Extended memory lifetime in spiking neural networks employing memristive synapses with nonlinear conductance dynamics.

Spiking neural networks (SNNs) employing memristive synapses are capable of life-long online learning. Because of their ability to process and classify large amounts of data in real-time using compact and low-power electronic systems, they promise a substantial technology breakthrough. However, the critical issue that memristor-based SNNs have to face is the fundamental limitation in their memory capacity due to finite resolution of the synaptic elements, which leads to the replacement of old memories with new ones and to a finite memory lifetime. In this study we demonstrate that the nonlinear conductance dynamics of memristive devices can be exploited to improve the memory lifetime of a network. The network is simulated on the basis of a spiking neuron model of mixed-signal digital-analogue sub-threshold neuromorphic CMOS circuits, and on memristive synapse models derived from the experimental nonlinear conductance dynamics of resistive memory devices when stimulated by trains of identical pulses. The network learning circuits implement a spike-based plasticity rule compatible with both spike-timing and rate-based learning rules. In order to get an insight on the memory lifetime of the network, we analyse the learning dynamics in the context of a classical benchmark of neural network learning, that is hand-written digit classification. In the proposed architecture, the memory lifetime and the performance of the network are improved for memristive synapses with nonlinear dynamics with respect to linear synapses with similar resolution. These results demonstrate the importance of following holistic approaches that combine the study of theoretical learning models with the development of neuromorphic CMOS SNNs with memristive devices used to implement life-long on-chip learning.

Morphofunctional alterations in ventral tegmental area dopamine neurons in acute and prolonged opiates withdrawal. A computational perspective.

Dopamine (DA) neurons of the ventral tegmental area (VTA) play a key role in the neurobiological basis of goal-directed behaviors and addiction. Morphine (MOR) withdrawal induces acute and long-term changes in the morphology and physiology of VTA DA cells, but the mechanisms underlying these modifications are poorly understood. Because of their predictive value, computational models are a powerful tool in neurobiological research, and are often used to gain further insights and deeper understanding on the molecular and physiological mechanisms underlying the development of various psychiatric disorders. Here we present a biophysical model of a DA VTA neuron based on 3D morphological reconstruction and electrophysiological data, showing how opiates withdrawal-driven morphological and electrophysiological changes could affect the firing rate and discharge pattern. The model findings suggest how and to what extent a change in the balance of GABA/GLU inputs can take into account the experimentally observed hypofunction of VTA DA neurons during acute and prolonged withdrawal, whereas morphological changes may play a role in the increased excitability of VTA DA cell to opiate administration observed during opiate withdrawal.

Flip-chip assembly of VCSELs to silicon grating couplers via laser fabricated SU8 prisms.

This article presents the flip-chip bonding of vertical-cavity surface-emitting lasers (VCSELs) to silicon grating couplers (GCs) via SU8 prisms. The SU8 prisms are defined on top of the GCs using non-uniform laser ablation process. The prisms enable perfectly vertical coupling from the bonded VCSELs to the GCs. The VCSELs are flip-chip bonded on top of the silicon GCs employing the laser-induced forward transfer (LIFT)-assisted thermocompression technique. An excess loss of < 1 dB at 1.55 µm measured from the bonded assemblies is reported in this paper. The results of high speed transmission experiments performed on the bonded assemblies with clear eye openings up to 20 Gb/s are also presented.

Solid-state dewetting of ultra-thin Au films on SiO2 and HfO2.

Ultra-thin Au films with thickness (h) ranging from 0.5 to 6.0 nm were deposited at room temperature (RT) by means of e-beam evaporation on SiO2 and HfO2. Due to the natural solid-state dewetting (SSD) of the as-deposited films, Au nanoparticles (NPs) were formed on the substrates. By properly adjusting the h value, the size and the density of the Au NPs can be finely tuned. For h = 0.5 nm, spherical-like Au NPs with diameter below 5 nm and density in the order of 10(12) Au NPs cm(-2) were obtained without any additional thermal treatment independently from the substrate. The dependence of the Au NPs characteristics on the substrate starts to be effective for h ≥ 1.0 nm where the Au NPs diameter is in the 5-10 nm range and the density is around 10(11) Au NPs cm(-2). The effect of a subsequent high temperature (400-800 °C) annealing in N2 atmosphere on the Au NPs was investigated as well. For h ≤ 1.0 nm, the Au NPs characteristics evidenced an excellent thermal stability. Whereas the thermal treatment affects the cristallinity of the Au NPs. For the thicker films (2.0 ≤ h ≤ 6.0 nm), the thermal treatment becomes effective to induce the SSD. The proposed methodology can be exploited for the synthesis of Au NPs with diameter below 10 nm on different substrates at RT.

