Individual Spines Research Articles

Imaging membrane potential changes from dendritic spines using computer-generated holography.

Electrical properties of neuronal processes are extraordinarily complex, dynamic, and, in the general case, impossible to predict in the absence of detailed measurements. To obtain such a measurement one would, ideally, like to be able to monitor electrical subthreshold events as they travel from synapses on distal dendrites and summate at particular locations to initiate action potentials. It is now possible to carry out these measurements at the scale of individual dendritic spines using voltage imaging. In these measurements, the voltage-sensitive probes can be thought of as transmembrane voltmeters with a linear scale, which directly monitor electrical signals. Grinvald etal. were important early contributors to the methodology of voltage imaging, and they pioneered some of its significant results. We combined voltage imaging and glutamate uncaging using computer-generated holography. The results demonstrated that patterned illumination, by reducing the surface area of illuminated membrane, reduces photodynamic damage. Additionally, region-specific illumination practically eliminated the contamination of optical signals from individual spines by the scattered light from the parent dendrite. Finally, patterned illumination allowed one-photon uncaging of glutamate on multiple spines to be carried out in parallel with voltage imaging from the parent dendrite and neighboring spines.

Time-lapse changes of in vivo injured neuronal substructures in the central nervous system after low energy two-photon nanosurgery.

There is currently very little research regarding the dynamics of the subcellular degenerative events that occur in the central nervous system in response to injury. To date, multi-photon excitation has been primarily used for imaging applications; however, it has been recently used to selectively disrupt neural structures in living animals. However, understanding the complicated processes and the essential underlying molecular pathways involved in these dynamic events is necessary for studying the underlying process that promotes neuronal regeneration. In this study, we introduced a novel method allowing in vivo use of low energy (less than 30 mW) two-photon nanosurgery to selectively disrupt individual dendrites, axons, and dendritic spines in the murine brain and spinal cord to accurately monitor the time-lapse changes in the injured neuronal structures. Individual axons, dendrites, and dendritic spines in the brain and spinal cord were successfully ablated and in vivo imaging revealed the time-lapse alterations in these structures in response to the two-photon nanosurgery induced lesion. The energy (less than 30 mW) used in this study was very low and caused no observable additional damage in the neuronal sub-structures that occur frequently, especially in dendritic spines, with current commonly used methods using high energy levels. In addition, our approach includes the option of monitoring the time-varying dynamics to control the degree of lesion. The method presented here may be used to provide new insight into the growth of axons and dendrites in response to acute injury.

State-dependent diffusion of actin-depolymerizing factor/cofilin underlies the enlargement and shrinkage of dendritic spines.

Dendritic spines are the postsynaptic sites of most excitatory synapses in the brain, and spine enlargement and shrinkage give rise to long-term potentiation and depression of synapses, respectively. Because spine structural plasticity is accompanied by remodeling of actin scaffolds, we hypothesized that the filamentous actin regulatory protein cofilin plays a crucial role in this process. Here we investigated the diffusional properties of cofilin, the actin-severing and depolymerizing actions of which are activated by dephosphorylation. Cofilin diffusion was measured using fluorescently labeled cofilin fusion proteins and two-photon imaging. We show that cofilins are highly diffusible along dendrites in the resting state. However, during spine enlargement, wild-type cofilin and a phosphomimetic cofilin mutant remain confined to the stimulated spine, whereas a nonphosphorylatable mutant does not. Moreover, inhibition of cofilin phosphorylation with a competitive peptide disables spine enlargement, suggesting that phosphorylated-cofilin accumulation is a key regulator of enlargement, which is localized to individual spines. Conversely, spine shrinkage spreads to neighboring spines, even though triggered by weaker stimuli than enlargement. Diffusion of exogenous cofilin injected into a pyramidal neuron soma causes spine shrinkage and reduced PSD95 in spines, suggesting that diffusion of dephosphorylated endogenous cofilin underlies the spreading of spine shrinkage and long-term depression.

