Aktin-szabályozó fehérjék molekuláris organizációja hippokampális idegsejtekben, különös tekintettel az idegi plaszticitás szabályozásában betöltött szerepükre = Organization of actin-regulatory proteins in hippocampal neurons and their relation to synaptic plasticity

A dendrittüskékben magas koncentrációban található szerkezeti fehérje az aktin. Megállapítottuk, hogy a cofilin (amely a filamentumok depolimerizációjáért felelős) a dendrittüskék citoplazmájának membránhoz közeli régiójában található, míg a dendrittüske centrális részén alig fordul elő. Az Arp2/3 komplex (amely a fiamentum elágazódásokért felelős) ugyanakkor a tüskék nem-szinaptikus membránjához közel, de azzal nem asszociálódva egy sávban helyezkedik el és a tüskék geometriai középpontját is elkerüli, de magasabb koncentrációt mutat a tüskék ún. endocitótikus zónájának területén. Továbbá megállapítottuk, hogy az aktin citoszkeleton nem játszik aktív szerepet az endocitótikus zónája helyének kialakításában, ebben elsősorban szinaptikus fehérjék vesznek részt a dynamin nevű fehérjével kölcsönhatásban. Eredmények alátámasztják azt a feltételezést, hogy a dendrittüskék citoszkeletonja rendkívüli módon rendezett. Az aktin szabályozó fehérjék nagyfokú térbeli szegregáltságának köszönhetően az egyes aktin-átalakítási folyamatok egymástól szeparáltan történnek. Ez alapvetően hozzájárul a dendrittüskék aktivitásfüggő plasztikus tulajdonságainak kialakításához. | Actin can be found in high concentration in dendritic spines and serves as the primary cytoskeletal protein. We described, that cofilin (an actin depolimerizator) concentrates within the spinoplasm just beneath the plasma membrane, while it is scarce in the center of the spine. The Arp2/3 complex, which is responsible for the branching of actin filaments, is localized within a torroidal domain, away from the plasma membrane, but also away from the geometrical center of the spine. However, it is also highly concentrated at the endocytic zone. Furthermore we described, that the actin cytoskeleton is not responsible for the definition of the exact location of the endocytic zone, however synaptic proteins (shank, homer) define the location of the EZ with their interaction with dynamin. Our results support that the cytoskeleton of dendritic spines are highly organized. Due to the precise spatial organization of actin-binding proteins, actin remodeling is also likely to be spatially segregated. This actin-cytoskeletal design may play a pivotal role in the precise activity-dependent remodeling of dendritic spines

Minireview: high-fructose diet and the ultrastructure of brain synapses

The brain is the hungriest organ. With this great energy demand, the brain’s function may depend on what it is being fed to a greater extent than previously appreciated. Consumption of fructose and glucose in sustained high quantities in industrially processed foods and beverages in the modern Western diet raises complex questions of metabolic, and neurological well-being. Here, we review the effects of sugar on hippocampus associated short term memory. The following work on rodent models, and human clinical trials expound the influence of increased fructose versus glucose, or starch intake on the synaptic organization of a brain region extensively involved in cognitive functions. Through the well supported structure-function relationship of dendritic synapse profiles, synaptic functionality effects of increased fructose versus glucose consumption on hippocampal synapse ultrastructure may be seen. Together with behavioral, and functional findings, ultrastructural data demonstrate potential changes in hippocampal associated cognitive processes directly related to either elevated fructose or glucose intake

A GABAerg és peptiderg rendszerek kölcsönhatásainak morfológiai alapjai a patkány agy lateralis septumában = Morphological basis of interactions between the GABAergic and peptidergic systems in the lateral septal area of the rat brain

