Spine Clusters Research Articles

Synapse-specific structural plasticity that protects and refines local circuits during LTP and LTD.

Synapses form trillions of connections in the brain. Long-term potentiation (LTP) and long-term depression (LTD) are cellular mechanisms vital for learning that modify the strength and structure of synapses. Three-dimensional reconstruction from serial section electron microscopy reveals three distinct pre- to post-synaptic arrangements: strong active zones (AZs) with tightly docked vesicles, weak AZs with loose or non-docked vesicles, and nascent zones (NZs) with a postsynaptic density but no presynaptic vesicles. Importantly, LTP can be temporarily saturated preventing further increases in synaptic strength. At the onset of LTP, vesicles are recruited to NZs, converting them to AZs. During recovery of LTP from saturation (1-4 h), new NZs form, especially on spines where AZs are most enlarged by LTP. Sentinel spines contain smooth endoplasmic reticulum (SER), have the largest synapses and form clusters with smaller spines lacking SER after LTP recovers. We propose a model whereby NZ plasticity provides synapse-specific AZ expansion during LTP and loss of weak AZs that drive synapse shrinkage during LTD. Spine clusters become functionally engaged during LTP or disassembled during LTD. Saturation of LTP or LTD probably acts to protect recently formed memories from ongoing plasticity and may account for the advantage of spaced over massed learning. This article is part of a discussion meeting issue 'Long-term potentiation: 50 years on'.

Engram mechanisms of memory linking and identity.

Memories are thought to be stored in neuronal ensembles referred to as engrams. Studies have suggested that when two memories occur in quick succession, a proportion of their engrams overlap and the memories become linked (in a process known as prospective linking) while maintaining their individual identities. In this Review, we summarize the key principles of memory linking through engram overlap, as revealed by experimental and modelling studies. We describe evidence of the involvement of synaptic memory substrates, spine clustering and non-linear neuronal capacities in prospective linking, and suggest a dynamic somato-synaptic model, in which memories are shared between neurons yet remain separable through distinct dendritic and synaptic allocation patterns. We also bring into focus retrospective linking, in which memories become associated after encoding via offline reactivation, and discuss key temporal and mechanistic differences between prospective and retrospective linking, as well as the potential differences in their cognitive outcomes.

Taphonomy of the middle Miocene regular echinoid spines from Cairo-Suez District, Egypt: Palaeoecological and palaeoenvironmental interpretations

The palaeoecology and palaeoenvironment of a dense cluster of regular echinoid spines that occur in an oyster-rich limestone layer are interpreted based on detailed taphonomic study. The paucispecific macrobenthic assemblage associated with these echinoid spines have been studied in the middle Miocene Geniefa Formation, Gebel Gharra, Cairo-Suez District of Egypt. Both echinoid spines and macrobenthic assemblages are dominated by moderately to well-preserved, moderately packed, highly disarticulated, moderately to poorly sorted, re-oriented, and moderately to highly fragmented specimens, confirming parautochthonous nature of this assemblage. The spines are commonly encrusted and bored. At least four taxonomic groups of encrusters are identified, including juvenile oysters, sheet-like cheilostome bryozoans, serpulids, and balanoid barnacles. The diversity of bioerosional ichnotaxa is moderate and includes Gastrochaenolites, Entobia, Maeandropolydora, Trypanites, and Spirolites. Moreover, some echinoid spines display distinct biting traces of fish, representing the first recorded of fish tooth bite marks on remains of regular echinoid spines from the Miocene deposits of Egypt. The faunal composition and trophic structure of the studied faunal assemblage indicate fully oxygenated and euhaline shallow-marine environment with meso- to eutrophic productivity level. The controlling environmental parameters include substrate consistency, bathymetry, water energy, surface-water productivity, and rate of sedimentation. Furthermore, two scenarios for sclerobionts colonisation and development of fish bite marks have been proposed. In the first syn vivo scenario, predatory fish either focused on the encrusting organisms attached to the spines or attacked the echinoid as a food source, resulting in the separation of spines from their original test during the echinoid’s life. In the second post-mortem scenario, disarticulated spines serve as a hard substrate for the colonisation of sclerobionts. Once again, the spines became subject to attacks by fish that fed on the encrusters, resulting in additional bite marks.

Synaptic Plasticity Is Predicted by Spatiotemporal Firing Rate Patterns and Robust to In Vivo-like Variability.