COMPUTED TOMOGRAPHY MORPHOMETRIC ANALYSIS OF THE VERTEBRAE C7 AND T1

ABSTRACT Objective: The anatomical study of the vertebrae C7 and T1 of the cervicothoracic junction aimed to evaluate quantitatively, by axial computerized tomography (CT), the linear and angular dimensions of the anatomical laminae of the vertebrae of the cervicothoracic junction C7 and T1 in adults over 18 years. Methods: We retrospectively analyzed 49 CT of the cervical and thoracic spine (C7 and T1) of individuals over 18 years, of both sexes. We also evaluated the length and thickness of the laminae, as well as spinolaminar angle in axial sections of C7 and T1 at the point of least thickness between the inner cortical layers. The variables were correlated with age groups and sex of the individuals. Statistical analysis was performed using the t test and the results were considered significant when p<0.05. Results: After analyzing tomographic measurements of 49 patients, it was found that men had greater laminae thickness than women, both in C7 and T1, with 71% of C7 laminae and 92% of T1 laminae thicker than 5mm, and 97% of C7 laminae and 100% of T1 thicker than 4mm. The mean spinolaminar angle was 56.40 degrees in C7 and 57.31 degrees in T1. Conclusion: This study brings important anatomical information about the cervicothoracic junction C7 and T1 in the Brazilian population, showing that fixation of C7 and T1 with intralaminar screws is anatomically possible.

Loss of SynDIG1 Reduces Excitatory Synapse Maturation But Not Formation In Vivo.

Modification of the strength of excitatory synaptic connections is a fundamental mechanism by which neural circuits are refined during development and learning. Synapse Differentiation Induced Gene 1 (SynDIG1) has been shown to play a key role in regulating synaptic strength in vitro. Here, we investigated the role of SynDIG1 in vivo in mice with a disruption of the SynDIG1 gene rather than use an alternate loxP-flanked conditional mutant that we find retains a partial protein product. The gene-trap insertion with a reporter cassette mutant mice shows that the SynDIG1 promoter is active during embryogenesis in the retina with some activity in the brain, and postnatally in the mouse hippocampus, cortex, hindbrain, and spinal cord. Ultrastructural analysis of the hippocampal CA1 region shows a decrease in the average PSD length of synapses and a decrease in the number of synapses with a mature phenotype. Intriguingly, the total synapse number appears to be increased in SynDIG1 mutant mice. Electrophysiological analyses show a decrease in AMPA and NMDA receptor function in SynDIG1-deficient hippocampal neurons. Glutamate stimulation of individual dendritic spines in hippocampal slices from SynDIG1-deficient mice reveals increased short-term structural plasticity. Notably, the overall levels of PSD-95 or glutamate receptors enriched in postsynaptic biochemical fractions remain unaltered; however, activity-dependent synapse development is strongly compromised upon the loss of SynDIG1, supporting its importance for excitatory synapse maturation. Together, these data are consistent with a model in which SynDIG1 regulates the maturation of excitatory synapse structure and function in the mouse hippocampus in vivo.

Effects of Volitional Spine Stabilization and Lower-Extremity Fatigue on the Knee and Ankle During Landing Performance in a Population With Recurrent Low Back Pain

Recurrent lower back pain (rLBP) and neuromuscular fatigue are independently thought to increase the risk of lower extremity (LE) injury. Volitional preemptive abdominal contraction (VPAC) is thought to improve lumbar spine and pelvis control in individuals with rLBP. The effects of VPAC on fatigued landing performance in individuals with rLBP are unknown. To determine the effects of VPAC and LE fatigue on landing performance in a rLBP population. Cross-sectional pretest-posttest cohort control design. A clinical biomechanics laboratory. 32 rLBP (age 21.2 ± 2.7 y) but without current symptoms and 33 healthy (age 20.9 ± 2.3 y) subjects. (i) Volitional preemptive abdominal contraction using abdominal bracing and (ii) fatigue using submaximal free-weight squat protocol with 15% body weight until task failure was achieved. Knee and ankle angles, moments, electromyographic measurements from semitendinosus and vastus medialis muscles, and ground reaction force (GRF) were collected during 0.30 m drop-jump landings. The VPAC resulted in significantly earlier muscle onsets across all muscles with and without fatigue in both groups (mean ± SD, 0.063 ± 0.016 s earlier; P ≤ .001). Fatigue significantly delayed semitendinosus muscle onsets (0.033 ± 0.024 s later; P ≤ .001), decreased GRF (P ≤ .001), and altered landing kinematics in a variety of ways. The rLBP group exhibited delayed semitendinosus and vastus medialis muscle onsets (0.031 ± 0.028 s later; P ≤ .001) and 1.8° less knee flexion at initial contact (P ≤ .008). The VPAC decreases some of the detrimental effects of fatigue on landing biomechanics and thus may reduce LE injury risk in a rLBP population.

