-
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 -
Proceedings of the Japan Academy.... 2023Recent research extends our understanding of brain processes beyond just action potentials and chemical transmissions within neural circuits, emphasizing the mechanical...
Recent research extends our understanding of brain processes beyond just action potentials and chemical transmissions within neural circuits, emphasizing the mechanical forces generated by excitatory synapses on dendritic spines to modulate presynaptic function. From in vivo and in vitro studies, we outline five central principles of synaptic mechanics in brain function: P1: Stability - Underpinning the integral relationship between the structure and function of the spine synapses. P2: Extrinsic dynamics - Highlighting synapse-selective structural plasticity which plays a crucial role in Hebbian associative learning, distinct from pathway-selective long-term potentiation (LTP) and depression (LTD). P3: Neuromodulation - Analyzing the role of G-protein-coupled receptors, particularly dopamine receptors, in time-sensitive modulation of associative learning frameworks such as Pavlovian classical conditioning and Thorndike's reinforcement learning (RL). P4: Instability - Addressing the intrinsic dynamics crucial to memory management during continual learning, spotlighting their role in "spine dysgenesis" associated with mental disorders. P5: Mechanics - Exploring how synaptic mechanics influence both sides of synapses to establish structural traces of short- and long-term memory, thereby aiding the integration of mental functions. We also delve into the historical background and foresee impending challenges.
Topics: Humans; Neuronal Plasticity; Dendritic Spines; Long-Term Potentiation; Synapses; Cognition
PubMed: 37821392
DOI: 10.2183/pjab.99.018 -
The Journal of Comparative Neurology May 2023An important factor that can modulate neuron properties is sex-specific hormone fluctuations, including the human menstrual cycle and rat estrous cycle in adult females....
An important factor that can modulate neuron properties is sex-specific hormone fluctuations, including the human menstrual cycle and rat estrous cycle in adult females. Considering the striatal brain regions, the nucleus accumbens (NAc) core, NAc shell, and caudate-putamen (CPu), the estrous cycle has previously been shown to impact relevant behaviors and disorders, neuromodulator action, and medium spiny neuron (MSN) electrophysiology. Whether the estrous cycle impacts MSN dendritic spine attributes has not yet been examined, even though MSN spines and glutamatergic synapse properties are sensitive to exogenously applied estradiol. Thus, we hypothesized that MSN dendritic spine attributes would differ by estrous cycle phase. To test this hypothesis, brains from adult male rats and female rats in diestrus, proestrus AM, proestrus PM, and estrus were processed for Rapid Golgi-Cox staining. MSN dendritic spine density, size, and type were analyzed in the NAc core, NAc shell, and CPu. Overall spine size differed across estrous cycle phases in female NAc core and NAc shell, and spine length differed across estrous cycle phase in NAc shell and CPu. Consistent with previous work, dendritic spine density was increased in the NAc core compared to the NAc shell and CPu, independent of sex and estrous cycle. Spine attributes in all striatal regions did not differ by sex when estrous cycle was disregarded. These results indicate, for the first time, that estrous cycle phase impacts dendritic spine plasticity in striatal regions, providing a neuroanatomical avenue by which sex-specific hormone fluctuations can impact striatal function and disorders.
Topics: Humans; Rats; Female; Male; Animals; Nucleus Accumbens; Dendritic Spines; Rats, Sprague-Dawley; Putamen; Estrous Cycle; Estradiol
PubMed: 36756791
DOI: 10.1002/cne.25460 -
Nature Medicine Jun 2017Impaired learning and cognitive function often occurs during systemic infection or inflammation. Although activation of the innate immune system has been linked to the...
Impaired learning and cognitive function often occurs during systemic infection or inflammation. Although activation of the innate immune system has been linked to the behavioral and cognitive effects that are associated with infection, the underlying mechanisms remain poorly understood. Here we mimicked viral immune activation with poly(I:C), a synthetic analog of double-stranded RNA, and longitudinally imaged postsynaptic dendritic spines of layer V pyramidal neurons in the mouse primary motor cortex using two-photon microscopy. We found that peripheral immune activation caused dendritic spine loss, impairments in learning-dependent dendritic spine formation and deficits in multiple learning tasks in mice. These observed synaptic alterations in the cortex were mediated by peripheral-monocyte-derived cells and did not require microglial function in the central nervous system. Furthermore, activation of CX3CR1Ly6C monocytes impaired motor learning and learning-related dendritic spine plasticity through tumor necrosis factor (TNF)-α-dependent mechanisms. Taken together, our results highlight CX3CR1 monocytes and TNF-α as potential therapeutic targets for preventing infection-induced cognitive dysfunction.
Topics: Animals; Behavior, Animal; CX3C Chemokine Receptor 1; Dendritic Spines; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Immunohistochemistry; Intravital Microscopy; Learning; Mice; Microscopy; Monocytes; Motor Cortex; Neuronal Plasticity; Poly I-C; Polynucleotides; Pyramidal Cells; Receptors, Chemokine; Tumor Necrosis Factor-alpha
PubMed: 28504723
DOI: 10.1038/nm.4340 -
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 -
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 -
Molecular Neurobiology Jan 2017Changes in the morphology of dendritic spines are prominent during learning and in different neurological and neuropsychiatric diseases, including those in which...