Synaptic plasticity, the experience-induced change in connections between neurons, underlies learning and memory in the brain. Most of our understanding of synaptic plasticity derives from in vitro experiments with precisely repeated stimulus patterns; however, neurons exhibit significant variability in vivo during repeated experiences. Further, the spatial pattern of synaptic inputs to the dendritic tree influences synaptic plasticity, yet is not considered in most synaptic plasticity rules. Here, we investigate how spatiotemporal synaptic input patterns produce plasticity with in vivo-like conditions using a data-driven computational model with a plasticity rule based on calcium dynamics. Using in vivo spike train recordings as inputs to different size clusters of spines, we show that plasticity is strongly robust to trial-to-trial variability of spike timing. In addition, we derive general synaptic plasticity rules describing how spatiotemporal patterns of synaptic inputs control the magnitude and direction of plasticity. Synapses that strongly potentiated have greater firing rates and calcium concentration later in the trial, whereas strongly depressing synapses have hiring firing rates early in the trial. The neighboring synaptic activity influences the direction and magnitude of synaptic plasticity, with small clusters of spines producing the greatest increase in synaptic strength. Together, our results reveal that calcium dynamics can unify diverse plasticity rules and reveal how spatiotemporal firing rate patterns control synaptic plasticity.

Dendritic Spine Density Scales with Microtubule Number in Rat Hippocampal Dendrites

Microtubules deliver essential resources to and from synapses. Three-dimensional reconstructions in rat hippocampus reveal a sampling bias regarding spine density that needs to be controlled for dendrite caliber and resource delivery based on microtubule number. The strength of this relationship varies across dendritic arbors, as illustrated for area CA1 and dentate gyrus. In both regions, proximal dendrites had more microtubules than distal dendrites. For CA1 pyramidal cells, spine density was greater on thicker than thinner dendrites in stratum radiatum, or on the more uniformly thin terminal dendrites in stratum lacunosum moleculare. In contrast, spine density was constant across the cone shaped arbor of tapering dendrites from dentate granule cells. These differences suggest that thicker dendrites supply microtubules to subsequent dendritic branches and local dendritic spines, whereas microtubules in thinner dendrites need only provide resources to local spines. Most microtubules ran parallel to dendrite length and associated with long, presumably stable mitochondria, which occasionally branched into lateral dendritic branches. Short, presumably mobile, mitochondria were tethered to microtubules that bent and appeared to direct them into a thin lateral branch. Prior work showed that dendritic segments with the same number of microtubules had elevated resources in subregions of their dendritic shafts where spine synapses had enlarged, and spine clusters had formed. Thus, additional microtubules were not required for redistribution of resources locally to growing spines or synapses. These results provide new understanding about the potential for microtubules to regulate resource delivery to and from dendritic branches and locally among dendritic spines.

Dual imaging of dendritic spines and mitochondria in vivo reveals hotspots of plasticity and metabolic adaptation to stress

Metabolic adaptation is a critical feature of synaptic plasticity. Indeed, synaptic plasticity requires the utilization and resupply of metabolites, in particular when the turnover is high and fast such as in stress conditions. What accounts for the localized energy burden of the post-synaptic compartment to the build up of chronic stress is currently not understood. We used in vivo microscopy of genetically encoded fluorescent probes to track changes of mitochondria, dendritic spines, ATP and H2O2 levels in pyramidal neurons of cortex before and after chronic unpredictable mild stress. Data revealed hotspots of postsynaptic mitochondria and dendritic spine turnover. Pharmacogenetic approach to force expression of the metabolic stress gene NR4A1 caused the fragmentation of postsynaptic mitochondria and loss of proximal dendritic spine clusters, whereas a dominant-negative mutant counteracted the effect of chronic stress. When fragmented, dendritic mitochondria produced lesser ATP at resting state and more on acute demand. This corresponded with significant production of mitochondrial H2O2 oxidative species in the dendritic compartment. Together, data indicate that pyramidal neurons adjust proximal dendritic spine turnover and mitochondria functions in keeping with synaptic demands.

Inhibition of Elevated Ras-MAPK Signaling Normalizes Enhanced Motor Learning and Excessive Clustered Dendritic Spine Stabilization in the MECP2-Duplication Syndrome Mouse Model of Autism.