Secular trends in fracture incidence in the UK between 1990 and 2012.

There is increasing evidence of secular changes in age- and sex- adjusted fracture incidence globally. Such observations broadly suggest decreasing rates in developed countries and increasing rates in transitioning populations. Since altered fracture rates have major implications for healthcare provision and planning, we investigated secular changes to age- and sex-adjusted fracture risk amongst the UK population aged 50years or above from 1990 till 2012. We undertook a retrospective observational study using the Clinical Practice Research Datalink (CPRD), which contains the health records of 6.9% of the UK population. Site-specific fracture incidence was calculated by calendar year for men and women separately, with fracture type categorised according to ICD-9 classification. Linear regression analysis was used to calculate mean annualised change in absolute incidence. For presentational purposes, mean rates in the first 5years and last 5years of the period were calculated. Overall fracture incidence was unchanged in both women and men from 1990 to 2012. The incidence of hip fracture remained stable amongst women (1990-1994 33.8 per 10,000py; 2008-2012 33.5 per 10,000py; p trend annualised change in incidence = 0.80) but rose in men across the same period (10.8 to 13.4 per 10,000py; p = 0.002). Clinical vertebral fractures became more common in women (8.9 to 11.8 per 10,000py; p = 0.005) but remained comparable in men (4.6 to 5.9 per 10,000py; p = 0.72). Similarly, the frequency of radius/ulna fractures did not change in men (9.6 to 9.6 per 10,000py; p = 0.25), but, in contrast, became less frequent in women (50.4 to 41.2 per 10,000py; p = 0.001). Secular trends amongst fractures of the carpus, scapula, humerus, foot, pelvis, skull, clavicle, ankle, patella, and ribs varied according to fracture site and sex. Although overall sex-specific fracture incidence in the UK population 50years or over appears to have remained stable over the last two decades, there have been noticeable changes in rates of individual fracture types. Given that the impact of a fracture on morbidity, mortality, and health economy varies according to fracture site, these data inform the provision of healthcare services in the UK and elsewhere.

Degenerative Changes in the Cervical Spine Are More Common in Middle-Aged Individuals with Thalidomide Embryopathy than in Healthy Controls.

BackgroundThalidomide was used as a sedative drug for pregnant women in the 1950–60:s and resulted in children born with thalidomide embryopathy (TE), including upper limb malformations. These may alter the motion pattern of the cervical spine by the use of head/shoulder and mouth grip.AimsTo compare degenerative changes in the cervical spine in TE individuals with healthy controls (CTR).Methods and ProceduresTwenty-seven middle-aged TE individuals and 27 age- and gender-matched CTR were examined by cervical spine MRI. The presence of malformations, disc herniation(s), osteophytes, nerve and medullary compression and the degree of disc degeneration (DD) were evaluated.Outcomes and ResultsSignificantly higher degree of DD was seen in the TE group compared with the controls (p<0.001). Similar frequencies of disc herniation and disc space narrowing were observed in the two groups, but more foraminal narrowing was seen in the TE group (p = 0.002). DD was observed relatively frequently at all cervical levels in the TE group, however, mainly at the two lower levels in the CTR.Conclusions and ImplicationsMiddle-aged individuals with TE have a higher frequency of degenerative changes in the cervical spine than controls, possibly caused by an altered load on the cervical spine.

Location-dependent synaptic plasticity rules by dendritic spine cooperativity.

