A geophysical survey in the archaeological site of Archontiko, Yannitsa

The ancient settlement of Archontiko is 4.5 km NW of ancient Pella in North Greece (Figure 1). The findings showed that the area was first occupied by the end of the Iron Age, i.e. 650-550 B.C. Also, showed that the topographic table of Archontiko was a major settlement of the Yannitsa province due to its concessive position by the main roads of Macedonia (Chrysostomou A. and Chrysostomou P., 1993). At the upper layers of the ruins, findings of the Roman and Byzantine times were also unearthed. The geophysical methods have been used in order to detect and map antiquities in various sites in Greece (e.g., Tsokas et al., 1994; 1995; Sawaidis et al., 1999). The resistivity mapping employing the twin probe array, the total magnetic field variations, the airborne photos and the Ground Probing Radar are the most popular methods in this respect. However, almost all geophysical methods can be used to tackle specific problems. From 1992 till 1994, many geophysical surveys were carried out in the area of Archontiko to collect mainly magnetic data. Resistivity measurements were also conducted in a small part of the area. The data presented in this study cover the northern side of the topographic table of Archontiko and they were collected during two campaigns during the summer of the years 1992 and 1993 (Figure 2)

The structure of the ophiolitic beltin Albania inferred from geomagnetic anomalies

The ground magnetic measurements in Albania were used for the compilation of the Total Magnetic Field (TMF) anomaly map of Albania. The magnetic data were processed and interpreted in order to study the structure of the ophiolitic belts of Albania. The ophiolites of Albania are placed at the Mirdita zone and are divided into two parallel alignments which are called the eastern and western ophiolitic belts. They are associated with strong potential field anomalies and their characteristics are considered crucial for a better understanding of the tectonic settings of Albania. The ground TMF data used in this study were acquired over various campaigns (1990-1994) and cover most of Albania's territory. The data were compiled to a map after reduction to the epoch 1990.4. The strongest magnetic anomalies in Albania appear along the known ophiolitic belts which trend NE-SW to the north and NW-SE to the south. Several processing steps were applied to the unified and gridded data in order to obtain information on the distribution of the magnetic sources. The magnetic sources were subsequently modeled using a 2.5D inversion technique. The magnetic properties of the ophiolites determined from laboratory measurements on rock samples, while their lateral extent was calculated from the processing of the magnetic data and used as constraints to the inversion procedure. The bottom of the ophiolitic belts is considered to be predominated by harzburgites. They exhibit lower magnetization than other rocks of the complex, i.e. gabbros, basalt. In fact gabbros are associated with the observed high frequency magnetic anomalies. The modeling results indicate that the thickness of the ophiolites is reduced from east to west. The eastern ophiolitic belt has a maximum thickness of approximately 12 km at its northern section (Kukesi and Lura massifs). The magnetic sources appear with relatively small thickness at the western ophiolitic belt. Boundaries of the eastern ophiolites are characterized by vertical contacts

Striatal Proteomic Analysis Suggests that First L-Dopa Dose Equates to Chronic Exposure

L-3,4-dihydroxypheylalanine (L-dopa)-induced dyskinesia represent a debilitating complication of therapy for Parkinson's disease (PD) that result from a progressive sensitization through repeated L-dopa exposures. The MPTP macaque model was used to study the proteome in dopamine-depleted striatum with and without subsequent acute and chronic L-dopa treatment using two-dimensional difference in-gel electrophoresis (2D-DIGE) and mass spectrometry. The present data suggest that the dopamine-depleted striatum is so sensitive to de novo L-dopa treatment that the first ever administration alone would be able (i) to induce rapid post-translational modification-based proteomic changes that are specific to this first exposure and (ii), possibly, lead to irreversible protein level changes that would be not further modified by chronic L-dopa treatment. The apparent equivalence between first and chronic L-dopa administration suggests that priming would be the direct consequence of dopamine loss, the first L-dopa administrations only exacerbating the sensitization process but not inducing it

A Model of Late Long-Term Potentiation Simulates Aspects of Memory Maintenance

Late long-term potentiation (L-LTP) appears essential for the formation of long-term memory, with memories at least partly encoded by patterns of strengthened synapses. How memories are preserved for months or years, despite molecular turnover, is not well understood. Ongoing recurrent neuronal activity, during memory recall or during sleep, has been hypothesized to preferentially potentiate strong synapses, preserving memories. This hypothesis has not been evaluated in the context of a mathematical model representing biochemical pathways important for L-LTP. I incorporated ongoing activity into two such models: a reduced model that represents some of the essential biochemical processes, and a more detailed published model. The reduced model represents synaptic tagging and gene induction intuitively, and the detailed model adds activation of essential kinases by Ca. Ongoing activity was modeled as continual brief elevations of [Ca]. In each model, two stable states of synaptic weight resulted. Positive feedback between synaptic weight and the amplitude of ongoing Ca transients underlies this bistability. A tetanic or theta-burst stimulus switches a model synapse from a low weight to a high weight stabilized by ongoing activity. Bistability was robust to parameter variations. Simulations illustrated that prolonged decreased activity reset synapses to low weights, suggesting a plausible forgetting mechanism. However, episodic activity with shorter inactive intervals maintained strong synapses. Both models support experimental predictions. Tests of these predictions are expected to further understanding of how neuronal activity is coupled to maintenance of synaptic strength.Comment: Accepted to PLoS One. 8 figures at en