The inflexible repetitive behaviors and "insistence on sameness" seen in autism imply a defect in neural processes controlling the balance between stability and plasticity of synaptic connections in the brain. It has been proposed that abnormalities in the Ras-ERK/MAPK pathway, a key plasticity-related cell signaling pathway known to drive consolidation of clustered synaptic connections, underlie altered learning phenotypes in autism. However, a link between altered Ras-ERK signaling and clustered dendritic spine plasticity has yet to be explored in an autism animal model in vivo The formation and stabilization of dendritic spine clusters is abnormally increased in the MECP2-duplication syndrome mouse model of syndromic autism, suggesting that ERK signaling may be increased. Here, we show that the Ras-ERK pathway is indeed hyperactive following motor training in MECP2-duplication mouse motor cortex. Pharmacological inhibition of ERK signaling normalizes the excessive clustered spine stabilization and enhanced motor learning behavior in MECP2-duplication mice. We conclude that hyperactive ERK signaling may contribute to abnormal clustered dendritic spine consolidation and motor learning in this model of syndromic autism.

An early Miocene spatangoid assemblage on a submarine volcanic ash dune from Patagonia (Argentina)

A single 27 m2 spatangoid-dominated bed yielding 65 specimens from the Punta Entrada Member of the Monte León Formation was studied. Most of the fossils were preserved oral side down, with clusters of spines attached to the tests, showing no evidence of preburial transport. The deposit is interpreted as the result of sedimentation in a subtidal environment coeval with strong and continuous explosive volcanic activity, indicated by the significant amount of volcanic ash within the sediment. Echinoids assigned to Brisaster aff. B. iheringi De Loriol, 1902 colonized a distal part of the subtidal environment dominated by large-scale migrant bedforms. During dormant periods, it was characterized by low energy and low sedimentation rate, allowing colonization by several groups of infaunal organisms. Upon reactivation of sediment migration, a high sedimentary influx trapped the echinoids and prevented them from escaping.

Heterosynaptic cross-talk of pre- and postsynaptic strengths along segments of dendrites

Dendrites are crucial for integrating incoming synaptic information. Individual dendritic branches are thought to constitute a signal processing unit, yet how neighboring synapses shape the boundaries of functional dendritic units is not well understood. Here, we address the cellular basis underlying the organization of the strengths of neighboring Schaffer collateral-CA1 synapses by optical quantal analysis and spine size measurements. Inducing potentiation at clusters of spines produces NMDA-receptor-dependent heterosynaptic plasticity. The direction of postsynaptic strength change shows distance dependency to the stimulated synapses where proximal synapses predominantly depress, whereas distal synapses potentiate; potentiation and depression are regulated by CaMKII and calcineurin, respectively. In contrast, heterosynaptic presynaptic plasticity is confined to weakening of presynaptic strength of nearby synapses, which requires CaMKII and the retrograde messenger nitric oxide. Our findings highlight the parallel engagement of multiple signaling pathways, each with characteristic spatial dynamics in shaping the local pattern of synaptic strengths.

Excessive Formation and Stabilization of Dendritic Spine Clusters in the MECP2-Duplication Syndrome Mouse Model of Autism.

Autism-associated genetic mutations may perturb the balance between stability and plasticity of synaptic connections in the brain. Here, we report an increase in the formation and stabilization of dendritic spines in the cerebral cortex of the mouse model of MECP2-duplication syndrome, a high-penetrance form of syndromic autism. Increased stabilization is mediated entirely by spines that form cooperatively in 10-μm clusters and is observable across multiple cortical areas both spontaneously and following motor training. Excessive stability of dendritic spine clusters could contribute to behavioral rigidity and other phenotypes in syndromic autism.

Structural LTP: from synaptogenesis to regulated synapse enlargement and clustering.

Nature teaches us that form precedes function, yet structure and function are intertwined. Such is the case with synapse structure, function, and plasticity underlying learning, especially in the hippocampus, a crucial brain region for memory formation. As the hippocampus matures, enduring changes in synapse structure produced by long-term potentiation (LTP) shift from synaptogenesis to synapse enlargement that is homeostatically balanced by stalled spine outgrowth and local spine clustering. Production of LTP leads to silent spine outgrowth at P15, and silent synapse enlargement in adult hippocampus at 2hours, but not at 5 or 30min following induction. Here we consider structural LTP in the context of developmental stage and variation in the availability of local resources of endosomes, smooth endoplasmic reticulum and polyribosomes. The emerging evidence supports a need for more nuanced analysis of synaptic plasticity in the context of subcellular resource availability and developmental stage.

Lack of change in CA1 dendritic spine density or clustering in rats following training on a radial-arm maze task.