Nonlinear interactions between coactive synapses enable neurons to discriminate between spatiotemporal patterns of inputs. Using patterned postsynaptic stimulation by two-photon glutamate uncaging, here we investigate the sensitivity of synaptic Ca2+ signalling and long-term plasticity in individual spines to coincident activity of nearby synapses. We find a proximodistally increasing gradient of nonlinear NMDA receptor (NMDAR)-mediated amplification of spine Ca2+ signals by a few neighbouring coactive synapses along individual perisomatic dendrites. This synaptic cooperativity does not require dendritic spikes, but is correlated with dendritic Na+ spike propagation strength. Furthermore, we show that repetitive synchronous subthreshold activation of small spine clusters produces input specific, NMDAR-dependent cooperative long-term potentiation at distal but not proximal dendritic locations. The sensitive synaptic cooperativity at distal dendritic compartments shown here may promote the formation of functional synaptic clusters, which in turn can facilitate active dendritic processing and storage of information encoded in spatiotemporal synaptic activity patterns.

In vivo imaging demonstrates dendritic spine stabilization by SynCAM 1.

Formation and stability of synapses are required for proper brain function. While it is well established that synaptic adhesion molecules are important regulators of synapse formation, their specific role during different phases of synapse development remains unclear. To investigate the function of the synaptic cell adhesion molecule SynCAM 1 in the formation, stability, and maintenance of spines we used 2-photon in vivo imaging to follow individual spines over a long period of time. In SynCAM 1 knockout mice the survival rate of existing spines was reduced and fewer filopodia-like structures were converted into stable spines. SynCAM 1flag overexpression resulted in more stable spines and fewer filopodia-like structures. When SynCAM 1flag overexpression is turned on the spine density rapidly increases within a few days. Interestingly, the spine density stayed at an elevated level when SynCAM 1flag overexpression was turned off. Our data indicate that the SynCAM 1 induced altered spine density is not caused by the formation of newly emerging protrusions, instead SynCAM 1 stabilizes nascent synaptic contacts which promotes their maturation. Concomitant with the synaptic stabilization, SynCAM 1 generally prolongs the lifetime of spines. In summary, we demonstrate that SynCAM 1 is a key regulator of spine stability.

2dSpAn: semiautomated 2-d segmentation, classification and analysis of hippocampal dendritic spine plasticity.

Accurate and effective dendritic spine segmentation from the dendrites remains as a challenge for current neuroimaging research community. In this article, we present a new method (2dSpAn) for 2-d segmentation, classification and analysis of structural/plastic changes of hippocampal dendritic spines. A user interactive segmentation method with convolution kernels is designed to segment the spines from the dendrites. Formal morphological definitions are presented to describe key attributes related to the shape of segmented spines. Spines are automatically classified into one of four classes: Stubby, Filopodia, Mushroom and Spine-head Protrusions. The developed method is validated using confocal light microscopy images of dendritic spines from dissociated hippocampal cultures for: (i) quantitative analysis of spine morphological changes, (ii) reproducibility analysis for assessment of user-independence of the developed software and (iii) accuracy analysis with respect to the manually labeled ground truth images, and also with respect to the available state of the art. The developed method is monitored and used to precisely describe the morphology of individual spines in real-time experiments, i.e. consequent images of the same dendritic fragment. The software and the source code are available at https://sites.google.com/site/2dspan/ under open-source license for non-commercial use. subhadip@cse.jdvu.ac.in or j.wlodarczyk@nencki.gov.pl Supplementary data are available at Bioinformatics online.

Dynamic impact testing of hedgehog spines using a dual-arm crash pendulum

Hedgehog spines are a potential model for impact resistant structures and material. While previous studies have examined static mechanical properties of individual spines, actual collision tests on spines analogous to those observed in the wild have not previously been investigated. In this study, samples of roughly 130 keratin spines were mounted vertically in thin substrates to mimic the natural spine layout on hedgehogs. A weighted crash pendulum was employed to induce and measure the effects of repeated collisions against samples, with the aim to evaluate the influence of various parameters including humidity effect, impact energy, and substrate hardness. Results reveal that softer samples—due to humidity conditioning and/or substrate material used—exhibit greater durability over multiple impacts, while the more rigid samples exhibit greater energy absorption performance at the expense of durability. This trend is exaggerated during high-energy collisions. Comparison of the results to baseline tests with industry standard impact absorbing foam, wherein the spines exhibit similar energy absorption, verifies the dynamic impact absorption capabilities of hedgehog spines and their candidacy as a structural model for engineered impact technology.

