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The Journal of General Physiology Aug 2019Dendritic spines are small subcompartments that protrude from the dendrites of neurons and are important for signaling activity and synaptic communication. These...
Dendritic spines are small subcompartments that protrude from the dendrites of neurons and are important for signaling activity and synaptic communication. These subcompartments have been characterized to have different shapes. While it is known that these shapes are associated with spine function, the specific nature of these shape-function relationships is not well understood. In this work, we systematically investigated the relationship between the shape and size of both the spine head and spine apparatus, a specialized endoplasmic reticulum compartment within the spine head, in modulating rapid calcium dynamics using mathematical modeling. We developed a spatial multicompartment reaction-diffusion model of calcium dynamics in three dimensions with various flux sources, including N-methyl-D-aspartate receptors (NMDARs), voltage-sensitive calcium channels (VSCCs), and different ion pumps on the plasma membrane. Using this model, we make several important predictions. First, the volume to surface area ratio of the spine regulates calcium dynamics. Second, membrane fluxes impact calcium dynamics temporally and spatially in a nonlinear fashion. Finally, the spine apparatus can act as a physical buffer for calcium by acting as a sink and rescaling the calcium concentration. These predictions set the stage for future experimental investigations of calcium dynamics in dendritic spines.
Topics: Animals; Calcium; Calcium Channels; Calcium Signaling; Dendritic Spines; Models, Theoretical; Rats; Receptors, N-Methyl-D-Aspartate
PubMed: 31324651
DOI: 10.1085/jgp.201812261 -
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 -
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 -
Neuron Jul 2023Dendritic spine remodeling in the dorsal horn is associated with many chronic pain models. Li et al. demonstrate that Tiam1 links Rac1-mediated spine changes to NMDA...
Dendritic spine remodeling in the dorsal horn is associated with many chronic pain models. Li et al. demonstrate that Tiam1 links Rac1-mediated spine changes to NMDA receptor activity to promote behavioral signs of chronic pain in rodents.
Topics: Humans; Receptors, N-Methyl-D-Aspartate; Chronic Pain; Dendritic Spines; Signal Transduction; Neurons; rac1 GTP-Binding Protein
PubMed: 37413965
DOI: 10.1016/j.neuron.2023.06.001 -
Advances in Neurobiology 2023Dendritic spines, key sites for neural plasticity, are influenced by gonadal steroids. In this chapter, we review the effects of gonadal steroids on dendritic spine... (Review)
Review
Dendritic spines, key sites for neural plasticity, are influenced by gonadal steroids. In this chapter, we review the effects of gonadal steroids on dendritic spine density in areas important to cognitive function, the hippocampus, and prefrontal cortex. Most of these animal model studies investigated the effects of estrogen in females, but we also include more recent data on androgen effects in both males and females. The underlying genomic and non-genomic mechanisms related to gonadal steroid-induced spinogenesis are also reviewed. Subsequently, we discuss possible reasons for the observed sex differences in many neuropsychiatric diseases, which appear to be caused, in part, by aberrant synaptic connections that may involve dendritic spine pathology. Overall, knowledge concerning the regulation of dendritic spines by gonadal hormones has grown since the initial discoveries in the 1990s, and current research points to a potential role for aberrant spine functioning in many neuropsychiatric disorders.
Topics: Female; Male; Animals; Dendritic Spines; Steroids; Cognition; Genomics; Hormones
PubMed: 37962800
DOI: 10.1007/978-3-031-36159-3_8 -
Molecular Neurobiology Jan 2018Dendritic spines, a special kind of structure in nerve cells, play a key role in performing cellular function. Structural abnormalities of the dendritic spine may...
Dendritic spines, a special kind of structure in nerve cells, play a key role in performing cellular function. Structural abnormalities of the dendritic spine may contribute to synaptic dysfunction and have been implicated in memory formation. However, the molecular mechanisms that trigger dendritic spine loss remain unclear. Here, we show that the absence of dendritic cell factor 1 (Dcf1) appeared dendritic spines dysplasia, which in turn leads to the damage of learning and memory; in contrast, enhancing Dcf1 expression rescues dendritic spines morphology and function, indicating a pivotal role of Dcf1 in cellular function. Electrophysiological test indicates that there is a significant reduction in the frequency of miniature excitatory postsynaptic currents in Dcf1 knockout (KO) mice. Subsequent to optogenetic ignition, we observed a weaker neuronal activation in Dcf1 KO mice, explaining the neural circuit cause. On molecular mechanism, we demonstrated an unprecedented discovery that Dcf1 triggers the dendritic spine and synaptic function through the recruitment of Lcn2 and activation of PSD95-NMDAR signaling. Removing this brake leads to memory damage. Our results highlight an unexpected regulatory mechanism of dendritic spine development and formation.
Topics: Animals; Cerebral Cortex; Dendritic Spines; Disks Large Homolog 4 Protein; Excitatory Postsynaptic Potentials; Hippocampus; Lipocalin-2; Membrane Proteins; Memory; Mice, Knockout; Nerve Tissue Proteins; Receptors, N-Methyl-D-Aspartate; Signal Transduction; rac1 GTP-Binding Protein
PubMed: 28058580
DOI: 10.1007/s12035-016-0349-6 -
Biological Research May 2023Previous studies have shown that peripheral nerve injury can lead to abnormal dendritic spine remodeling in spinal dorsal horn neurons. Inhibition of abnormal dendritic...
