WorldWideScience

Sample records for circuit synaptic connectivity

  1. Activity-dependent modulation of neural circuit synaptic connectivity

    Directory of Open Access Journals (Sweden)

    Charles R Tessier

    2009-07-01

    Full Text Available In many nervous systems, the establishment of neural circuits is known to proceed via a two-stage process; 1 early, activity-independent wiring to produce a rough map characterized by excessive synaptic connections, and 2 subsequent, use-dependent pruning to eliminate inappropriate connections and reinforce maintained synapses. In invertebrates, however, evidence of the activity-dependent phase of synaptic refinement has been elusive, and the dogma has long been that invertebrate circuits are “hard-wired” in a purely activity-independent manner. This conclusion has been challenged recently through the use of new transgenic tools employed in the powerful Drosophila system, which have allowed unprecedented temporal control and single neuron imaging resolution. These recent studies reveal that activity-dependent mechanisms are indeed required to refine circuit maps in Drosophila during precise, restricted windows of late-phase development. Such mechanisms of circuit refinement may be key to understanding a number of human neurological diseases, including developmental disorders such as Fragile X syndrome (FXS and autism, which are hypothesized to result from defects in synaptic connectivity and activity-dependent circuit function. This review focuses on our current understanding of activity-dependent synaptic connectivity in Drosophila, primarily through analyzing the role of the fragile X mental retardation protein (FMRP in the Drosophila FXS disease model. The particular emphasis of this review is on the expanding array of new genetically-encoded tools that are allowing cellular events and molecular players to be dissected with ever greater precision and detail.

  2. Development of synaptic connectivity in the retinal direction selective circuit.

    Science.gov (United States)

    Morrie, Ryan D; Feller, Marla B

    2016-10-01

    Direction selectivity is a classic neuronal computation that has been described in many different sensory systems. The circuit basis of this computation is perhaps best understood in the retina, where direction selectivity is the result of asymmetric connectivity patterns between excitatory and inhibitory circuit components. Retinal direction selective circuits emerge before eye-opening, though components of the circuit undergo refinement after vision begins. These features make the direction selective circuit a rich model in which to investigate neuronal circuit assembly. In this Opinion, we highlight recent experiments investigating the contribution of various molecular cues, as well as neuronal activity, to the development of the retinal direction selective circuit.

  3. Effects of homeostatic constraints on associative memory storage and synaptic connectivity of cortical circuits

    Directory of Open Access Journals (Sweden)

    Julio eChapeton

    2015-06-01

    Full Text Available The impact of learning and long-term memory storage on synaptic connectivity is not completely understood. In this study, we examine the effects of associative learning on synaptic connectivity in adult cortical circuits by hypothesizing that these circuits function in a steady-state, in which the memory capacity of a circuit is maximal and learning must be accompanied by forgetting. Steady-state circuits should be characterized by unique connectivity features. To uncover such features we developed a biologically constrained, exactly solvable model of associative memory storage. The model is applicable to networks of multiple excitatory and inhibitory neuron classes and can account for homeostatic constraints on the number and the overall weight of functional connections received by each neuron. The results show that in spite of a large number of neuron classes, functional connections between potentially connected cells are realized with less than 50% probability if the presynaptic cell is excitatory and generally a much greater probability if it is inhibitory. We also find that constraining the overall weight of presynaptic connections leads to Gaussian connection weight distributions that are truncated at zero. In contrast, constraining the total number of functional presynaptic connections leads to non-Gaussian distributions, in which weak connections are absent. These theoretical predictions are compared with a large dataset of published experimental studies reporting amplitudes of unitary postsynaptic potentials and probabilities of connections between various classes of excitatory and inhibitory neurons in the cerebellum, neocortex, and hippocampus.

  4. Reflections on the specificity of synaptic connections.

    Science.gov (United States)

    White, Edward L

    2007-10-01

    The principal focus of this treatise is the specificity of synaptic connectivity in the mammalian central nervous system. The occurrence of stereotypical patterns of connection at the macro level (e.g., the general consistency with which axonal pathways impinge on and originate within specific cortical areas and layers) implies that the cerebral cortex is a highly ordered structure. Order is seen also at the more micro level of synaptic connectivity, for instance, in the contrasting synaptic patterns of spiny vs. non-spiny neurons. Quantitative electron microscopic studies of synapses between identified neurons and correlative anatomical/electrophysiological investigations indicate that the high degree of order characterizing many aspects of cortical organization is mirrored by an equally ordered arrangement of synaptic connections between specific types of neurons. The recognition of recurring synaptic patterns has generated increased support for the notion of synaptic specificity as opposed to randomness, and we have begun now to understand the role of specificity in cortical function. At the core of cortical processing lie myriad possibilities for computation provided by the wealth of synaptic connections involving each neuron. Specificity, by limiting possibilities for connection, imposes an order on synaptic interactions even as processes of dynamic selection or synaptic remodeling ensure the constant formation and dissolution of cortical circuits. Collectively, these operations make maximal use of the richness of cortical synaptic connections to produce a highly flexible system, irrespective of the degree of hard-wiring, mutability, randomness or specificity that obtains for cortical wiring at any particular time. A brief, historical account of developments leading to our current understanding of cortical synaptic organization will precede the presentation of evidence for synaptic specificity.

  5. Synaptic polarity of the interneuron circuit controlling C. elegans locomotion

    Directory of Open Access Journals (Sweden)

    Franciszek eRakowski

    2013-10-01

    Full Text Available C. elegans is the only animal for which a detailed neural connectivity diagram has been constructed. However, synaptic polarities in this diagram, and thus, circuit functions are largely unknown. Here, we deciphered the likely polarities of 7 pre-motor neurons implicated in the control of worm's locomotion, using a combination of experimental and computational tools. We performed single and multiple laser ablations in the locomotor interneuron circuit and recorded times the worms spent in forward and backward locomotion. We constructed a theoretical model of the locomotor circuit and searched its all possible synaptic polarity combinations and sensory input patterns in order to find the best match to the timing data. The optimal solution is when either all or most of the interneurons are inhibitory and forward interneurons receive the strongest input, which suggests that inhibition governs the dynamics of the locomotor interneuron circuit. From the five pre-motor interneurons, only AVB and AVD are equally likely to be excitatory, i.e. they have probably similar number of inhibitory and excitatory connections to distant targets. The method used here has a general character and thus can be also applied to other neural systems consisting of small functional networks.

  6. Synaptic polarity of the interneuron circuit controlling C. elegans locomotion.

    Science.gov (United States)

    Rakowski, Franciszek; Srinivasan, Jagan; Sternberg, Paul W; Karbowski, Jan

    2013-01-01

    Caenorhabditis elegans is the only animal for which a detailed neural connectivity diagram has been constructed. However, synaptic polarities in this diagram, and thus, circuit functions are largely unknown. Here, we deciphered the likely polarities of seven pre-motor neurons implicated in the control of worm's locomotion, using a combination of experimental and computational tools. We performed single and multiple laser ablations in the locomotor interneuron circuit and recorded times the worms spent in forward and backward locomotion. We constructed a theoretical model of the locomotor circuit and searched its all possible synaptic polarity combinations and sensory input patterns in order to find the best match to the timing data. The optimal solution is when either all or most of the interneurons are inhibitory and forward interneurons receive the strongest input, which suggests that inhibition governs the dynamics of the locomotor interneuron circuit. From the five pre-motor interneurons, only AVB and AVD are equally likely to be excitatory, i.e., they have probably similar number of inhibitory and excitatory connections to distant targets. The method used here has a general character and thus can be also applied to other neural systems consisting of small functional networks.

  7. Synaptic connectivity in engineered neuronal networks.

    Science.gov (United States)

    Molnar, Peter; Kang, Jung-Fong; Bhargava, Neelima; Das, Mainak; Hickman, James J

    2014-01-01

    We have developed a method to organize cells in dissociated cultures using engineered chemical clues on a culture surface and determined their connectivity patterns. Although almost all elements of the synaptic transmission machinery can be studied separately in single cell models in dissociated cultures, the complex physiological interactions between these elements are usually lost. Thus, factors affecting synaptic transmission are generally studied in organotypic cultures, brain slices, or in vivo where the cellular architecture generally remains intact. However, by utilizing engineered neuronal networks complex phenomenon such as synaptic transmission or synaptic plasticity can be studied in a simple, functional, cell culture-based system. We have utilized self-assembled monolayers and photolithography to create the surface templates. Embryonic hippocampal cells, plated on the resultant patterns in serum-free medium, followed the surface clues and formed the engineered neuronal networks. Basic whole-cell patch-clamp electrophysiology was applied to characterize the synaptic connectivity in these engineered two-cell networks. The same technology has been used to pattern other cell types such as cardiomyocytes or skeletal muscle fibers.

  8. Statistical theory of synaptic connectivity in the neocortex

    Science.gov (United States)

    Escobar, Gina

    Learning and long-term memory rely on plasticity of neural circuits. In adult cerebral cortex plasticity can be mediated by modulation of existing synapses and structural reorganization of circuits through growth and retraction of dendritic spines. In the first part of this thesis, we describe a theoretical framework for the analysis of spine remodeling plasticity. New synaptic contacts appear in the neuropil where gaps between axonal and dendritic branches can be bridged by dendritic spines. Such sites are termed potential synapses. We derive expressions for the densities of potential synapses in the neuropil. We calculate the ratio of actual to potential synapses, called the connectivity fraction, and use it to find the number of structurally different circuits attainable with spine remodeling. These parameters are calculated in four systems: mouse occipital cortex, rat hippocampal area CA1, monkey primary visual (V1), and human temporal cortex. The neurogeometric results indicate that a dendritic spine can choose among an average of 4-7 potential targets in rodents, while in primates it can choose from 10-20 potential targets. The potential of the neuropil to undergo circuit remodeling is found to be highest in rat CA1 (4.9-6.0 nats/mum 3) and lowest in monkey V1 (0.9-1.0 nats/mum3). We evaluate the lower bound of neuron selectivity in the choice of synaptic partners and find that post-synaptic excitatory neurons in rodents make synaptic contacts with more than 21-30% of pre-synaptic axons encountered with new spine growth. Primate neurons appear to be more selective, making synaptic connections with more than 7-15% of encountered axons. Another plasticity mechanism is included in the second part of this work: long-term potentiation and depression of excitatory synaptic connections. Because synaptic strength is correlated with the size of the synapse, the former can be inferred from the distribution of spine head volumes. To this end we analyze and compare 166

  9. Circuit reactivation dynamically regulates synaptic plasticity in neocortex

    Science.gov (United States)

    Kruskal, Peter B.; Li, Lucy; Maclean, Jason N.

    2013-10-01

    Circuit reactivations involve a stereotyped sequence of neuronal firing and have been behaviourally linked to memory consolidation. Here we use multiphoton imaging and patch-clamp recording, and observe sparse and stereotyped circuit reactivations that correspond to UP states within active neurons. To evaluate the effect of the circuit on synaptic plasticity, we trigger a single spike-timing-dependent plasticity (STDP) pairing once per circuit reactivation. The pairings reliably fall within a particular epoch of the circuit sequence and result in long-term potentiation. During reactivation, the amplitude of plasticity significantly correlates with the preceding 20-25 ms of membrane depolarization rather than the depolarization at the time of pairing. This circuit-dependent plasticity provides a natural constraint on synaptic potentiation, regulating the inherent instability of STDP in an assembly phase-sequence model. Subthreshold voltage during endogenous circuit reactivations provides a critical informative context for plasticity and facilitates the stable consolidation of a spatiotemporal sequence.

  10. Synaptic connectivity of the cholinergic axons in the olfactory bulb of the cynomolgus monkey

    Directory of Open Access Journals (Sweden)

    Teresa eLiberia

    2015-03-01

    Full Text Available The olfactory bulb of mammals receives cholinergic afferents from the horizontal limb of the diagonal band of Broca. At present, the synaptic connectivity of the cholinergic axons on the circuits of the olfactory bulb has only been investigated in the rat. In this report, we analyze the synaptic connectivity of the cholinergic axons in the olfactory bulb of the cynomolgus monkey (Macaca fascicularis. Our aim is to investigate whether the cholinergic innervation of the bulbar circuits is phylogenetically conserved between macrosmatic and microsmatic mammals. Our results demonstrate that the cholinergic axons form synaptic contacts on interneurons. In the glomerular layer, their main targets are the periglomerular cells, which receive axo-somatic and axo-dendritic synapses. In the inframitral region, their main targets are the granule cells, which receive synaptic contacts on their dendritic shafts and spines. Although the cholinergic boutons were frequently found in close vicinity of the dendrites of principal cells, we have not found synaptic contacts on them. From a comparative perspective, our data indicate that the synaptic connectivity of the cholinergic circuits is highly preserved in the olfactory bulb of macrosmatic and microsmatic mammals.

  11. Mild hypoxia affects synaptic connectivity in cultured neuronal networks.

    Science.gov (United States)

    Hofmeijer, Jeannette; Mulder, Alex T B; Farinha, Ana C; van Putten, Michel J A M; le Feber, Joost

    2014-04-01

    Eighty percent of patients with chronic mild cerebral ischemia/hypoxia resulting from chronic heart failure or pulmonary disease have cognitive impairment. Overt structural neuronal damage is lacking and the precise cause of neuronal damage is unclear. As almost half of the cerebral energy consumption is used for synaptic transmission, and synaptic failure is the first abrupt consequence of acute complete anoxia, synaptic dysfunction is a candidate mechanism for the cognitive deterioration in chronic mild ischemia/hypoxia. Because measurement of synaptic functioning in patients is problematic, we use cultured networks of cortical neurons from new born rats, grown over a multi-electrode array, as a model system. These were exposed to partial hypoxia (partial oxygen pressure of 150Torr lowered to 40-50Torr) during 3 (n=14) or 6 (n=8) hours. Synaptic functioning was assessed before, during, and after hypoxia by assessment of spontaneous network activity, functional connectivity, and synaptically driven network responses to electrical stimulation. Action potential heights and shapes and non-synaptic stimulus responses were used as measures of individual neuronal integrity. During hypoxia of 3 and 6h, there was a statistically significant decrease of spontaneous network activity, functional connectivity, and synaptically driven network responses, whereas direct responses and action potentials remained unchanged. These changes were largely reversible. Our results indicate that in cultured neuronal networks, partial hypoxia during 3 or 6h causes isolated disturbances of synaptic connectivity.

  12. Energy Efficient Sparse Connectivity from Imbalanced Synaptic Plasticity Rules.

    Directory of Open Access Journals (Sweden)

    João Sacramento

    2015-06-01

    Full Text Available It is believed that energy efficiency is an important constraint in brain evolution. As synaptic transmission dominates energy consumption, energy can be saved by ensuring that only a few synapses are active. It is therefore likely that the formation of sparse codes and sparse connectivity are fundamental objectives of synaptic plasticity. In this work we study how sparse connectivity can result from a synaptic learning rule of excitatory synapses. Information is maximised when potentiation and depression are balanced according to the mean presynaptic activity level and the resulting fraction of zero-weight synapses is around 50%. However, an imbalance towards depression increases the fraction of zero-weight synapses without significantly affecting performance. We show that imbalanced plasticity corresponds to imposing a regularising constraint on the L1-norm of the synaptic weight vector, a procedure that is well-known to induce sparseness. Imbalanced plasticity is biophysically plausible and leads to more efficient synaptic configurations than a previously suggested approach that prunes synapses after learning. Our framework gives a novel interpretation to the high fraction of silent synapses found in brain regions like the cerebellum.

  13. Dynamic effective connectivity of inter-areal brain circuits.

    Directory of Open Access Journals (Sweden)

    Demian Battaglia

    Full Text Available Anatomic connections between brain areas affect information flow between neuronal circuits and the synchronization of neuronal activity. However, such structural connectivity does not coincide with effective connectivity (or, more precisely, causal connectivity, related to the elusive question "Which areas cause the present activity of which others?". Effective connectivity is directed and depends flexibly on contexts and tasks. Here we show that dynamic effective connectivity can emerge from transitions in the collective organization of coherent neural activity. Integrating simulation and semi-analytic approaches, we study mesoscale network motifs of interacting cortical areas, modeled as large random networks of spiking neurons or as simple rate units. Through a causal analysis of time-series of model neural activity, we show that different dynamical states generated by a same structural connectivity motif correspond to distinct effective connectivity motifs. Such effective motifs can display a dominant directionality, due to spontaneous symmetry breaking and effective entrainment between local brain rhythms, although all connections in the considered structural motifs are reciprocal. We show then that transitions between effective connectivity configurations (like, for instance, reversal in the direction of inter-areal interactions can be triggered reliably by brief perturbation inputs, properly timed with respect to an ongoing local oscillation, without the need for plastic synaptic changes. Finally, we analyze how the information encoded in spiking patterns of a local neuronal population is propagated across a fixed structural connectivity motif, demonstrating that changes in the active effective connectivity regulate both the efficiency and the directionality of information transfer. Previous studies stressed the role played by coherent oscillations in establishing efficient communication between distant areas. Going beyond these early

  14. The neural circuit and synaptic dynamics underlying perceptual decision-making

    Science.gov (United States)

    Liu, Feng

    2015-03-01

    Decision-making with several choice options is central to cognition. To elucidate the neural mechanisms of multiple-choice motion discrimination, we built a continuous recurrent network model to represent a local circuit in the lateral intraparietal area (LIP). The network is composed of pyramidal cells and interneurons, which are directionally tuned. All neurons are reciprocally connected, and the synaptic connectivity strength is heterogeneous. Specifically, we assume two types of inhibitory connectivity to pyramidal cells: opposite-feature and similar-feature inhibition. The model accounted for both physiological and behavioral data from monkey experiments. The network is endowed with slow excitatory reverberation, which subserves the buildup and maintenance of persistent neural activity, and predominant feedback inhibition, which underlies the winner-take-all competition and attractor dynamics. The opposite-feature and opposite-feature inhibition have different effects on decision-making, and only their combination allows for a categorical choice among 12 alternatives. Together, our work highlights the importance of structured synaptic inhibition in multiple-choice decision-making processes.

  15. Long-tailed distribution of synaptic strength reveals origin and functional roles of ongoing fluctuation in cortical circuit

    Science.gov (United States)

    Teramae, Jun-nosuke

    2016-06-01

    Neurons in the cortical circuit continuous to generate irregular spike firing with extremely low firing rate (about 1-2 Hz) even when animals neither receive any external stimuli nor they do not show any significant motor movement. The ongoing activity is often called neuronal noise because measured spike trains are often highly irregular and also spike timings are highly asynchronous among neurons. Many experiments imply that neural networks themselves must generate the noisy activity as an intrinsic property of cortical circuit. However, how a network of neurons sustains the irregular spike firings with low firing rate remains unclear. Recently, by focusing on long-tailed distribution of amplitude of synaptic connections or EPSP (Excitatory Post-Synaptic Potential), we successfully revealed that due to coexistence of a few extremely strong synaptic connections and majority of weak synapses, nonlinear dynamics of population of spiking neurons can have a nontrivial stable state that corresponding to the intrinsic ongoing fluctuation of the cortical circuit. We also found that due to the fluctuation fidelity of spike transmission between neurons are optimized. Here, we report our recent findings of the ongoing fluctuation from viewpoints of mathematical and computational side.

  16. Functioning of Circuits Connecting Thalamus and Cortex.

    Science.gov (United States)

    Sherman, S Murray

    2017-03-16

    Glutamatergic pathways in thalamus and cortex are divided into two distinct classes: driver, which carries the main information between cells, and modulator, which modifies how driver inputs function. Identifying driver inputs helps to reveal functional computational circuits, and one set of such circuits identified by this approach are cortico-thalamo-cortical (or transthalamic corticocortical) circuits. This, in turn, leads to the conclusion that there are two types of thalamic relay: first order nuclei (such as the lateral geniculate nucleus) that relay driver input from a subcortical source (i.e., retina), and higher order nuclei (such as the pulvinar) which are involved in these transthalamic pathways by relaying driver input from layer 5 of one cortical area to another. This thalamic division is also seen in other sensory pathways and beyond these so that most of thalamus by volume consists of higher-order relays. Many, and perhaps all, direct driver connections between cortical areas are paralleled by an indirect cortico-thalamo-cortical (transthalamic) driver route involving higher order thalamic relays. Such thalamic relays represent a heretofore unappreciated role in cortical functioning, and this assessment challenges and extends conventional views regarding both the role of thalamus and mechanisms of corticocortical communication. Finally, many and perhaps the vast majority of driver inputs relayed through thalamus arrive via branching axons, with extrathalamic targets often being subcortical motor centers. This raises the possibility that inputs relayed by thalamus to cortex also serve as efference copies, and this may represent an important feature of information relayed up the cortical hierarchy via transthalamic circuits. © 2017 American Physiological Society. Compr Physiol 7:713-739, 2017.

  17. ON THE BASIS OF SYNAPTIC INTEGRATION CONSTANCY DURING GROWTH OF A NEURONAL CIRCUIT

    Directory of Open Access Journals (Sweden)

    Adriana De la Rosa

    2016-08-01

    Full Text Available We studied how a neuronal circuit composed of two neuron types connected by chemical and electrical synapses maintains constant its integrative capacities as neurons grow. For this we combined electrophysiological experiments with mathematical modeling in pairs of electrically-coupled Retzius neurons from postnatal to adult leeches. The electrically-coupled dendrites of both Retzius neurons receive a common chemical input, which produces EPSPs with varying amplitudes. Each EPSP spreads to the soma, but also crosses the electrical synapse to arrive at the soma of the coupled neuron. The leak of synaptic current across the electrical synapse reduces the amplitude of the EPSPs in proportion to the coupling ratio. In addition, summation of EPSPs generated in both neurons generates the baseline action potentials of these serotonergic neurons. To study how integration is adjusted as neurons grow we first studied the characteristics of the chemical and electrical connections onto the coupled dendrites of neuron pairs with soma diameters ranging from 21 to 75 µm. Then by feeding a mathematical model with the neuronal voltage responses to pseudorandom noise currents we obtained the values of the coupling ratio, the membrane resistance of the soma (rm and dendrites (rdend, the space constant (λ and the characteristic dendritic length (L=l/λ . We found that the EPSPs recorded from the somata were similar regardless on the neuron size. However, the amplitude of the EPSPs and the firing frequency of the neurons were inversely proportional to the coupling ratio of the neuron pair, which also was independent form the neuronal size. This data indicated that the integrative constancy relied on the passive membrane properties. We show that the growth of Retzius neurons was compensated by increasing the membrane resistance of the dendrites and therefore the λ value. By solely increasing the dendrite resistance this circuit maintains constant its integrative

  18. On the Basis of Synaptic Integration Constancy during Growth of a Neuronal Circuit

    Science.gov (United States)

    De-La-Rosa Tovar, Adriana; Mishra, Prashant K.; De-Miguel, Francisco F.

    2016-01-01

    We studied how a neuronal circuit composed of two neuron types connected by chemical and electrical synapses maintains constant its integrative capacities as neurons grow. For this we combined electrophysiological experiments with mathematical modeling in pairs of electrically-coupled Retzius neurons from postnatal to adult leeches. The electrically-coupled dendrites of both Retzius neurons receive a common chemical input, which produces excitatory postsynaptic potentials (EPSPs) with varying amplitudes. Each EPSP spreads to the soma, but also crosses the electrical synapse to arrive at the soma of the coupled neuron. The leak of synaptic current across the electrical synapse reduces the amplitude of the EPSPs in proportion to the coupling ratio. In addition, summation of EPSPs generated in both neurons generates the baseline action potentials of these serotonergic neurons. To study how integration is adjusted as neurons grow, we first studied the characteristics of the chemical and electrical connections onto the coupled dendrites of neuron pairs with soma diameters ranging from 21 to 75 μm. Then by feeding a mathematical model with the neuronal voltage responses to pseudorandom noise currents we obtained the values of the coupling ratio, the membrane resistance of the soma (rm) and dendrites (rdend), the space constant (λ) and the characteristic dendritic length (L = l/λ). We found that the EPSPs recorded from the somata were similar regardless on the neuron size. However, the amplitude of the EPSPs and the firing frequency of the neurons were inversely proportional to the coupling ratio of the neuron pair, which also was independent from the neuronal size. This data indicated that the integrative constancy relied on the passive membrane properties. We show that the growth of Retzius neurons was compensated by increasing the membrane resistance of the dendrites and therefore the λ value. By solely increasing the dendrite resistance this circuit maintains

  19. Human-Specific Cortical Synaptic Connections and Their Plasticity: Is That What Makes Us Human?

    Science.gov (United States)

    Lourenço, Joana; Bacci, Alberto

    2017-01-01

    One outstanding difference between Homo sapiens and other mammals is the ability to perform highly complex cognitive tasks and behaviors, such as language, abstract thinking, and cultural diversity. How is this accomplished? According to one prominent theory, cognitive complexity is proportional to the repetition of specific computational modules over a large surface expansion of the cerebral cortex (neocortex). However, the human neocortex was shown to also possess unique features at the cellular and synaptic levels, raising the possibility that expanding the computational module is not the only mechanism underlying complex thinking. In a study published in PLOS Biology, Szegedi and colleagues analyzed a specific cortical circuit from live postoperative human tissue, showing that human-specific, very powerful excitatory connections between principal pyramidal neurons and inhibitory neurons are highly plastic. This suggests that exclusive plasticity of specific microcircuits might be considered among the mechanisms endowing the human neocortex with the ability to perform highly complex cognitive tasks. PMID:28103228

  20. Synaptic Conversion of Chloride-Dependent Synapses in Spinal Nociceptive Circuits: Roles in Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Mark S. Cooper

    2011-01-01

    Full Text Available Electrophysiological conversion of chloride-dependent synapses from inhibitory to excitatory function, as a result of aberrant neuronal chloride homeostasis, is a known mechanism for the genesis of neuropathic pain. This paper examines theoretically how this type of synaptic conversion can disrupt circuit logic in spinal nociceptive circuits. First, a mathematical scaling factor is developed to represent local aberration in chloride electrochemical driving potential. Using this mathematical scaling factor, electrophysiological symbols are developed to represent the magnitude of synaptic conversion within nociceptive circuits. When inserted into a nociceptive circuit diagram, these symbols assist in understanding the generation of neuropathic pain associated with the collapse of transmembrane chloride gradients. A more generalized scaling factor is also derived to represent the interplay of chloride and bicarbonate driving potentials on the function of GABAergic and glycinergic synapses. These mathematical and symbolic representations of synaptic conversion help illustrate the critical role that anion driving potentials play in the transduction of pain. Using these representations, we discuss ramifications of glial-mediated synaptic conversion in the genesis, and treatment, of neuropathic pain.

  1. Synaptic connectivity and spatial memory: a topological approach

    Science.gov (United States)

    Milton, Russell; Babichev, Andrey; Dabaghian, Yuri

    2015-03-01

    In the hippocampus, a network of place cells generates a cognitive map of space, in which each cell is responsive to a particular area of the environment - its place field. The peak response of each cell and the size of each place field have considerable variability. Experimental evidence suggests that place cells encode a topological map of space that serves as a basis of spatial memory and spatial awareness. Using a computational model based on Persistent Homology Theory we demonstrate that if the parameters of the place cells spiking activity fall inside of the physiological range, the network correctly encodes the topological features of the environment. We next introduce parameters of synaptic connectivity into the model and demonstrate that failures in synapses that detect coincident neuronal activity lead to spatial learning deficiencies similar to the ones that are observed in rodent models of neurodegenerative diseases. Moreover, we show that these learning deficiencies may be mitigated by increasing the number of active cells and/or by increasing their firing rate, suggesting the existence of a compensatory mechanism inherent to the cognitive map.