Formation and disruption of conductive filaments in a HfO2/TiN structure.

The process of the formation and disruption of nanometric conductive filaments in a HfO2/TiN structure is investigated by conductive atomic force microscopy. The preforming state evidences nonhomogeneous conduction at high fields through conductive paths, which are associated with pre-existing defects and develop into conductive filaments with a forming procedure. The disruption of the same filaments is demonstrated as well, according to a bipolar operation. In addition, the conductive tip of the microscopy is exploited to perform electrical operations on single conductive spots, which evidences that neighboring conductive filaments are not electrically independent. We propose a picture that describes the evolution of the shape of the conductive filaments in the processes of their formation and disruption, which involves the development of conductive branches from a common root; this root resides in the pre-existing defects that lay at the HfO2/TiN interface.

Imaging assessment of groin pain.

Groin pain is a common condition in athletes, especially those who play certain sports, for instance soccer, ice hockey, fencing which request rapid acceleration and frequent changes of movement. This condition represents a diagnostic difficulty for the radiologist due to either the anatomical pubic region complexity than the many causes that can be a source of pain, because the groin pain can be determined by conditions affecting the bony structures, cartilage and muscle tendons that are part of the proper pubis but also from those involving the hip. The approach to the groin through diagnostic imaging is multidisciplinary: The study of the patient is performed by traditional radiographs, ultrasound examination, magnetic resonance imaging or computed tomography, based on clinical suspicion, and each of these methods provides different results depending on the disease in question. The purpose of this article is to examine what are the optimal imaging techniques to investigate the various diseases affecting the patient with groin pain.

Femoroacetabular impingement: role of imaging.

The femoroacetabular impingement (FAI) is an impingement characterized by repetitive abutment between the femur and the acetabular rim during hip motion due to loss of joint clearance (Imam and Khanduja in Int Orthop 35(10):1427-1435, 2011; James et al. in AJR Am J Roentgenol 187(6):1412-1419, 2006). Femoroacetabular impingement (FAI) can be classified as either cam or pincer type, and it can be differentiated on the basis of a predominance of either a femoral or an acetabular abnormality (Pfirrmann et al. in Radiology 244(2):626, 2007; Ganz et al. in Clin Orthop Relat Res 466(2):264-272, 2008). In cases of cam FAI, the nonspherical shape of the femoral head at the femoral head-neck junction and reduced depth of the femoral waist lead to abutment of the femoral head-neck junction against the acetabular rim. In cases of pincer FAI, acetabular overcoverage limits the range of motion and leads to a conflict between the acetabulum and the femur. The most important role of preoperative MR evaluation in patients affected by FAI is the accurate assessment of the damage's extension.

Diagnostic imaging of ankle impingement syndromes in athletes.

The chronic ankle pain is a very frequent clinical problem, which is often characterized by a painful mechanical limitation of full-range ankle movement. A large amount of causes are involved in its pathogenesis, but the most common forms are secondary to an osseous or soft tissue abnormality. Especially for professional athletes, impingement lesions are the most important causes of chronic pain; however, this symptomatology can also affect ordinary people, mostly in those who work in environments that cause severe mechanical stress on the joints. This group of pathologies is characterized by a joint conflict secondary to an abnormal contact among bone surfaces or between bones and soft tissues. Diagnosis is mainly clinic and secondly supported by imaging in order to localize the critical area of impingement and determine the organic cause responsible for the joint conflict. Treatments for different forms of impingement are similar. Usually, the first step is a conservative approach (rest, physiotherapy, ankle bracing, shoe modification and local injection of corticosteroids), and only in case of unsuccessful response, the second step is the operative treatment with open and arthroscopic techniques. The aim of the study is to describe different MR imaging patterns, comparing our data with those reported in the literature, in order to identify the best accurate diagnostic protocol.