Néhány orexigén és anorexigén neuropeptid megoszlását és denzitásbeli változásait vizsgáltuk normál, éheztetett hím, nőstény és ovariectomizált Wistar patkányok lateralis septumában (LS). A peptid-GABA kölcsönhatásra vonatkozó morfológiai adatokat GFP-GAD-65 transzgénikus egerek lateralis septumán végzett immunfluoreszcens vizsgálatokkal kerestünk. Eredményeink: 1./ Kontroll patkányokban megállapítottuk, hogy az egyes neuropeptidek megoszlása eltérő a LS rostrocaudalis tengelye mentén. 2./ A CART és NPY axodendritikus, ill. tüskeszinapszisokat létesítenek, míg a gal- és enk- terminálisok gyakran képeznek más sejtek körül pericelluláris kosárszerű képleteket. 3./ A transzgénikus egereken végzett immunfluoreszcens és konfokális mikroszkópos vizsgálatok a fentiekkel összhangban a GAD-GFP (GABAerg) sejteken is hasonló kapcsolatok meglétét igazolták. 4./ Négy hetes részleges éhezés hatására hím patkányokban a gal és NPY rostok denzitása az 1. és 2. héten nőtt, a 3. hétre a kontroll értékre csökkent, majd a 4. héten ez alá süllyedt. A leu-enk ezzel ellentétben hétről-hétre fokozatos csökkenést mutatott. 5./ Intakt nőstény és ovariectomizált patkányok esetében az 1 hetes részleges éhezés mindkét csoportban szignifikánsan növelte az NPY denzitását saját kontrolljához képest. Gal esetében mind a részleges éhezés, mind az ovariectomia csökkentette a rostok denzitását, míg az enk esetében az éhezés csökkentette, viszont az ovariectomia önmagában növelte a denzitást. | We examined the rostrocaudal distribution and density changes of some orexigenic and anorexigenic neuropeptides in the lateral septum (LS) of normal, and food-deprived male, female and ovariectomized Wistar rats. Morphological basis of peptide-GABA interactions were studied in GFP-GAD-65 transgenic mice. Our result: 1./ In normal male rats we established that the distribution of the neuropeptides is diverse along the rostrocaudal axis of the LS. 2./ CART- and NPY-boutons establish mainly axodendritic and axospinous synapses, gal- and enk-fibers very often form pericellular baskets . 3./ Immunofluorescence and confocal microscopic studies on transgenic mice showed similar types of connectivity. 4./ The density changes of gal and NPY were similar after 4 weeks of partial food deprivation in males: it increased during the 1st and 2nd week, decreased to control values by the 3rd week and further decreased after the 4th week. The density of leu-enk was continuously decreasing. 5./ One week partial food deprivation significantly increased the density of NPY-ergic fibers in both intact females and ovariectomized groups as compared to their own controls. Fasted and ovariectomized animals exhibited considerable reduction. In the case of gal both partial food deprivation and ovariectomy reduced the density of fibers, whereas in the case of enk fasting reduced, and ovariectomy alone increased density

Gaussian-mixture-model-based cluster analysis of gamma-ray bursts in the BATSE catalog

Clustering is an important tool to describe gamma-ray bursts (GRBs). We analyzed the Final BATSE Catalog using Gaussian-mixture-models-based clustering methods for six variables (durations, peak flux, total fluence and spectral hardness ratios) that contain information on clustering. Our analysis found that the five kinds of GRBs previously found by other authors are only the cut groups of the previously well-known three types (short, long and intermediate in duration). The two short and intermediate duration groups differ mostly in the peak flux. Therefore, the reanalysis of the BATSE data finds similar group structures than previously. Because the brightness distribution is asymmetric and not correlated with durations or hardnesses the Gaussian mixture model cuts the Short and the Intermediate duration groups into two subgroups, the dim ones and the bright ones.Comment: 6 pages, 5 figure

Polarized Secretory Trafficking Directs Cargo for Asymmetric Dendrite Growth and Morphogenesis