Mesoscale morphology at nanoscale resolution: serial block-face scanning electron microscopy reveals fine 3D detail of a novel silk spinneret system in a tube-building tanaid crustacean.

BackgroundThe study of morphology is experiencing a renaissance due to rapid improvements in technologies for 3D visualization of complex internal and external structures. But 3D visualization of the internal structure of mesoscale objects — those in the 10–1000 μm range — remains problematic. They are too small for microCT, many lack suitable specific fluorescent markers for confocal microscopy, or they require labor-intensive stacking and smoothing of individual TEM images. Here we illustrate the first comprehensive morphological description of a complete mesoscale biological system at nanoscopic resolution using ultra-modern technology for 3D visualization — serial block-face scanning electron microscopy (SBF-SEM). The SBF-SEM machine combines an in-chamber ultramicrotome, which creates a serial array of exposed surfaces, with an SEM that images each surface as it is exposed. The serial images are then stacked automatically by 3D reconstruction software. We used SBF-SEM to study the spinneret (thread-producing) system of a small, tube-dwelling crustacean that weaves tubes of silk. Thread-producing ability is critical for the survival of many small-bodied animals but the basic morphology of these systems remains mysterious due to the limits of traditional microscopy.ResultsSBF-SEM allowed us to describe — in full 3D — well-resolved components (glands, ducts, pores, and associated nerves and muscles) of the spinneret system in the thoracic legs and body segments of Sinelobus sp. (Crustacea, Peracarida, Tanaidacea), a tube-building tanaid only 2 mm in body length. The 3D reconstruction by SBF-SEM revealed at nanoscale resolution a unique structure to the gland and duct systems: In each of three thread-producing thoracic segments, two separate ducts, derived from two separate glands located in the body, run through the entire leg and merge at the leg tip just before the spinneret pore opening. We also resolved nerves connecting to individual setae, spines and pores on the walking legs, and individual muscles within each leg segment.ConclusionsOur results significantly expand our understanding of the diversity of spinneret systems in the Crustacea by providing the first well-resolved view of spinneret components in the peracarid crustacean order, Tanaidacea. More significantly, our results reveal the great power of SBF-SEM technology for comprehensive studies of the morphology of microscopic animals.Electronic supplementary materialThe online version of this article (doi:10.1186/s12983-016-0146-0) contains supplementary material, which is available to authorized users.

17β-Estradiol Acutely Potentiates Glutamatergic Synaptic Transmission in the Hippocampus through Distinct Mechanisms in Males and Females

Estradiol (E2) acutely potentiates glutamatergic synaptic transmission in the hippocampus of both male and female rats. Here, we investigated whether E2-induced synaptic potentiation occurs via presynaptic and/or postsynaptic mechanisms and which estrogen receptors (ERs) mediate E2's effects in each sex. Whole-cell voltage-clamp recordings of mEPSCs in CA1 pyramidal neurons showed that E2 increases both mEPSC frequency and amplitude within minutes, but often in different cells. This indicated that both presynaptic and postsynaptic mechanisms are involved, but that they occur largely at different synapses. Two-photon (2p) glutamate uncaging at individual dendritic spines showed that E2 increases the amplitude of uncaging-evoked EPSCs (2pEPSCs) and calcium transients (2pCaTs) at a subset of spines on a dendrite, demonstrating synapse specificity of E2's postsynaptic effects. All of these results were essentially the same in males and females. However, additional experiments using ER-selective agonists indicated sex differences in the mechanisms underlying E2-induced potentiation. In males, an ERβ agonist mimicked the postsynaptic effects of E2 to increase mEPSC, 2pEPSC, and 2pCaT amplitude, whereas in females, these effects were mimicked by an agonist of G protein-coupled ER-1. The presynaptic effect of E2, increased mEPSC frequency, was mimicked by an ERα agonist in males, whereas in females, an ERβ agonist increased mEPSC frequency. Thus, E2 acutely potentiates glutamatergic synapses similarly in both sexes, but distinct ER subtypes mediate the presynaptic and postsynaptic aspects of potentiation in each sex. This indicates a latent sex difference in which different molecular mechanisms converge to the same functional endpoint in males versus females. Some sex differences in the brain may be latent differences, in which the same functional endpoint is achieved through distinct underlying mechanisms in males versus females. Here we report a latent sex difference in molecular regulation of excitatory synapses in the hippocampus. The steroid 17β-estradiol is known to acutely potentiate glutamatergic synaptic transmission in both sexes. We find that this occurs through a combination of increased presynaptic glutamate release probability and increased postsynaptic sensitivity to glutamate in both sexes, but that distinct estrogen receptor subtypes underlie each aspect of potentiation in each sex. These results indicate that therapeutics targeting a specific estrogen receptor subtype or its downstream signaling would likely affect synaptic transmission differently in the hippocampus of each sex.