Previous studies have shown that peripheral nerve injury can lead to abnormal dendritic spine remodeling in spinal dorsal horn neurons. Inhibition of abnormal dendritic spine remodeling can relieve neuropathic pain. Electroacupuncture (EA) has a beneficial effect on the treatment of neuropathic pain, but the specific mechanism remains unclear. Evidence has shown that slit-robo GTPase activating protein 3 (srGAP3) and Rho GTPase (Rac1) play very important roles in dendritic spine remodeling. Here, we used srGAP3 siRNA and Rac1 activator CN04 to confirm the relationship between SrGAP3 and Rac1 and their roles in improving neuropathic pain with EA. Spinal nerve ligation (SNL) was used as the experimental model, and thermal withdrawal latency (TWL), mechanical withdrawal threshold (MWT), Western blotting, immunohistochemistry and Golgi-Cox staining were used to examine changes in behavioral performance, protein expression and dendritic spines. More dendritic spines and higher expression levels of srGAP3 were found in the initial phase of neuropathic pain. During the maintenance phase, dendritic spines were more mature, which was consistent with lower expression levels of srGAP3 and higher expression levels of Rac1-GTP. EA during the maintenance phase reduced the density and maturity of dendritic spines of rats with SNL, increased the levels of srGAP3 and reduced the levels of Rac1-GTP, while srGAP3 siRNA and CN04 reversed the therapeutic effects of EA. These results suggest that dendritic spines have different manifestations in different stages of neuropathic pain and that EA may inhibit the abnormal dendritic spine remodeling by regulating the srGAP3/Rac1 signaling pathway to alleviate neuropathic pain.
Topics: Animals; Rats; Dendritic Spines; Electroacupuncture; GTP Phosphohydrolases; Guanosine Triphosphate; Neuralgia; rac1 GTP-Binding Protein; Rats, Sprague-Dawley; Signal Transduction; Spinal Nerves
PubMed: 37211600
DOI: 10.1186/s40659-023-00439-0 -
Neuroscience and Biobehavioral Reviews Dec 2015The structure and dynamics of dendritic spines reflect the strength of synapses, which are severely affected in different brain diseases. Therefore, understanding the... (Review)
Review
The structure and dynamics of dendritic spines reflect the strength of synapses, which are severely affected in different brain diseases. Therefore, understanding the ultra-structure, molecular signaling mechanism(s) regulating dendritic spine dynamics is crucial. Although, since last century, dynamics of spine have been explored by several investigators in different neurological diseases, but despite countless efforts, a comprehensive understanding of the fundamental etiology and molecular signaling pathways involved in spine pathology is lacking. The purpose of this review is to provide a contextual framework of our current understanding of the molecular mechanisms of dendritic spine signaling, as well as their potential impact on different neurodegenerative and psychiatric diseases, as a format for highlighting some commonalities in function, as well as providing a format for new insights and perspectives into this critical area of research. Additionally, the potential strategies to restore spine structure-function in different diseases are also pointed out. Overall, these informations should help researchers to design new drugs to restore the structure-function of dendritic spine, a "hot site" of synaptic plasticity.
Topics: Animals; Dendritic Spines; Humans; Nervous System Diseases; Neuronal Plasticity; Neurons; Signal Transduction; Synapses
PubMed: 26562682
DOI: 10.1016/j.neubiorev.2015.09.020 -
Brain Research Bulletin Mar 2017The configuration of synaptic circuits underlies their ability to process and store information. Research on dendritic spines has revealed that their structural and... (Review)
Review
The configuration of synaptic circuits underlies their ability to process and store information. Research on dendritic spines has revealed that their structural and functional alterations are clustered along the parent dendrite. Here we review the evidence supporting such notion of clustered synaptic plasticity, discuss its functional implications and possible contributing factors, and suggest potential strategies to deal with open challenges.
Topics: Animals; Dendritic Spines; Humans; Neuronal Plasticity
PubMed: 27637453
DOI: 10.1016/j.brainresbull.2016.09.008 -
ELife Dec 2020Previously, we showed that cryo fixation of adult mouse brain tissue gave a truer representation of brain ultrastructure in comparison with a standard chemical fixation... (Comparative Study)
Comparative Study
Previously, we showed that cryo fixation of adult mouse brain tissue gave a truer representation of brain ultrastructure in comparison with a standard chemical fixation method (Korogod et al., 2015). Extracellular space matched physiological measurements, there were larger numbers of docked vesicles and less glial coverage of synapses and blood capillaries. Here, using the same preservation approaches, we compared the morphology of dendritic spines. We show that the length of the spine and the volume of its head is unchanged; however, the spine neck width is thinner by more than 30% after cryo fixation. In addition, the weak correlation between spine neck width and head volume seen after chemical fixation was not present in cryo-fixed spines. Our data suggest that spine neck geometry is independent of the spine head volume, with cryo fixation showing enhanced spine head compartmentalization and a higher predicted electrical resistance between spine head and parent dendrite.
Topics: Animals; Artifacts; Brain; Cryopreservation; Dendritic Spines; Fixatives; Male; Mice; Mice, Inbred C57BL; Tissue Fixation
PubMed: 33274717
DOI: 10.7554/eLife.56384