  2. Mapping synaptic pathology within cerebral cortical circuits in subjects with schizophrenia

    Directory of Open Access Journals (Sweden)

    Robert Sweet

    2010-06-01

    Full Text Available Converging lines of evidence indicate that schizophrenia is characterized by impairments of synaptic machinery within cerebral cortical circuits. Efforts to localize these alterations in brain tissue from subjects with schizophrenia have frequently been limited to the quantification of structures that are non-selectively identified (e.g. dendritic spines labeled in Golgi preparations, axon boutons labeled with synaptophysin, or to quantification of proteins using methods unable to resolve relevant cellular compartments. Multiple label fluorescence confocal microscopy represents a means to circumvent many of these limitations, by concurrently extracting information regarding the number, morphology, and relative protein content of synaptic structures. An important adaptation required for studies of human disease is coupling this approach to stereologic methods for systematic random sampling of relevant brain regions. In this review article we consider the application of multiple label fluorescence confocal microscopy to the mapping of synaptic alterations in subjects with schizophrenia and describe the application of a novel, readily automated, iterative intensity/morphological segmentation algorithm for the extraction of information regarding synaptic structure number, size, and relative protein level from tissue sections obtained using unbiased stereological principles of sampling. In this context, we provide examples of the examination of pre- and post-synaptic structures within excitatory and inhibitory circuits of the cerebral cortex.

  3. Functional dissection of synaptic circuits: in vivo patch-clamp recording in neuroscience

    Directory of Open Access Journals (Sweden)

    Can eTao

    2015-05-01

    Full Text Available Neuronal activity is dominated by synaptic inputs from excitatory or inhibitory neural circuits. With the development of in vivo patch-clamp recording, especially in vivo voltage-clamp recording, researchers can not only directly measure neuronal activity, such as spiking responses or membrane potential dynamics, but also quantify synaptic inputs from excitatory and inhibitory circuits in living animals. This approach enables researchers to directly unravel different synaptic components and to understand their underlying roles in particular brain functions. Combining in vivo patch-clamp recording with other techniques, such as two-photon imaging or optogenetics, can provide even clearer functional dissection of the synaptic contributions of different neurons or nuclei. Here, we summarized current applications and recent research progress using the in vivo patch-clamp recording method and focused on its role in the functional dissection of different synaptic inputs. The key factors of a successful in vivo patch-clamp experiment and possible solutions based on references and our experiences were also discussed.

  4. Computer science: Nanoscale connections for brain-like circuits

    Science.gov (United States)

    Legenstein, Robert

    2015-05-01

    Tiny circuit elements called memristors have been used as connections in an artificial neural network - enabling the system to learn to recognize letters of the alphabet from imperfect images. See Letter p.61

  5. Cellular and molecular connections between sleep and synaptic plasticity.

    Science.gov (United States)

    Benington, Joel H; Frank, Marcos G

    2003-02-01

    The hypothesis that sleep promotes learning and memory has long been a subject of active investigation. This hypothesis implies that sleep must facilitate synaptic plasticity in some way, and recent studies have provided evidence for such a function. Our knowledge of both the cellular neurophysiology of sleep states and of the cellular and molecular mechanisms underlying synaptic plasticity has expanded considerably in recent years. In this article, we review findings in these areas and discuss possible mechanisms whereby the neurophysiological processes characteristic of sleep states may serve to facilitate synaptic plasticity. We address this issue first on the cellular level, considering how activation of T-type Ca(2+) channels in nonREM sleep may promote either long-term depression or long-term potentiation, as well as how cellular events of REM sleep may influence these processes. We then consider how synchronization of neuronal activity in thalamocortical and hippocampal-neocortical networks in nonREM sleep and REM sleep could promote differential strengthening of synapses according to the degree to which activity in one neuron is synchronized with activity in other neurons in the network. Rather than advocating one specific cellular hypothesis, we have intentionally taken a broad approach, describing a range of possible mechanisms whereby sleep may facilitate synaptic plasticity on the cellular and/or network levels. We have also provided a general review of evidence for and against the hypothesis that sleep does indeed facilitate learning, memory, and synaptic plasticity.

  6. Associative memory model with long-tail-distributed Hebbian synaptic connections

    Directory of Open Access Journals (Sweden)

    Naoki eHiratani

    2013-02-01

    Full Text Available The postsynaptic potentials of pyramidal neurons have a non-Gaussian amplitude distribution with a heavy tail in both hippocampus and neocortex. Such distributions of synaptic weights were recently shown to generate spontaneous internal noise optimal for spike propagation in recurrent cortical circuits. However, whether this internal noise generation by heavy-tailed weight distributions is possible for and beneficial to other computational functions remains unknown. To clarify this point, we construct an associative memory network model of spiking neurons that stores multiple memory patterns in a connection matrix with a lognormal weight distribution. In associative memory networks, non-retrieved memory patterns generate a cross-talk noise that severely disturbs memory recall. We demonstrate that neurons encoding a retrieved memory pattern and those encoding non-retrieved memory patterns have different subthreshold membrane-potential distributions in our model. Consequently, the probability of responding to inputs at strong synapses increases for the encoding neurons, whereas it decreases for the non-encoding neurons. Our results imply that heavy-tailed distributions of connection weights can generate noise useful for associative memory recall.

  7. Statistical traces of long-term memories stored in strengths and patterns of synaptic connections

    OpenAIRE

    2011-01-01

    Learning and long-term memory rely on plasticity of neural circuits. In adult cerebral cortex plasticity can result from potentiation and depression of synaptic strengths and structural reorganization of circuits through growth and retraction of dendritic spines. By analyzing 166 distributions of spine head volumes and spine lengths from mouse, rat, monkey, and human brains, we determine the “generalized cost” of dendritic spines. This cost universally depends on spine shape, i.e. the depende...

  8. Temporal requirements of the fragile X mental retardation protein in modulating circadian clock circuit synaptic architecture

    Directory of Open Access Journals (Sweden)

    Cheryl L Gatto

    2009-08-01

    Full Text Available Loss of fragile X mental retardation 1 (FMR1 gene function is the most common cause of inherited mental retardation and autism spectrum disorders, characterized by attention disorder, hyperactivity and disruption of circadian activity cycles. Pursuit of effective intervention strategies requires determining when the FMR1 product (FMRP is required in the regulation of neuronal circuitry controlling these behaviors. In the well-characterized Drosophila disease model, loss of the highly conserved dFMRP causes circadian arrhythmicity and conspicuous abnormalities in the circadian clock circuitry. Here, a novel Sholl Analysis was used to quantify over-elaborated synaptic architecture in dfmr1-null small ventrolateral neurons (sLNvs, a key subset of clock neurons. The transgenic Gene-Switch system was employed to drive conditional neuronal dFMRP expression in the dfmr1-null mutant background in order to dissect temporal requirements within the clock circuit. Introduction of dFMRP during early brain development, including the stages of neurogenesis, neuronal fate specification and early pathfinding, provided no rescue of dfmr1 mutant phenotypes. Similarly, restoring normal dFMRP expression in the adult failed to restore circadian circuit architecture. In sharp contrast, supplying dFMRP during a transient window of very late brain development, wherein synaptogenesis and substantial subsequent synaptic reorganization (e.g. use-dependent pruning occur, provided strong morphological rescue to reestablish normal sLNvs synaptic arbors. We conclude that dFMRP plays a developmentally restricted role in sculpting synaptic architecture in these neurons that cannot be compensated for by later reintroduction of the protein at maturity.

  9. Multiple effects of β-amyloid on single excitatory synaptic connections in the PFC

    Directory of Open Access Journals (Sweden)

    Yun eWang

    2013-09-01

    Full Text Available Prefrontal cortex (PFC is recognized as an AD-vulnerable region responsible for defects in cognitive functioning. Pyramidal cell (PC connections are typically facilitating (F or depressing (D in PFC. Excitatory post-synaptic potentials (EPSPs were recorded using patch-clamp from single connections in PFC slices of rats and ferrets in the presence of Aβ. Synaptic transmission was significantly enhanced or reduced depending on their intrinsic type (facilitating or depressing, A species (A40 or A42 and concentration (1-200 nM vs. 0.3 - 1M. Nanomolar Aβ40 and Aβ42 had opposite effects on F-connections, resulting in fewer or increased EPSP failure rates, strengthening or weakening EPSPs and enhancing or inhibiting short-term potentiation (STP: SA and PTP, respectively. High Aβ40 concentrations induced inhibition regardless of synaptic type. D-connections were inhibited regardless of Aβ species or concentration. The inhibition induced with bath application was hard to recover by washout, but a complete recovery was obtained with brief local application and prompt washout. Our data suggests that Aβ40 modulates facilitation and depression of synaptic activity. At higher levels, Aβ40 and Aβ42 may induce inhibition only, further irreversible toxicity once diffusely accumulated in the synaptic environment.

  10. Synaptic organizations and dynamical properties of weakly connected neural oscillators. I. Analysis of a canonical model.

    Science.gov (United States)

    Hoppensteadt, F C; Izhikevich, E M

    1996-08-01

    We study weakly connected networks of neural oscillators near multiple Andronov-Hopf bifurcation points. We analyze relationships between synaptic organizations (anatomy) of the networks and their dynamical properties (function). Our principal assumptions are: (1) Each neural oscillator comprises two populations of neurons; excitatory and inhibitory ones; (2) activity of each population of neurons is described by a scalar (one-dimensional) variable; (3) each neural oscillator is near a nondegenerate supercritical Andronov-Hopf bifurcation point; (4) the synaptic connections between the neural oscillators are weak. All neural networks satisfying these hypotheses are governed by the same dynamical system, which we call the canonical model. Studying the canonical model shows that: (1) A neural oscillator can communicate only with those oscillators which have roughly the same natural frequency. That is, synaptic connections between a pair of oscillators having different natural frequencies are functionally insignificant. (2) Two neural oscillators having the same natural frequencies might not communicate if the connections between them are from among a class of pathological synaptic configurations. In both cases the anatomical presence of synaptic connections between neural oscillators does not necessarily guarantee that the connections are functionally significant. (3) There can be substantial phase differences (time delays) between the neural oscillators, which result from the synaptic organization of the network, not from the transmission delays. Using the canonical model we can illustrate self-ignition and autonomous quiescence (oscillator death) phenomena. That is, a network of passive elements can exhibit active properties and vice versa. We also study how Dale's principle affects dynamics of the networks, in particular, the phase differences that the network can reproduce. We present a complete classification of all possible synaptic organizations from this

  11. Network burst dynamics under heterogeneous cholinergic modulation of neural firing properties and heterogeneous synaptic connectivity.

    Science.gov (United States)

    Knudstrup, Scott; Zochowski, Michal; Booth, Victoria

    2016-05-01

    The characteristics of neural network activity depend on intrinsic neural properties and synaptic connectivity in the network. In brain networks, both of these properties are critically affected by the type and levels of neuromodulators present. The expression of many of the most powerful neuromodulators, including acetylcholine (ACh), varies tonically and phasically with behavioural state, leading to dynamic, heterogeneous changes in intrinsic neural properties and synaptic connectivity properties. Namely, ACh significantly alters neural firing properties as measured by the phase response curve in a manner that has been shown to alter the propensity for network synchronization. The aim of this simulation study was to build an understanding of how heterogeneity in cholinergic modulation of neural firing properties and heterogeneity in synaptic connectivity affect the initiation and maintenance of synchronous network bursting in excitatory networks. We show that cells that display different levels of ACh modulation have differential roles in generating network activity: weakly modulated cells are necessary for burst initiation and provide synchronizing drive to the rest of the network, whereas strongly modulated cells provide the overall activity level necessary to sustain burst firing. By applying several quantitative measures of network activity, we further show that the existence of network bursting and its characteristics, such as burst duration and intraburst synchrony, are dependent on the fraction of cell types providing the synaptic connections in the network. These results suggest mechanisms underlying ACh modulation of brain oscillations and the modulation of seizure activity during sleep states.

  12. Membrane properties and synaptic connectivity of fast-spiking interneurons in rat ventral striatum

    NARCIS (Netherlands)

    Taverna, S.; Canciani, B.; Pennartz, C.M.A.

    2007-01-01

    In vitro patch-clamp recordings were made to study the membrane properties and synaptic connectivity of fast-spiking interneurons in rat ventral striatum. Using a whole-cell configuration in acutely prepared slices, fast-spiking interneurons were recognized based on their firing properties and their

  13. Chemical Detection using Electrically Open Circuits having no Electrical Connections

    Science.gov (United States)

    Woodward, Stanley E.; Olgesby, Donald M.; Taylor, Bryant D.; Shams, Qamar A.

    2008-01-01

    This paper presents investigations to date on chemical detection using a recently developed method for designing, powering and interrogating sensors as electrically open circuits having no electrical connections. In lieu of having each sensor from a closed circuit with multiple electrically connected components, an electrically conductive geometric pattern that is powered using oscillating magnetic fields and capable of storing an electric field and a magnetic field without the need of a closed circuit or electrical connections is used. When electrically active, the patterns respond with their own magnetic field whose frequency, amplitude and bandwidth can be correlated with the magnitude of the physical quantities being measured. Preliminary experimental results of using two different detection approaches will be presented. In one method, a thin film of a reactant is deposited on the surface of the open-circuit sensor. Exposure to a specific targeted reactant shifts the resonant frequency of the sensor. In the second method, a coating of conductive material is placed on a thin non-conductive plastic sheet that is placed over the surface of the sensor. There is no physical contact between the sensor and the electrically conductive material. When the conductive material is exposed to a targeted reactant, a chemical reaction occurs that renders the material non-conductive. The change in the material s electrical resistance within the magnetic field of the sensor alters the sensor s response bandwidth and amplitude, allowing detection of the reaction without having the reactants in physical contact with the sensor.

  14. Synaptic dynamics in analog VLSI.

    Science.gov (United States)

    Bartolozzi, Chiara; Indiveri, Giacomo

    2007-10-01

    Synapses are crucial elements for computation and information transfer in both real and artificial neural systems. Recent experimental findings and theoretical models of pulse-based neural networks suggest that synaptic dynamics can play a crucial role for learning neural codes and encoding spatiotemporal spike patterns. Within the context of hardware implementations of pulse-based neural networks, several analog VLSI circuits modeling synaptic functionality have been proposed. We present an overview of previously proposed circuits and describe a novel analog VLSI synaptic circuit suitable for integration in large VLSI spike-based neural systems. The circuit proposed is based on a computational model that fits the real postsynaptic currents with exponentials. We present experimental data showing how the circuit exhibits realistic dynamics and show how it can be connected to additional modules for implementing a wide range of synaptic properties.

  15. Neurobiology of stress, depression, and rapid acting antidepressants: remodeling synaptic connections.

    Science.gov (United States)

    Duman, Ronald S

    2014-04-01

    Stress and depression are associated with atrophy and loss of neurons in limbic and cortical brain regions that could contribute to the symptoms of depression. Typical monoamine reuptake inhibitor antidepressants have only modest efficacy and require long-term treatment, and are only weakly effective in blocking or reversing these structural changes caused by stress. Recent findings demonstrate that ketamine, an NMDA receptor antagonist, produces rapid antidepressant actions in difficult to treat depressed patients. In addition, preclinical studies demonstrate that ketamine rapidly increases synaptic connections in the prefrontal cortex by increasing glutamate signaling and activation of pathways that control the synthesis of synaptic proteins. Moreover, ketamine rapidly reverses the synaptic deficits caused by exposure to chronic stress in rodent models. Studies of the signaling mechanisms underlying the actions of ketamine have provided novel approaches and targets for new rapid acting antidepressants with decreased side effects, as well as a better understanding of the neurobiology of stress, depression, and treatment response.

  16. LTS and FS inhibitory interneurons, short-term synaptic plasticity, and cortical circuit dynamics.

    Directory of Open Access Journals (Sweden)

    Itai Hayut

    2011-10-01

    Full Text Available Somatostatin-expressing, low threshold-spiking (LTS cells and fast-spiking (FS cells are two common subtypes of inhibitory neocortical interneuron. Excitatory synapses from regular-spiking (RS pyramidal neurons to LTS cells strongly facilitate when activated repetitively, whereas RS-to-FS synapses depress. This suggests that LTS neurons may be especially relevant at high rate regimes and protect cortical circuits against over-excitation and seizures. However, the inhibitory synapses from LTS cells usually depress, which may reduce their effectiveness at high rates. We ask: by which mechanisms and at what firing rates do LTS neurons control the activity of cortical circuits responding to thalamic input, and how is control by LTS neurons different from that of FS neurons? We study rate models of circuits that include RS cells and LTS and FS inhibitory cells with short-term synaptic plasticity. LTS neurons shift the RS firing-rate vs. current curve to the right at high rates and reduce its slope at low rates; the LTS effect is delayed and prolonged. FS neurons always shift the curve to the right and affect RS firing transiently. In an RS-LTS-FS network, FS neurons reach a quiescent state if they receive weak input, LTS neurons are quiescent if RS neurons receive weak input, and both FS and RS populations are active if they both receive large inputs. In general, FS neurons tend to follow the spiking of RS neurons much more closely than LTS neurons. A novel type of facilitation-induced slow oscillations is observed above the LTS firing threshold with a frequency determined by the time scale of recovery from facilitation. To conclude, contrary to earlier proposals, LTS neurons affect the transient and steady state responses of cortical circuits over a range of firing rates, not only during the high rate regime; LTS neurons protect against over-activation about as well as FS neurons.

  17. Neuromimetic Circuits with Synaptic Devices Based on Strongly Correlated Electron Systems

    Science.gov (United States)

    Ha, Sieu D.; Shi, Jian; Meroz, Yasmine; Mahadevan, L.; Ramanathan, Shriram

    2014-12-01

    Strongly correlated electron systems such as the rare-earth nickelates (R NiO3 , R denotes a rare-earth element) can exhibit synapselike continuous long-term potentiation and depression when gated with ionic liquids; exploiting the extreme sensitivity of coupled charge, spin, orbital, and lattice degrees of freedom to stoichiometry. We present experimental real-time, device-level classical conditioning and unlearning using nickelate-based synaptic devices in an electronic circuit compatible with both excitatory and inhibitory neurons. We establish a physical model for the device behavior based on electric-field-driven coupled ionic-electronic diffusion that can be utilized for design of more complex systems. We use the model to simulate a variety of associate and nonassociative learning mechanisms, as well as a feedforward recurrent network for storing memory. Our circuit intuitively parallels biological neural architectures, and it can be readily generalized to other forms of cellular learning and extinction. The simulation of neural function with electronic device analogs may provide insight into biological processes such as decision making, learning, and adaptation, while facilitating advanced parallel information processing in hardware.

  18. Binary synaptic connections based on memory switching in a-Si:H for artificial neural networks

    Science.gov (United States)

    Thakoor, A. P.; Lamb, J. L.; Moopenn, A.; Khanna, S. K.

    1987-01-01

    A scheme for nonvolatile associative electronic memory storage with high information storage density is proposed which is based on neural network models and which uses a matrix of two-terminal passive interconnections (synapses). It is noted that the massive parallelism in the architecture would require the ON state of a synaptic connection to be unusually weak (highly resistive). Memory switching using a-Si:H along with ballast resistors patterned from amorphous Ge-metal alloys is investigated for a binary programmable read only memory matrix. The fabrication of a 1600 synapse test array of uniform connection strengths and a-Si:H switching elements is discussed.

  19. Development of synaptic connectivity onto interneurons in stratum radiatum in the CA1 region of the rat hippocampus

    Directory of Open Access Journals (Sweden)

    Riebe Ilse

    2012-01-01

    Full Text Available Abstract Background The impact of a given presynaptic neuron on the firing probability of the postsynaptic neuron critically depends on the number of functional release sites that connect the two neurons. One way of determining the average functional synaptic connectivity onto a postsynaptic neuron is to compare the amplitudes of action potential dependent spontaneous synaptic currents with the amplitude of the synaptic currents that are independent of action potentials ("minis". With this method it has been found that average synaptic connectivity between glutamatergic CA3 and CA1 pyramidal cells increases from single connections in the neonatal rat, to multiple connections in the young adult rat. On the other hand, γ-aminobutyric acid (GABAergic interneurons form multiple connections onto CA1 pyramidal cells already in the neonatal rat, and the degree of multiple GABAergic connectivity is preserved into adulthood. In the present study, we have examined the development of glutamate and GABA connectivity onto GABAergic CA1 stratum radiatum interneurons in the hippocampal slice, and compared this to the connectivity onto CA1 pyramidal neurons. Results In GABAergic interneurons in the CA1 stratum radiatum, irrespective of developmental stage, we found that the average amplitude of action potential dependent spontaneous AMPA receptor-mediated synaptic currents were of the same magnitude as the mini AMPA receptor mediated synaptic currents. This finding indicates that these GABAergic interneurons, in contrast to the CA1 pyramidal neurons, preserve single glutamate connectivity throughout development. For GABA connectivity, on the other hand, we found multiple functional synaptic connections onto the interneurons, as onto the pyramidal cells. Conclusions The results presented here confirm that glutamate and GABA synaptic connectivity develop very differently in the hippocampal CA1 region. Thus, whereas average GABA connectivity is multiple

  20. Synaptic Dynamics and Neuronal Network Connectivity are reflected in the Distribution of Times in Up states

    Directory of Open Access Journals (Sweden)

    Khanh eDao Duc

    2015-07-01

    Full Text Available The dynamics of neuronal networks connected by synaptic dynamics can sustain long periods of depolarization that can last for hundreds of milliseconds such as Up states recorded during sleep or anesthesia. Yet the underlying mechanism driving these periods remain unclear. We show here within a mean-field model that the residence times of the neuronal membrane potential in cortical Up states does not follow a Poissonian law, but presents several peaks. Furthermore, the present modeling approach allows extracting some information about the neuronal network connectivity from the time distribution histogram. Based on a synaptic-depression model, we find that these peaks, that can be observed in histograms of patch-clamp recordings are not artifacts of electrophysiological measurements, but rather are an inherent property of the network dynamics. Analysis of the equations reveals a stable focus located close to the unstable limit cycle, delimiting a region that defines the Up state. The model further shows that the peaks observed in the Up state time distribution are due to winding around the focus before escaping from the basin of attraction. Finally, we use in vivo recordings of intracellular membrane potential and we recover from the peak distribution, some information about the network connectivity. We conclude that it is possible to recover the network connectivity from the distribution of times that the neuronal membrane voltage spends in Up states.

  1. Effect of Synaptic Connectivity on Long-Range Synchronization of Fast Cortical Oscillations

    Science.gov (United States)

    Bazhenov, M.; Rulkov, N. F.; Timofeev, I.

    2008-01-01

    Cortical gamma oscillations in the 20- to 80-Hz range are associated with attentiveness and sensory perception and have strong connections to both cognitive processing and temporal binding of sensory stimuli. These gamma oscillations become synchronized within a few milliseconds over distances spanning a few millimeters in spite of synaptic delays. In this study using in vivo recordings and large-scale cortical network models, we reveal a critical role played by the network geometry in achieving precise long-range synchronization in the gamma frequency band. Our results indicate that the presence of many independent synaptic pathways in a two-dimensional network facilitate precise phase synchronization of fast gamma band oscillations with nearly zero phase delays between remote network sites. These findings predict a common mechanism of precise oscillatory synchronization in neuronal networks. PMID:18632897

  2. Forebrain deletion of αGDI in adult mice worsens the pre-synaptic deficit at cortico-lateral amygdala synaptic connections.

    Directory of Open Access Journals (Sweden)

    Veronica Bianchi

    Full Text Available The GDI1 gene encodes αGDI, which retrieves inactive GDP-bound RAB from membranes to form a cytosolic pool awaiting vesicular release. Mutations in GDI1 are responsible for X-linked Intellectual Disability. Characterization of the Gdi1-null mice has revealed alterations in the total number and distribution of hippocampal and cortical synaptic vesicles, hippocampal short-term synaptic plasticity and specific short-term memory deficits in adult mice, which are possibly caused by alterations of different synaptic vesicle recycling pathways controlled by several RAB GTPases. However, interpretation of these studies is complicated by the complete ablation of Gdi1 in all cells in the brain throughout development. In this study, we generated conditionally gene-targeted mice in which the knockout of Gdi1 is restricted to the forebrain, hippocampus, cortex and amygdala and occurs only during postnatal development. Adult mutant mice reproduce the short-term memory deficit previously reported in Gdi1-null mice. Surprisingly, the delayed ablation of Gdi1 worsens the pre-synaptic phenotype at cortico-amygdala synaptic connections compared to Gdi1-null mice. These results suggest a pivotal role of αGDI via specific RAB GTPases acting specifically in forebrain regions at the pre-synaptic sites involved in memory formation.

  3. A realistic neural mass model of the cortex with laminar-specific connections and synaptic plasticity - evaluation with auditory habituation.

    Directory of Open Access Journals (Sweden)

    Peng Wang

    Full Text Available In this work we propose a biologically realistic local cortical circuit model (LCCM, based on neural masses, that incorporates important aspects of the functional organization of the brain that have not been covered by previous models: (1 activity dependent plasticity of excitatory synaptic couplings via depleting and recycling of neurotransmitters and (2 realistic inter-laminar dynamics via laminar-specific distribution of and connections between neural populations. The potential of the LCCM was demonstrated by accounting for the process of auditory habituation. The model parameters were specified using Bayesian inference. It was found that: (1 besides the major serial excitatory information pathway (layer 4 to layer 2/3 to layer 5/6, there exists a parallel "short-cut" pathway (layer 4 to layer 5/6, (2 the excitatory signal flow from the pyramidal cells to the inhibitory interneurons seems to be more intra-laminar while, in contrast, the inhibitory signal flow from inhibitory interneurons to the pyramidal cells seems to be both intra- and inter-laminar, and (3 the habituation rates of the connections are unsymmetrical: forward connections (from layer 4 to layer 2/3 are more strongly habituated than backward connections (from Layer 5/6 to layer 4. Our evaluation demonstrates that the novel features of the LCCM are of crucial importance for mechanistic explanations of brain function. The incorporation of these features into a mass model makes them applicable to modeling based on macroscopic data (like EEG or MEG, which are usually available in human experiments. Our LCCM is therefore a valuable building block for future realistic models of human cognitive function.

  4. ApoER2 Function in the Establishment and Maintenance of Retinal Synaptic Connectivity

    Science.gov (United States)

    Trotter, Justin H.; Klein, Martin; Jinwal, Umesh K.; Abisambra, Jose F.; Dickey, Chad A.; Tharkur, Jeremy; Masiulis, Irene; Ding, Jindong; Locke, Kirstin G.; Rickman, Catherine Bowes; Birch, David G.; Weeber, Edwin J.; Herz, Joachim

    2011-01-01

    The cellular and molecular mechanisms responsible for the development of inner retinal circuitry are poorly understood. Reelin and apolipoprotein E (apoE), ligands of apoE receptor 2 (ApoER2), are involved in retinal development and degeneration, respectively. Here we describe the function of ApoER2 in the developing and adult retina. ApoER2 expression was highest during postnatal inner retinal synaptic development and was considerably lower in the mature retina. Both during development and in the adult ApoER2 was expressed by A-II amacrine cells. ApoER2 knockout (KO) mice had rod bipolar morphogenic defects, altered A-II amacrine dendritic development, and impaired rod-driven retinal responses. The presence of an intact ApoER2 NPxY motif, necessary for binding disabled-1 (Dab1) and transducing the Reelin signal, was also necessary for development of the rod bipolar pathway while the alternatively-spliced exon19 was not. Mice deficient in another Reelin receptor, very low-density lipoprotein receptor (VLDLR), had normal rod bipolar morphology but altered A-II amacrine dendritic development. VLDLR KO mice also had reductions in oscillatory potentials and delayed synaptic response intervals. Interestingly, age-related reductions in rod and cone function were observed in both ApoER2 and VLDLR KOs. These results support a pivotal role for ApoER2 in the establishment and maintenance of normal retinal synaptic connectivity. PMID:21976526

  5. Using expression profiles of Caenorhabditis elegans neurons to identify genes that mediate synaptic connectivity.

    Science.gov (United States)

    Baruch, Leehod; Itzkovitz, Shalev; Golan-Mashiach, Michal; Shapiro, Ehud; Segal, Eran

    2008-07-11

    Synaptic wiring of neurons in Caenorhabditis elegans is largely invariable between animals. It has been suggested that this feature stems from genetically encoded molecular markers that guide the neurons in the final stage of synaptic formation. Identifying these markers and unraveling the logic by which they direct synapse formation is a key challenge. Here, we address this task by constructing a probabilistic model that attempts to explain the neuronal connectivity diagram of C. elegans as a function of the expression patterns of its neurons. By only considering neuron pairs that are known to be connected by chemical or electrical synapses, we focus on the final stage of synapse formation, in which neurons identify their designated partners. Our results show that for many neurons the neuronal expression map of C. elegans can be used to accurately predict the subset of adjacent neurons that will be chosen as its postsynaptic partners. Notably, these predictions can be achieved using the expression patterns of only a small number of specific genes that interact in a combinatorial fashion.