Posttranslational Modifications Regulate the Postsynaptic Localization of PSD-95.

The postsynaptic density (PSD) consists of a lattice-like array of interacting proteins that organizes and stabilizes synaptic receptors, ion channels, structural proteins, and signaling molecules required for normal synaptic transmission and synaptic function. The scaffolding and hub protein postsynaptic density protein-95 (PSD-95) is a major element of central chemical synapses and interacts with glutamate receptors, cell adhesion molecules, and cytoskeletal elements. In fact, PSD-95 can regulate basal synaptic stability as well as the activity-dependent structural plasticity of the PSD and, therefore, of the excitatory chemical synapse. Several studies have shown that PSD-95 is highly enriched at excitatory synapses and have identified multiple protein structural domains and protein-protein interactions that mediate PSD-95 function and trafficking to the postsynaptic region. PSD-95 is also a target of several signaling pathways that induce posttranslational modifications, including palmitoylation, phosphorylation, ubiquitination, nitrosylation, and neddylation; these modifications determine the synaptic stability and function of PSD-95 and thus regulate the fates of individual dendritic spines in the nervous system. In the present work, we review the posttranslational modifications that regulate the synaptic localization of PSD-95 and describe their functional consequences. We also explore the signaling pathways that induce such changes.

Calibration of Sub-Threshold Evoked EPSPs in Dendritic Spines using Voltage-Sensitive Dyes

Dendritic spines are specialized structures in the brain that receive excitatory synaptic inputs. Activation of synaptic receptors on spines leads to current influx that depolarizes the activated spine, the parent dendrite and the neuron's somatic and axonal compartments. Local membrane potential fluctuations affect voltage-dependent channels producing calcium influx in an interplay of electrical and biochemical signaling. We combine 2-photon glutamate uncaging with 2-photon voltage-sensitive dye (VSD) imaging to study changes in membrane potential in individual spines. We compare two methods of calibrating these signals in spines that may be spatially distant from the somatic compartment. Subthreshold calibration signals have limited amplitude, and actual amplitudes can fall short of the expected values due to patch clamp limitations and space clamp effects, both leading to over-estimated EPSP amplitudes. Backpropagating action potentials have large amplitude but an average attenuation decay rate must be incorporated leading to some uncertainty. We measure the small but significant nonlinearity in dye response that would lead to under-estimated EPSP amplitudes if not accounted for. Calibrated evoked spine EPSP (spEPSP) amplitudes, along with somatic EPSP (soEPSP) amplitudes are input to a compartmental model (NEURON) to predict spine neck resistance (Rneck) values that are consistent with our measurements. While highly variable, predicted Rneck is centered on 200MOhm and is consistent with independent estimates based on FRAP experiments using a cytosolic dye in the absence of the VSD.

A brief history of endoscopic spine surgery.

Few neurosurgeons practicing today have had training in the field of endoscopic spine surgery during residency or fellowship. Nevertheless, over the past 40 years individual spine surgeons from around the world have worked to create a subfield of minimally invasive spine surgery that takes the point of visualization away from the surgeon's eye or the lens of a microscope and puts it directly at the point of spine pathology. What follows is an attempt to describe the story of how endoscopic spine surgery developed and to credit some of those who have been the biggest contributors to its development.