Role of imaging in the management of endometriosis.

The imaging techniques have a fundamental role in the diagnosis of endometriosis. Ovarian endometriosis (endometrioma) and deep endometriosis can be recognized using transvaginal ultrasound and/or magnetic resonance imaging (MRI). Although transvaginal ultrasound is the first choice of imaging modality when investigating women with pelvic pain, MRI have a role for the wider field of visions. The reproducibility of both techniques has been investigated. The three-dimensional ultrasonography has been proposed. Also studies regarding unusual localizations are reported in the literature. New insights are present about the role of imaging in the detection of the malignant transformations. This review summarizes the current evidence on the diagnostic accuracy of these two techniques in the pre-surgical assessment of endometriosis.

Altered Mesolimbic Dopamine System in THC Dependence.

To explore the functional consequences of cannabinoid withdrawal in the rat mesolimbic dopamine system, we investigated the anatomical morphology of the mesencephalic, presumed dopaminergic, neurons and their main post-synaptic target in the Nucleus Accumbens. We found that TH-positive neurons shrink and Golgi-stained medium spiny neurons loose dendritic spines in withdrawal rats after chronic cannabinoids administration. Similar results were observed after administration of the cannabinoid antagonist rimonabant to drug-naïve rats supporting a role for endocannabinoids in neurogenesis, axonal growth and synaptogenesis. This evidence supports the tenet that withdrawal from addictive compounds alters functioning of the mesolimbic system. The data add to a growing body of work which indicates a hypodopaminergic state as a distinctive feature of the "addicted brain".

Rosiglitazone decreases peroxisome proliferator receptor-γ levels in microglia and inhibits TNF-α production: new evidences on neuroprotection in a progressive Parkinson's disease model.

Thiazolidinedione (TZD) class of peroxisome proliferator receptor gamma (PPAR-γ) agonists display neuroprotective effects in experimental Parkinson's disease (PD) models. Neurons and microglia express PPAR-γ, therefore both of them are potential targets for neuroprotection, although the role of each cell type is not clear. Moreover, receptor-dependent as well as receptor-independent mechanisms have been involved. This study further investigated mechanisms of TZD-mediated neuroprotection in PD. We investigated the rosiglitazone effect in the progressive MPTP/probenecid (MPTPp) model of PD. C57BL/6J mice received MPTP (25 mg/kg) plus probenecid (100 mg/kg) twice per week for 5 weeks. Rosiglitazone (10 mg/kg) was given daily until sacrifice, starting on the fourth week of MPTPp treatment, in presence of an ongoing neurodegeneration with microgliosis. Changes in PPAR-γ levels were measured by immunofluorescence and confocal microscopy in tyrosine hydroxylase (TH)-positive neurons and CD11b-positive microglia of the substantia nigra pars compacta (SNc). Chronic MPTPp treatment induced a PPAR-γ overexpression in both TH-positive neurons and microglia (139.9% and 121.7% over vehicle, respectively). Rosiglitazone administration to MPTPp-treated mice, reverted PPAR-γ overexpression in microglia without affecting TH-positive neurons. Thereafter, changes in CD11b and tumor necrosis factor α (TNF-α) immunoreactivity in microglia were evaluated in the SNc. MPTPp progressively increased CD11b immunoreactivity, conferring to microglia a highly activated morphology. Moreover, TNF-α levels were increased (457.38% over vehicle) after MPTPp. Rosiglitazone administration counteracted the increase in CD11b immunoreactivity caused by MPTPp. Moreover, rosiglitazone reverted TNF-α expression to control levels. Nigrostriatal degeneration was assessed by high pressure liquid chromatography (HPLC) measurement of striatal dopamine, and counting of TH-positive neurons in the SNc. MPTPp treatment caused a severe decline of striatal dopamine and a partial degeneration of the SNc. Rosiglitazone arrested the degenerative process in both areas. Results suggest that PPAR-γ expression in microglia and TNF-α production by these cells are crucial changes by which rosiglitazone exerts neuroprotection in PD.

Impaired decision-making in opiate-dependent subjects: effect of pharmacological therapies.