Background:Neuronal plasticity is thought to underlie learning and memory formation. The density of dendritic spines in the CA1 region of the hippocampus has been repeatedly linked to mnemonic processes. Both the number and spatial location of the spines, in terms of proximity to nearest neighbour, have been implicated in memory formation. To examine how spatial training impacts synaptic structure in the hippocampus, Lister-Hooded rats were trained on a hippocampal-dependent spatial task in the radial-arm maze. Methods:One group of rats were trained on a hippocampal-dependent spatial task in the radial arm maze. Two further control groups were included: a yoked group which received the same sensorimotor stimulation in the radial-maze but without a memory load, and home-cage controls. At the end of behavioural training, the brains underwent Golgi staining. Spines on CA1 pyramidal neuron dendrites were imaged and quantitatively assessed to provide measures of density and distance from nearest neighbour. Results: There was no difference across behavioural groups either in terms of spine density or in the clustering of dendritic spines. Conclusions:Spatial learning is not always accompanied by changes in either the density or clustering of dendritic spines on the basal arbour of CA1 pyramidal neurons when assessed using Golgi imaging.

Individual and synergistic effects of male external genital traits in sexual selection.

Male genital traits exhibit extraordinary interspecific phenotypic variation. This remarkable and general evolutionary trend is widely considered to be the result of sexual selection. However, we still do not have a good understanding of whether or how individual genital traits function in different competitive arenas (episodes of sexual selection), or how different genital traits may interact to influence competitive outcomes. Here, we use an experimental approach based on high-precision laser phenotypic engineering to address these outstanding questions, focusing on three distinct sets of micron-scale external (nonintromittent) genital spines in male Drosophila kikkawai Burla (Diptera: Drosophilidae). Elimination of the large pair of spines on the male secondary claspers sharply reduced male ability to copulate, yet elimination of the other sets of spines on the primary and secondary claspers had no significant effects on copulation probability. Intriguingly, both the large spines on the secondary claspers and the cluster of spines on the primary claspers were found to independently promote male competitive fertilization success. Moreover, when large and small secondary clasper spines were simultaneously shortened in individual males, these males suffered greater reductions in fertilization success relative to males whose traits were altered individually, providing evidence for synergistic effects of external genital traits on fertilization success. Overall, the results are significant in demonstrating that a given genital trait (the large spines on the secondary claspers) can function in different episodes of sexual selection, and distinct genital traits may interact in sexual selection. The results offer an important contribution to evolutionary biology by demonstrating an understudied selective mechanism, operating via subtle trait interactions in a post-insemination context, by which genital traits may be co-evolving.

Dendritic Spine Density and Dynamics of Layer 5 Pyramidal Neurons of the Primary Motor Cortex Are Elevated With Aging.

It is well established that motor impairment often occurs alongside healthy aging, leading to problems with fine motor skills and coordination. Although previously thought to be caused by neuronal death accumulating across the lifespan, it is now believed that the source of this impairment instead stems from more subtle changes in neural connectivity. The dendritic spine is a prime target for exploration of this problem because it is the postsynaptic partner of most excitatory synapses received by the pyramidal neuron, a cortical cell that carries much of the information processing load in the cerebral cortex. We repeatedly imaged the same dendrites in young adult and aged mouse motor cortex over the course of 1month to look for differences in the baseline state of the dendritic spine population. These experiments reveal increased dendritic spine density, without obvious changes in spine clustering, occurring at the aged dendrite. Additionally, aged dendrites exhibit elevated spine turnover and stabilization alongside decreased long-term spine survival. These results suggest that at baseline the aged motor cortex may exist in a perpetual state of relative instability and attempts at compensation. This phenotype of aging may provide clues for future targets of aging-related motor impairment remediation.

Reduced sensory-evoked structural plasticity in the aging barrel cortex

Impairments in synaptic connectivity have been linked to cognitive deficits in age-related neurodegenerative disorders and healthy aging. However, the anatomical and structural bases of these impairments have not been identified yet. A hallmark of neural plasticity in young adults is short-term synaptic rearrangement, yet aged animals already display higher synaptic turnover rates at the baseline. Using two-photon excitation (2PE) microscopy, we explored if this elevated turnover alters the aged brain's response to plasticity. Following a sensory-evoked plasticity protocol involving whisker stimulation, aged mice display reduced spine dynamics (gain, loss, and turnover), decreased spine clustering, and lower spine stability when compared to young adult mice. These results suggest a deficiency of the cortical neurons of aged mice to structurally incorporate new sensory experiences, in the form of clustered, long-lasting synapses, into already existing cortical circuits. This research provides the first evidence linking experience-dependent plasticity with in vivo spine dynamics in the aged brain and supports a model of both reduced synaptic plasticity and reduced synaptic tenacity in the aged somatosensory system.