Mass upflows and magnetic-field dynamics in a forming sunspot penumbra

The formation of the penumbra of the leading spot of the active region NOAA 11117 has been studied using data fromthe Solar DynamicObservatory (SDO). HMI data on longitudinal magnetic fields, line-of-sight velocities, and continuum images were used. The appearance of localized upflows between the umbra and undisturbed photosphere precedes the penumbra formation. The sizes of them reach 1.5″–2″ and the velocity increases to 1 km/s over several minutes. These localized upflows change themselves to a region of material flowing horizontally from the penumbra (the Evershed effect). The formation of individual spine namely fine radial element of the penumbra magnetic field with higher strength and lower inclination than in the surrounding is traced for the first time. The formation of the spine manifests itself as appearance of region of 2″–3″ in size with enhanced upflow near the sunspot umbra, protrusion in longitudinal-field contours on one side of the upwelling center, and the subsequent appearance of magnetic pole of opposite polarity on the other side of the upwelling. This process is accompanied by a bending of the contour marking the boundary of the undisturbed photosphere, which puts the upwelling center in a zone of higher brightness. One possible explanation for this is the emergence of hot magnetic tube. The appearance and growth of the sunspot spines results in the formation of the penumbra.

Precise Synaptic Efficacy Alignment Suggests Potentiation Dominated Learning

Recent evidence suggests that parallel synapses from the same axonal branch onto the same dendritic branch have almost identical strength. It has been proposed that this alignment is only possible through learning rules that integrate activity over long time spans. However, learning mechanisms such as spike-timing-dependent plasticity (STDP) are commonly assumed to be temporally local. Here, we propose that the combination of temporally local STDP and a multiplicative synaptic normalization mechanism is sufficient to explain the alignment of parallel synapses. To address this issue, we introduce three increasingly complex models: First, we model the idealized interaction of STDP and synaptic normalization in a single neuron as a simple stochastic process and derive analytically that the alignment effect can be described by a so-called Kesten process. From this we can derive that synaptic efficacy alignment requires potentiation-dominated learning regimes. We verify these conditions in a single-neuron model with independent spiking activities but more realistic synapses. As expected, we only observe synaptic efficacy alignment for long-term potentiation-biased STDP. Finally, we explore how well the findings transfer to recurrent neural networks where the learning mechanisms interact with the correlated activity of the network. We find that due to the self-reinforcing correlations in recurrent circuits under STDP, alignment occurs for both long-term potentiation- and depression-biased STDP, because the learning will be potentiation dominated in both cases due to the potentiating events induced by correlated activity. This is in line with recent results demonstrating a dominance of potentiation over depression during waking and normalization during sleep. This leads us to predict that individual spine pairs will be more similar after sleep compared to after sleep deprivation. In conclusion, we show that synaptic normalization in conjunction with coordinated potentiation—in this case, from STDP in the presence of correlated pre- and post-synaptic activity—naturally leads to an alignment of parallel synapses.

Hippocampal Dendritic Spines Are Segregated Depending on Their Actin Polymerization.

Dendritic spines are mushroom-shaped protrusions of the postsynaptic membrane. Spines receive the majority of glutamatergic synaptic inputs. Their morphology, dynamics, and density have been related to synaptic plasticity and learning. The main determinant of spine shape is filamentous actin. Using FRAP, we have reexamined the actin dynamics of individual spines from pyramidal hippocampal neurons, both in cultures and in hippocampal organotypic slices. Our results indicate that, in cultures, the actin mobile fraction is independently regulated at the individual spine level, and mobile fraction values do not correlate with either age or distance from the soma. The most significant factor regulating actin mobile fraction was the presence of astrocytes in the culture substrate. Spines from neurons growing in the virtual absence of astrocytes have a more stable actin cytoskeleton, while spines from neurons growing in close contact with astrocytes show a more dynamic cytoskeleton. According to their recovery time, spines were distributed into two populations with slower and faster recovery times, while spines from slice cultures were grouped into one population. Finally, employing fast lineal acquisition protocols, we confirmed the existence of loci with high polymerization rates within the spine.