Dysregulation of the mTOR Pathway Mediates Impairment of Synaptic Plasticity in a Mouse Model of Alzheimer's Disease

Background: The mammalian target of rapamycin (mTOR) is an evolutionarily conserved Ser/Thr protein kinase that plays a pivotal role in multiple fundamental biological processes, including synaptic plasticity. We explored the relationship between the mTOR pathway and b-amyloid (Ab)-induced synaptic dysfunction, which is considered to be critical in the pathogenesis of Alzheimer’s disease (AD). Methodology/Principal Findings: We provide evidence that inhibition of mTOR signaling correlates with impairment in synaptic plasticity in hippocampal slices from an AD mouse model and in wild-type slices exposed to exogenous Ab1-42. Importantly, by up-regulating mTOR signaling, glycogen synthase kinase 3 (GSK3) inhibitors rescued LTP in the AD mouse model, and genetic deletion of FK506-binding protein 12 (FKBP12) prevented Ab-induced impairment in long-term potentiation (LTP). In addition, confocal microscopy demonstrated co-localization of intraneuronal Ab42 with mTOR. Conclusions/Significance: These data support the notion that the mTOR pathway modulates Ab-related synaptic dysfunctio

Rapid and Long-Lasting Increase in Sites for Synapse Assembly during Late-Phase Potentiation in Rat Hippocampal Neurons

Long-term potentiation in hippocampal neurons has stages that correspond to the stages of learning and memory. Early-phase (10–30 min) potentiation is accompanied by rapid increases in clusters or puncta of presynaptic and postsynaptic proteins, which depend on actin polymerization but not on protein synthesis. We have now examined changes in pre- and postsynaptic puncta and structures during glutamate-induced late-phase (3 hr) potentiation in cultured hippocampal neurons. We find that (1) the potentiation is accompanied by long-lasting maintenance of the increases in puncta, which depends on protein synthesis, (2) most of the puncta and synaptic structures are very dynamic, continually assembling and disassembling at sites that are more stable than the puncta or structures themselves, (3) the increase in presynaptic puncta appears to be due to both rapid and more gradual increases in the number of sites where the puncta may form, and also to the stabilization of existing puncta, (4) under control conditions, puncta of postsynaptic proteins behave similarly to puncta of presynaptic proteins and share sites with them, and (5) the increase in presynaptic puncta is accompanied by a similar increase in presumably presynaptic structures, which may form at distinct as well as shared sites. The new sites could contribute to the transition between the early and late phase mechanisms of plasticity by serving as seeds for the formation and maintenance of new synapses, thus acting as local “tags” for protein synthesis-dependent synaptic growth during late-phase plasticity

The Interaction between Early Life Epilepsy and Autistic-Like Behavioral Consequences: A Role for the Mammalian Target of Rapamycin (mTOR) Pathway

Early life seizures can result in chronic epilepsy, cognitive deficits and behavioral changes such as autism, and conversely epilepsy is common in autistic children. We hypothesized that during early brain development, seizures could alter regulators of synaptic development and underlie the interaction between epilepsy and autism. The mammalian Target of Rapamycin (mTOR) modulates protein translation and is dysregulated in Tuberous Sclerosis Complex, a disorder characterized by epilepsy and autism. We used a rodent model of acute hypoxia-induced neonatal seizures that results in long term increases in neuronal excitability, seizure susceptibility, and spontaneous seizures, to determine how seizures alter mTOR Complex 1 (mTORC1) signaling. We hypothesized that seizures occurring at a developmental stage coinciding with a critical period of synaptogenesis will activate mTORC1, contributing to epileptic networks and autistic-like behavior in later life. Here we show that in the rat, baseline mTORC1 activation peaks during the first three postnatal weeks, and induction of seizures at postnatal day 10 results in further transient activation of its downstream targets phospho-4E-BP1 (Thr37/46), phospho-p70S6K (Thr389) and phospho-S6 (Ser235/236), as well as rapid induction of activity-dependent upstream signaling molecules, including BDNF, phospho-Akt (Thr308) and phospho-ERK (Thr202/Tyr204). Furthermore, treatment with the mTORC1 inhibitor rapamycin immediately before and after seizures reversed early increases in glutamatergic neurotransmission and seizure susceptibility and attenuated later life epilepsy and autistic-like behavior. Together, these findings suggest that in the developing brain the mTORC1 signaling pathway is involved in epileptogenesis and altered social behavior, and that it may be a target for development of novel therapies that eliminate the progressive effects of neonatal seizures

Functional Characterization of the Dendritically Localized mRNA Neuronatin in Hippocampal Neurons

Local translation of dendritic mRNAs plays an important role in neuronal development and synaptic plasticity. Although several hundred putative dendritic transcripts have been identified in the hippocampus, relatively few have been verified by in situ hybridization and thus remain uncharacterized. One such transcript encodes the protein neuronatin. Neuronatin has been shown to regulate calcium levels in non-neuronal cells such as pancreatic or embryonic stem cells, but its function in mature neurons remains unclear. Here we report that neuronatin is translated in hippocampal dendrites in response to blockade of action potentials and NMDA-receptor dependent synaptic transmission by TTX and APV. Our study also reveals that neuronatin can adjust dendritic calcium levels by regulating intracellular calcium storage. We propose that neuronatin may impact synaptic plasticity by modulating dendritic calcium levels during homeostatic plasticity, thereby potentially regulating neuronal excitability, receptor trafficking, and calcium dependent signaling