  6. Using expression profiles of Caenorhabditis elegans neurons to identify genes that mediate synaptic connectivity.

    Directory of Open Access Journals (Sweden)

    Leehod Baruch

    Full Text Available Synaptic wiring of neurons in Caenorhabditis elegans is largely invariable between animals. It has been suggested that this feature stems from genetically encoded molecular markers that guide the neurons in the final stage of synaptic formation. Identifying these markers and unraveling the logic by which they direct synapse formation is a key challenge. Here, we address this task by constructing a probabilistic model that attempts to explain the neuronal connectivity diagram of C. elegans as a function of the expression patterns of its neurons. By only considering neuron pairs that are known to be connected by chemical or electrical synapses, we focus on the final stage of synapse formation, in which neurons identify their designated partners. Our results show that for many neurons the neuronal expression map of C. elegans can be used to accurately predict the subset of adjacent neurons that will be chosen as its postsynaptic partners. Notably, these predictions can be achieved using the expression patterns of only a small number of specific genes that interact in a combinatorial fashion.

  7. Cell-type-specific circuit connectivity of hippocampal CA1 revealed through Cre-dependent rabies tracing.

    Science.gov (United States)

    Sun, Yanjun; Nguyen, Amanda Q; Nguyen, Joseph P; Le, Luc; Saur, Dieter; Choi, Jiwon; Callaway, Edward M; Xu, Xiangmin

    2014-04-10

    We developed and applied a Cre-dependent, genetically modified rabies-based tracing system to map direct synaptic connections to specific CA1 neuron types in the mouse hippocampus. We found common inputs to excitatory and inhibitory CA1 neurons from CA3, CA2, the entorhinal cortex (EC), the medial septum (MS), and, unexpectedly, the subiculum. Excitatory CA1 neurons receive inputs from both cholinergic and GABAergic MS neurons, whereas inhibitory neurons receive a great majority of inputs from GABAergic MS neurons. Both cell types also receive weaker input from glutamatergic MS neurons. Comparisons of inputs to CA1 PV+ interneurons versus SOM+ interneurons showed similar strengths of input from the subiculum, but PV+ interneurons received much stronger input than SOM+ neurons from CA3, the EC, and the MS. Thus, rabies tracing identifies hippocampal circuit connections and maps how the different input sources to CA1 are distributed with different strengths on each of its constituent cell types.

  8. Novel Low Loss Active Voltage Clamp Circuit for Series Connection of RCGCT thyristors

    Science.gov (United States)

    Ito, Hiroshi; Suzuki, Akihiro; Iwata, Akihiko

    This paper describes novel low loss active voltage clamp circuits for the series connection of RCGCT thyristors. For high voltage converters the series connection of power semiconductor devices is an essential technique for direct switching of high voltages. Several protection circuits have been applied to the series connection of RCGCT thyristors such as CRD snubber circuits which suppress over-voltages across RCGCT thyristors, and voltage balancing resistors to equalize voltage sharing in steady states. However, significant losses in these protection circuits lower the converter’s efficiency. We propose novel low-loss protection circuits, which have active voltage clamp snubber circuits and static voltage balancing circuits. The clamp capacitor voltage of the active voltage clamp snubber circuits are designed to be higher than the equally divided DC-Link voltage. This method can reduce the loss of the clamp circuit to no more than 1/10 of that of the conventional CRD snubber. Also the static voltage balancing circuits compensate for the voltage imbalance generated by the difference in the leakage current between the series connection RCGCT thyristors.

  9. Developmental Profile, Morphology, and Synaptic Connectivity of Cajal-Retzius Cells in the Postnatal Mouse Hippocampus.

    Science.gov (United States)

    Anstötz, Max; Huang, Hao; Marchionni, Ivan; Haumann, Iris; Maccaferri, Gianmaria; Lübke, Joachim H R

    2016-02-01

    Cajal-Retzius (CR) cells are early generated neurons, involved in the assembly of developing neocortical and hippocampal circuits. However, their roles in networks of the postnatal brain remain poorly understood. In order to get insights into these latter functions, we have studied their morphological and synaptic properties in the postnatal hippocampus of the CXCR4-EGFP mouse, where CR cells are easily identifiable. Our data indicate that CR cells are nonuniformly distributed along different subfields of the hippocampal formation, and that their postnatal decline is regulated in a region-specific manner. In fact, CR cells persist in distinct areas of fully mature animals. Subclasses of CR cells project and target either local (molecular layers) or distant regions [subicular complex and entorhinal cortex (EC)] of the hippocampal formation, but have similar firing patterns. Lastly, CR cells are biased toward targeting dendritic shafts compared with spines, and produce large-amplitude glutamatergic unitary postsynaptic potentials on γ-aminobutyric acid (GABA) containing interneurons. Taken together, our results suggest that CR cells are involved in a novel excitatory loop of the postnatal hippocampal formation, which potentially contributes to shaping the flow of information between the hippocampus, parahippocampal regions and entorhinal cortex, and to the low seizure threshold of these brain areas.

  10. EDITORIAL: Synaptic electronics Synaptic electronics

    Science.gov (United States)

    Demming, Anna; Gimzewski, James K.; Vuillaume, Dominique

    2013-09-01

    Conventional computers excel in logic and accurate scientific calculations but make hard work of open ended problems that human brains handle easily. Even von Neumann—the mathematician and polymath who first developed the programming architecture that forms the basis of today's computers—was already looking to the brain for future developments before his death in 1957 [1]. Neuromorphic computing uses approaches that better mimic the working of the human brain. Recent developments in nanotechnology are now providing structures with very accommodating properties for neuromorphic approaches. This special issue, with guest editors James K Gimzewski and Dominique Vuillaume, is devoted to research at the serendipitous interface between the two disciplines. 'Synaptic electronics', looks at artificial devices with connections that demonstrate behaviour similar to synapses in the nervous system allowing a new and more powerful approach to computing. Synapses and connecting neurons respond differently to incident signals depending on the history of signals previously experienced, ultimately leading to short term and long term memory behaviour. The basic characteristics of a synapse can be replicated with around ten simple transistors. However with the human brain having around 1011 neurons and 1015 synapses, artificial neurons and synapses from basic transistors are unlikely to accommodate the scalability required. The discovery of nanoscale elements that function as 'memristors' has provided a key tool for the implementation of synaptic connections [2]. Leon Chua first developed the concept of the 'The memristor—the missing circuit element' in 1971 [3]. In this special issue he presents a tutorial describing how memristor research has fed into our understanding of synaptic behaviour and how they can be applied in information processing [4]. He also describes, 'The new principle of local activity, which uncovers a minuscule life-enabling "Goldilocks zone", dubbed the

  11. Potential Synaptic Connectivity of Different Neurons onto Pyramidal Cells in a 3D Reconstruction of the Rat Hippocampus

    Directory of Open Access Journals (Sweden)

    Deepak eRopireddy

    2011-07-01

    Full Text Available Most existing connectomic data and ongoing efforts focus either on individual synapses (e.g. with electron microscopy or on regional connectivity (tract tracing. An individual pyramidal cell extends thousands of synapses over macroscopic distances (~cm. The contrasting requirements of high resolution and large field of view make it too challenging to acquire the entire synaptic connectivity for even a single typical cortical neuron. Light microscopy can image whole neuronal arbors and resolve dendritic branches. Analyzing connectivity in terms of close spatial appositions between axons and dendrites could thus bridge the opposite scales, from synaptic level to whole systems. In the mammalian cortex, structural plasticity of spines and boutons makes these ‘potential synapses’ functionally relevant to learning capability and memory capacity. To date, however, potential synapses have only been mapped in the surrounding of a neuron and relative to its local orientation rather than in a system-level anatomical reference. Here we overcome this limitation by estimating the potential connectivity of different neurons embedded into a detailed 3D reconstruction of the rat hippocampus. Axonal and dendritic trees were oriented with respect to hippocampal cytoarchitecture according to longitudinal and transversal curvatures. We report the potential connectivity onto pyramidal cell dendrites from the axons of a dentate granule cell, three CA3 pyramidal cells, one CA2 pyramidal cell, and 13 CA3b interneurons. The numbers, densities, and distributions of potential synapses were analyzed in each sub-region (e.g. CA3 vs. CA1, layer (e.g. oriens vs. radiatum, and septo-temporal location (e.g. dorsal vs. ventral. The overall ratio between the numbers of actual and potential synapses was ~0.20 for the granule and CA3 pyramidal cells. All potential connectivity patterns are strikingly dependent on the anatomical location of both pre-synaptic and post-synaptic

  12. Stimulus number, duration and intensity encoding in randomly connected attractor networks with synaptic depression

    Directory of Open Access Journals (Sweden)

    Paul eMiller

    2013-05-01

    Full Text Available Randomly connected recurrent networks of excitatory groups of neurons can possess a multitude of attractor states. When the internal excitatory synapses of these networks are depressing, the attractor states can be destabilized with increasing input. This leads to an itinerancy, where with either repeated transient stimuli, or increasing duration of a single stimulus, the network activity advances through sequences of attractor states. We find that the resulting network state, which persists beyond stimulus offset, can encode the number of stimuli presented via a distributed representation of neural activity with non-monotonic tuning curves for most neurons. Increased duration of a single stimulus is encoded via different distributed representations, so unlike an integrator, the network distinguishes separate successive presentations of a short stimulus from a single presentation of a longer stimulus with equal total duration. Moreover, different amplitudes of stimulus cause new, distinct activity patterns, such that changes in stimulus number, duration and amplitude can be distinguished from each other. These properties of the network depend on dynamic depressing synapses, as they disappear if synapses are static. Thus short-term synaptic depression allows a network to store separately the different dynamic properties of a spatially constant stimulus.

  13. Synaptic connectivity in the midget-parvocellular pathway of primate central retina.

    Science.gov (United States)

    Jusuf, Patricia R; Martin, Paul R; Grünert, Ulrike

    2006-01-10

    The synaptic connectivity of OFF midget bipolar cells was investigated in the central retina of two primate species, the New World common marmoset monkey, Callithrix jacchus, and the Old World macaque monkey, Macaca fascicularis. In marmosets, dichromatic and trichromatic animals were compared. Bipolar output synapses were identified with antibodies against ribbon proteins (kinesin, C-terminal binding protein 2) or with an antiserum that recognizes postsynaptic glutamate receptor clusters (GluR4). The midget bipolar cells were identified immunocytochemically with antibodies to CD15 (marmoset) or an antiserum to recoverin (macaque). In marmosets, midget ganglion cells were retrogradely labeled from the parvocellular layers of the dorsal lateral geniculate nucleus. Consistent with previous studies of Old World primates, in marmoset, midget bipolar cells contacted midget ganglion cells at a ratio of 1:1. The number of output synapses made by OFF midget bipolar cells was quantified for 104 cells in two dichromatic marmosets, 108 cells in one trichromatic marmoset, and 118 cells in one macaque. The number of output synapses was comparable for all animals, ranging from 10-71 in the dichromatic marmoset (average 29.7 +/- 12.4 SD), 12-86 in the trichromatic marmoset (average 28.6 +/- 11.7 SD) and 9-48 in the macaque (average 26.5 +/- 9.3 SD) per axon terminal. In all animals the number of output synapses per axon terminal showed a unimodal distribution. Our results suggest that the midget circuitry is comparable in dichromatic and trichromatic animals.

  14. Open-circuit fault diagnosis for a grid-connected NPC inverter with unity Power Factor

    DEFF Research Database (Denmark)

    Choi, Uimin; Blaabjerg, Frede; Lee, June-Seok;

    2015-01-01

    This paper presents an open-circuit fault detection method for a grid-connected Neutral-Point Clamped (NPC) inverter. The open-circuit fault mainly occurs due to bonding wire failures like lift-off and crack in the power module where the thermal stress is major factor among the stresses that can ...

  15. Persistent ERK Activation Maintains Learning-Induced Long-Lasting Modulation of Synaptic Connectivity

    Science.gov (United States)

    Cohen-Matsliah, Sivan Ida; Seroussi, Yaron; Rosenblum, Kobi; Barkai, Edi

    2008-01-01

    Pyramidal neurons in the piriform cortex from olfactory-discrimination (OD) trained rats undergo synaptic modifications that last for days after learning. A particularly intriguing modification is reduced paired-pulse facilitation (PPF) in the synapses interconnecting these cells; a phenomenon thought to reflect enhanced synaptic release. The…

  16. The Genesis of Chua's Circuit:. Connecting Science, Art and Creativity

    Science.gov (United States)

    Bertacchini, Francesca; Bilotta, Eleonora; Laria, Giuseppe; Pantano, Pietro

    2013-01-01

    The Chua's circuit has provided science with a real scientific and technological advancement in the field of dynamical systems. But the origin of the Chua's circuit, which has resulted in major areas of study within Chaos Theory, with thousands of printed scientific articles, is not widely known. In this chapter, we trace the fundamental stages of the Genesis of the Chua's circuit. To make the story more appealing for the new generations, a 3D movie was made (issued on DVD, with this volume). Besides presenting the main characters from the history of such system, it also introduces Lorenz, Poincare, Julia and Cantor as the precursors of the studies on chaos, which discuss the need for a physical system that demonstrates chaos, a phenomenon not yet understood, in a numerical, physical and experimental way. The story, enriched by the conversations of the above mentioned characters, was staged exactly as it occurred, derived from Professor Chua's famous article of 1983, The Genesis of the Chua's circuit. And the story continues with the authors contribution in expanding Chaos Theory, with the discovery of almost one thousand attractors, which have provided new important elements for the advancement of science in the field of nonlinear chaotic systems.

  17. Functional connectivity of the entorhinal - Hippocampal space circuit

    NARCIS (Netherlands)

    S.-J. Zhang (Sheng-Jia); J. Ye (Jian); J.J. Couey (Jonathan J); M.P. Witter (Menno); E.I. Moser (Edvard); M.-B. Moser (May-Britt)

    2014-01-01

    textabstractThe mammalian space circuit is known to contain several functionally specialized cell types, such as place cells in the hippocampus and grid cells, head-direction cells and border cells in the medial entorhinal cortex (MEC). The interaction between the entorhinal and hippocampal spatial

  18. Connecting Time and Frequency in the RC Circuit

    Science.gov (United States)

    Moya, A. A.

    2017-04-01

    Charging and discharging processes of a capacitor through a resistor, as well as the concept of impedance in alternating current circuits, are topics covered in introductory physics courses. The experimental study of the charge and discharge of a capacitor through a resistor is a well-established lab exercise that is used to introduce concepts such as exponential increase or decrease and time constant. Determining the time constant of the RC circuit has important practical applications because, for example, it can be used to measure unknown values of resistance or capacitance. The transient experiment can be done by using a voltmeter and stopwatch, signal generator and oscilloscope, or even low-cost data acquisition systems such as Arduino. An equivalent topic when studying alternating current circuits arises from the characterization of the impedance of the series or parallel combination of the capacitor and the resistor as a function of frequency. Determining the time constant of the RC circuit by means of impedance measurements for different frequencies is a known experimental technique that can be done using not only LCR meters but also basic instrumentation in the physics lab such as a signal generator, frequency counter, and multimeter. However, lab exercises dealing with RC circuits in alternating current usually focus on their use as filters, and the potential applications in the field of the electrical characterization of material systems are ignored. In this work, we describe a simple exercise showing how the time constant of the RC circuit can easily be determined in the introductory physics lab by means of impedance measurements as a function of frequency. This exercise allows students to learn experimental techniques that find application to characterize the time constants of the charge transport processes in material systems. Moreover, comparison of the time constants obtained from transient and frequency analysis allows us to relate the time and

  19. Modulation of GABAA receptor-mediated synaptic transmission by Zn2+ at a dentate gyrus circuit

    OpenAIRE

    Grauert, A.

    2013-01-01

    Zinc (ionic form Zn2+) is a common trace element in the forebrain, and is especially enriched in the hippocampus, a brain structure important for learning and memory. A large amount of vesicular Zn2+ which is thought to be released upon presynaptic depolarisation is found at synapses formed by the axons of dentate granule cells (GCs), known as mossy fibres (MFs). Zn2+ inhibits NMDA and GABAA receptors (NMDAR and GABAAR) at mono-synaptic inputs between MFs and CA3 pyramidal neurons but its rol...

  20. Toward on-chip functional neuronal networks: computational study on the effect of synaptic connectivity on neural activity.

    Science.gov (United States)

    Foroushani, Armin Najarpour; Ghafar-Zadeh, Ebrahim

    2014-01-01

    This paper presents a new unified computational-experimental approach to study the role of the synaptic activity on the activity of neurons in the small neuronal networks (NNs). In a neuronal tissue/organ, this question is investigated with higher complexities by recording action potentials from population of neurons in order to find the relationship between connectivity and the recorded activities. In this approach, we study the dynamics of very small cortical neuronal networks, which can be experimentally synthesized on chip with constrained connectivity. Multi-compartmental Hodgkin-Huxley model is used in NEURON software to reproduce cells by extracting the experimental data from the synthesized NNs. We thereafter demonstrate how the type of synaptic activity affects the network response to specific spike train using the simulation results.

  1. Pharmacological characterization of cultivated neuronal networks: relevance to synaptogenesis and synaptic connectivity.

    Science.gov (United States)

    Verstraelen, Peter; Pintelon, Isabel; Nuydens, Rony; Cornelissen, Frans; Meert, Theo; Timmermans, Jean-Pierre

    2014-07-01

    Mental disorders, such as schizophrenia or Alzheimer's disease, are associated with impaired synaptogenesis and/or synaptic communication. During development, neurons assemble into neuronal networks, the primary supracellular mediators of information processing. In addition to the orchestrated activation of genetic programs, spontaneous electrical activity and associated calcium signaling have been shown to be critically involved in the maturation of such neuronal networks. We established an in vitro model that recapitulates the maturation of neuronal networks, including spontaneous electrical activity. Upon plating, mouse primary hippocampal neurons grow neurites and interconnect via synapses to form a dish-wide neuronal network. Via live cell calcium imaging, we identified a limited period of time in which the spontaneous activity synchronizes across neurons, indicative of the formation of a functional network. After establishment of network activity, the neurons grow dendritic spines, the density of which was used as a morphological readout for neuronal maturity and connectivity. Hence, quantification of neurite outgrowth, synapse density, spontaneous neuronal activity, and dendritic spine density allowed to study neuronal network maturation from the day of plating until the presence of mature neuronal networks. Via acute pharmacological intervention, we show that synchronized network activity is mediated by the NMDA-R. The balance between kynurenic and quinolinic acid, both neuro-active intermediates in the tryptophan/kynurenine pathway, was shown to be decisive for the maintenance of network activity. Chronic modulation of the neurotrophic support influenced the network formation and revealed the extreme sensitivity of calcium imaging to detect subtle alterations in neuronal physiology. Given the reproducible cultivation in a 96-well setup in combination with fully automated analysis of the calcium recordings, this approach can be used to build a high

  2. Using circuit theory to model connectivity in ecology, evolution, and conservation.

    Science.gov (United States)

    McRae, Brad H; Dickson, Brett G; Keitt, Timothy H; Shah, Viral B

    2008-10-01

    Connectivity among populations and habitats is important for a wide range of ecological processes. Understanding, preserving, and restoring connectivity in complex landscapes requires connectivity models and metrics that are reliable, efficient, and process based. We introduce a new class of ecological connectivity models based in electrical circuit theory. Although they have been applied in other disciplines, circuit-theoretic connectivity models are new to ecology. They offer distinct advantages over common analytic connectivity models, including a theoretical basis in random walk theory and an ability to evaluate contributions of multiple dispersal pathways. Resistance, current, and voltage calculated across graphs or raster grids can be related to ecological processes (such as individual movement and gene flow) that occur across large population networks or landscapes. Efficient algorithms can quickly solve networks with millions of nodes, or landscapes with millions of raster cells. Here we review basic circuit theory, discuss relationships between circuit and random walk theories, and describe applications in ecology, evolution, and conservation. We provide examples of how circuit models can be used to predict movement patterns and fates of random walkers in complex landscapes and to identify important habitat patches and movement corridors for conservation planning.

  3. Latent and Abnormal Functional Connectivity Circuits in Autism Spectrum Disorder

    Science.gov (United States)

    Chen, Shuo; Xing, Yishi; Kang, Jian

    2017-01-01

    Autism spectrum disorder (ASD) is associated with disrupted brain networks. Neuroimaging techniques provide noninvasive methods of investigating abnormal connectivity patterns in ASD. In the present study, we compare functional connectivity networks in people with ASD with those in typical controls, using neuroimaging data from the Autism Brain Imaging Data Exchange (ABIDE) project. Specifically, we focus on the characteristics of intrinsic functional connectivity based on data collected by resting-state functional magnetic resonance imaging (rs-fMRI). Our aim was to identify disrupted brain connectivity patterns across all networks, instead of in individual edges, by using advanced statistical methods. Unlike many brain connectome studies, in which networks are prespecified before the edge connectivity in each network is compared between clinical groups, we detected the latent differentially expressed networks automatically. Our network-level analysis identified abnormal connectome networks that (i) included a high proportion of edges that were differentially expressed between people with ASD and typical controls; and (ii) showed highly-organized graph topology. These findings provide new insight into the study of the underlying neuropsychiatric mechanism of ASD.

  4. Stimulation of the Hippocampal POMC/MC4R Circuit Alleviates Synaptic Plasticity Impairment in an Alzheimer’s Disease Model

    Directory of Open Access Journals (Sweden)

    Yang Shen

    2016-11-01

    Full Text Available Hippocampal synaptic plasticity is modulated by neuropeptides, the disruption of which might contribute to cognitive deficits observed in Alzheimer’s disease (AD. Although pro-opiomelanocortin (POMC-derived neuropeptides and melanocortin 4 receptor (MC4R are implicated in hippocampus-dependent synaptic plasticity, how the POMC/MC4R system functions in the hippocampus and its role in synaptic dysfunction in AD are largely unknown. Here, we mapped a functional POMC circuit in the mouse hippocampus, wherein POMC neurons in the cornu ammonis 3 (CA3 activate MC4R in the CA1. Suppression of hippocampal MC4R activity in the APP/PS1 transgenic mouse model of AD exacerbates long-term potentiation impairment, which is alleviated by the replenishment of hippocampal POMC/MC4R activity or activation of hippocampal MC4R-coupled Gs signaling. Importantly, MC4R activation rescues amyloid-β-induced synaptic dysfunction via a Gs/cyclic AMP (cAMP/PKA/cAMP-response element binding protein (CREB-dependent mechanism. Hence, disruption of this hippocampal POMC/MC4R circuit might contribute to synaptic dysfunction observed in AD, revealing a potential therapeutic target for the disease.

  5. A multicenter study of the early detection of synaptic dysfunction in Mild Cognitive Impairment using Magnetoencephalography-derived functional connectivity.

    Science.gov (United States)

    Maestú, Fernando; Peña, Jose-Maria; Garcés, Pilar; González, Santiago; Bajo, Ricardo; Bagic, Anto; Cuesta, Pablo; Funke, Michael; Mäkelä, Jyrki P; Menasalvas, Ernestina; Nakamura, Akinori; Parkkonen, Lauri; López, Maria E; Del Pozo, Francisco; Sudre, Gustavo; Zamrini, Edward; Pekkonen, Eero; Henson, Richard N; Becker, James T

    2015-01-01

    Synaptic disruption is an early pathological sign of the neurodegeneration of Dementia of the Alzheimer's type (DAT). The changes in network synchronization are evident in patients with Mild Cognitive Impairment (MCI) at the group level, but there are very few Magnetoencephalography (MEG) studies regarding discrimination at the individual level. In an international multicenter study, we used MEG and functional connectivity metrics to discriminate MCI from normal aging at the individual person level. A labeled sample of features (links) that distinguished MCI patients from controls in a training dataset was used to classify MCI subjects in two testing datasets from four other MEG centers. We identified a pattern of neuronal hypersynchronization in MCI, in which the features that best discriminated MCI were fronto-parietal and interhemispheric links. The hypersynchronization pattern found in the MCI patients was stable across the five different centers, and may be considered an early sign of synaptic disruption and a possible preclinical biomarker for MCI/DAT.

  6. Behavioral and synaptic circuit features in a zebrafish model of fragile X syndrome.

    Directory of Open Access Journals (Sweden)

    Ming-Chong Ng

    Full Text Available Fragile X syndrome (FXS is the most frequent inherited form of human mental retardation. It is characterized by cognitive impairment and physical and behavioral problems and is caused by the silencing of fmr1 transcription and the absence of the fmr1 protein (FMRP. Recently, animal models of FXS have greatly facilitated the investigation of the molecular and cellular mechanisms of this loss-of-function disorder. The present study was aimed to further characterize the role of FMRP in behavior and synaptic function by using fmr1 knockout zebrafish. In adult zebrafish, we found that fmr1 knockout produces the anxiolytic-like responses of increased exploratory behavior in light/dark and open-field tests and avoidance learning impairment. Furthermore, electrophysiological recordings from telencephalic slice preparations of knockout fish displayed markedly reduced long-term potentiation and enhanced long-term depression compared to wild-type fish; however, basal glutamatergic transmission and presynaptic function at the lateral (Dl and medial (Dm division of the dorsal telencephalon synapse remained normal. Taken together, our study not only evaluates the mechanism of FRMP but also suggests that zebrafish have valuable potential as a complementary vertebrate model in studying the molecular pathogenesis of human fragile X syndrome.

  7. Cell-Type-Specific Circuit Connectivity of Hippocampal CA1 Revealed through Cre-Dependent Rabies Tracing

    Directory of Open Access Journals (Sweden)

    Yanjun Sun

    2014-04-01

    Full Text Available We developed and applied a Cre-dependent, genetically modified rabies-based tracing system to map direct synaptic connections to specific CA1 neuron types in the mouse hippocampus. We found common inputs to excitatory and inhibitory CA1 neurons from CA3, CA2, the entorhinal cortex (EC, the medial septum (MS, and, unexpectedly, the subiculum. Excitatory CA1 neurons receive inputs from both cholinergic and GABAergic MS neurons, whereas inhibitory neurons receive a great majority of inputs from GABAergic MS neurons. Both cell types also receive weaker input from glutamatergic MS neurons. Comparisons of inputs to CA1 PV+ interneurons versus SOM+ interneurons showed similar strengths of input from the subiculum, but PV+ interneurons received much stronger input than SOM+ neurons from CA3, the EC, and the MS. Thus, rabies tracing identifies hippocampal circuit connections and maps how the different input sources to CA1 are distributed with different strengths on each of its constituent cell types.