A green algae (Chaetophorales: Chaetophoraceae) in Burmese amber

ABSTRACT A green alga in Burmese amber is described as Electrophycus astroplethus gen. et spec. nov. and tentatively placed in the extant family Chaetophoraceae. The new species is characterised by apical–basal polarity as defined by a holdfast located at the base of the filament cluster, and uniseriate filaments with many attached star-shaped clusters of spines. Reproductive units are produced in the spines. The species is considered to represent a terrestrial aerial alga that quite possibly was growing on the bark of the resin-producing tree. The presence of an oribatid mite (Acari: Oribatida), species of which are known to feed on algae, adjacent to the filaments, supports this view.

Local resources of polyribosomes and SER promote synapse enlargement and spine clustering after long-term potentiation in adult rat hippocampus

Synapse clustering facilitates circuit integration, learning, and memory. Long-term potentiation (LTP) of mature neurons produces synapse enlargement balanced by fewer spines, raising the question of how clusters form despite this homeostatic regulation of total synaptic weight. Three-dimensional reconstruction from serial section electron microscopy (3DEM) revealed the shapes and distributions of smooth endoplasmic reticulum (SER) and polyribosomes, subcellular resources important for synapse enlargement and spine outgrowth. Compared to control stimulation, synapses were enlarged two hours after LTP on resource-rich spines containing polyribosomes (4% larger than control) or SER (15% larger). SER in spines shifted from a single tubule to complex spine apparatus after LTP. Negligible synapse enlargement (0.6%) occurred on resource-poor spines lacking SER and polyribosomes. Dendrites were divided into discrete synaptic clusters surrounded by asynaptic segments. Spine density was lowest in clusters having only resource-poor spines, especially following LTP. In contrast, resource-rich spines preserved neighboring resource-poor spines and formed larger clusters with elevated total synaptic weight following LTP. These clusters also had more shaft SER branches, which could sequester cargo locally to support synapse growth and spinogenesis. Thus, resources appear to be redistributed to synaptic clusters with LTP-related synapse enlargement while homeostatic regulation suppressed spine outgrowth in resource-poor synaptic clusters.

Phyllocnistis podocarpa sp. nov. (Lepidoptera, Gracillariidae), a buddhist pine leaf-miner from Japan: taxonomy, DNA barcodes, damage and parasitoids.

Phyllocnistis podocarpa sp. nov., is described from mines in Podocarpus macrophyllus (Family Podocarpaceae). The host plant P. macrophyllus, also known as buddhist pine on the IUCN Red List, is a noticeable garden plant and thus of high economic value. Buddhist pine has been introduced to many other countries from its native habitat in southern Japan. Special attention has been paid for it during the overseas import in China. The morphology of the pupae of P. podocarpa, particularly the frontal process of the head and the spine clusters on terga, ones of the most useful diagnostic characters for species identification of Phyllocnistis on morphology, is demonstrated using SEM. Two parasitoid species of Eulophidae (Hymenoptera) are identified and illustrated. COI barcode sequences are provided along with a Neighbor Joining Tree covering related species for aiding identification.

Hotspots of dendritic spine turnover facilitate clustered spine addition and learning and memory

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.

Effects of location and extent of spine clustering on synaptic integration in striatal medium spiny neurons—a computational study

The nucleus accumbens (NAc) is known widely for its role in the reward circuit, which is dysregulated in a number of psychological disorders. Recent evidence also suggests the contribution of this structure in spatial and gustatory memories. Because of its role in different types of memories, similar to the hippocampus, we assumed the formation of spine clusters, which are engrams of memory, to be present on dendrites of medium spiny neurons (MSNs). We found that the activation of clustered inputs resulted in sublinear summation when clusters were present on the same branch and also when inputs were distributed on different branches. The size, as well as the location of clusters, was found to affect the summation. With an increase in cluster size and distance from soma, the summation was increasingly sublinear. When the temporal integration window was measured for clustered spines, it was found to be narrower as compared to that for a single spine. Also, distally located clusters resulted in a wider temporal window, as compared to proximal clusters. Our results suggest that depending on the location of clusters, the modes of integration will differ in MSNs possessing clustered spines.