptic compartment that isolates chemical and electrical signaling. How neuronal activity modifies the morphology of the spine and how these modifications affect synaptic transmission and plasticity are intriguing issues. Indeed, the induction of long-term potentiation (LTP) or depression (LTD) is associated with the enlargement or shrinkage of the spine, respectively. This structural plasticity is mainly controlled by actin filaments, the principal cytoskeletal component of the spine. Here we review the pioneering microscopic studies examining the structural plasticity of spines and propose how changes in actin treadmilling might regulate spine morphology.
Topics: Animals; Dendritic Spines; Models, Biological; Neuronal Plasticity; Neurons; Ultrasonography
PubMed: 21963169
DOI: 10.1016/j.conb.2011.09.002 -
Physiology (Bethesda, Md.) Feb 2006Dendritic spines are small protrusions from neuronal dendrites that form the postsynaptic component of most excitatory synapses in the brain. They play critical roles in... (Review)
Review
Dendritic spines are small protrusions from neuronal dendrites that form the postsynaptic component of most excitatory synapses in the brain. They play critical roles in synaptic transmission and plasticity. Recent advances in imaging and molecular technologies reveal that spines are complex, dynamic structures that contain a dense array of cytoskeletal, transmembrane, and scaffolding molecules. Several neurological and psychiatric disorders exhibit dendritic spine abnormalities.
Topics: Animals; Cytoskeleton; Dendrites; Dendritic Spines; Humans; Nervous System Diseases; Neuronal Plasticity; Signal Transduction; Synapses; Synaptic Transmission; rho GTP-Binding Proteins
PubMed: 16443821
DOI: 10.1152/physiol.00042.2005 -
Molecular Brain Mar 2019It is well established that estrogens affect neuroplasticity in a number of brain regions. In particular, estrogens modulate and mediate spine and synapse formation as... (Review)
Review
It is well established that estrogens affect neuroplasticity in a number of brain regions. In particular, estrogens modulate and mediate spine and synapse formation as well as neurogenesis in the hippocampal formation. In this review, we discuss current research exploring the effects of estrogens on dendritic spine plasticity and neurogenesis with a focus on the modulating factors of sex, age, and pregnancy. Hormone levels, including those of estrogens, fluctuate widely across the lifespan from early life to puberty, through adulthood and into old age, as well as with pregnancy and parturition. Dendritic spine formation and modulation are altered both by rapid (likely non-genomic) and classical (genomic) actions of estrogens and have been suggested to play a role in the effects of estrogens on learning and memory. Neurogenesis in the hippocampus is influenced by age, the estrous cycle, pregnancy, and parity in female rodents. Furthermore, sex differences exist in hippocampal cellular and molecular responses to estrogens and are briefly discussed throughout. Understanding how structural plasticity in the hippocampus is affected by estrogens and how these effects can influence function and be influenced by other factors, such as experience and sex, is critical and can inform future treatments in conditions involving the hippocampus.
Topics: Animals; Dendritic Spines; Estrogens; Female; Hippocampus; Neurogenesis; Neuronal Plasticity; Rodentia
PubMed: 30885239
DOI: 10.1186/s13041-019-0442-7 -
Neuron May 2005Dendritic spines are tiny protrusions on dendritic shafts where most excitatory synapses are located. Recent advances in imaging technologies have given us great insight... (Review)
Review
Dendritic spines are tiny protrusions on dendritic shafts where most excitatory synapses are located. Recent advances in imaging technologies have given us great insight into the function of spines as biochemical compartments. Here we review recent evidence suggesting that the geometry of dendritic spines controls postsynaptic calcium signaling and is bidirectionally regulated during synaptic plasticity.
Topics: Animals; Calcium; Dendritic Spines; Models, Neurological; Neuronal Plasticity; Receptors, Glutamate; Signal Transduction
PubMed: 15944122
DOI: 10.1016/j.neuron.2005.05.006 -
Brain Research Sep 2011Fyn is a Src-family tyrosine kinase that affects long term potentiation (LTP), synapse formation, and learning and memory. Fyn is also implicated in dendritic spine...
Fyn is a Src-family tyrosine kinase that affects long term potentiation (LTP), synapse formation, and learning and memory. Fyn is also implicated in dendritic spine formation both in vitro and in vivo. However, whether Fyn's regulation of dendritic spine formation is brain-region specific and age-dependent is unknown. In the present study, we systematically examined whether Fyn altered dendritic spine density and morphology in the cortex and hippocampus and if these effects were age-dependent. We found that Fyn knockout mice trended toward a decrease in dendritic spine density in cortical layers II/III, but not in the hippocampus, at 1 month of age. Additionally, Fyn knockout mice had significantly decreased dendritic spine density in both the cortex and hippocampus at 3 months and 1 year, and Fyn's effect on dendritic spine density was age-dependent in the hippocampus. Moreover, Fyn knockout mice had wider spines at the three time points (1 month, 3 months, 1 year) in the cortex. These findings suggest that Fyn regulates dendritic spine number and morphology over time and provide further support for Fyn's role in maintaining proper synaptic function in vivo.
Topics: Age Factors; Animals; Cerebral Cortex; Dendrites; Dendritic Spines; Hippocampus; Mice; Mice, Knockout; Neurons; Proto-Oncogene Proteins c-fyn
PubMed: 21872217
DOI: 10.1016/j.brainres.2011.07.059 -
The Journal of General Physiology Aug 2022Dendritic spines act as biochemical computational units and must adapt their responses according to their activation history. Calcium influx acts as the first signaling...
Dendritic spines act as biochemical computational units and must adapt their responses according to their activation history. Calcium influx acts as the first signaling step during postsynaptic activation and is a determinant of synaptic weight change. Dendritic spines also come in a variety of sizes and shapes. To probe the relationship between calcium dynamics and spine morphology, we used a stochastic reaction-diffusion model of calcium dynamics in idealized and realistic geometries. We show that despite the stochastic nature of the various calcium channels, receptors, and pumps, spine size and shape can modulate calcium dynamics and subsequently synaptic weight updates in a deterministic manner. Through a series of exhaustive simulations and analyses, we found that the calcium dynamics and synaptic weight change depend on the volume-to-surface area of the spine. The relationships between calcium dynamics and spine morphology identified in idealized geometries also hold in realistic geometries, suggesting that there are geometrically determined deterministic relationships that may modulate synaptic weight change.
Topics: Calcium; Calcium Channels; Calcium Signaling; Dendritic Spines; Diffusion
PubMed: 35819365
DOI: 10.1085/jgp.202112980