  8. The wiring of developing sensory circuits - from patterned spontaneous activity to mechanisms of synaptic plasticity

    Directory of Open Access Journals (Sweden)

    Alexandra Helen Leighton

    2016-09-01

    Full Text Available In order to accurately process incoming sensory stimuli, neurons must be organized into functional networks, with both genetic and environmental factors influencing the precise arrangement of connections between cells. Teasing apart the relative contributions of molecular guidance cues, spontaneous activity and visual experience during this maturation is on-going. During development of the sensory system, the first, rough organization of connections is created by molecular factors. These connections are then modulated by the intrinsically generated activity of neurons, even before the senses have become operational. Spontaneous waves of depolarisations sweep across the nervous system, placing them in a prime position to strengthen correct connections and weaken others, shaping synapses into a useful network. A large body of work now supports the idea that, rather than being a mere side-effect of the system, spontaneous activity actually contains information which readies the nervous system so that, as soon as the senses become active, sensory information can be utilized by the animal. An example is the neonatal mouse. As soon as the eyelids first open, neurons in the cortex respond to visual information without the animal having previously encountered structured sensory input (Cang et al., 2005a; Ko et al., 2013; Rochefort et al., 2011; Zhang et al., 2012. In vivo imaging techniques have advanced considerably, allowing observation of the natural activity in the brain of living animals down to the level of the individual synapse. New (optogenetic methods make it possible to subtly modulate the spatio-temporal properties of activity, aiding our understanding of how these characteristics relate to the function of spontaneous activity. Such experiments have had a huge impact on our knowledge by permitting direct testing of ideas about the plasticity mechanisms at play in the intact system, opening up a provocative range of fresh questions. Here, we

  9. LSPS/Optogenetics to Improve Synaptic Connectivity Mapping: Unmasking the Role of Basket Cell-Mediated Feedforward Inhibition

    Science.gov (United States)

    Brill, Julia; Mattis, Joanna; Deisseroth, Karl

    2016-01-01

    Abstract Neocortical pyramidal cells (PYRs) receive synaptic inputs from many types of GABAergic interneurons. Connections between parvalbumin (PV)-positive, fast-spiking interneurons (“PV cells”) and PYRs are characterized by perisomatic synapses and high-amplitude, short-latency IPSCs. Here, we present novel methods to study the functional influence of PV cells on layer 5 PYRs using optogenetics combined with laser-scanning photostimulation (LSPS). First, we examined the strength and spatial distribution of PV-to-PYR inputs. To that end, the fast channelrhodopsin variant AAV5-EF1α-DIO-hChR2(E123T)-eYFP (ChETA) was expressed in PV cells in somatosensory cortex of mice using an adeno-associated virus-based viral construct. Focal blue illumination (100–150 µm half-width) was directed through the microscope objective to excite PV cells along a spatial grid covering layers 2–6, while IPSCs were recorded in layer 5 PYRs. The resulting optogenetic input maps showed evoked PV cell inputs originating from an ∼500-μm-diameter area surrounding the recorded PYR. Evoked IPSCs had the short-latency/high-amplitude characteristic of PV cell inputs. Second, we investigated how PV cell activity modulates PYR output in response to synaptic excitation. We expressed halorhodopsin (eNpHR3.0) in PV cells using the same strategy as for ChETA. Yellow illumination hyperpolarized eNpHR3.0-expressing PV cells, effectively preventing action potential generation and thus decreasing the inhibition of downstream targets. Synaptic input maps onto layer 5 PYRs were acquired using standard glutamate-photolysis LSPS either with or without full-field yellow illumination to silence PV cells. The resulting IPSC input maps selectively lacked short-latency perisomatic inputs, while EPSC input maps showed increased connectivity, particularly from upper layers. This indicates that glutamate uncaging LSPS-based excitatory synaptic maps will consistently underestimate connectivity. PMID

  10. Childhood trauma and emotional processing circuits in schizophrenia: A functional connectivity study.

    Science.gov (United States)

    Cancel, Aïda; Comte, Magali; Boutet, Claire; Schneider, Fabien C; Rousseau, Pierre-François; Boukezzi, Sarah; Gay, Aurélia; Sigaud, Torrance; Massoubre, Catherine; Berna, Fabrice; Zendjidjian, Xavier Y; Azorin, Jean-Michel; Blin, Olivier; Fakra, Eric

    2016-12-13

    Childhood trauma strongly impacts emotional responses in schizophrenia. We have explored an association between early trauma and the amygdala functional connectivity using generalized psychophysiological interaction during an emotional task. Twenty-one schizophrenia patients and twenty-five controls were included. In schizophrenia patients, higher levels of sexual abuse and physical neglect during childhood were associated with decreased connectivity between the amygdala and the posterior cingulate/precuneus region. Additionally, patients showed decreased coupling between the amygdala and the posterior cingulate/precuneus region compared to controls. These findings suggest that early trauma could impact later connectivity in specific stress-related circuits affecting self-consciousness and social cognition in schizophrenia.

  11. Synapse rearrangements upon learning: from divergent-sparse connectivity to dedicated sub-circuits.

    Science.gov (United States)

    Caroni, Pico; Chowdhury, Ananya; Lahr, Maria

    2014-10-01

    Learning can involve formation of new synapses and loss of synapses, providing memory traces of learned skills. Recent findings suggest that these synapse rearrangements reflect assembly of task-related sub-circuits from initially broadly distributed and sparse connectivity in the brain. These local circuit remodeling processes involve rapid emergence of synapses upon learning, followed by protracted validation involving strengthening of some new synapses, and selective elimination of others. The timing of these consolidation processes can vary. Here, we review these findings, focusing on how molecular/cellular mechanisms of synapse assembly, strengthening, and elimination might interface with circuit/system mechanisms of learning and memory consolidation. An integrated understanding of these learning-related processes should provide a better basis to elucidate how experience, genetic background, and disease influence brain function.

  12. Series-connected substrate-integrated lead-carbon hybrid ultracapacitors with voltage-management circuit

    Indian Academy of Sciences (India)

    A Banerjee; R Srinivasan; A K Shukla

    2015-02-01

    Cell voltage for a fully charged-substrate-integrated lead-carbon hybrid ultracapacitor is about 2.3 V. Therefore, for applications requiring higher DC voltage, several of these ultracapacitors need to be connected in series. However, voltage distribution across each series-connected ultracapacitor tends to be uneven due to tolerance in capacitance and parasitic parallel-resistance values. Accordingly, voltage-management circuit is required to protect constituent ultracapacitors from exceeding their rated voltage. In this study, the design and characterization of the substrate-integrated lead-carbon hybrid ultracapacitor with co-located terminals is discussed. Voltage-management circuit for the ultracapacitor is presented, and its effectiveness is validated experimentally.

  13. TRANSGENIC STRATEGY FOR IDENTIFYING SYNAPTIC CONNECTIONS IN MICE BY FLUORESCENCE COMPLEMENTATION (GRASP

    Directory of Open Access Journals (Sweden)

    Masahito eYamagata

    2012-02-01

    Full Text Available In the "GFP reconstitution across synaptic partners" (GRASP method, non-fluorescent fragments of GFP are expressed in two different neurons; the fragments self-assemble at synapses between the two to form a fluorophore. GRASP has proven useful for light microscopic identification of synapses in two invertebrate species, Caenorhabditis elegans and Drosophila melanogaster, but has not yet been applied to vertebrates. Here, we describe GRASP constructs that function in mammalian cells and implement a transgenic strategy in which a Cre-dependent gene switch leads to expression of the two fragments in mutually exclusive neuronal subsets in mice. Using a transgenic line that expresses Cre selectively in rod photoreceptors, we demonstrate labeling of synapses in the outer plexiform layer of the retina. Labeling is specific, in that synapses made by rods remain labeled for at least 6 months whereas nearby synapses made by intercalated cone photoreceptors on many of the same interneurons remain unlabeled. We also generated antisera that label reconstituted GFP but neither fragment in order to amplify the GRASP signal and thereby increase the sensitivity of the method.

  14. Frontostriatal circuits, resting state functional connectivity and cognitive control in internet gaming disorder.

    Science.gov (United States)

    Yuan, Kai; Yu, Dahua; Cai, Chenxi; Feng, Dan; Li, Yangding; Bi, Yanzhi; Liu, Jixin; Zhang, Yi; Jin, Chenwang; Li, Linling; Qin, Wei; Tian, Jie

    2017-05-01

    Converging evidence has identified cognitive control deficits in internet gaming disorder (IGD). Recently, mounting evidence had revealed that resting state functional connectivity (RSFC) and structural connectivity of frontostriatal circuits could modulate cognitive control in healthy individuals. Unfortunately, relatively little is known about the thoroughly circuit-level characterization of the frontostriatal pathways (both the dorsal and ventral striatum) during resting-state and their association with cognitive control in IGD. In the current study, the differences of striatum volume and RSFC networks were investigated between 43 young IGD individuals and 44 healthy controls. Meanwhile, cognitive control deficits were assessed by Stroop task performances. The neuroimaging findings were then correlated with the Stroop task behaviors. In IGD subjects, we demonstrated an increased volume of right caudate and nucleus accumbens (NAc) as well as reduced RSFC strength of dorsal prefrontal cortex (DLPFC)-caudate and orbitofrontal cortex (OFC)-NAc. NAc volumes were positively correlated with internet addiction test scores in IGD. The caudate volume and DLPFC-caudate RSFC was correlated with the impaired cognitive control (more incongruent errors in Stroop task) in IGD. Consistent with substance use disorder (SUD) findings, we detected striatum volume and frontostriatal circuits RSFC differences between IGD and healthy controls, which provided evidence of some degree of the similarity between IGD and SUD. More importantly, the cognitive control deficits in IGD were correlated with the reduced frontostrital RSFC strength. It is hoped that our results could shed insight on the neurobiological mechanisms of IGD and suggest potential novel therapeutic targets for treatment.

  15. Wiring olfaction: the cellular and molecular mechanisms that guide the development of synaptic connections from the nose to the cortex

    Directory of Open Access Journals (Sweden)

    Fernando De Castro

    2009-12-01

    Full Text Available Within the central nervous system, the olfactory system fascinates by its developmental and physiological particularities, and is one of the most studied models to understand the mechanisms underlying the guidance of growing axons to their appropriate targets. A constellation of contact-mediated (laminins, CAMs, ephrins, etc. and secreted mechanisms (semaphorins, slits, growth factors, etc. are known to play different roles in the establishment of synaptic interactions between the olfactory epithelium, olfactory bulb (OB and olfactory cortex. Specific mechanisms of this system (including the amazing family of about 1000 different olfactory receptors have been also proposed. In the last years, different reviews have focused in partial sights, specially in the mechanisms involved in the formation of the olfactory nerve, but a detailed review of the mechanisms implicated in the development of the connections among the different olfactory structures (olfactory epithelium, OB, olfactory cortex remains to be written. In the present work, we afford this systematic review: the different cellular and molecular mechanisms which rule the formation of the olfactory nerve, the lateral olfactory tract and the intracortical connections, as well as the few data available regarding the accessory olfactory system. These mechanisms are compared, and the implications of the differences and similarities discussed in this fundamental scenario of ontogeny.

  16. Structural and functional analysis of single neurons to correlate synaptic connectivity with grooming behavior.

    Science.gov (United States)

    Kays, Ibrahim; Cvetkovska, Vedrana; Chen, Brian E

    2014-01-01

    We describe a protocol to image the complex axonal branching structure of identified mechanosensory neurons in Drosophila, combined with a behavioral assay to evaluate the functional output of the neuron. The stimulation of identified mechanosensory neurons in live animals produces a stereotyped grooming reflex. The mechanosensory axonal arbor within the CNS is subsequently labeled with a lipophilic fluorescent dye and imaged by fluorescence microscopy. The behavioral output can therefore be correlated to the axonal morphology of the stimulated neuron in the same animal. Combining this protocol with genetic analysis provides a powerful tool for identifying the roles of molecules involved in different aspects of hard-wired neural circuit formation underlying an innate behavior. From behavioral analysis to axonal imaging, the protocol takes 4 d.

  17. [How is the sense of smell connected? Cellular and molecular mechanisms guiding the development of the synaptic connections from the nose to the cortex (II)].

    Science.gov (United States)

    Garcia-Gonzalez, Diego; de Castro, Fernando

    2011-05-01

    As discussed in the first part of this review, the development of the olfactory system offers a series of fascinating peculiarities that make it one of the models that has been most widely studied in order to reach an understanding of the mechanisms involved in the development of the nervous system. In the first part we reviewed the different mechanisms based on contact (laminins, cell adhesion molecules, ephrins, etc.) and on secretion (semaphorins, slits, growth factors, etc.) that are involved in the formation of the synaptic connections among the olfactory epithelium, the olfactory bulb and the olfactory cortex. In this second part we will review the molecular mechanisms responsible for the intracortical connections in the main olfactory system, as well as the limited information available concerning the accessory olfactory system. We shall also review the mechanisms involved in the migration of the interneuron precursors from the sub-ventricular area of the forebrain to the olfactory bulb, which is another crucial event in the development of this system.

  18. Effect of auditory deafferentation on the synaptic connectivity of a pair of identified interneurons in adult field crickets.

    Science.gov (United States)

    Brodfuehrer, P D; Hoy, R R

    1988-01-01

    In adult crickets, Teleogryllus oceanicus, unilateral auditory deafferentation causes the medial dendrites of an afferent-deprived, identified auditory interneuron (Int-1) in the prothoracic ganglion to sprout and form new functional connections in the contralateral auditory neuropil. The establishment of these new functional connections by the deafferented Int-1, however, does not appear to affect the physiological responses of Int-1's homolog on the intact side of the prothoracic ganglion which also innervates this auditory neuropil. Thus it appears that the sprouting dendrites of the deafferented Int-1 are not functionally competing with those of the intact Int-1 for synaptic connections in the remaining auditory neuropil following unilateral deafferentation in adult crickets. Moreover, we demonstrate that auditory function is restored to the afferent-deprived Int-1 within 4-6 days following deafferentation, when few branches of Int-1's medial dendrites can be seen to have sprouted. The strength of the physiological responses and extent of dendritic sprouting in the deafferented Int-1 progressively increase with time following deafferentation. By 28 days following deafferentation, most of the normal physiological responses of Int-1 to auditory stimuli have been restored in the deafferented Int-1, and the medial dendrites of the deafferented Int-1 have clearly sprouted and grown across into the contralateral auditory afferent field. The strength of the physiological responses of the deafferented Int-1 to auditory stimuli and extent of dendritic sprouting in the deafferented Int-1 are greater in crickets deafferented as juveniles than as adults. Thus, neuronal plasticity persists in Int-1 following sensory deprivation from the earliest juvenile stages through adulthood.

  19. Enhanced Synaptic Connectivity in the Dentate Gyrus during Epileptiform Activity: Network Simulation

    Science.gov (United States)

    França, Keite Lira de Almeida; Guimarães de Almeida, Antônio-Carlos; Infantosi, Antonio Fernando Catelli; Duarte, Mario Antônio; da Silveira, Gilcélio Amaral; Scorza, Fulvio Alexandre; Arida, Ricardo Mario; Cavalheiro, Esper Abrão; Rodrigues, Antônio Márcio

    2013-01-01

    Structural rearrangement of the dentate gyrus has been described as the underlying cause of many types of epilepsies, particularly temporal lobe epilepsy. It is said to occur when aberrant connections are established in the damaged hippocampus, as described in human epilepsy and experimental models. Computer modelling of the dentate gyrus circuitry and the corresponding structural changes has been used to understand how abnormal mossy fibre sprouting can subserve seizure generation observed in experimental models when epileptogenesis is induced by status epilepticus. The model follows the McCulloch-Pitts formalism including the representation of the nonsynaptic mechanisms. The neuronal network comprised granule cells, mossy cells, and interneurons. The compensation theory and the Hebbian and anti-Hebbian rules were used to describe the structural rearrangement including the effects of the nonsynaptic mechanisms on the neuronal activity. The simulations were based on neuroanatomic data and on the connectivity pattern between the cells represented. The results suggest that there is a joint action of the compensation theory and Hebbian rules during the inflammatory process that accompanies the status epilepticus. The structural rearrangement simulated for the dentate gyrus circuitry promotes speculation about the formation of the abnormal mossy fiber sprouting and its role in epileptic seizures. PMID:23431287

  20. Enhanced Synaptic Connectivity in the Dentate Gyrus during Epileptiform Activity: Network Simulation

    Directory of Open Access Journals (Sweden)

    Keite Lira de Almeida França

    2013-01-01

    Full Text Available Structural rearrangement of the dentate gyrus has been described as the underlying cause of many types of epilepsies, particularly temporal lobe epilepsy. It is said to occur when aberrant connections are established in the damaged hippocampus, as described in human epilepsy and experimental models. Computer modelling of the dentate gyrus circuitry and the corresponding structural changes has been used to understand how abnormal mossy fibre sprouting can subserve seizure generation observed in experimental models when epileptogenesis is induced by status epilepticus. The model follows the McCulloch-Pitts formalism including the representation of the nonsynaptic mechanisms. The neuronal network comprised granule cells, mossy cells, and interneurons. The compensation theory and the Hebbian and anti-Hebbian rules were used to describe the structural rearrangement including the effects of the nonsynaptic mechanisms on the neuronal activity. The simulations were based on neuroanatomic data and on the connectivity pattern between the cells represented. The results suggest that there is a joint action of the compensation theory and Hebbian rules during the inflammatory process that accompanies the status epilepticus. The structural rearrangement simulated for the dentate gyrus circuitry promotes speculation about the formation of the abnormal mossy fiber sprouting and its role in epileptic seizures.

  1. Theory of coupled electromagnetic circuits, the connection to quantum mechanical resonance interactions and relevance to chronobiology

    CERN Document Server

    Ulmer, W; Halberg, F; Schwarzkopff, O

    2011-01-01

    The existence of specific biorhythms and the role of geomagnetic and/or solar magnetic activities are well-established by appropriate correlations in chronobiology. From a physical viewpoint, there are two different accesses to biorhythms to set up connections to molecular processes: 1. Diffusion of charged molecules in magnetic fields. 2. Quantum mechanical perturbation theoretical methods and their resonance dominators to characterize specific interactions between constituents. The methods of point 2 permit the treatment of molecular processes by circuits with characteristic resonances and 'beat-frequencies', which result from the primarily fast physical processes. As examples the tunneling processes between DNA base pairs (H bonds) and the ATP decomposition are considered.

  2. Cell biology in neuroscience: Architects in neural circuit design: glia control neuron numbers and connectivity.

    Science.gov (United States)

    Corty, Megan M; Freeman, Marc R

    2013-11-11

    Glia serve many important functions in the mature nervous system. In addition, these diverse cells have emerged as essential participants in nearly all aspects of neural development. Improved techniques to study neurons in the absence of glia, and to visualize and manipulate glia in vivo, have greatly expanded our knowledge of glial biology and neuron-glia interactions during development. Exciting studies in the last decade have begun to identify the cellular and molecular mechanisms by which glia exert control over neuronal circuit formation. Recent findings illustrate the importance of glial cells in shaping the nervous system by controlling the number and connectivity of neurons.

  3. Research on a Novel Power Inductor-Based Bidirectional Lossless Equalization Circuit for Series-Connected Battery Packs

    Directory of Open Access Journals (Sweden)

    Xiangwei Guo

    2015-06-01

    Full Text Available Cell balancing plays an important role in preserving the life of series-connected battery packs; without a suitable balancing system, the individual cell voltages will differ over time, and the battery pack capacity will decrease quickly. This paper presents a novel power inductor-based bidirectional lossless equalization circuit. This circuit consists of several balancing sub-circuits, which allow the dynamic adjustment of the equalization path and equalization threshold. The simulation and experiment results demonstrate that the proposed circuit, which features a simple control method, fast balancing, and a large equalization current, exhibits outstanding equalization performance.

  4. Constrained Synaptic Connectivity in Functional Mammalian Neuronal Networks Grown on Patterned Surfaces

    Science.gov (United States)

    Bourdieu, Laurent; Wyart, Claire; Ybert, Christophe; Herr, Catherine; Chatenay, Didier

    2002-03-01

    The use of ordered neuronal networks in vitro is a promising approach to study the development and the activity of neuronal assemblies. However in previous attempts, sufficient growth control and physiological maturation of neurons could not be achieved. We describe an original protocol in which polylysine patterns confine the adhesion of cellular bodies to prescribed spots and the neuritic growth to thin lines. Hippocampal neurons are maintained healthy in serum free medium up to five weeks in vitro. Electrophysiology and immunochemistry show that neurons exhibit mature excitatory and inhibitory synapses and calcium imaging reveals spontaneous bursting activity of neurons in isolated networks. Neurons in these geometrical networks form functional synapses preferentially to their first neighbors. We have therefore established a simple and robust protocol to constrain both the location of neuronal cell bodies and their pattern of connectivity.

  5. [How is the sense of smell connected? Cellular and molecular mechanisms guiding the development of the synaptic connections from the nose to the cortex (I)].

    Science.gov (United States)

    García-González, Diego; de Castro, Fernando

    2011-04-16

    The physiological particularities that occur during the development of the olfactory system make it one of the most fascinating parts of the central nervous system and one of models that has been most widely studied in order to understand the mechanisms related with axonal growth and guidance towards the right targets. A variety of mechanisms are known, some mediated by contact (laminins, cell adhesion molecules, ephrins, etc.) and others that are secreted (semaphorins, slits, growth factors, etc.), to play diverse roles in establishing the synaptic interactions among the olfactory epithelium, the olfactory bulb and the olfactory cortex. In relation to this, other specific mechanisms for this system have also been proposed, including the incredible family of close to 1000 different olfactory receptors. In recent years, different reviews have focused on the partial elements of this system, especially on the mechanisms involved in the formation of the olfactory nerve. However, no detailed review of those related with the development of the connections between the different olfactory structures (epithelium, bulb and cortex) has been put forward to date. In this first part of the review, we address this topic from the following perspective: the different cellular and molecular mechanisms that guide the formation of the olfactory nerve and the lateral olfactory tract.

  6. Microglomerular synaptic complexes in the sky-compass network of the honeybee connect parallel pathways from the anterior optic tubercle to the central complex

    Directory of Open Access Journals (Sweden)

    Martina Held

    2016-10-01

    Full Text Available While the ability of honeybees to navigate relying on sky-compass information has been investigated in a large number of behavioral studies, the underlying neuronal system has so far received less attention. The sky-compass pathway has recently been described from its input region, the dorsal rim area of the compound eye, to the anterior optic tubercle (AOTU. The aim of this study is to reveal the connection from the AOTU to the central complex. For this purpose we investigated the anatomy of large microglomerular synaptic complexes in the medial and lateral bulbs of the lateral complex. The synaptic complexes are formed by TuLAL1 neurons of the AOTU and GABAergic tangential neurons of the central body’s lower division (TL neurons. Both TuLAL1 and TL neurons strongly resemble neurons forming these complexes in other insect species. We further investigated the ultrastructure of these synaptic complexes using transmission electron microscopy. We found that single large presynaptic terminals of TuLAL1 neurons enclose many small profiles of TL neurons. The synaptic connections between these neurons are established by two types of synapses: divergent dyads and divergent tetrads. Our data support the assumption that these complexes are a highly conserved feature in the insect brain and play an important role in reliable signal transmission within the sky-compass pathway.

  7. Correlated network activity enhances synaptic efficacy via BDNF and the ERK pathway at immature CA3–CA1 connections in the hippocampus

    OpenAIRE

    Mohajerani, Majid H.; Sivakumaran, Sudhir; Zacchi, Paola; Aguilera, Pedro de (O.P.); Cherubini, Enrico

    2007-01-01

    At early developmental stages, correlated neuronal activity is thought to exert a critical control on functional and structural refinement of synaptic connections. In the hippocampus, between postnatal day 2 (P2) and P6, network-driven giant depolarizing potentials (GDPs) are generated by the synergistic action of glutamate and GABA, which is depolarizing and excitatory. Here the rising phase of GDPs was used to trigger Schaffer collateral stimulation in such a way that synchronized network a...

  8. Involvement of pre- and postsynaptic NMDA receptors at local circuit interneuron connections in rat neocortex.

    Science.gov (United States)

    De-May, C L; Ali, A B

    2013-01-03

    To investigate the involvement of N-Methyl-D-aspartate (NMDA) receptors in local neocortical synaptic transmission, dual whole-cell recordings - combined with biocytin labelling - were obtained from bitufted adapting, multipolar adapting or multipolar non-adapting interneurons and pyramidal cells in layers II-V of rat (postnatal days 17-22) sensorimotor cortex. The voltage dependency of the amplitude of Excitatory postsynaptic potentials (EPSPs) received by the three types of interneuron appeared to coincide with the interneuron subclass; upon depolarisation, EPSPs received by multipolar non-adapting interneurons either decreased in amplitude or appeared insensitive, multipolar adapting interneuron EPSP amplitudes increased or appeared insensitive, whereas bitufted interneuron EPSP amplitudes increased or decreased. Connections were challenged with the NMDA receptor antagonist d-(-)-2-amino-5-phosphonopentanoic acid (d-AP5) (50μM) revealing NMDA receptors to contribute to EPSPs received by all cell types, this also abolished the non-conventional voltage dependency. Reciprocal connections were frequent between pyramidal cells and multipolar interneurons, and inhibitory postsynaptic potentials (IPSPs) elicited in pyramidal cells by both multipolar adapting and multipolar non-adapting interneurons were sensitive to a significant reduction in amplitude by d-AP5. The involvement of presynaptic NMDA receptors was indicated by coefficient of variation analysis and an increase in the failures of transmission. Furthermore, by loading MK-801 into the pre- or postsynaptic neurons, we observed that a reduction in inhibition requires presynaptic and not postsynaptic NMDA receptors. These results suggest that NMDA receptors possess pre- and postsynaptic roles at selective neocortical synapses that are probably important in governing spike-timing and information flow.

  9. Correlated network activity enhances synaptic efficacy via BDNF and the ERK pathway at immature CA3 CA1 connections in the hippocampus.

    Science.gov (United States)

    Mohajerani, Majid H; Sivakumaran, Sudhir; Zacchi, Paola; Aguilera, Pedro; Cherubini, Enrico

    2007-08-07

    At early developmental stages, correlated neuronal activity is thought to exert a critical control on functional and structural refinement of synaptic connections. In the hippocampus, between postnatal day 2 (P2) and P6, network-driven giant depolarizing potentials (GDPs) are generated by the synergistic action of glutamate and GABA, which is depolarizing and excitatory. Here the rising phase of GDPs was used to trigger Schaffer collateral stimulation in such a way that synchronized network activity was coincident with presynaptic activation of afferent input. This procedure produced a persistent increase in spontaneous and evoked alpha-amino-3-hydroxy-5-methyl-4-isoxadepropionic acid-mediated glutamatergic currents, an effect that required calcium influx through postsynaptic L-type calcium channels. No potentiation was observed when a delay of 3 sec was introduced between GDPs and afferent stimulation. Pairing-induced potentiation was prevented by scavengers of endogenous BDNF or tropomyosin-related kinase receptor B (TrkB) receptor antagonists. Blocking TrkB receptors in the postsynaptic cell did not prevent the effects of pairing, suggesting that BDNF, possibly secreted from the postsynaptic cell during GDPs, acts on TrkB receptors localized on presynaptic neurons. Application of exogenous BDNF mimicked the effects of pairing on synaptic transmission. In addition, pairing-induced synaptic potentiation was blocked by ERK inhibitors, suggesting that BDNF activates the MAPK/ERK cascade, which may lead to transcriptional regulation and new protein synthesis in the postsynaptic neuron. These results support the hypothesis that, during a critical period of postnatal development, GABAA-mediated GDPs are instrumental in tuning excitatory synaptic connections and provide insights into the molecular mechanisms involved in this process.

  10. Structural-functional connectivity deficits of neocortical circuits in the Fmr1 (-/y) mouse model of autism

    NARCIS (Netherlands)

    Haberl, M.G.; Zerbi, V.; Veltien, A.A.; Ginger, M.; Heerschap, A.; Frick, A.

    2015-01-01

    Fragile X syndrome (FXS), the most common inherited form of intellectual disability disorder and a frequent cause of autism spectrum disorder (ASD), is characterized by a high prevalence of sensory symptoms. Perturbations in the anatomical connectivity of neocortical circuits resulting in their func

  11. An iterative approach for symmetrical and asymmetrical Short-circuit calculations with converter-based connected renewable energy sources

    DEFF Research Database (Denmark)

    Göksu, Ömer; Teodorescu, Remus; Bak-Jensen, Birgitte;

    2012-01-01

    As more renewable energy sources, especially more wind turbines are installed in the power system, analysis of the power system with the renewable energy sources becomes more important. Short-circuit calculation is a well known fault analysis method which is widely used for early stage analysis...... and design purposes and tuning of the network protection equipments. However, due to current controlled power converter-based grid connection of the wind turbines, short-circuit calculation cannot be performed with its current form for networks with power converter-based wind turbines. In this paper......, an iterative approach for short-circuit calculation of networks with power converter-based wind turbines is developed for both symmetrical and asymmetrical short-circuit grid faults. As a contribution to existing solutions, negative sequence current injection from the wind turbines is also taken into account...

  12. Altered structural and effective connectivity in anorexia and bulimia nervosa in circuits that regulate energy and reward homeostasis.