Changes in the morphology of dendritic spines are prominent during learning and in different neurological and neuropsychiatric diseases, including those in which glycogen synthase kinase-3β (GSK-3β) has been implicated. Despite much evidence of the involvement of GSK-3β in functional synaptic plasticity, it is unclear how GSK-3β controls structural synaptic plasticity (i.e., the number and shape of dendritic spines). In the present study, we used two mouse models overexpressing and lacking GSK-3β in neurons to investigate how GSK-3β affects the structural plasticity of dendritic spines. Following visualization of dendritic spines with DiI dye, we found that increasing GSK-3β activity increased the number of thin spines, whereas lacking GSK-3β increased the number of stubby spines in the dentate gyrus. Under conditions of neuronal excitation, increasing GSK-3β activity caused higher activity of extracellularly acting matrix metalloproteinase-9 (MMP-9), and MMP inhibition normalized thin spines in GSK-3β overexpressing mice. Administration of the nonspecific GSK-3β inhibitor lithium in animals with active MMP-9 and animals lacking MMP-9 revealed that GSK-3β and MMP-9 act in concert to control dendritic spine morphology. Altogether, our data demonstrate that the dysregulation of GSK-3β activity has dramatic consequences on dendritic spine morphology, implicating MMP-9 as a mediator of GSK-3β-induced synaptic alterations.
Topics: Animals; Cell Size; Cells, Cultured; Dendritic Spines; Glycogen Synthase Kinase 3 beta; Hippocampus; Matrix Metalloproteinase 9; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Organ Culture Techniques; Phosphorylation; Protein Kinase Inhibitors; Rats; Rats, Transgenic; Rats, Wistar
PubMed: 26738851
DOI: 10.1007/s12035-015-9625-0 -
International Journal of Molecular... Apr 2021Numerous brain diseases are associated with abnormalities in morphology and density of dendritic spines, small membranous protrusions whose structural geometry... (Review)
Review
Numerous brain diseases are associated with abnormalities in morphology and density of dendritic spines, small membranous protrusions whose structural geometry correlates with the strength of synaptic connections. Thus, the quantitative analysis of dendritic spines remodeling in microscopic images is one of the key elements towards understanding mechanisms of structural neuronal plasticity and bases of brain pathology. In the following article, we review experimental approaches designed to assess quantitative features of dendritic spines under physiological stimuli and in pathological conditions. We compare various methodological pipelines of biological models, sample preparation, data analysis, image acquisition, sample size, and statistical analysis. The methodology and results of relevant experiments are systematically summarized in a tabular form. In particular, we focus on quantitative data regarding the number of animals, cells, dendritic spines, types of studied parameters, size of observed changes, and their statistical significance.
Topics: Actin Cytoskeleton; Animals; Brain Diseases; Dendritic Spines; Disease Models, Animal; Neuronal Plasticity; Synaptic Transmission
PubMed: 33919977
DOI: 10.3390/ijms22084053 -
Molecular and Cellular Neurosciences Sep 2013Dendritic spines are major sites of excitatory synaptic transmission and changes in their numbers and morphology have been associated with neurodevelopmental and...
Dendritic spines are major sites of excitatory synaptic transmission and changes in their numbers and morphology have been associated with neurodevelopmental and neurodegenerative disorders. Brain-derived Neurotrophic Factor (BDNF) is a secreted growth factor that influences hippocampal, striatal and neocortical pyramidal neuron dendritic spine density. However, the mechanisms by which BDNF regulates dendritic spines and how BDNF interacts with other regulators of spines remain unclear. We propose that one mechanism by which BDNF promotes dendritic spine formation is through an interaction with Wnt signaling. Here, we show that Wnt signaling inhibition in cultured cortical neurons disrupts dendritic spine development, reduces dendritic arbor size and complexity, and blocks BDNF-induced dendritic spine formation and maturation. Additionally, we show that BDNF regulates expression of Wnt2, and that Wnt2 is sufficient to promote cortical dendrite growth and dendritic spine formation. Together, these data suggest that BDNF and Wnt signaling cooperatively regulate dendritic spine formation.
Topics: Animals; Brain-Derived Neurotrophic Factor; Cell Growth Processes; Cells, Cultured; Cerebral Cortex; Dendritic Spines; Mice; Wnt Signaling Pathway; Wnt2 Protein
PubMed: 23639831
DOI: 10.1016/j.mcn.2013.04.006 -
Developmental Neurobiology Jul 2021Dendritic spines are membranous protrusions that receive essentially all excitatory inputs in most mammalian neurons. Spines, with a bulbous head connected to the...
Dendritic spines are membranous protrusions that receive essentially all excitatory inputs in most mammalian neurons. Spines, with a bulbous head connected to the dendrite by a thin neck, have a variety of morphologies that likely impact their functional properties. Nevertheless, the question of whether spines belong to distinct morphological subtypes is still open. Addressing this quantitatively requires clear identification and measurements of spine necks. Recent advances in electron microscopy enable large-scale systematic reconstructions of spines with nanometer precision in 3D. Analyzing ultrastructural reconstructions from mouse neocortical neurons with computer vision algorithms, we demonstrate that the vast majority of spine structures can be rigorously separated into heads and necks, enabling morphological measurements of spine necks. We then used a database of spine morphological parameters to explore the potential existence of different spine classes. Without exception, our analysis revealed unimodal distributions of individual morphological parameters of spine heads and necks, without evidence for subtypes of spines. The postsynaptic density size was strongly correlated with the spine head volume. The spine neck diameter, but not the neck length, was also correlated with the head volume. Spines with larger head volumes often had a spine apparatus and pairs of spines in a post-synaptic cell contacted by the same axon had similar head volumes. Our data reveal a lack of morphological subtypes of spines and indicate that the spine neck length and head volume must be independently regulated. These results have repercussions for our understanding of the function of dendritic spines in neuronal circuits.
Topics: Animals; Axons; Dendrites; Dendritic Spines; Mammals; Mice; Microscopy, Electron; Neurons; Synapses
PubMed: 33977655
DOI: 10.1002/dneu.22829