Cognitive dysfunction is a major feature of drug addiction. In the present paper, we compared the decision-making ability using the Iowa gambling task of methadone- and buprenorphine-maintained individuals to non opiate-dependent drug-free controls. Buprenorphine-maintained individuals performed better than methadone-maintained individuals, and not differently than non opiate-dependent controls. In addition, methadone-maintained individuals had more perseverative errors on the Wisconsin card sorting task (WCST) as compared with non opiate-dependent drug-free controls whereas buprenorphine-maintained individuals had intermediate scores. Scores on Weschler adult intelligence scale (WAIS-R) were similar for methadone- and buprenorphine-maintained individuals whereas drug-free controls had significantly higher scores. In addition, both opiate-dependent groups performed more poorly than drug-free controls on the Benton visual retention test (BVRT). The results suggest that buprenorphine in contrast to methadone improves decision-making, and thus may be more effective in rehabilitation programs of opiate-dependent subjects and this improvement may be related to its distinct pharmacological action as a k antagonist.

Astroglial in vivo response to cocaine in mouse dentate gyrus: a quantitative and qualitative analysis by confocal microscopy.

Astrocytes have been proved to play a critical role in neuromodulation, neuroprotection, pH maintenance, axon guidance control during development, homeostasis preservation and blood brain barrier maintenance in the CNS (Kimmelberg and Norenberg, 1989). Quantitative changes in the expression of glial fibrillary acidic protein (GFAP), a cytoskeletal intermediate filament protein exclusively expressed in astrocytes (Bignami et al, 1972), have been observed after administration of alcohol (Framke, 1995), morphine (Beitner-Johnson et al., 1993), amphetamine and its derivates (Aguirre et al., 1999), cannabinoids (Suarez et al., 2000), nicotine (Janson and Moller, 1993), caffeine (Marret et al., 1993) and prenatal exposure to cocaine (Clarke et al., 1996; Nassogne et al., 1998). However, the general astrocytic response to drugs of abuse is still far from being defined. In the present study we examined the in vivo astroglial response to cocaine in mouse dentate gyrus, the hippocampus being a common target of neurotoxic agents (Walsh and Emerich, 1988) which has a prominent effect on learning and memory processes (Eichenbaum et al., 1992). Quantitative changes in immunoreactivity of GFAP were investigated 24 h after acute and repeated daily administration of intraperitoneal cocaine (20 mg/kg). Drug-induced morphological alterations and spatial distribution of astrocytes were evaluated by means of confocal microscope. The results show that, compared to control animals, GFAP expression is two-fold enhanced after a single cocaine injection, still significantly higher after seven consecutive daily administrations, but not statistically different after prolonged (14 days) drug treatment. Moreover, morphological and morphometric analyses reveal significant modifications in astrocytic numbers, cell size and shape complexity. These data demonstrate that in mouse dentate gyrus, cocaine exposure differently affects the expression of GFAP and induces strong changes in astrocytes proliferation rate and cell morphology. Taken together, our findings provide the first in vivo quantitative and qualitative evaluation of astrocytic response to several regimens of cocaine in adult animals brain.

Immunohistochemical localization of atrial natriuretic factor and autoradiographic distribution of atrial natriuretic factor-binding sites in the brain of the cave salamander Hydromantes genei (Amphibia, Plethodontidae).

The distribution of atrial natriuretic factor (ANF)-like immunoreactivity in the central nervous system of the cave salamander Hydromantes genei (Amphibia, Plethodontidae) was investigated by using antisera raised against rat and human ANF(1-28). Concurrently, the location of ANF-binding sites was determined by autoradiography, using radioiodinated human ANF(1-28) as a tracer. In several regions of the brain, including the olfactory bulb, the preoptic area, the ventral thalamus, the tectum of the mesencephalon, and the choroid plexuses inside the ventricles, a good correlation was observed between the distribution of ANF-immunoreactive elements and the location of ANF-binding sites. Mismatching was found in the habenular nucleus, the commissura habenularis, the fasciculum retroflexus, and the interpeduncular nucleus, which contained high levels of binding sites but were devoid of ANF-immunoreactive structures. In contrast, a few other regions, such as the pineal gland and the subcommissural organ, showed a high concentration of ANF-like immunoreactivity but did not contain ANF-binding sites. This study provides the first localization of ANF-like immunoreactivity and ANF-binding sites in the brain of an urodele amphibian. The results show that the ANF peptidergic system in the cave salamander has an organization more simple than the organizations described for the brain of frog or other vertebrates. This feature is probably related to the expression of highly pedomorphic characters in plethodontids. The anatomical distribution of ANF-immunoreactive elements and ANF-binding sites suggests that ANF-related peptides may act as hypophysiotropic hormones as well as neurotransmitters and/or neuromodulators in the salamander brain.