    Science.gov (United States)

    Frank, G K W; Shott, M E; Riederer, J; Pryor, T L

    2016-11-01

    Anorexia and bulimia nervosa are severe eating disorders that share many behaviors. Structural and functional brain circuits could provide biological links that those disorders have in common. We recruited 77 young adult women, 26 healthy controls, 26 women with anorexia and 25 women with bulimia nervosa. Probabilistic tractography was used to map white matter connectivity strength across taste and food intake regulating brain circuits. An independent multisample greedy equivalence search algorithm tested effective connectivity between those regions during sucrose tasting. Anorexia and bulimia nervosa had greater structural connectivity in pathways between insula, orbitofrontal cortex and ventral striatum, but lower connectivity from orbitofrontal cortex and amygdala to the hypothalamus (Panorexia and bulimia nervosa effective connectivity was directed from anterior cingulate via ventral striatum to the hypothalamus. Across all groups, sweetness perception was predicted by connectivity strength in pathways connecting to the middle orbitofrontal cortex. This study provides evidence that white matter structural as well as effective connectivity within the energy-homeostasis and food reward-regulating circuitry is fundamentally different in anorexia and bulimia nervosa compared with that in controls. In eating disorders, anterior cingulate cognitive-emotional top down control could affect food reward and eating drive, override hypothalamic inputs to the ventral striatum and enable prolonged food restriction.

  13. The basic circuit of the IC: tectothalamic neurons with different patterns of synaptic organization send different messages to the thalamus.

    Science.gov (United States)

    Ito, Tetsufumi; Oliver, Douglas L

    2012-01-01

    The inferior colliculus (IC) in the midbrain of the auditory system uses a unique basic circuit to organize the inputs from virtually all of the lower auditory brainstem and transmit this information to the medial geniculate body (MGB) in the thalamus. Here, we review the basic circuit of the IC, the neuronal types, the organization of their inputs and outputs. We specifically discuss the large GABAergic (LG) neurons and how they differ from the small GABAergic (SG) and the more numerous glutamatergic neurons. The somata and dendrites of LG neurons are identified by axosomatic glutamatergic synapses that are lacking in the other cell types and exclusively contain the glutamate transporter VGLUT2. Although LG neurons are most numerous in the central nucleus of the IC (ICC), an analysis of their distribution suggests that they are not specifically associated with one set of ascending inputs. The inputs to ICC may be organized into functional zones with different subsets of brainstem inputs, but each zone may contain the same three neuron types. However, the sources of VGLUT2 axosomatic terminals on the LG neuron are not known. Neurons in the dorsal cochlear nucleus, superior olivary complex, intermediate nucleus of the lateral lemniscus, and IC itself that express the gene for VGLUT2 only are the likely origin of the dense VGLUT2 axosomatic terminals on LG tectothalamic neurons. The IC is unique since LG neurons are GABAergic tectothalamic neurons in addition to the numerous glutamatergic tectothalamic neurons. SG neurons evidently target other auditory structures. The basic circuit of the IC and the LG neurons in particular, has implications for the transmission of information about sound through the midbrain to the MGB.

  14. Excitatory Synaptic Drive and Feedforward Inhibition in the Hippocampal CA3 Circuit Are Regulated by SynCAM 1

    OpenAIRE

    Park, Kellie A.; Ribic, Adema; Laage Gaupp, Fabian M.; Coman, Daniel; Huang, Yuegao; Dulla, Chris G.; Hyder, Fahmeed; Biederer, Thomas

    2016-01-01

    Select adhesion proteins control the development of synapses and modulate their structural and functional properties. Despite these important roles, the extent to which different synapse-organizing mechanisms act across brain regions to establish connectivity and regulate network properties is incompletely understood. Further, their functional roles in different neuronal populations remain to be defined. Here, we applied diffusion tensor imaging (DTI), a modality of magnetic resonance imaging...

  15. Transient Analysis of Grid-Connected Wind Turbines with DFIG After an External Short-Circuit Fault

    DEFF Research Database (Denmark)

    Sun, Tao; Chen, Zhe; Blaabjerg, Frede

    2004-01-01

    on transient analysis of variable speed wind turbines with doubly fed induction generator (DFIG) after an external short-circuit fault. A simulation model of a MW-level variable speed wind turbine with DFIG developed in PSCAD/EMTDC is presented, and the control and protection schemes are described in detail......The fast development of wind power generation brings new requirements for wind turbine integration to the network. After the clearance of an external short-circuit fault, the grid-connected wind turbine should restore its normal operation with minimized power losses. This paper concentrates...

  16. A nanoCryotron comparator can connect single-flux quantum circuits to conventional electronics

    CERN Document Server

    Zhao, Qing-Yuan; Dane, Andrew E; Berggren, Karl K; Ortlepp, Thomas

    2016-01-01

    Integration with conventional electronics offers a straightforward and economical approach to upgrading existing superconducting technologies, such as scaling up superconducting detectors into large arrays and combining single flux quantum (SFQ) digital circuits with semiconductor logic and memories. However, direct output signals from superconducting devices (e.g., Josephson junctions) are usually not compatible with the input requirements of conventional devices (e.g., transistors). Here, we demonstrate the use of a single three-terminal superconducting-nanowire device, called the nanocryotron (nTron), as a digital comparator to combine SFQ circuits with mature semiconductor circuits such as complementary metal oxide semiconductor (CMOS) circuits. Since SFQ circuits can digitize output signals from general superconducting devices and CMOS circuits can interface existing CMOS-compatible electronics, our results demonstrate the feasibility of a general architecture that uses an nTron as an interface to realiz...

  17. Fetal neural tube stem cells from Pax3 mutant mice proliferate, differentiate, and form synaptic connections when stimulated with folic acid.

    Science.gov (United States)

    Ichi, Shunsuke; Nakazaki, Hiromichi; Boshnjaku, Vanda; Singh, Ravneet Monny; Mania-Farnell, Barbara; Xi, Guifa; McLone, David G; Tomita, Tadanori; Mayanil, Chandra Shekhar K

    2012-01-20

    Although maternal intake of folic acid (FA) prevents neural tube defects in 70% of the population, the exact mechanism of prevention has not been elucidated. We hypothesized that FA affects neural stem cell (NSC) proliferation and differentiation. This hypothesis was examined in a folate-responsive spina bifida mouse model, Splotch (Sp(-/-)), which has a homozygous loss-of-function mutation in the Pax3 gene. Neurospheres were generated with NSCs from the lower lumbar neural tube of E10.5 wild-type (WT) and Sp(-/-) embryos, in the presence and absence of FA. In the absence of FA, the number of neurospheres generated from Sp(-/-) embryos compared with WT was minimal (Pcell differentiation, FA-stimulated Sp(-/-) neurospheres were allowed to differentiate in the continued presence or absence of FA. Neurospheres from both conditions expressed multi-potent stem cell characteristics and the same differentiation potential as WT. Further, multiple neurospheres from both WT and FA-stimulated Sp(-/-) cell cultures formed extensive synaptic connections. On the whole, FA-mediated rescue of neural tube defects in Sp(-/-) embryos promotes NSC proliferation at an early embryonic stage. FA-stimulated Sp(-/-) neurospheres differentiate and form synaptic connections, comparable to WT.

  18. Pulse Responses of a Two-layered Printed Circuit with an Improved Line-Pad Connected Structure

    Science.gov (United States)

    Kobayashi, Daisuke; Furukawa, Shinichi; Hinata, Takashi

    The peak value of transmitted pulse in printed circuit boards (PCB) is important for a pulse peak detection devices. When an input line and an output line are connected to each pad with the direction of right angle, the propagating pulses with the narrow time duration separate into some parts and decrease the peak value of pulse response. This paper presents an improved line-pad connected structure. The microstrip line is in contact with a pad from outside by considering the pulse propagation time passing through the via structure. We obtained the large peak value of the pulse response for which the time duration is larger than 0.2ps.

  19. Applying circuit theory for corridor expansion and management at regional scales: tiling, pinch points, and omnidirectional connectivity.

    Directory of Open Access Journals (Sweden)

    David Pelletier

    Full Text Available Connectivity models are useful tools that improve the ability of researchers and managers to plan land use for conservation and preservation. Most connectivity models function in a point-to-point or patch-to-patch fashion, limiting their use for assessing connectivity over very large areas. In large or highly fragmented systems, there may be so many habitat patches of interest that assessing connectivity among all possible combinations is prohibitive. To overcome these conceptual and practical limitations, we hypothesized that minor adaptation of the Circuitscape model can allow the creation of omnidirectional connectivity maps illustrating flow paths and variations in the ease of travel across a large study area. We tested this hypothesis in a 24,300 km(2 study area centered on the Montérégie region near Montréal, Québec. We executed the circuit model in overlapping tiles covering the study region. Current was passed across the surface of each tile in orthogonal directions, and then the tiles were reassembled to create directional and omnidirectional maps of connectivity. The resulting mosaics provide a continuous view of connectivity in the entire study area at the full original resolution. We quantified differences between mosaics created using different tile and buffer sizes and developed a measure of the prominence of seams in mosaics formed with this approach. The mosaics clearly show variations in current flow driven by subtle aspects of landscape composition and configuration. Shown prominently in mosaics are pinch points, narrow corridors where organisms appear to be required to traverse when moving through the landscape. Using modest computational resources, these continuous, fine-scale maps of nearly unlimited size allow the identification of movement paths and barriers that affect connectivity. This effort develops a powerful new application of circuit models by pinpointing areas of importance for conservation, broadening the

  20. Aberrant functional connectivity in Papez circuit correlates with memory performance in cognitively intact middle-aged APOE4 carriers.

    Science.gov (United States)

    Li, Wenjun; Antuono, Piero G; Xie, Chunming; Chen, Gang; Jones, Jennifer L; Ward, B Douglas; Singh, Suraj P; Franczak, Malgorzata B; Goveas, Joseph S; Li, Shi-Jiang

    2014-08-01

    The main objective of this study is to detect the early changes in resting-state Papez circuit functional connectivity using the hippocampus as the seed, and to determine the associations between altered functional connectivity (FC) and the episodic memory performance in cognitively intact middle-aged apolipoprotein E4 (APOE4) carriers who are at risk of Alzheimer's disease (AD). Forty-six cognitively intact, middle-aged participants, including 20 APOE4 carriers and 26 age-, sex-, and education-matched noncarriers were studied. The resting-state FC of the hippocampus (HFC) was compared between APOE4 carriers and noncarriers. APOE4 carriers showed significantly decreased FC in brain areas that involve learning and memory functions, including the frontal, cingulate, thalamus and basal ganglia regions. Multiple linear regression analysis showed significant correlations between HFC and the episodic memory performance. Conjunction analysis between neural correlates of memory and altered HFC showed the overlapping regions, especially the subcortical regions such as thalamus, caudate nucleus, and cingulate cortices involved in the Papez circuit. Thus, changes in connectivity in the Papez circuit may be used as an early risk detection for AD.

  1. Learning-Related Synaptic Reconfiguration in Hippocampal Networks: Memory Storage or Waveguide Tuning?

    Directory of Open Access Journals (Sweden)

    Eduardo Mercado III

    2015-03-01

    Full Text Available A fundamental assumption of current hypotheses regarding hippocampal involvement in memory formation is that changes in synaptic connections between hippocampal neurons serve to encode information about recent events. An alternative possibility is that synaptic changes are “ruts” left by dynamic traveling waves involved in memory processes rather than a mechanism for storing memories of events. Specifically, traveling waves of activity in corticohippocampal circuits may sometimes modify those circuits as they propagate through them, thereby changing the paths and qualities of future wave patterns.

  2. Involvement of pre- and postsynaptic NMDA receptors at local circuit interneuron connections in rat neocortex

    OpenAIRE

    De-May, C.L.; Ali, A. B.

    2013-01-01

    To investigate the involvement of N-Methyl-D-aspartate (NMDA) receptors in local neocortical synaptic transmission, dual whole-cell recordings – combined with biocytin labelling – were obtained from bitufted adapting, multipolar adapting or multipolar non-adapting interneurons and pyramidal cells in layers II–V of rat (postnatal days 17–22) sensorimotor cortex. The voltage dependency of the amplitude of Excitatory postsynaptic potentials (EPSPs) received by the three types of interneuron appe...

  3. INVOLVEMENT OF PRE- AND POSTSYNAPTIC NMDA RECEPTORS AT LOCAL CIRCUIT INTERNEURON CONNECTIONS IN RAT NEOCORTEX

    OpenAIRE

    De-May, C.L.; Ali, A.B.

    2013-01-01

    To investigate the involvement of N-Methyl-D-aspartate (NMDA) receptors in local neocortical synaptic transmission, dual whole-cell recordings – combined with biocytin labelling – were obtained from bitufted adapting, multipolar adapting or multipolar non-adapting interneurons and pyramidal cells in layers II–V of rat (postnatal days 17–22) sensorimotor cortex. The voltage dependency of the amplitude of Excitatory postsynaptic potentials (EPSPs) received by the three types of interneuron appe...

  4. Study on Snubber Circuit of Series Connected IGBT's%IGBT串联阀吸收电路的研究

    Institute of Scientific and Technical Information of China (English)

    范镇淇; 侯凯; 李伟邦

    2013-01-01

    绝缘栅双极型晶体管IGBT综合了GTR和MOSFET的优点,近年来得到了广泛的应用,但是受限于耐压等级,单个IGBT高压大功率电能变换场合还不能满足需求,而串联使用是一种较好的解决方案.在串联使用中为了抑制器件关断过程中产生浪涌过冲,仍然需要吸收电路进行保护.通过对比分析详细阐述了RCD吸收电路在IGBT串联中的使用优势,并给出了参数选取的原则,同时分析了RCD吸收电路对器件动、静态电压均压的影响,并通过实验予以了验证.%Isolate gate bipolar transistor (IGBT) combines the advantage of GTR and MOSFET,which has been widely used in recent years.However,due to the voltage level,single IGBT cannot meet the requirements of highpower power converting.In such application fields,serial connection of IGBT' s is a good solution.In a serial IGBT valve,snubber circuit is indispensable to suppress voltage overshoot while IGBT switching from on state to off state.By analyzing the different snubber circuits,why RCD snubber circuit could be used in IGBT's serial connection was described,and gave the principle of parameter selection.Then investigated how the RCD snubber circuit influenced voltage balance in IGBT 's serial connection,and the results were verified by experiment.

  5. A nanocryotron comparator can connect single-flux-quantum circuits to conventional electronics

    Science.gov (United States)

    Zhao, Qing-Yuan; McCaughan, Adam N.; Dane, Andrew E.; Berggren, Karl K.; Ortlepp, Thomas

    2017-04-01

    Integration with conventional electronics offers a straightforward and economical approach to upgrading existing superconducting technologies, such as scaling up superconducting detectors into large arrays and combining single flux quantum (SFQ) digital circuits with semiconductor logic gates and memories. However, direct output signals from superconducting devices (e.g., Josephson junctions) are usually not compatible with the input requirements of conventional devices (e.g., transistors). Here, we demonstrate the use of a single three-terminal superconducting-nanowire device, called the nanocryotron (nTron), as a digital comparator to combine SFQ circuits with mature semiconductor circuits such as complementary metal oxide semiconductor (CMOS) circuits. Since SFQ circuits can digitize output signals from general superconducting devices and CMOS circuits can interface existing CMOS-compatible electronics, our results demonstrate the feasibility of a general architecture that uses an nTron as an interface to realize a ‘super-hybrid’ system consisting of superconducting detectors, superconducting quantum electronics, CMOS logic gates and memories, and other conventional electronics.

  6. On the estimation of population-specific synaptic currents from laminar multielectrode recordings.

    Science.gov (United States)

    Gratiy, Sergey L; Devor, Anna; Einevoll, Gaute T; Dale, Anders M

    2011-01-01

    Multielectrode array recordings of extracellular electrical field potentials along the depth axis of the cerebral cortex are gaining popularity as an approach for investigating the activity of cortical neuronal circuits. The low-frequency band of extracellular potential, i.e., the local field potential (LFP), is assumed to reflect synaptic activity and can be used to extract the laminar current source density (CSD) profile. However, physiological interpretation of the CSD profile is uncertain because it does not disambiguate synaptic inputs from passive return currents and does not identify population-specific contributions to the signal. These limitations prevent interpretation of the CSD in terms of synaptic functional connectivity in the columnar microcircuit. Here we present a novel anatomically informed model for decomposing the LFP signal into population-specific contributions and for estimating the corresponding activated synaptic projections. This involves a linear forward model, which predicts the population-specific laminar LFP in response to synaptic inputs applied at different positions along each population and a linear inverse model, which reconstructs laminar profiles of synaptic inputs from laminar LFP data based on the forward model. Assuming spatially smooth synaptic inputs within individual populations, the model decomposes the columnar LFP into population-specific contributions and estimates the corresponding laminar profiles of synaptic input as a function of time. It should be noted that constant synaptic currents at all positions along a neuronal population cannot be reconstructed, as this does not result in a change in extracellular potential. However, constraining the solution using a priori knowledge of the spatial distribution of synaptic connectivity provides the further advantage of estimating the strength of active synaptic projections from the columnar LFP profile thus fully specifying synaptic inputs.

  7. Ultrastructure and synaptic connectivity of main and accessory olfactory bulb efferent projections terminating in the rat anterior piriform cortex and medial amygdala.

    Science.gov (United States)

    Park, Sook Kyung; Kim, Jong Ho; Yang, Eun Sun; Ahn, Dong Kuk; Moon, Cheil; Bae, Yong Chul

    2014-09-01

    Neurons in the main olfactory bulb relay peripheral odorant signals to the anterior piriform cortex (aPir), whereas neurons of the accessory olfactory bulb relay pheromone signals to the medial amygdala (MeA), suggesting that they belong to two functionally distinct systems. To help understand how odorant and pheromone signals are further processed in the brain, we investigated the synaptic connectivity of identified axon terminals of these neurons in layer Ia of the aPir and posterodorsal part of the MeA, using anterograde tracing with horseradish peroxidase, quantitative ultrastructural analysis of serial thin sections, and immunogold staining. All identified boutons contained round vesicles and some also contained many large dense core vesicles. The number of postsynaptic dendrites per labeled bouton was significantly higher in the aPir than in the MeA, suggesting higher synaptic divergence at a single bouton level. While a large fraction of identified boutons (29%) in the aPir contacted 2-4 postsynaptic dendrites, only 7% of the identified boutons in the MeA contacted multiple postsynaptic dendrites. In addition, the majority of the identified boutons in the aPir (95%) contacted dendritic spines, whereas most identified boutons in the MeA (64%) contacted dendritic shafts. Identified boutons and many of the postsynaptic dendrites showed glutamate immunoreactivity. These findings suggest that odorant and pheromone signals are processed differently in the brain centers of the main and accessory olfactory systems.

  8. Double Labeling Immunoelectron Microscopic Study on the Synaptic Connections between Glutamic Acid Neurons and GABA Neurons in the Hippocampus of Rats

    Institute of Scientific and Technical Information of China (English)

    ZHU Changgeng; CAI Qiuyun; LIU Qingying; WEI Ying

    2000-01-01

    In order to explore the roles of different neurotransmitters in epileptic pathogenesis,the synaptic connections between glutamic acid (Glu) neurons and GABA neurons in normal rat hippocampus were studied by pre-embedding double labeling immunoelectron microscopy. The GABA immunoreaction was first demonstrated by chromogen DAB, then the Glu immunoreaction was demonstrated by molybdic acid-TMB method. After being stabilized by DAB-cobalt chloride,the sections were processed for electron microscopic embedding. Under electron microscope, there were many Glu immunoreaction-positive neurons in the pyramidal layer of hippocampal CA1 area and some GABA immunoreaction-positive neurons with pyramidal or polygonal perikarya in the pyramidal, polymorphic and radiant layer of CA1 area. There were also symmetric dendro-axonic synapses formed by GABA-positive dendrites and Glu-positive axons in the polymorphic layer and symmetric axo-dendritic synapses formed by GABA-positive axons and Glu-positive dendrites in the radiant layer. In addition, there were symmetric autoregulatory axo-dendritic synapses between Glu-positive axons and dendrites and autoregulatory axo-axonic synapses (both symmetric and asymmetric) between GABA-positive axons. Above mentioned results, for the first time,showed that there were complex synaptic regulatory relationships between excitatory Glu neurons and inhibitory GABA neurons in the hippocampal CA1 area, thereby, providing ultrastructural evidence for different neurotransmitters participating in epileptic pathogenesis.

  9. Heterogeneous reallocation of presynaptic efficacy in recurrent excitatory circuits adapting to inactivity.

    Science.gov (United States)

    Mitra, Ananya; Mitra, Siddhartha S; Tsien, Richard W

    2011-12-18

    Recurrent excitatory circuits face extreme challenges in balancing efficacy and stability. We recorded from CA3 pyramidal neuron pairs in rat hippocampal slice cultures to characterize synaptic and circuit-level changes in recurrent synapses resulting from long-term inactivity. Chronic tetrodotoxin treatment greatly reduced the percentage of connected CA3-CA3 neurons, but enhanced the strength of the remaining connections; presynaptic release probability sharply increased, whereas quantal size was unaltered. Connectivity was decreased in activity-deprived circuits by functional silencing of synapses, whereas three-dimensional anatomical analysis revealed no change in spine or bouton density or aggregate dendrite length. The silencing arose from enhanced Cdk5 activity and could be reverted by acute Cdk5 inhibition with roscovitine. Our results suggest that recurrent circuits adapt to chronic inactivity by reallocating presynaptic weights heterogeneously, strengthening certain connections while silencing others. This restricts synaptic output and input, preserving signaling efficacy among a subset of neuronal ensembles while protecting network stability.

  10. A winding road: Alzheimer’s disease increases circuitous functional connectivity pathways

    Directory of Open Access Journals (Sweden)

    John eSuckling

    2015-11-01

    Full Text Available Neuroimaging has been successful in characterising the pattern of cerebral atrophy that accompanies the progression of Alzheimer’s disease (AD. Examination of functional connectivity, the strength of signal synchronicity between brain regions, has gathered pace as another way of understanding changes to the brain that are associated with AD. It appears to have good sensitivity and detect effects that precede cognitive decline, and thus offers the possibility to understand the neurobiology of the disease in its earliest phases. However, functional connectivity analyses to date generally consider only the strongest connections, with weaker links ignored. This proof-of-concept study compared patients with mild-to-moderate AD (N=11 and matched control individuals (N=12 based on functional connectivities derived from blood-oxygenation level dependent (BOLD sensitive functional MRI acquired during resting wakefulness. All positive connectivities irrespective of their strength were included. Transitive closures of the resulting connectome were calculated that classified connections as either direct or indirect. Between-group differences in the proportion of indirect paths were observed. In AD, there was broadly increased indirect connectivity across greater spatial distances. Furthermore, the indirect pathways in AD had greater between-subject topological variance than controls.The prevailing characterisation of AD as being a disconnection syndrome is refined by the observation that direct links between regions that are impaired are perhaps replaced by an increase in indirect functional pathways that is only detectable through inclusion of connections across the entire range of connection strengths.

  11. Circuito eléctrico equivalente de una vesícula sináptica Electric Circuit Equivalent to a Synaptic Vesicle

    Directory of Open Access Journals (Sweden)

    Cortés Xaira

    2003-06-01

    Full Text Available En el presente trabajo se desarrolla un modelo eléctrico de uno de los elementosprimordiales en la sinapsis nerviosa: la vesícula sináptica. Dicha vesícula se consideracomo un organelo esferoidal, despojada de neurotransmisores y se asume, además, quesu lumen, su membrana y el citoplasma neuronal se comportan como medios lineales,homogéneos e isotrópicos caracterizados por conductividades y permitividades especí-ficas. El método utilizado será la aplicación teórica de un campo eléctrico (que varía enel tiempo a bajas frecuencias sobre esta vesícula, lo que induce a través de su membra-na una diferencia de potencial cuya caracterización se obtiene a partir de las ecuacionesde Maxwell sometidas a condiciones de contorno adecuadas, en la denominada aproxi-mación cuasi-estacionaria. A su vez, mediante aplicación de la Transformada de Laplacea las expresiones resultantes se obtiene la FUNCIÓN DE TRANSFERENCIA, que condu-ce a sintetizar un circuito RLC equivalente de la vesícula en estudio. El modelo predicevalores de capacitancia para vesículas esféricas individuales que, al ser contrastados conlos que presenta la literatura existente derivada de procesos experimentales previos,alienta la perseverancia en este enfoque teórico germinal.In the present work an electrical model of the synaptic vesicle is developed. The vesicleis considered as a spheroidal organelle without neurotransmitters in its inner space. Inaddition, its lumen, its membrane and the neuronal cytoplasm behave like linear,homogenous and isotropic media characterized by specific conductivities and permi-tivities. The theoretical approach considers the application of an electric field (varying intime at low frequencies on this vesicle. A transmembrane potential difference is inducedand its characterization is obtained from Maxwell's equations subject to appropriateboundary conditions, in the so-called quasi-stationary approach. By applying theLaplace Transform to

  12. Sub-Anesthetic Ketamine Modulates Intrinsic BOLD Connectivity Within the Hippocampal-Prefrontal Circuit in the Rat

    Science.gov (United States)

    Gass, Natalia; Schwarz, Adam James; Sartorius, Alexander; Schenker, Esther; Risterucci, Celine; Spedding, Michael; Zheng, Lei; Meyer-Lindenberg, Andreas; Weber-Fahr, Wolfgang

    2014-01-01

    Dysfunctional connectivity within the hippocampal-prefrontal circuit (HC-PFC) is associated with schizophrenia, major depression, and neurodegenerative disorders, and both the hippocampus and prefrontal cortex have dense populations of N-methyl-D-aspartate (NMDA) receptors. Ketamine, a potent NMDA receptor antagonist, is of substantial current interest as a mechanistic model of glutamatergic dysfunction in animal and human studies, a psychotomimetic agent and a rapidly acting antidepressant. In this study, we sought to understand the modulatory effect of acute ketamine administration on functional connectivity in the HC-PFC system of the rat brain using resting-state fMRI. Sprague–Dawley rats in four parallel groups (N=9 per group) received either saline or one of three behaviorally relevant, sub-anesthetic doses of S-ketamine (5, 10, and 25 mg/kg, s.c.), and connectivity changes 15- and 30-min post-injection were studied. The strongest effects were dose- and exposure-dependent increases in functional connectivity within the prefrontal cortex and in anterior–posterior connections between the posterior hippocampus and retrosplenial cortex, and prefrontal regions. The increased prefrontal connectivity is consistent with ketamine-induced increases in HC-PFC electroencephalographic gamma band power, possibly reflecting a psychotomimetic aspect of ketamine's effect, and is contrary to the data from chronic schizophrenic patients suggesting that ketamine effect does not necessarily parallel the disease pattern but might rather reflect a hyperglutamatergic state. These findings may help to clarify the brain systems underlying different dose-dependent behavioral profiles of ketamine in the rat. PMID:24136293

  13. Voltage Recovery of Grid-Connected Wind Turbines with DFIG After a Short-Circuit Fault

    DEFF Research Database (Denmark)

    Sun, Tao; Chen, Zhe; Blaabjerg, Frede

    2004-01-01

    recovery of variable speed wind turbines with doubly fed induction generators (DFIG). A simulation model of a MW-level variable speed wind turbine with a DFIG developed in PSCAD/EMTDC is presented, and the control and protection schemes are described. A new control strategy is proposed to re......-establish the wind turbine terminal voltage after the clearance of an external short-circuit fault, and the restore the normal operation of the variable speed wind turbine with DFIG, which has been demonstrated by simulation results....

  14. Open-circuit fault detection and tolerant operation for a parallel-connected SAB DC-DC converter

    DEFF Research Database (Denmark)

    Park, Kiwoo; Chen, Zhe

    2014-01-01

    This paper presents an open-circuit fault detection method and its tolerant control strategy for a Parallel-Connected Single Active Bridge (PCSAB) dc-dc converter. The structural and operational characteristics of the PCSAB converter lead to several advantages especially for high power applications....... By paralleling modular converters, the power and current ratings of each modular converter can be lowered and by interleaving the switching patterns, the input and output current ripples can be significantly reduced without increasing switching losses or device stresses. Apart from these, the PCSAB converter...... of the converter unaffected or to improve the quality of the output current under the fault condition. The feasibility of the proposed fault detection and fault-tolerant methods are verified by simulations and experiments....