SummaryProper growth of dendrites is critical to the formation of neuronal circuits, but the cellular machinery that directs the addition of membrane components to generate dendritic architecture remains obscure. Here, we demonstrate that post-Golgi membrane trafficking is polarized toward longer dendrites of hippocampal pyramidal neurons in vitro and toward apical dendrites in vivo. Small Golgi outposts partition selectively into longer dendrites and are excluded from axons. In dendrites, Golgi outposts concentrate at branchpoints where they engage in post-Golgi trafficking. Within the cell body, the Golgi apparatus orients toward the longest dendrite, and this Golgi polarity precedes asymmetric dendrite growth. Manipulations that selectively block post-Golgi trafficking halt dendrite growth in developing neurons and cause a shrinkage of dendrites in mature pyramidal neurons. Further, disruption of Golgi polarity produces neurons with symmetric dendritic arbors lacking a single longest principal dendrite. These results define a novel polarized organization of neuronal secretory trafficking and demonstrate a mechanistic link between directed membrane trafficking and asymmetric dendrite growth

Disruption of Arp2/3 results in asymmetric structural plasticity of dendritic spines and progressive synaptic and behavioral abnormalities

Despite evidence for a strong genetic contribution to several major psychiatric disorders, individual candidate genes account for only a small fraction of these disorders, leading to the suggestion that multigenetic pathways may be involved. Several known genetic risk factors for psychiatric disease are related to the regulation of actin polymerization, which plays a key role in synaptic plasticity. To gain insight into and test the possible pathogenetic role of this pathway, we designed a conditional knock-out of the Arp2/3 complex, a conserved final output for actin signaling pathways that orchestrates de novo actin polymerization. Here we report that postnatal loss of the Arp2/3 subunit ArpC3 in forebrain excitatory neurons leads to an asymmetric structural plasticity of dendritic spines, followed by a progressive loss of spine synapses. This progression of synaptic deficits corresponds with an evolution of distinct cognitive, psychomotor, and social disturbances as the mice age. Together, these results point to the dysfunction of actin signaling, specifically that which converges to regulate Arp2/3, as an important cellular pathway that may contribute to the etiology of complex psychiatric disorders

Ultrastructural Abnormalities in CA1 Hippocampus Caused by Deletion of the Actin Regulator WAVE-1

By conveying signals from the small GTPase family of proteins to the Arp2/3 complex, proteins of the WAVE family facilitate actin remodeling. The WAVE-1 isoform is expressed at high levels in brain, where it plays a role in normal synaptic processing, and is implicated in hippocampus-dependent memory retention. We used electron microscopy to determine whether synaptic structure is modified in the hippocampus of WAVE-1 knockout mice, focusing on the neuropil of CA1 stratum radiatum. Mice lacking WAVE-1 exhibited alterations in the morphology of both axon terminals and dendritic spines; the relationship between the synaptic partners was also modified. The abnormal synaptic morphology we observed suggests that signaling through WAVE-1 plays a critical role in establishing normal synaptic architecture in the rodent hippocampus

Postsynaptic Positioning of Endocytic Zones and AMPA Receptor Cycling by Physical Coupling of Dynamin-3 to Homer

Endocytosis of AMPA receptors and other postsynaptic cargo occurs at endocytic zones (EZs), stably positioned sites of clathrin assembly adjacent to the postsynaptic density (PSD). The tight localization of postsynaptic endocytosis is thought to control spine composition and regulate synaptic transmission and plasticity. However, the molecular mechanisms that situate the EZ near the PSD, and the role of local spine endocytosis in synaptic transmission, are unknown. Here we report that a physical link between dynamin-3 and the postsynaptic adaptor Homer positions the EZ near the PSD. Disruption of dynamin-3 or its interaction with Homer uncouples the PSD from the EZ, resulting in synapses devoid of postsynaptic clathrin. This loss of the EZ leads to a loss of synaptic AMPA receptors and reduced excitatory synaptic transmission that corresponds with impaired synaptic recycling. Thus, a physical link between the PSD and the EZ ensures localized endocytosis and recycling by recapturing and maintaining a proximate pool of cycling AMPA receptors