Evidence of pituitary adenylate cyclase activating polypeptide (PACAP) in pancreatic islet cells by confocal microscopy.

Several studies have shown that pituitary adenylate cyclase activating polypeptide (PACAP) stimulates at very low concentration insulin release from pancreatic beta cells. In addition, PACAP has been evidenced in pancreatic nervous fibers surrounding the islets, the core of the islet, and the capillaries. The aim of the present study was to demonstrate internalization of PACAP in pancreatic islet cells. Pancreatic islets were obtained from Wistar rat pancreata by modified Lacy's isolation method. The isolated islets were incubated in the presence of Fluo-PACAP 27, a fluorescent ligand specific for PACAP receptors. At the end of incubation the islets were fixed in paraformaldehyde and then observed by confocal microscope. Fluo-PACAP 27 was internalized into pancreatic islet cells, and this process was time- and temperature-dependent (37 degrees C). The fluorescent molecules converged toward the nucleus where an intense fluorescence was evidenced after 60 minutes. Incubation with phenyl arsine oxide as well as with PACAP 6-38, a receptor antagonist, prevented the internalization process. Further studies are required to explain the internalization process of PACAP 27 into the nucleus of pancreatic islet cells.

Application of the Cajal-De Castro method to the laser scanning confocal microscope in studying the peripheral nervous system.

We tested the Cajal-De Castro method with the Laser Scanning Confocal Microscope (LSCM). This method is a valid investigatory tool for anatomical-morphological study and for the tridimensional reconstruction of the structures of the peripheral nervous system. The combination technique makes it possible to exploit the properties of reflection and fluorescence of the deposited reduced silver. The quantity of which is dependent on the different tissue affinity. On the other hand, since scanning in fluorescence is not selective, both the nerve structures and the surrounding tissue are evidenced and the structures that demonstrate more specific affinity for silver salt are more prominent. Being able to study the preparations using both methods contemporaneously makes it possible to obtain very significant tridimensional images that abound in detail. The Cajal-De Castro method also offers interesting possibilities in the morphometric field and in image analysis.

[An atrial hematopoietic locus in the heart of the cave salamander (urodele amphibian)]. / Un locus emopoietico atriale nel cuore del geotritone (anfibi urodeli).

Lungless Salamanders of the family Plethodontidae have a reduced interatrial septum. The pulmonary vein is lacking. In these species, the septum as a membranous thin sheet attaches near the dorsal lip of the sino-atrial valve where a connective and muscular column, supporting the valve, extends its branches over the upper wall of the undivided atrial cavity where a sponge-like structure is formed. The meshes of this structure are the site of a erythropoietic activity as shown in the plates. Early stages in active reproduction are found in the external acid layer while in the basic inner layer the red cells undergo differentiation. This locus may be correlated to the particular anatomy of the heart concerning the lacking of the pulmonary vein, the position of the sino-arterial aperture shifted to the left side and the reduced interatrial septum. In the large upper cavity of the atrium a certain degree of blood stagnation could be possible which could allow the settlement of this locus. No ventricular erythropoiesis nor epicardial granulopoiesis have been found. This hemopoietic locus is lacking in the family Salamandridae and Anura.

[The epithelial bell]. / La campana epiteliale.

The epithelial bell which surrounds the clitoris in most mammals arises by fusion of visceral and parietal layers of the prepuce. Adhesion of the epithelia occurs between the squamous cells and a normal connection is formed by desmosomes and other junctions. There is total absence of cornifications. The squamous epithelial double lamina splits occasionally in some patches where the free surfaces are getting back to a normal process of keratinization as in the wall of the vestibule. In the closed pits the keratin scales form squamous granules without sebaceous secretion. Sometimes a similar process occurs in the human prepuce with the same results as described in cat and rabbit. The granules of keratin are different from the smegmaliths as they do not contain sebaceous secretion.