  15. Circuits regulating pleasure and happiness: the evolution of the amygdalar-hippocampal-habenular connectivity in vertebrates.

    Directory of Open Access Journals (Sweden)

    Anton J.M. Loonen

    2016-11-01

    Full Text Available Appetitive-searching (reward-seeking and distress-avoiding (misery-fleeing behavior are essential for all free moving animals to stay alive and to have offspring. Therefore, even the oldest ocean-dwelling animal creatures, living about 560 million years ago and human ancestors, must have been capable of generating these behaviors. The current article describes the evolution of the forebrain with special reference to the development of the misery-fleeing system. Although the earliest vertebrate ancestor already possessed a dorsal pallium, which corresponds to the human neocortex, the structure and function of the neocortex was acquired quite recently within the mammalian evolutionary line. Up to, and including, amphibians, the dorsal pallium can be considered to be an extension of the medial pallium, which later develops into the hippocampus. The ventral and lateral pallium largely go up into the corticoid part of the amygdala. The striatopallidum of these early vertebrates becomes extended amygdala, consisting of centromedial amygdala (striatum connected with the bed nucleus of the stria terminalis (pallidum. This amygdaloid system gives output to hypothalamus and brainstem, but also a connection with the cerebral cortex exists, which in part was created after the development of the more recent cerebral neocortex. Apart from bidirectional connectivity with the hippocampal complex, this route can also be considered to be an output channel as the fornix connects the hippocampus with the medial septum, which is the most important input structure of the medial habenula. The medial habenula regulates the activity of midbrain structures adjusting the intensity of the misery-fleeing response. Within the bed nucleus of the stria terminalis the human homologue of the ancient lateral habenula-projecting globus pallidus may exist; this structure is important for the evaluation of efficacy of the reward-seeking response. The described organization offers a

  16. Circuits Regulating Pleasure and Happiness: The Evolution of the Amygdalar-Hippocampal-Habenular Connectivity in Vertebrates

    Science.gov (United States)

    Loonen, Anton J. M.; Ivanova, Svetlana A.

    2016-01-01

    Appetitive-searching (reward-seeking) and distress-avoiding (misery-fleeing) behavior are essential for all free moving animals to stay alive and to have offspring. Therefore, even the oldest ocean-dwelling animal creatures, living about 560 million years ago and human ancestors, must have been capable of generating these behaviors. The current article describes the evolution of the forebrain with special reference to the development of the misery-fleeing system. Although, the earliest vertebrate ancestor already possessed a dorsal pallium, which corresponds to the human neocortex, the structure and function of the neocortex was acquired quite recently within the mammalian evolutionary line. Up to, and including, amphibians, the dorsal pallium can be considered to be an extension of the medial pallium, which later develops into the hippocampus. The ventral and lateral pallium largely go up into the corticoid part of the amygdala. The striatopallidum of these early vertebrates becomes extended amygdala, consisting of centromedial amygdala (striatum) connected with the bed nucleus of the stria terminalis (pallidum). This amygdaloid system gives output to hypothalamus and brainstem, but also a connection with the cerebral cortex exists, which in part was created after the development of the more recent cerebral neocortex. Apart from bidirectional connectivity with the hippocampal complex, this route can also be considered to be an output channel as the fornix connects the hippocampus with the medial septum, which is the most important input structure of the medial habenula. The medial habenula regulates the activity of midbrain structures adjusting the intensity of the misery-fleeing response. Within the bed nucleus of the stria terminalis the human homolog of the ancient lateral habenula-projecting globus pallidus may exist; this structure is important for the evaluation of efficacy of the reward-seeking response. The described organization offers a framework for the

  17. Wireless Open-Circuit In-Plane Strain and Displacement Sensor Requiring No Electrical Connections

    Science.gov (United States)

    Woodard, Stanley E. (Inventor)

    2014-01-01

    A wireless in-plane strain and displacement sensor includes an electrical conductor fixedly coupled to a substrate subject to strain conditions. The electrical conductor is shaped between its ends for storage of an electric field and a magnetic field, and remains electrically unconnected to define an unconnected open-circuit having inductance and capacitance. In the presence of a time-varying magnetic field, the electrical conductor so-shaped resonates to generate harmonic electric and magnetic field responses. The sensor also includes at least one electrically unconnected electrode having an end and a free portion extending from the end thereof. The end of each electrode is fixedly coupled to the substrate and the free portion thereof remains unencumbered and spaced apart from a portion of the electrical conductor so-shaped. More specifically, at least some of the free portion is disposed at a location lying within the magnetic field response generated by the electrical conductor. A motion guidance structure is slidingly engaged with each electrode's free portion in order to maintain each free portion parallel to the electrical conductor so-shaped.

  18. An Automatic Switched-Capacitor Cell Balancing Circuit for Series-Connected Battery Strings

    Directory of Open Access Journals (Sweden)

    Yuanmao Ye

    2016-02-01

    Full Text Available In this paper, a novel voltage equalizer is developed for series battery strings based on the two-phase switched capacitor technique. Different from the conventional voltage equalizers which are developed by switched-mode power converters, bulky magnetic components and complex monitoring and control system are avoided in the proposed system. Just a pair of complementary pulse signals with constant switching frequency and fixed duty ratio are required to control all of switches employed in the proposed voltage equalizer, and charge transfers from the higher voltage battery cells to lower voltage ones automatically. The circuit configuration and operation principle are provided in this paper. The model of the proposed voltage equalizer is also derived. Comparison with other works indicates that the proposed method is superior to the conventional switched-capacitor (SC voltage equalizer for the high stack of series battery strings. Experimental results demonstrate that the proposed voltage equalization system is capable of excellent voltage balancing performance with a simple control method.

  19. CD4-CD8 differentiation in the thymus: connecting circuits and building memories.

    Science.gov (United States)

    Xiong, Yumei; Bosselut, Rémy

    2012-04-01

    The proper choice of the CD4-helper or CD8-cytotoxic lineages by developing T cells is crucial for the generation of an antigen-responsive and functionally fit T cell repertoire. Here we present a brief overview of the transcriptional control of this process, with emphasis on two issues. The study of Cd4 expression, that had previously generated important paradigms for transcriptional regulation in eukaryotic cells, now brings new twists to the concept of 'epigenetic memory'. And connections are emerging between transcriptional regulators critical for commitment to either lineage. The present review attempts to integrate these findings and discusses the still elusive mechanisms that match CD4-CD8 lineage differentiation to MHC specificity.

  20. Synaptic encoding of temporal contiguity

    Directory of Open Access Journals (Sweden)

    Srdjan eOstojic

    2013-04-01

    Full Text Available Often we need to perform tasks in an environment that changes stochastically. In these situations it is important to learn the statistics of sequences of events in order to predict the future and the outcome of our actions. The statistical description of many of these sequences can be reduced to the set of probabilities that a particular event follows another event (temporal contiguity. Under these conditions, it is important to encode and store in our memory these transition probabilities. Here we show that for a large class of synaptic plasticity models, the distribution of synaptic strengths encodes transitions probabilities. Specifically, when the synaptic dynamics depend on pairs of contiguous events and the synapses can remember multiple instances of the transitions, then the average synaptic weights are a monotonic function of the transition probabilities. The synaptic weights converge to the distribution encoding the probabilities also when the correlations between consecutive synaptic modifications are considered. We studied how this distribution depends on the number of synaptic states for a specific model of a multi-state synapse with hard bounds. In the case of bistable synapses, the average synaptic weights are a smooth function of the transition probabilities and the accuracy of the encoding depends on the learning rate. As the number of synaptic states increases, the average synaptic weights become a step function of the transition probabilities. We finally show that the information stored in the synaptic weights can be read out by a simple rate-based neural network. Our study shows that synapses encode transition probabilities under general assumptions and this indicates that temporal contiguity is likely to be encoded and harnessed in almost every neural circuit in the brain.

  1. Experience-Dependent Equilibration of AMPAR-Mediated Synaptic Transmission during the Critical Period

    Directory of Open Access Journals (Sweden)

    Kyung-Seok Han

    2017-01-01

    Full Text Available Experience-dependent synapse refinement is essential for functional optimization of neural circuits. However, how sensory experience sculpts excitatory synaptic transmission is poorly understood. Here, we show that despite substantial remodeling of synaptic connectivity, AMPAR-mediated synaptic transmission remains at equilibrium during the critical period in the mouse primary visual cortex. The maintenance of this equilibrium requires neurogranin (Ng, a postsynaptic calmodulin-binding protein important for synaptic plasticity. With normal visual experience, loss of Ng decreased AMPAR-positive synapse numbers, prevented AMPAR-silent synapse maturation, and increased spine elimination. Importantly, visual deprivation halted synapse loss caused by loss of Ng, revealing that Ng coordinates experience-dependent AMPAR-silent synapse conversion to AMPAR-active synapses and synapse elimination. Loss of Ng also led to sensitized long-term synaptic depression (LTD and impaired visually guided behavior. Our synaptic interrogation reveals that experience-dependent coordination of AMPAR-silent synapse conversion and synapse elimination hinges upon Ng-dependent mechanisms for constructive synaptic refinement during the critical period.

  2. Pulmonary vein flow pattern in children with bidirectional cavopulmonary connection or Fontan circuit

    Energy Technology Data Exchange (ETDEWEB)

    Shariat, Masoud; Yoo, Shi-Joon [Hospital for Sick Children, Department of Radiology, Toronto (Canada); Grosse-Wortmann, Lars; Windram, Jonathan [Hospital for Sick Children, Department of Cardiology, Toronto (Canada)

    2012-02-15

    Typical flow velocity profiles in the extraparenchymal pulmonary veins (PVs) demonstrate two major antegrade flow waves: a biphasic systolic wave (S), with S1 and S2 peaks and a monophasic early diastolic wave (D). Flow reversal during atrial systole (A) is common. There is agreement that the forward diastolic PV flow wave is caused by left ventricular relaxation with opening of the mitral valve. The origin of the PV systolic wave, however, remains a topic of debate. Some studies have suggested that the S wave is created by the relaxation of the left atrium and descent of the mitral valve plane. These studies have concluded that forces generated by the right ventricle (RV) have no effect on the S wave. Others suggest that the forward propagation of the right ventricular systolic pressure pulse is the major contributor to the S wave. To determine whether any part of the systolic wave of PV flow is dependent on forces created by the right ventricle. We assessed PV flow pattern, as obtained by cardiac MRI in 12 cases (39 pulmonary veins) with RV-independent pulmonary circulation (bidirectional cavopulmonary connection or Fontan circulation). Phase-contrast imaging of the PVs was performed on a 1.5-T MR scanner with velocity encoding set at 120 cm/s. We compared these flow patterns with those of a control group of ten children (15 pulmonary veins) who had RV-dependent pulmonary circulation and underwent CMR for other indications. In all PVs of children with RV-independent pulmonary circulation the flow curves showed a single systolic peak in early systole (S1) with the S2 peak consistently absent. PV flow pattern in the control group consistently showed distinct early and late systolic peaks. This study supports the concept that S2 is caused by forward propagation of the right ventricular systolic pressure pulse. It also demonstrates that the S1 is independent of the right ventricle. (orig.)

  3. On the estimation of population-specific synaptic currents from laminar multielectrode recordings

    Directory of Open Access Journals (Sweden)

    Sergey L Gratiy

    2011-12-01

    Full Text Available Multielectrode array recordings of extracellular electrical field potentials along the depth axis of the cerebral cortex is an up-and-coming approach for investigating activity of cortical neuronal circuits. The low-frequency band of extracellular potential, i.e., the local field potential (LFP, is assumed to reflect the synaptic activity and can be used to extract the current source density (CSD profile. However, physiological interpretation of CSD profiles is uncertain because the analysis does not disambiguate synaptic inputs from passive return currents. Here we present a novel mathematical framework for identifying excited neuronal populations and for separating synaptic input currents from return currents based on LFP recordings. This involves a combination of the linear forward model, which predicts population-specific laminar LFP in response to sinusoidal synaptic inputs applied at different locations along the population cells having realistic morphologies and the linear inverse model, which reconstructs laminar profiles of synaptic inputs from the Fourier spectrum of the laminar LFP data based on the forward prediction. The model allows reconstruction of synaptic input profiles on a spatial scale comparable to known anatomical organization of synaptic projections within a cortical column. Assuming spatial correlation of synaptic inputs within individual populations, the model decomposes the columnar LFP into population-specific contributions. Constraining the solution with a priori knowledge of the spatial distribution of synaptic connectivity further allows prediction of active projections from the composite LFP profile. This modeling framework successfully delineates the main relationships between the synaptic input currents and the evoked LFP and can serve as a foundation for modeling more realistic processing of active dendritic conductances.

  4. A spiking neuron circuit based on a carbon nanotube transistor.

    Science.gov (United States)

    Chen, C-L; Kim, K; Truong, Q; Shen, A; Li, Z; Chen, Y

    2012-07-11

    A spiking neuron circuit based on a carbon nanotube (CNT) transistor is presented in this paper. The spiking neuron circuit has a crossbar architecture in which the transistor gates are connected to its row electrodes and the transistor sources are connected to its column electrodes. An electrochemical cell is incorporated in the gate of the transistor by sandwiching a hydrogen-doped poly(ethylene glycol)methyl ether (PEG) electrolyte between the CNT channel and the top gate electrode. An input spike applied to the gate triggers a dynamic drift of the hydrogen ions in the PEG electrolyte, resulting in a post-synaptic current (PSC) through the CNT channel. Spikes input into the rows trigger PSCs through multiple CNT transistors, and PSCs cumulate in the columns and integrate into a 'soma' circuit to trigger output spikes based on an integrate-and-fire mechanism. The spiking neuron circuit can potentially emulate biological neuron networks and their intelligent functions.

  5. Morphology, input-output relations and synaptic connectivity of Cajal-Retzius cells in layer 1 of the developing neocortex of CXCR4-EGFP mice.

    Science.gov (United States)

    Anstötz, Max; Cosgrove, Kathleen E; Hack, Iris; Mugnaini, Enrico; Maccaferri, Gianmaria; Lübke, Joachim H R

    2014-11-01

    Layer 1 (L1) neurons, in particular Cajal-Retzius (CR) cells are among the earliest generated neurons in the neocortex. However, their role and that of L1 GABAergic interneurons in the establishment of an early cortical microcircuit are still poorly understood. Thus, the morphology of whole-cell recorded and biocytin-filled CR cells was investigated in postnatal day (P) 7-11 old CXCR4-EGFP mice where CR cells can be easily identified by their fluorescent appearance. Confocal-, light- and subsequent electron microscopy was performed to investigate their developmental regulation, morphology, synaptic input-output relationships and electrophysiological properties. CR cells reached their peak in occurrence between P4 to P7 and from thereon declined to almost complete disappearance at P14 by undergoing selective cell death through apoptosis. CR cells formed a dense and long-range horizontal network in layer 1 with a remarkable high density of synaptic boutons along their axons. They received dense GABAergic and non-GABAergic synaptic input and in turn provided synaptic output preferentially with spines or shafts of terminal tuft dendrites of pyramidal neurons. Interestingly, no dye-coupling between CR cells with other cortical neurons was observed as reported for other species, however, biocytin-labeling of individual CR cells leads to co-staining of L1 end foot astrocytes. Electrophysiologically, CR cells are characterized by a high input resistance and a characteristic firing pattern. Increasing depolarizing currents lead to action potential of decreasing amplitude and increasing half width, often terminated by a depolarization block. The presence of membrane excitability, the high density of CR cells in layer 1, their long-range horizontal axonal projection together with a high density of synaptic boutons and their synaptic input-output relationship suggest that they are an integral part of an early cortical network important not only in layer 1 but also for the

  6. Layer-specific experience-dependent rewiring of thalamocortical circuits.

    Science.gov (United States)

    Wang, Lang; Kloc, Michelle; Gu, Yan; Ge, Shaoyu; Maffei, Arianna

    2013-02-27

    Thalamocortical circuits are central to sensory and cognitive processing. Recent work suggests that the thalamocortical inputs onto L4 and L6, the main input layers of neocortex, are activated differently by visual stimulation. Whether these differences depend on layer-specific organization of thalamocortical circuits; or on specific properties of synapses onto receiving neurons is unknown. Here we combined optogenetic stimulation of afferents from the visual thalamus and paired recording electrophysiology in L4 and L6 of rat primary visual cortex to determine the organization and plasticity of thalamocortical synapses. We show that thalamocortical inputs onto L4 and L6 differ in synaptic dynamics and sensitivity to visual drive. We also demonstrate that the two layers differ in the organization of thalamocortical and recurrent intracortical connectivity. In L4, a significantly larger proportion of excitatory neurons responded to light activation of thalamocortical terminal fields than in L6. The local microcircuit in L4 showed a higher degree of recurrent connectivity between excitatory neurons than the microcircuit in L6. In addition, L4 recurrently connected neurons were driven by thalamocortical inputs of similar magnitude indicating the presence of local subnetworks that may be activated by the same axonal projection. Finally, brief manipulation of visual drive reduced the amplitude of light-evoked thalamocortical synaptic currents selectively onto L4. These data are the first direct indication that thalamocortical circuits onto L4 and L6 support different aspects of cortical function through layer-specific synaptic organization and plasticity.

  7. 一种改进控制电路在IGBT串联中的应用%Application of An Improved Control Circuit for Series Connected IGBT

    Institute of Scientific and Technical Information of China (English)

    颜文旭; 程盼飞

    2015-01-01

    The key of insolated gate bipolar transistor(IGBT) series-connected application is to make the IGBT series-connected in a circuit being voltage-balanced. Firstly, This article analyzes the effects of parasitic capacitances in the series connection of IGBT, which exist naturally due to control circuit. And then an improved control circuit is introduced, which is based on the power of gate driver supplied by the main circuit. Without external power supplies and the necessary insulation components, this solution has the advantage over the classical supply to eliminate parasitic capacitances. Finally, the Simulation and experimental data show that the circuit is effective and feasible. It will be reference in practice.%绝缘栅双极型晶体管IGBTs(insolated gate bipolar transistor)串联应用实现的关键在于动态均压。首先,从理论上分析了传统IGBT控制电路中寄生电容存在的主要原因,以及其对IGBT串联均压产生的影响;然后,提出了一种改进型控制电路,与传统的控制电路相比,改进型控制电路从主电路获取控制信号驱动IGBT所需功率,无需外接直流电源和电源隔离,减少了寄生电容的引入,能在一定程度改善IGBT的串联均压;最后,通过仿真和实验验证了该电路的有效性。在工程应用上具有一定的参考价值。

  8. Spatiotemporal discrimination in neural networks with short-term synaptic plasticity

    Science.gov (United States)

    Shlaer, Benjamin; Miller, Paul

    2015-03-01

    Cells in recurrently connected neural networks exhibit bistability, which allows for stimulus information to persist in a circuit even after stimulus offset, i.e. short-term memory. However, such a system does not have enough hysteresis to encode temporal information about the stimuli. The biophysically described phenomenon of synaptic depression decreases synaptic transmission strengths due to increased presynaptic activity. This short-term reduction in synaptic strengths can destabilize attractor states in excitatory recurrent neural networks, causing the network to move along stimulus dependent dynamical trajectories. Such a network can successfully separate amplitudes and durations of stimuli from the number of successive stimuli. Stimulus number, duration and intensity encoding in randomly connected attractor networks with synaptic depression. Front. Comput. Neurosci. 7:59., and so provides a strong candidate network for the encoding of spatiotemporal information. Here we explicitly demonstrate the capability of a recurrent neural network with short-term synaptic depression to discriminate between the temporal sequences in which spatial stimuli are presented.

  9. Commutation circuit for an HVDC circuit breaker

    Science.gov (United States)

    Premerlani, William J.

    1981-01-01

    A commutation circuit for a high voltage DC circuit breaker incorporates a resistor capacitor combination and a charging circuit connected to the main breaker, such that a commutating capacitor is discharged in opposition to the load current to force the current in an arc after breaker opening to zero to facilitate arc interruption. In a particular embodiment, a normally open commutating circuit is connected across the contacts of a main DC circuit breaker to absorb the inductive system energy trapped by breaker opening and to limit recovery voltages to a level tolerable by the commutating circuit components.

  10. Integrated mechanisms of anticipation and rate-of-change computations in cortical circuits.

    Science.gov (United States)

    Puccini, Gabriel D; Sanchez-Vives, Maria V; Compte, Albert

    2007-05-01

    Local neocortical circuits are characterized by stereotypical physiological and structural features that subserve generic computational operations. These basic computations of the cortical microcircuit emerge through the interplay of neuronal connectivity, cellular intrinsic properties, and synaptic plasticity dynamics. How these interacting mechanisms generate specific computational operations in the cortical circuit remains largely unknown. Here, we identify the neurophysiological basis of both the rate of change and anticipation computations on synaptic inputs in a cortical circuit. Through biophysically realistic computer simulations and neuronal recordings, we show that the rate-of-change computation is operated robustly in cortical networks through the combination of two ubiquitous brain mechanisms: short-term synaptic depression and spike-frequency adaptation. We then show how this rate-of-change circuit can be embedded in a convergently connected network to anticipate temporally incoming synaptic inputs, in quantitative agreement with experimental findings on anticipatory responses to moving stimuli in the primary visual cortex. Given the robustness of the mechanism and the widespread nature of the physiological machinery involved, we suggest that rate-of-change computation and temporal anticipation are principal, hard-wired functions of neural information processing in the cortical microcircuit.

  11. Integrated mechanisms of anticipation and rate-of-change computations in cortical circuits.

    Directory of Open Access Journals (Sweden)

    Gabriel D Puccini

    2007-05-01

    Full Text Available Local neocortical circuits are characterized by stereotypical physiological and structural features that subserve generic computational operations. These basic computations of the cortical microcircuit emerge through the interplay of neuronal connectivity, cellular intrinsic properties, and synaptic plasticity dynamics. How these interacting mechanisms generate specific computational operations in the cortical circuit remains largely unknown. Here, we identify the neurophysiological basis of both the rate of change and anticipation computations on synaptic inputs in a cortical circuit. Through biophysically realistic computer simulations and neuronal recordings, we show that the rate-of-change computation is operated robustly in cortical networks through the combination of two ubiquitous brain mechanisms: short-term synaptic depression and spike-frequency adaptation. We then show how this rate-of-change circuit can be embedded in a convergently connected network to anticipate temporally incoming synaptic inputs, in quantitative agreement with experimental findings on anticipatory responses to moving stimuli in the primary visual cortex. Given the robustness of the mechanism and the widespread nature of the physiological machinery involved, we suggest that rate-of-change computation and temporal anticipation are principal, hard-wired functions of neural information processing in the cortical microcircuit.

  12. Remodelling of spared proprioceptive circuit involving a small number of neurons supports functional recovery.

    Science.gov (United States)

    Hollis, Edmund R; Ishiko, Nao; Pessian, Maysam; Tolentino, Kristine; Lee-Kubli, Corinne A; Calcutt, Nigel A; Zou, Yimin

    2015-01-19

    Studies show that limited functional recovery can be achieved by plasticity and adaptation of the remaining circuitry in partial injuries in the central nervous system, although the new circuits that arise in these contexts have not been clearly identified or characterized. We show here that synaptic contacts from dorsal root ganglions to a small number of dorsal column neurons, a caudal extension of nucleus gracilis, whose connections to the thalamus are spared in a precise cervical level 1 lesion, underwent remodeling over time. These connections support proprioceptive functional recovery in a conditioning lesion paradigm, as silencing or eliminating the remodelled circuit completely abolishes the recovered proprioceptive function of the hindlimb. Furthermore, we show that blocking repulsive Wnt signalling increases axon plasticity and synaptic connections that drive greater functional recovery.

  13. A conserved juxtacrine signal regulates synaptic partner recognition in Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Mock Natalyn

    2011-06-01

    Full Text Available Abstract Background An essential stage of neural development involves the assembly of neural circuits via formation of inter-neuronal connections. Early steps in neural circuit formation, including cell migration, axon guidance, and the localization of synaptic components, are well described. However, upon reaching their target region, most neurites still contact many potential partners. In order to assemble functional circuits, it is critical that within this group of cells, neurons identify and form connections only with their appropriate partners, a process we call synaptic partner recognition (SPR. To understand how SPR is mediated, we previously developed a genetically encoded fluorescent trans-synaptic marker called NLG-1 GRASP, which labels synaptic contacts between individual neurons of interest in dense cellular environments in the genetic model organism Caenorhabditis elegans. Results Here, we describe the first use of NLG-1 GRASP technology, to identify SPR genes that function in this critical process. The NLG-1 GRASP system allows us to assess synaptogenesis between PHB sensory neurons and AVA interneurons instantly in live animals, making genetic analysis feasible. Additionally, we employ a behavioral assay to specifically test PHB sensory circuit function. Utilizing this approach, we reveal a new role for the secreted UNC-6/Netrin ligand and its transmembrane receptor UNC-40/Deleted in colorectal cancer (DCC in SPR. Synapses between PHB and AVA are severely reduced in unc-6 and unc-40 animals despite normal axon guidance and subcellular localization of synaptic components. Additionally, behavioral defects indicate a complete disruption of PHB circuit function in unc-40 mutants. Our data indicate that UNC-40 and UNC-6 function in PHB and AVA, respectively, to specify SPR. Strikingly, overexpression of UNC-6 in postsynaptic neurons is sufficient to promote increased PHB-AVA synaptogenesis and to potentiate the behavioral response

  14. GATING CIRCUITS

    Science.gov (United States)

    Merrill, L.C.

    1958-10-14

    Control circuits for vacuum tubes are described, and a binary counter having an improved trigger circuit is reported. The salient feature of the binary counter is the application of the input signal to the cathode of each of two vacuum tubes through separate capacitors and the connection of each cathode to ground through separate diodes. The control of the binary counter is achieved in this manner without special pulse shaping of the input signal. A further advantage of the circuit is the simplicity and minimum nuruber of components required, making its use particularly desirable in computer machines.

  15. From synapses to behavior: development of a sensory-motor circuit in the leech.

    Science.gov (United States)

    Marin-Burgin, Antonia; Kristan, William B; French, Kathleen A

    2008-05-01

    The development of neuronal circuits has been advanced greatly by the use of imaging techniques that reveal the activity of neurons during the period when they are constructing synapses and forming circuits. This review focuses on experiments performed in leech embryos to characterize the development of a neuronal circuit that produces a simple segmental behavior called "local bending." The experiments combined electrophysiology, anatomy, and FRET-based voltage-sensitive dyes (VSDs). The VSDs offered two major advantages in these experiments: they allowed us to record simultaneously the activity of many neurons, and unlike other imaging techniques, they revealed inhibition as well as excitation. The results indicated that connections within the circuit are formed in a predictable sequence: initially neurons in the circuit are connected by electrical synapses, forming a network that itself generates an embryonic behavior and prefigures the adult circuit; later chemical synapses, including inhibitory connections, appear, "sculpting" the circuit to generate a different, mature behavior. In this developmental process, some of the electrical connections are completely replaced by chemical synapses, others are maintained into adulthood, and still others persist and share their targets with chemical synaptic connections.

  16. Controllable circuit

    DEFF Research Database (Denmark)

    2010-01-01

    A switch-mode power circuit comprises a controllable element and a control unit. The controllable element is configured to control a current in response to a control signal supplied to the controllable element. The control unit is connected to the controllable element and provides the control...

  17. Synaptic consolidation across multiple timescales

    Directory of Open Access Journals (Sweden)

    Lorric Ziegler

    2014-03-01

    Full Text Available The brain is bombarded with a continuous stream of sensory events, but retains only a small subset in memory. The selectivity of memory formation prevents our memory from being overloaded with irrelevant items that would rapidly bring the brain to its storage limit; moreover, selectivity also prevents overwriting previously formed memories with new ones. Memory formation in the hippocampus, as well as in other brain regions, is thought to be linked to changes in the synaptic connections between neurons. In this view, sensory events imprint traces at the level of synapses that reflect potential memory items. The question of memory selectivity can therefore be reformulated as follows: what are the reasons and conditions that some synaptic traces fade away whereas others are consolidated and persist? Experimentally, changes in synaptic strength induced by 'Hebbian' protocols fade away over a few hours (early long-term potentiation or e-LTP, unless these changes are consolidated. The experiments and conceptual theory of synaptic tagging and capture (STC provide a mechanistic explanation for the processes involved in consolidation. This theory suggests that the initial trace of synaptic plasticity sets a tag at the synapse, which then serves as a marker for potential consolidation of the changes in synaptic efficacy. The actual consolidation processes, transforming e-LTP into late LTP (l-LTP, require the capture of plasticity-related proteins (PRP. We translate the above conceptual model into a compact computational model that accounts for a wealth of in vitro data including experiments on cross-tagging, tag-resetting and depotentiation. A central ingredient is that synaptic traces are described with several variables that evolve on different time scales. Consolidation requires the transmission of information from a 'fast' synaptic trace to a 'slow' one through a 'write' process, including the formation of tags and the production of PRP for the

  18. Synaptic determinants of Rett syndrome

    Directory of Open Access Journals (Sweden)

    Elena M B Boggio

    2010-08-01

    Full Text Available There is mounting evidence showing that the structural and molecular organization of synaptic connections are affected both in human patients and in animal models of neurological and psychiatric diseases. As a consequence of these experimental observations, it has been introduced the concept of synapsopathies, a notion describing brain disorders of synaptic function and plasticity. A close correlation between neurological diseases and synaptic abnormalities is especially relevant for those syndromes including also mental retardation in their symptomatology, such as Rett Syndrome (RS. RS (MIM312750 is an X-linked dominant neurological disorder that is caused, in the majority of cases by mutations in methyl-CpG-binding protein 2 (MeCP2. This review will focus on the current knowledge of the synaptic alterations produced by mutations of the gene MeCP2 in mouse models of RS and will highlight prospects experimental therapies currently in use. Different experimental approaches have revealed that RS could be the consequence of an impairment in the homeostasis of synaptic transmission in specific brain regions. Indeed, several forms of experience-induced neuronal plasticity are impaired in the absence of MeCP2. Based on the results presented in this review, it is reasonable to propose that understanding how the brain is affected by diseases such as RS is at reach. This effort will bring us closer to identify the neurobiological bases of human cognition.

  19. Matching tutors and students: effective strategies for information transfer between circuits

    Science.gov (United States)

    Tesileanu, Tiberiu; Balasubramanian, Vijay; Olveczky, Bence

    Many neural circuits transfer learned information to downstream circuits: hippocampal-dependent memories are consolidated into long-term memories elsewhere; motor cortex is essential for skill learning but dispensable for execution; anterior forebrain pathway (AFP) in songbirds drives short-term improvements in song that are later consolidated in pre-motor area RA. We show how to match instructive signals from tutor circuits to synaptic plasticity rules in student circuits to achieve effective two-stage learning. We focus on learning sequential patterns where a timebase is transformed into motor commands by connectivity with a `student' area. If the sign of the synaptic change is given by the magnitude of tutor input, a good teaching strategy uses a strong (weak) tutor signal if student output is below (above) its target. If instead timing of tutor input relative to the timebase determines the sign of synaptic modifications, a good instructive signal accumulates the errors in student output as the motor program progresses. We demonstrate song learning in a biologically-plausible model of the songbird circuit given diverse plasticity rules interpolating between those described above. The model also reproduces qualitative firing statistics of RA neurons in juveniles and adults. Also affiliated to CUNY - Graduate Center.

  20. GABAergic interneurons form transient layer-specific circuits in early postnatal neocortex.

    Science.gov (United States)

    Anastasiades, Paul G; Marques-Smith, Andre; Lyngholm, Daniel; Lickiss, Tom; Raffiq, Sayda; Kätzel, Dennis; Miesenböck, Gero; Butt, Simon J B

    2016-02-04

    GABAergic interneurons play key roles in cortical circuits, yet little is known about their early connectivity. Here we use glutamate uncaging and a novel optogenetic strategy to track changes in the afferent and efferent synaptic connections of developing neocortical interneuron subtypes. We find that Nkx2-1-derived interneurons possess functional synaptic connections before emerging pyramidal cell networks. Subsequent interneuron circuit maturation is both subtype and layer dependent. Glutamatergic input onto fast spiking (FS), but not somatostatin-positive, non-FS interneurons increases over development. Interneurons of both subtype located in layers (L) 4 and 5b engage in transient circuits that disappear after the somatosensory critical period. These include a pathway mediated by L5b somatostatin-positive interneurons that specifically targets L4 during the first postnatal week. The innervation patterns of immature cortical interneuron circuits are thus neither static nor progressively strengthened but follow a layer-specific choreography of transient connections that differ from those of the adult brain.

  1. Load testing circuit

    DEFF Research Database (Denmark)

    2009-01-01

    A load testing circuit a circuit tests the load impedance of a load connected to an amplifier. The load impedance includes a first terminal and a second terminal, the load testing circuit comprising a signal generator providing a test signal of a defined bandwidth to the first terminal of the load...

  2. Short-circuit logic

    NARCIS (Netherlands)

    Bergstra, J.A.; Ponse, A.

    2010-01-01

    Short-circuit evaluation denotes the semantics of propositional connectives in which the second argument is only evaluated if the first argument does not suffice to determine the value of the expression. In programming, short-circuit evaluation is widely used. A short-circuit logic is a variant of p

  3. Signal sampling circuit

    NARCIS (Netherlands)

    Louwsma, Simon Minze; Vertregt, Maarten

    2011-01-01

    A sampling circuit for sampling a signal is disclosed. The sampling circuit comprises a plurality of sampling channels adapted to sample the signal in time-multiplexed fashion, each sampling channel comprising a respective track-and-hold circuit connected to a respective analogue to digital converte

  4. Signal sampling circuit

    NARCIS (Netherlands)

    Louwsma, Simon Minze; Vertregt, Maarten

    2010-01-01

    A sampling circuit for sampling a signal is disclosed. The sampling circuit comprises a plurality of sampling channels adapted to sample the signal in time-multiplexed fashion, each sampling channel comprising a respective track-and-hold circuit connected to a respective analogue to digital converte

  5. Synaptic vesicle proteins and active zone plasticity

    Directory of Open Access Journals (Sweden)

    Robert J Kittel

    2016-04-01

    Full Text Available Neurotransmitter is released from synaptic vesicles at the highly specialized presynaptic active zone. The complex molecular architecture of active zones mediates the speed, precision and plasticity of synaptic transmission. Importantly, structural and functional properties of active zones vary significantly, even for a given connection. Thus, there appear to be distinct active zone states, which fundamentally influence neuronal communication by controlling the positioning and release of synaptic vesicles. Vice versa, recent evidence has revealed that synaptic vesicle components also modulate organizational states of the active zone.The protein-rich cytomatrix at the active zone (CAZ provides a structural platform for molecular interactions guiding vesicle exocytosis. Studies in Drosophila have now demonstrated that the vesicle proteins Synaptotagmin-1 (Syt1 and Rab3 also regulate glutamate release by shaping differentiation of the CAZ ultrastructure. We review these unexpected findings and discuss mechanistic interpretations of the reciprocal relationship between synaptic vesicles and active zone states, which has heretofore received little attention.

  6. Synaptic Vesicle Proteins and Active Zone Plasticity.

    Science.gov (United States)

    Kittel, Robert J; Heckmann, Manfred

    2016-01-01

    Neurotransmitter is released from synaptic vesicles at the highly specialized presynaptic active zone (AZ). The complex molecular architecture of AZs mediates the speed, precision and plasticity of synaptic transmission. Importantly, structural and functional properties of AZs vary significantly, even for a given connection. Thus, there appear to be distinct AZ states, which fundamentally influence neuronal communication by controlling the positioning and release of synaptic vesicles. Vice versa, recent evidence has revealed that synaptic vesicle components also modulate organizational states of the AZ. The protein-rich cytomatrix at the active zone (CAZ) provides a structural platform for molecular interactions guiding vesicle exocytosis. Studies in Drosophila have now demonstrated that the vesicle proteins Synaptotagmin-1 (Syt1) and Rab3 also regulate glutamate release by shaping differentiation of the CAZ ultrastructure. We review these unexpected findings and discuss mechanistic interpretations of the reciprocal relationship between synaptic vesicles and AZ states, which has heretofore received little attention.

  7. Attempt of correlative observation of morphological synaptic connectivity by combining confocal laser-scanning microscope and FIB-SEM for immunohistochemical staining technique.

    Science.gov (United States)

    Sonomura, Takahiro; Furuta, Takahiro; Nakatani, Ikuko; Yamamoto, Yo; Honma, Satoru; Kaneko, Takeshi

    2014-11-01

    Ten years have passed since a serial block-face scanning electron microscopy (SBF-SEM) method was developed [1]. In this innovative method, samples were automatically sectioned with an ultramicrotome placed inside a scanning electron microscope column, and the block surfaces were imaged one after another by SEM to capture back-scattered electrons. The contrast-inverted images obtained by the SBF-SEM were very similar to those acquired using conventional TEM. SFB-SEM has made easy to acquire image stacks of the transmission electron microscopy (TEM) in the mesoscale, which is taken with the confocal laser-scanning microcopy(CF-LSM).Furthermore, serial-section SEM has been combined with the focused ion beam (FIB) milling method [2]. FIB-incorporated SEM (FIB-SEM) has enabled the acquisition of three-dimensional images with a higher z-axis resolution com- pared to ultramicrotome-equipped SEM.We tried immunocytochemistry for FIB-SEM and correlated this immunoreactivity with that in CF-LSM. Dendrites of neurons in the rat neostriatum were visualized using a recombinant viral vector. Moreover, the thalamostriatal afferent terminals were immunolabeled with Cy5 fluorescence for vesicular glutamate transporter 2 (VGluT2). After detection of the sites of terminals apposed to the dendrites by using CF-LSM, GFP and VGluT2 immunoreactivities were further developed for EM by using immunogold/silver enhancement and immunoperoxidase/diaminobenzidine (DAB) methods, respectively.We showed that conventional immuno-cytochemical staining for TEM was applicable to FIB-SEM. Furthermore, several synaptic contacts, which were thought to exist on the basis of CF-LSM findings, were confirmed with FIB-SEM, revealing the usefulness of the combined method of CF-LSM and FIB-SEM.

  8. Hox genes: choreographers in neural development, architects of circuit organization.

    Science.gov (United States)

    Philippidou, Polyxeni; Dasen, Jeremy S

    2013-10-02

    The neural circuits governing vital behaviors, such as respiration and locomotion, are comprised of discrete neuronal populations residing within the brainstem and spinal cord. Work over the past decade has provided a fairly comprehensive understanding of the developmental pathways that determine the identity of major neuronal classes within the neural tube. However, the steps through which neurons acquire the subtype diversities necessary for their incorporation into a particular circuit are still poorly defined. Studies on the specification of motor neurons indicate that the large family of Hox transcription factors has a key role in generating the subtypes required for selective muscle innervation. There is also emerging evidence that Hox genes function in multiple neuronal classes to shape synaptic specificity during development, suggesting a broader role in circuit assembly. This Review highlights the functions and mechanisms of Hox gene networks and their multifaceted roles during neuronal specification and connectivity.

  9. Synaptic basis for intense thalamocortical activation of feedforward inhibitory cells in neocortex.

    Science.gov (United States)

    Cruikshank, Scott J; Lewis, Timothy J; Connors, Barry W

    2007-04-01

    The thalamus provides fundamental input to the neocortex. This input activates inhibitory interneurons more strongly than excitatory neurons, triggering powerful feedforward inhibition. We studied the mechanisms of this selective neuronal activation using a mouse somatosensory thalamocortical preparation. Notably, the greater responsiveness of inhibitory interneurons was not caused by their distinctive intrinsic properties but was instead produced by synaptic mechanisms. Axons from the thalamus made stronger and more frequent excitatory connections onto inhibitory interneurons than onto excitatory cells. Furthermore, circuit dynamics allowed feedforward inhibition to suppress responses in excitatory cells more effectively than in interneurons. Thalamocortical excitatory currents rose quickly in interneurons, allowing them to fire action potentials before significant feedforward inhibition emerged. In contrast, thalamocortical excitatory currents rose slowly in excitatory cells, overlapping with feedforward inhibitory currents that suppress action potentials. These results demonstrate the importance of selective synaptic targeting and precise timing in the initial stages of neocortical processing.

  10. Complement emerges as a masterful regulator of CNS homeostasis, neural synaptic plasticity and cognitive function.

    Science.gov (United States)

    Mastellos, Dimitrios C

    2014-11-01

    Growing evidence points to a previously elusive role of complement-modulated pathways in CNS development, neurogenesis and synaptic plasticity. Distinct complement effectors appear to play a multifaceted role in brain homeostasis by regulating synaptic pruning in the retinogeniculate system and sculpting functional neural circuits both in the developing and adult mammalian brain. A recent study by Perez-Alcazar et al. (2014) provides novel insights into this intricate interplay between complement and the dynamically regulated brain synaptic circuitry, by reporting that mice deficient in C3 exhibit enhanced hippocampus-dependent spatial learning and cognitive performance. This behavioral pattern is associated with an impact of C3 on the functional capacity of glutamatergic synapses, supporting a crucial role for complement in excitatory synapse elimination in the hippocampus. These findings add a fresh twist to this rapidly evolving research field, suggesting that discrete complement components may differentially modulate synaptic connectivity by wiring up with diverse neural effectors in different regions of the brain. The emerging role of complement in synaptogenesis and neural network plasticity opens new conceptual avenues for considering complement interception as a potential therapeutic modality for ameliorating progressive cognitive impairment in age-related, debilitating brain diseases with a prominent inflammatory signature.

  11. Synaptic plasticity in inhibitory neurons of the auditory brainstem.

    Science.gov (United States)

    Bender, Kevin J; Trussell, Laurence O

    2011-04-01

    There is a growing appreciation of synaptic plasticity in the early levels of auditory processing, and particularly of its role in inhibitory circuits. Synaptic strength in auditory brainstem and midbrain is sensitive to standard protocols for induction of long-term depression, potentiation, and spike-timing-dependent plasticity. Differential forms of plasticity are operative at synapses onto inhibitory versus excitatory neurons within a circuit, and together these could serve to tune circuits involved in sound localization or multisensory integration. Such activity-dependent control of synaptic function in inhibitory neurons may also be expressed after hearing loss and could underlie persistent neuronal activity in patients with tinnitus. This article is part of a Special Issue entitled 'Synaptic Plasticity & Interneurons'.

  12. Impaired structural connectivity of socio-emotional circuits in autism spectrum disorders: a diffusion tensor imaging study.

    Directory of Open Access Journals (Sweden)

    Stephanie H Ameis

    Full Text Available BACKGROUND: Abnormal white matter development may disrupt integration within neural circuits, causing particular impairments in higher-order behaviours. In autism spectrum disorders (ASDs, white matter alterations may contribute to characteristic deficits in complex socio-emotional and communication domains. Here, we used diffusion tensor imaging (DTI and tract based spatial statistics (TBSS to evaluate white matter microstructure in ASD. METHODS/PRINCIPAL FINDINGS: DTI scans were acquired for 19 children and adolescents with ASD (∼8-18 years; mean 12.4±3.1 and 16 age and IQ matched controls (∼8-18 years; mean 12.3±3.6 on a 3T MRI system. DTI values for fractional anisotropy, mean diffusivity, radial diffusivity and axial diffusivity, were measured. Age by group interactions for global and voxel-wise white matter indices were examined. Voxel-wise analyses comparing ASD with controls in: (i the full cohort (ii, children only (≤12 yrs., and (iii adolescents only (>12 yrs. were performed, followed by tract-specific comparisons. Significant age-by-group interactions on global DTI indices were found for all three diffusivity measures, but not for fractional anisotropy. Voxel-wise analyses revealed prominent diffusion measure differences in ASD children but not adolescents, when compared to healthy controls. Widespread increases in mean and radial diffusivity in ASD children were prominent in frontal white matter voxels. Follow-up tract-specific analyses highlighted disruption to pathways integrating frontal, temporal, and occipital structures involved in socio-emotional processing. CONCLUSIONS/SIGNIFICANCE: Our findings highlight disruption of neural circuitry in ASD, particularly in those white matter tracts that integrate the complex socio-emotional processing that is impaired in this disorder.

  13. The projection and synaptic organisation of NTS afferent connections with presympathetic neurons, GABA and nNOS neurons in the paraventricular nucleus of the hypothalamus.

    Science.gov (United States)

    Affleck, V S; Coote, J H; Pyner, S

    2012-09-01

    Elevated sympathetic nerve activity, strongly associated with cardiovascular disease, is partly generated from the presympathetic neurons of the paraventricular nucleus of the hypothalamus (PVN). The PVN-presympathetic neurons regulating cardiac and vasomotor sympathetic activity receive information about cardiovascular status from receptors in the heart and circulation. These receptors signal changes via afferent neurons terminating in the nucleus tractus solitarius (NTS), some of which may result in excitation or inhibition of PVN-presympathetic neurons. Understanding the anatomy and neurochemistry of NTS afferent connections within the PVN could provide important clues to the impairment in homeostasis cardiovascular control associated with disease. Transynaptic labelling has shown the presence of neuronal nitric oxide synthase (nNOS)-containing neurons and GABA interneurons that terminate on presympathetic PVN neurons any of which may be the target for NTS afferents. So far NTS connections to these diverse neuronal pools have not been demonstrated and were investigated in this study. Anterograde (biotin dextran amine - BDA) labelling of the ascending projection from the NTS and retrograde (fluorogold - FG or cholera toxin B subunit - CTB) labelling of PVN presympathetic neurons combined with immunohistochemistry for GABA and nNOS was used to identify the terminal neuronal targets of the ascending projection from the NTS. It was shown that NTS afferent terminals are apposed to either PVN-GABA interneurons or to nitric oxide producing neurons or even directly to presympathetic neurons. Furthermore, there was evidence that some NTS axons were positive for vesicular glutamate transporter 2 (vGLUT2). The data provide an anatomical basis for the different functions of cardiovascular receptors that mediate their actions via the NTS-PVN pathways.

  14. Discussion on the Design for Control Circuit of Connecting Turnout between Yards%场间衔接道岔控制电路设计探讨

    Institute of Scientific and Technical Information of China (English)

    王永州

    2012-01-01

    一站多场且在各场设置独立联锁设备的情况下,两个车场的股道间用交叉渡线形式的场间衔接道岔在实际工程中较为少见,为了解决场间进路办理、道岔控制和信号显示的问题,以集包线包头站包头Ⅰ场和包头Ⅱ场为实例,对场间衔接道岔的控制电路设计和特殊需求虚拟信号机的设置方案进行分析,并简要介绍两场间进路办理的过程和两场控显终端上控显表示及按钮设置的方案,上述设置方案和控制电路设计方案的可行性在实际工程中得到了充分验证.%When multiple yards are arranged within one station and each yard is equipped with independent interlocking device, it is rarely seen in actual project that the inter-yard connecting turnout of scissors crossover mode is used for track connection between two yards. In order to solve the problem of route handling, turnout controlling and signal displaying between two yards, the article takes Baotou Yard I and Baotou Yard II within Baotou Station of Jining-Baotou Railway as the examples and analyzes the control circuit design of inter-yard connecting turnout. The article also analyzes the allocation scheme of virtual signals for special needs, and briefly introduces the route handling process between two yards, the indication and button allocation scheme for controlling and displaying on the control desks of two yards. The feasibility of allocation schemes above-mentioned and control circuit design scheme have been verified in the actual project.

  15. Mitochondria, synaptic plasticity, and schizophrenia.

    Science.gov (United States)

    Ben-Shachar, Dorit; Laifenfeld, Daphna

    2004-01-01

    The conceptualization of schizophrenia as a disorder of connectivity, i.e., of neuronal?synaptic plasticity, suggests abnormal synaptic modeling and neuronal signaling, possibly as a consequence of flawed interactions with the environment, as at least a secondary mechanism underlying the pathophysiology of this disorder. Indeed, deficits in episodic memory and malfunction of hippocampal circuitry, as well as anomalies of axonal sprouting and synapse formation, are all suggestive of diminished neuronal plasticity in schizophrenia. Evidence supports a dysfunction of mitochondria in schizophrenia, including mitochondrial hypoplasia, and a dysfunction of the oxidative phosphorylation system, as well as altered mitochondrial-related gene expression. Mitochondrial dysfunction leads to alterations in ATP production and cytoplasmatic calcium concentrations, as well as reactive oxygen species and nitric oxide production. All of the latter processes have been well established as leading to altered synaptic strength or plasticity. Moreover, mitochondria have been shown to play a role in plasticity of neuronal polarity, and studies in the visual cortex show an association between mitochondria and synaptogenesis. Finally, mitochondrial gene upregulation has been observed following synaptic and neuronal activity. This review proposes that mitochondrial dysfunction in schizophrenia could cause, or arise from, anomalies in processes of plasticity in this disorder.

  16. Abnormal functional connectivity with mood regulating circuit in unmedicated individual with major depression: a resting-state functional magnetic resonance study

    Institute of Scientific and Technical Information of China (English)

    PENG Dai-hui; SHEN Ting; ZHANG Jie; HUANG Jia; LIU Jun; LIU Shu-yong; JIANG Kai-da; XU Yi-feng; FANG Yi-ru

    2012-01-01

    Background Reports on mood regulating circuit (MRC) indicated different activities between depressed patients and healthy controls.The functional networks based on MRC have not been described in major depression disorder (MDD).Both the anterior cingulate cortex (ACC) and thalamus are all the key regions of MRC.This study was to investigate the two functional networks related to ACC and thalamus in MDD.Methods Sixteen patients with MDD on first episode which never got any medication and sixteen matched health controls were scanned by 3.0 T functional magnetic resonance imaging (fMRI) during resting-state.The pregenual anterior cingulate cortex (pgACC) was used as seed region to construct the functional network by cortex section.The thalamus was used as seed region to construct the functional network by limbic section.Paired-t tests between-groups were performed for the seed-target correlations based on the individual fisher z-transformed correlation maps by SPM2.Results Depressed subjects exhibited significantly great functional connectivity (FC) between pgACC and the parahippocampus gyrus in one cluster (size 923) including left parahippocampus gyrus (-21,-49,7),left parietal lobe (-3,-46,52) and left frontal lobe (-27,-46,28).The one cluster (size 962) of increased FC on thalamus network overlapped the precuneus near to right parietal lobe (9,-52,46) and right cingulate gyrus (15,-43,43) in health controls.Conclusions Abnormal functional networks exist in earlier manifestation of MDD related to MRC by both cortex and limbic sections.The increased functional connectivity of pgACC and decreased functional connectivity of thalamus is mainly involved in bias mood processing and cognition.

  17. The mechanism of hetero-synaptic interaction based on spatiotemporal intracellular calcium dynamics.

    Directory of Open Access Journals (Sweden)

    Daiki Futagi

    2014-03-01

    Full Text Available In recent physiological experiments focusing on synaptic plasticity, it is shown that synaptic modifications induced at one synapse are accompanied by hetero-synaptic changes at neighbor sites (Bi, 2002. These evidences imply that the hetero-synaptic interaction plays an important role in reconfiguration of synaptic connections to form and maintain functional neural circuits (Takahashi et al., 2012. Although the mechanism of the interaction is still unclear, some physiological studies suggest that the hetero-synaptic interaction could be caused by propagation of intracellular calcium signals (Nishiyama et al., 2000. Concretely, a spike-triggered calcium increase initiates calcium ion propagation along a dendrite through activation of molecular processes at neighboring sites. Here we hypothesized that the mechanism of the hetero-synaptic interaction was based on the intracellular calcium signaling, which is regulated by interactions between NMDA receptors (NMDARs, voltage-dependent calcium channels (VDCCs and Ryanodine receptors (RyRs on endoplasmic reticulum (ER. To assess realizability of the hypothesized interaction mechanism, we simulated intracellular calcium dynamics at a cellular level, using the computational model that integrated the model of intracellular calcium dynamics (Keizer and Levine, 1996 and the multi-compartment neuron model (Poirazi et al., 2003. Using the proposed computational model, we induced calcium influxes at a local site in postsynaptic dendrite by controlling the spike timings of pre- and postsynaptic neurons. As a result, synchronized calcium influxes through NMDARs and VDCCs caused calcium release from ER. According to the phase plane analysis, RyR-mediated calcium release occurred when the calcium concentration in cytoplasm sufficiently increased under the condition of a high calcium concentration in ER. An NMDAR-mediated calcium influx was slow and persistent, consequently responsible for maintaining a high

  18. Role of perinatal long-chain omega-3 fatty acids in cortical circuit maturation: Mechanisms and implications for psychopathology.

    Science.gov (United States)

    McNamara, Robert K; Vannest, Jennifer J; Valentine, Christina J

    2015-03-22

    Accumulating translational evidence suggests that the long-chain omega-3 fatty acid docosahexaenoic acid (DHA) plays a role in the maturation and stability of cortical circuits that are impaired in different recurrent psychiatric disorders. Specifically, rodent and cell culture studies find that DHA preferentially accumulates in synaptic and growth cone membranes and promotes neurite outgrowth, dendritic spine stability, and synaptogenesis. Additional evidence suggests that DHA may play a role in microglia-mediated synaptic pruning, as well as myelin development and resilience. In non-human primates n-3 fatty acid insufficiency during perinatal development leads to widespread deficits in functional connectivity in adult frontal cortical networks compared to primates raised on DHA-fortified diet. Preterm delivery in non-human primates and humans is associated with early deficits in cortical DHA accrual. Human preterm birth is associated with long-standing deficits in myelin integrity and cortical circuit connectivity and increased risk for attention deficit/hyperactivity disorder (ADHD), mood, and psychotic disorders. In general, ADHD and mood and psychotic disorders initially emerge during rapid periods of cortical circuit maturation and are characterized by DHA deficits, myelin pathology, and impaired cortical circuit connectivity. Together these associations suggest that early and uncorrected deficits in fetal brain DHA accrual may represent a modifiable risk factor for cortical circuit maturation deficits in psychiatric disorders, and could therefore have significant implications for informing early intervention and prevention strategies.

  19. Synaptic vesicle endocytosis.

    Science.gov (United States)

    Saheki, Yasunori; De Camilli, Pietro

    2012-09-01

    Neurons can sustain high rates of synaptic transmission without exhausting their supply of synaptic vesicles. This property relies on a highly efficient local endocytic recycling of synaptic vesicle membranes, which can be reused for hundreds, possibly thousands, of exo-endocytic cycles. Morphological, physiological, molecular, and genetic studies over the last four decades have provided insight into the membrane traffic reactions that govern this recycling and its regulation. These studies have shown that synaptic vesicle endocytosis capitalizes on fundamental and general endocytic mechanisms but also involves neuron-specific adaptations of such mechanisms. Thus, investigations of these processes have advanced not only the field of synaptic transmission but also, more generally, the field of endocytosis. This article summarizes current information on synaptic vesicle endocytosis with an emphasis on the underlying molecular mechanisms and with a special focus on clathrin-mediated endocytosis, the predominant pathway of synaptic vesicle protein internalization.

  20. Trans-synaptic spread of tau pathology in vivo.

    Directory of Open Access Journals (Sweden)

    Li Liu

    Full Text Available Tauopathy in the brain of patients with Alzheimer's disease starts in the entorhinal cortex (EC and spreads anatomically in a defined pattern. To test whether pathology initiating in the EC spreads through the brain along synaptically connected circuits, we have generated a transgenic mouse model that differentially expresses pathological human tau in the EC and we have examined the distribution of tau pathology at different timepoints. In relatively young mice (10-11 months old, human tau was present in some cell bodies, but it was mostly observed in axons within the superficial layers of the medial and lateral EC, and at the terminal zones of the perforant pathway. In old mice (>22 months old, intense human tau immunoreactivity was readily detected not only in neurons in the superficial layers of the EC, but also in the subiculum, a substantial number of hippocampal pyramidal neurons especially in CA1, and in dentate gyrus granule cells. Scattered immunoreactive neurons were also seen in the deeper layers of the EC and in perirhinal and secondary somatosensory cortex. Immunoreactivity with the conformation-specific tau antibody MC1 correlated with the accumulation of argyrophilic material seen in old, but not young mice. In old mice, axonal human tau immunoreactivity, especially at the endzones of the perforant pathway, was greatly reduced. Relocalization of tau from axons to somatodendritic compartments and propagation of tauopathy to regions outside of the EC correlated with mature tangle formation in neurons in the EC as revealed by thioflavin-S staining. Our data demonstrate propagation of pathology from the EC and support a trans-synaptic mechanism of spread along anatomically connected networks, between connected and vulnerable neurons. In general, the mouse recapitulates the tauopathy that defines the early stages of AD and provides a model for testing mechanisms and functional outcomes associated with disease progression.

  1. Dynamic DNA methylation controls glutamate receptor trafficking and synaptic scaling.

    Science.gov (United States)

    Sweatt, J David

    2016-05-01

    Hebbian plasticity, including long-term potentiation and long-term depression, has long been regarded as important for local circuit refinement in the context of memory formation and stabilization. However, circuit development and stabilization additionally relies on non-Hebbian, homeostatic, forms of plasticity such as synaptic scaling. Synaptic scaling is induced by chronic increases or decreases in neuronal activity. Synaptic scaling is associated with cell-wide adjustments in postsynaptic receptor density, and can occur in a multiplicative manner resulting in preservation of relative synaptic strengths across the entire neuron's population of synapses. Both active DNA methylation and demethylation have been validated as crucial regulators of gene transcription during learning, and synaptic scaling is known to be transcriptionally dependent. However, it has been unclear whether homeostatic forms of plasticity such as synaptic scaling are regulated via epigenetic mechanisms. This review describes exciting recent work that has demonstrated a role for active changes in neuronal DNA methylation and demethylation as a controller of synaptic scaling and glutamate receptor trafficking. These findings bring together three major categories of memory-associated mechanisms that were previously largely considered separately: DNA methylation, homeostatic plasticity, and glutamate receptor trafficking. This review describes exciting recent work that has demonstrated a role for active changes in neuronal DNA methylation and demethylation as a controller of synaptic scaling and glutamate receptor trafficking. These findings bring together three major categories of memory-associated mechanisms that were previously considered separately: glutamate receptor trafficking, DNA methylation, and homeostatic plasticity.

  2. Dense neuron clustering explains connectivity statistics in cortical microcircuits.

    Directory of Open Access Journals (Sweden)

    Vladimir V Klinshov

    Full Text Available Local cortical circuits appear highly non-random, but the underlying connectivity rule remains elusive. Here, we analyze experimental data observed in layer 5 of rat neocortex and suggest a model for connectivity from which emerge essential observed non-random features of both wiring and weighting. These features include lognormal distributions of synaptic connection strength, anatomical clustering, and strong correlations between clustering and connection strength. Our model predicts that cortical microcircuits contain large groups of densely connected neurons which we call clusters. We show that such a cluster contains about one fifth of all excitatory neurons of a circuit which are very densely connected with stronger than average synapses. We demonstrate that such clustering plays an important role in the network dynamics, namely, it creates bistable neural spiking in small cortical circuits. Furthermore, introducing local clustering in large-scale networks leads to the emergence of various patterns of persistent local activity in an ongoing network activity. Thus, our results may bridge a gap between anatomical structure and persistent activity observed during working memory and other cognitive processes.

  3. Neural - glial circuits : Can Interneurons stop seizures

    Science.gov (United States)

    Nadkarni, Suhita; Jung, Peter

    2004-03-01

    Recent progress in neurobiology suggests that astrocytes - through calcium excitability - are active partners to the neurons by integrating their activity and, in turn, regulating synaptic transmission. In a similar fashion neurons and interneurons are the 'Yin and Yang' of the hippocampus. The dichotomy of excitation and inhibition between pyramidal neurons and interneurons plays a crucial role in the function of the neuronal circuit.We consider a model of a pyramidal cell in contact with one synaptic astrocytes. It has been shown that such a circuit - triggered by transient stimulation - can exhibit sustained oscillations ("seizures") for strong coupling. The question we are considering is, under what conditions synaptic inhibition can stop these seizures?

  4. Synaptic change in the posterior cingulate gyrus in the progression of Alzheimer's disease.

    Science.gov (United States)

    Scheff, Stephen W; Price, Douglas A; Ansari, Mubeen A; Roberts, Kelly N; Schmitt, Frederick A; Ikonomovic, Milos D; Mufson, Elliott J

    2015-01-01

    Mild cognitive impairment (MCI) is considered to be an early stage in the progression of Alzheimer's disease (AD) providing an opportunity to investigate brain pathogenesis prior to the onset of dementia. Neuroimaging studies have identified the posterior cingulate gyrus (PostC) as a cortical region affected early in the onset of AD. This association cortex is involved in a variety of different cognitive tasks and is intimately connected with the hippocampal/entorhinal cortex region, a component of the medial temporal memory circuit that displays early AD pathology. We quantified the total number of synapses in lamina 3 of the PostC using unbiased stereology coupled with electron microscopy from short postmortem autopsy tissue harvested from cases at different stage of AD progression. Individuals in the early stages of AD showed a significant decline in synaptic numbers compared to individuals with no cognitive impairment (NCI). Subjects with MCI exhibited synaptic numbers that were between the AD and NCI cohorts. Adjacent tissue was evaluated for changes in both pre and postsynaptic proteins levels. Individuals with MCI demonstrated a significant loss in presynaptic markers synapsin-1 and synaptophysin and postsynaptic markers PSD-95 and SAP-97. Levels of [3H]PiB binding was significantly increased in MCI and AD and correlated strongly with levels of synaptic proteins. All synaptic markers showed a significant association with Mini-Mental Status Examination scores. These results support the idea that the PostC synaptic function is affected during the prodromal stage of the disease and may underlie some of the early clinical sequelae associated with AD.

  5. Experimental Implementation of a Biometric Laser Synaptic Sensor

    Directory of Open Access Journals (Sweden)

    Alexander N. Pisarchik

    2013-12-01

    Full Text Available We fabricate a biometric laser fiber synaptic sensor to transmit information from one neuron cell to the other by an optical way. The optical synapse is constructed on the base of an erbium-doped fiber laser, whose pumped diode current is driven by a pre-synaptic FitzHugh–Nagumo electronic neuron, and the laser output controls a post-synaptic FitzHugh–Nagumo electronic neuron. The implemented laser synapse displays very rich dynamics, including fixed points, periodic orbits with different frequency-locking ratios and chaos. These regimes can be beneficial for efficient biorobotics, where behavioral flexibility subserved by synaptic connectivity is a challenge.

  6. Insulin-like growth factor 1 (IGF1) and its active peptide (1-3)IGF1 enhance the expression of synaptic markers in neuronal circuits through different cellular mechanisms.

    LENUS (Irish Health Repository)

    Corvin, Aiden P

    2012-06-27

    Insulin-like growth factor-1 (IGF1) and its active peptide (1-3)IGF1 modulate brain growth and plasticity and are candidate molecules for treatment of brain disorders. IGF1 N-terminal portion is naturally cleaved to generate the tri-peptide (1-3)IGF1 (glycine-praline-glutamate). IGF1 and (1-3)IGF have been proposed as treatment for neuropathologies, yet their effect on nerve cells has not been directly compared. In this study we examine the effects of IGF1 and (1-3)IGF1 in primary cortical cultures and measure the expression levels of markers for intracellular pathways and synaptic function. We find that both treatments activate the IGF1 receptor and enhance the expression of synaptic markers, however, they activate different intracellular pathways. Furthermore, (1-3)IGF1 administration increases the expression of endogenous IGF1, suggesting a direct interaction between the two molecules. The results show that the two molecules increase the expression of synaptic proteins through activating different cellular mechanisms.

  7. Developmental metaplasticity in neural circuit codes of firing and structure.

    Science.gov (United States)

    Baram, Yoram

    2017-01-01

    Firing-rate dynamics have been hypothesized to mediate inter-neural information transfer in the brain. While the Hebbian paradigm, relating learning and memory to firing activity, has put synaptic efficacy variation at the center of cortical plasticity, we suggest that the external expression of plasticity by changes in the firing-rate dynamics represents a more general notion of plasticity. Hypothesizing that time constants of plasticity and firing dynamics increase with age, and employing the filtering property of the neuron, we obtain the elementary code of global attractors associated with the firing-rate dynamics in each developmental stage. We define a neural circuit connectivity code as an indivisible set of circuit structures generated by membrane and synapse activation and silencing. Synchronous firing patterns under parameter uniformity, and asynchronous circuit firing are shown to be driven, respectively, by membrane and synapse silencing and reactivation, and maintained by the neuronal filtering property. Analytic, graphical and simulation representation of the discrete iteration maps and of the global attractor codes of neural firing rate are found to be consistent with previous empirical neurobiological findings, which have lacked, however, a specific correspondence between firing modes, time constants, circuit connectivity and cortical developmental stages.

  8. Autaptic self-inhibition of cortical GABAergic neurons: synaptic narcissism or useful introspection?

    Science.gov (United States)

    Deleuze, Charlotte; Pazienti, Antonio; Bacci, Alberto

    2014-06-01

    Fast synaptic inhibition sculpts all forms of cortical activity by means of a specialized connectivity pattern between highly heterogeneous inhibitory interneurons and principal excitatory cells. Importantly, inhibitory neurons connect also to each other extensively, following a detailed blueprint, and, indeed, specific forms of disinhibition affect important behavioral functions. Here we discuss a peculiar form of cortical disinhibition: the massive autaptic self-inhibition of parvalbumin-(PV) positive basket cells. Despite being described long ago, autaptic inhibition onto PV basket cells is rarely included in cortical circuit diagrams, perhaps because of its still elusive function. We propose here a potential dual role of autaptic feedback inhibition in temporally coordinating PV basket cells during cortical network activity.

  9. Nicotinic mechanisms influencing synaptic plasticity in the hippocampus

    Institute of Scientific and Technical Information of China (English)

    Andon Nicholas PLACZEK; Tao A ZHANG; John Anthony DANI

    2009-01-01

    Nicotinic acetylcholine receptors (nAChRs) are expressed throughout the hippocampus, and nicotinic signaling plays an important role in neuronal function. In the context of learning and memory related behaviors associated with hippocampal function, a potentially significant feature of nAChR activity is the impact it has on synaptic plasticity. Synaptic plasticity in hippocampal neurons has long been considered a contributing cellular mechanism of learning and memory. These same kinds of cellular mechanisms are a factor in the development of nicotine addiction. Nicotinic signaling has been demonstrated by in vitro studies to affect synaptic plasticity in hippocampal neurons via multiple steps, and the signaling has also been shown to evoke synaptic plasticity in vivo. This review focuses on the nAChRs subtypes that contribute to hippocampal synaptic plasticity at the cellular and circuit level. It also considers nicotinic influences over long-term changes in the hippocampus that may contribute to addiction.

  10. Regulation of NMDA-receptor synaptic transmission by Wnt signaling

    Science.gov (United States)

    Cerpa, Waldo; Gambrill, Abigail; Inestrosa, Nibaldo C.; Barria, Andres

    2011-01-01

    Wnt ligands are secreted glycoproteins controlling gene expression and cytoskeleton reorganization involved in embryonic development of the nervous system. However, their role in later stages of brain development, particularly in the regulation of established synaptic connections is not known. We found that Wnt-5a acutely and specifically up-regulates synaptic NMDAR currents in rat hippocampal slices facilitating induction of LTP, a cellular model of learning and memory. This effect requires an increase in postsynaptic Ca2+ and activation of non-canonical downstream effectors of the Wnt signaling pathway. In contrast, Wnt-7a, an activator of the canonical Wnt signaling pathway, has no effect on NMDAR mediated synaptic transmission. Moreover, endogenous Wnt ligands are necessary to maintain basal NMDAR synaptic transmission adjusting the threshold for synaptic potentiation. This novel role for Wnt ligands provides a mechanism for Wnt signaling to acutely modulate synaptic plasticity and brain function in later stages of development and in the mature organism. PMID:21715611

  11. Synaptic Contacts Enhance Cell-to-Cell Tau Pathology Propagation

    Directory of Open Access Journals (Sweden)

    Sara Calafate

    2015-05-01

    Full Text Available Accumulation of insoluble Tau protein aggregates and stereotypical propagation of Tau pathology through the brain are common hallmarks of tauopathies, including Alzheimer’s disease (AD. Propagation of Tau pathology appears to occur along connected neurons, but whether synaptic contacts between neurons are facilitating propagation has not been demonstrated. Using quantitative in vitro models, we demonstrate that, in parallel to non-synaptic mechanisms, synapses, but not merely the close distance between the cells, enhance the propagation of Tau pathology between acceptor hippocampal neurons and Tau donor cells. Similarly, in an artificial neuronal network using microfluidic devices, synapses and synaptic activity are promoting neuronal Tau pathology propagation in parallel to the non-synaptic mechanisms. Our work indicates that the physical presence of synaptic contacts between neurons facilitate Tau pathology propagation. These findings can have implications for synaptic repair therapies, which may turn out to have adverse effects by promoting propagation of Tau pathology.

  12. Synaptic Contacts Enhance Cell-to-Cell Tau Pathology Propagation.

    Science.gov (United States)

    Calafate, Sara; Buist, Arjan; Miskiewicz, Katarzyna; Vijayan, Vinoy; Daneels, Guy; de Strooper, Bart; de Wit, Joris; Verstreken, Patrik; Moechars, Diederik

    2015-05-26

    Accumulation of insoluble Tau protein aggregates and stereotypical propagation of Tau pathology through the brain are common hallmarks of tauopathies, including Alzheimer's disease (AD). Propagation of Tau pathology appears to occur along connected neurons, but whether synaptic contacts between neurons are facilitating propagation has not been demonstrated. Using quantitative in vitro models, we demonstrate that, in parallel to non-synaptic mechanisms, synapses, but not merely the close distance between the cells, enhance the propagation of Tau pathology between acceptor hippocampal neurons and Tau donor cells. Similarly, in an artificial neuronal network using microfluidic devices, synapses and synaptic activity are promoting neuronal Tau pathology propagation in parallel to the non-synaptic mechanisms. Our work indicates that the physical presence of synaptic contacts between neurons facilitate Tau pathology propagation. These findings can have implications for synaptic repair therapies, which may turn out to have adverse effects by promoting propagation of Tau pathology.

  13. Synaptic computation and sensory processing in neocortical layer 2/3.

    Science.gov (United States)

    Petersen, Carl C H; Crochet, Sylvain

    2013-04-10

    Computations in neocortical circuits are predominantly driven by synaptic integration of excitatory glutamatergic and inhibitory GABAergic inputs. New optical, electrophysiological, and genetic methods allow detailed in vivo investigation of the superficial neocortical layers 2 and 3 (L2/3). Here, we review current knowledge of mouse L2/3 sensory cortex, focusing on somatosensory barrel cortex with comparisons to visual and auditory cortex. Broadly tuned, dense subthreshold synaptic input accompanied by sparse action potential (AP) firing in excitatory neurons provides a simple and reliable neural code useful for associative learning. Sparse AP firing is enforced by strong inhibition from genetically defined classes of GABAergic neurons. Subnetworks of strongly and specifically connected excitatory neurons may drive L2/3 network function, with potential contributions from dendritic spikes evoked by spatiotemporally clustered synaptic input. These functional properties of L2/3 are under profound regulation by brain state and behavior, providing interesting avenues for future mechanistic investigations into context-specific processing of sensory information.

  14. Dense, unspecific connectivity of neocortical parvalbumin-positive interneurons: a canonical microcircuit for inhibition?

    Science.gov (United States)

    Packer, Adam M; Yuste, Rafael

    2011-09-14

    GABAergic interneurons play a major role in the function of the mammalian neocortex, but their circuit connectivity is still poorly understood. We used two-photon RuBi-Glutamate uncaging to optically map how the largest population of cortical interneurons, the parvalbumin-positive cells (PV+), are connected to pyramidal cells (PCs) in mouse neocortex. We found locally dense connectivity from PV+ interneurons onto PCs across cortical areas and layers. In many experiments, all nearby PV+ cells were connected to every local PC sampled. In agreement with this, we found no evidence for connection specificity, as PV+ interneurons contacted PC pairs similarly regardless of whether they were synaptically connected or not. We conclude that the microcircuit architecture for PV+ interneurons, and probably neocortical inhibition in general, is an unspecific, densely homogenous matrix covering all nearby pyramidal cells.

  15. Striatal cholinergic interneuron regulation and circuit effects

    Directory of Open Access Journals (Sweden)

    Sean Austin Lim

    2014-10-01

    Full Text Available The striatum plays a central role in motor control and motor learning. Appropriate responses to environmental stimuli, including pursuit of reward or avoidance of aversive experience all require functional striatal circuits. These pathways integrate synaptic inputs from limbic and cortical regions including sensory, motor and motivational information to ultimately connect intention to action. Although many neurotransmitters participate in striatal circuitry, one critically important player is acetylcholine (ACh. Relative to other brain areas, the striatum contains exceptionally high levels of ACh, the enzymes that catalyze its synthesis and breakdown, as well as both nicotinic and muscarinic receptor types that mediate its postsynaptic effects. The principal source of striatal ACh is the cholinergic interneuron (ChI, which comprises only about 1-2% of all striatal cells yet sends dense arbors of projections throughout the striatum. This review summarizes recent advances in our understanding of the factors affecting the excitability of these neurons through acute effects and long term changes in their synaptic inputs. In addition, we discuss the physiological effects of ACh in the striatum, and how changes in ACh levels may contribute to disease states during striatal dysfunction.

  16. Optical imaging as a link between cellular neurophysiology and circuit modeling

    Directory of Open Access Journals (Sweden)

    Walther Akemann

    2009-07-01

    Full Text Available The relatively simple and highly modular circuitry of the cerebellum raised expectations decades ago that a realistic computational model of cerebellar circuit operations would be feasible, and prove insightful for unraveling cerebellar information processing. To this end, the biophysical properties of most cerebellar cell types and their synaptic connections have been well characterized and integrated into realistic single cell models. Furthermore, large scale models of cerebellar circuits that extrapolate from single cell properties to circuit dynamics have been constructed. While the development of single cell models have been constrained by microelectrode recordings, guidance and validation as these models are scaled up to study network interactions requires an experimental methodology capable of monitoring cerebellar dynamics at the population level. Here we review the potential of optical imaging techniques to serve this purpose.

  17. Synaptic Plasticity and Nociception

    Institute of Scientific and Technical Information of China (English)

    ChenJianguo

    2004-01-01

    Synaptic plasticity is one of the fields that progresses rapidly and has a lot of success in neuroscience. The two major types of synaptie plasticity: long-term potentiation ( LTP and long-term depression (LTD are thought to be the cellular mochanisms of learning and memory. Recently, accumulating evidence suggests that, besides serving as a cellular model for learning and memory, the synaptic plasticity involves in other physiological or pathophysiological processes, such as the perception of pain and the regulation of cardiovascular system. This minireview will focus on the relationship between synaptic plasticity and nociception.

  18. BMP signaling and microtubule organization regulate synaptic strength.

    Science.gov (United States)

    Ball, R W; Peled, E S; Guerrero, G; Isacoff, E Y

    2015-04-16

    The strength of synaptic transmission between a neuron and multiple postsynaptic partners can vary considerably. We have studied synaptic heterogeneity using the glutamatergic Drosophila neuromuscular junction (NMJ), which contains multiple synaptic connections of varying strengths between a motor axon and muscle fiber. In larval NMJs, there is a gradient of synaptic transmission from weak proximal to strong distal boutons. We imaged synaptic transmission with the postsynaptically targeted fluorescent calcium sensor SynapCam, to investigate the molecular pathways that determine synaptic strength and set up this gradient. We discovered that mutations in the Bone Morphogenetic Protein (BMP) signaling pathway disrupt production of strong distal boutons. We find that strong connections contain unbundled microtubules in the boutons, suggesting a role for microtubule organization in transmission strength. The spastin mutation, which disorganizes microtubules, disrupted the transmission gradient, supporting this interpretation. We propose that the BMP pathway, shown previously to function in the homeostatic regulation of synaptic growth, also boosts synaptic transmission in a spatially selective manner that depends on the microtubule system.

  19. Ex Vivo Optogenetic Dissection of Fear Circuits in Brain Slices.

    Science.gov (United States)

    Bosch, Daniel; Asede, Douglas; Ehrlich, Ingrid

    2016-04-05

    Optogenetic approaches are now widely used to study the function of neural populations and circuits by combining targeted expression of light-activated proteins and subsequent manipulation of neural activity by light. Channelrhodopsins (ChRs) are light-gated cation-channels and when fused to a fluorescent protein their expression allows for visualization and concurrent activation of specific cell types and their axonal projections in defined areas of the brain. Via stereotactic injection of viral vectors, ChR fusion proteins can be constitutively or conditionally expressed in specific cells of a defined brain region, and their axonal projections can subsequently be studied anatomically and functionally via ex vivo optogenetic activation in brain slices. This is of particular importance when aiming to understand synaptic properties of connections that could not be addressed with conventional electrical stimulation approaches, or in identifying novel afferent and efferent connectivity that was previously poorly understood. Here, a few examples illustrate how this technique can be applied to investigate these questions to elucidating fear-related circuits in the amygdala. The amygdala is a key region for acquisition and expression of fear, and storage of fear and emotional memories. Many lines of evidence suggest that the medial prefrontal cortex (mPFC) participates in different aspects of fear acquisition and extinction, but its precise connectivity with the amygdala is just starting to be understood. First, it is shown how ex vivo optogenetic activation can be used to study aspects of synaptic communication between mPFC afferents and target cells in the basolateral amygdala (BLA). Furthermore, it is illustrated how this ex vivo optogenetic approach can be applied to assess novel connectivity patterns using a group of GABAergic neurons in the amygdala, the paracapsular intercalated cell cluster (mpITC), as an example.

  20. Persistent inflammation-induced up-regulation of brain-derived neurotrophic factor (BDNF) promotes synaptic delivery of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor GluA1 subunits in descending pain modulatory circuits.

    Science.gov (United States)

    Tao, Wenjuan; Chen, Quan; Zhou, Wenjie; Wang, Yunping; Wang, Lu; Zhang, Zhi

    2014-08-08

    The enhanced AMPA receptor phosphorylation at GluA1 serine 831 sites in the central pain-modulating system plays a pivotal role in descending pain facilitation after inflammation, but the underlying mechanisms remain unclear. We show here that, in the rat brain stem, in the nucleus raphe magnus, which is a critical relay in the descending pain-modulating system of the brain, persistent inflammatory pain induced by complete Freund adjuvant (CFA) can enhance AMPA receptor-mediated excitatory postsynaptic currents and the GluA2-lacking AMPA receptor-mediated rectification index. Western blot analysis showed an increase in GluA1 phosphorylation at Ser-831 but not at Ser-845. This was accompanied by an increase in distribution of the synaptic GluA1 subunit. In parallel, the level of histone H3 acetylation at bdnf gene promoter regions was reduced significantly 3 days after CFA injection, as indicated by ChIP assays. This was correlated with an increase in BDNF mRNA levels and BDNF protein levels. Sequestering endogenous extracellular BDNF with TrkB-IgG in the nucleus raphe magnus decreased AMPA receptor-mediated synaptic transmission and GluA1 phosphorylation at Ser-831 3 days after CFA injection. Under the same conditions, blockade of TrkB receptor functions, phospholipase C, or PKC impaired GluA1 phosphorylation at Ser-831 and decreased excitatory postsynaptic currents mediated by GluA2-lacking AMPA receptors. Taken together, these results suggest that epigenetic up-regulation of BDNF by peripheral inflammation induces GluR1 phosphorylation at Ser-831 sites through activation of the phospholipase C-PKC signaling cascade, leading to the trafficking of GluA1 to pain-modulating neuronal synapses.

  1. How to record a million synaptic weights in a hippocampal slice.

    Directory of Open Access Journals (Sweden)

    Upinder S Bhalla

    2008-06-01

    Full Text Available A key step toward understanding the function of a brain circuit is to find its wiring diagram. New methods for optical stimulation and optical recording of neurons make it possible to map circuit connectivity on a very large scale. However, single synapses produce small responses that are difficult to measure on a large scale. Here I analyze how single synaptic responses may be detectable using relatively coarse readouts such as optical recording of somatic calcium. I model a network consisting of 10,000 input axons and 100 CA1 pyramidal neurons, each represented using 19 compartments with voltage-gated channels and calcium dynamics. As single synaptic inputs cannot produce a measurable somatic calcium response, I stimulate many inputs as a baseline to elicit somatic action potentials leading to a strong calcium signal. I compare statistics of responses with or without a single axonal input riding on this baseline. Through simulations I show that a single additional input shifts the distribution of the number of output action potentials. Stochastic resonance due to probabilistic synaptic release makes this shift easier to detect. With approximately 80 stimulus repetitions this approach can resolve up to 35% of individual activated synapses even in the presence of 20% recording noise. While the technique is applicable using conventional electrical stimulation and extracellular recording, optical methods promise much greater scaling, since the number of synapses scales as the product of the number of inputs and outputs. I extrapolate from current high-speed optical stimulation and recording methods, and show that this approach may scale up to the order of a million synapses in a single two-hour slice-recording experiment.

  2. How to record a million synaptic weights in a hippocampal slice.

    Science.gov (United States)

    Bhalla, Upinder S

    2008-06-20

    A key step toward understanding the function of a brain circuit is to find its wiring diagram. New methods for optical stimulation and optical recording of neurons make it possible to map circuit connectivity on a very large scale. However, single synapses produce small responses that are difficult to measure on a large scale. Here I analyze how single synaptic responses may be detectable using relatively coarse readouts such as optical recording of somatic calcium. I model a network consisting of 10,000 input axons and 100 CA1 pyramidal neurons, each represented using 19 compartments with voltage-gated channels and calcium dynamics. As single synaptic inputs cannot produce a measurable somatic calcium response, I stimulate many inputs as a baseline to elicit somatic action potentials leading to a strong calcium signal. I compare statistics of responses with or without a single axonal input riding on this baseline. Through simulations I show that a single additional input shifts the distribution of the number of output action potentials. Stochastic resonance due to probabilistic synaptic release makes this shift easier to detect. With approximately 80 stimulus repetitions this approach can resolve up to 35% of individual activated synapses even in the presence of 20% recording noise. While the technique is applicable using conventional electrical stimulation and extracellular recording, optical methods promise much greater scaling, since the number of synapses scales as the product of the number of inputs and outputs. I extrapolate from current high-speed optical stimulation and recording methods, and show that this approach may scale up to the order of a million synapses in a single two-hour slice-recording experiment.

  3. Retinal synaptic regeneration via microfluidic guiding channels.

    Science.gov (United States)

    Su, Ping-Jung; Liu, Zongbin; Zhang, Kai; Han, Xin; Saito, Yuki; Xia, Xiaojun; Yokoi, Kenji; Shen, Haifa; Qin, Lidong

    2015-08-28

    In vitro culture of dissociated retinal neurons is an important model for investigating retinal synaptic regeneration (RSR) and exploring potentials in artificial retina. Here, retinal precursor cells were cultured in a microfluidic chip with multiple arrays of microchannels in order to reconstruct the retinal neuronal synapse. The cultured retinal cells were physically connected through microchannels. Activation of electric signal transduction by the cells through the microchannels was demonstrated by administration of glycinergic factors. In addition, an image-based analytical method was used to quantify the synaptic connections and to assess the kinetics of synaptic regeneration. The rate of RSR decreased significantly below 100 μM of inhibitor glycine and then approached to a relatively constant level at higher concentrations. Furthermore, RSR was enhanced by chemical stimulation with potassium chloride. Collectively, the microfluidic synaptic regeneration chip provides a novel tool for high-throughput investigation of RSR at the cellular level and may be useful in quality control of retinal precursor cell transplantation.

  4. Dynamic Control of Synaptic Adhesion and Organizing Molecules in Synaptic Plasticity

    Energy Technology Data Exchange (ETDEWEB)

    Rudenko, Gabby [Department of Pharmacology and Toxicology, Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, 301 University Boulevard Rm. 5.114B, Galveston, TX 77555, USA

    2017-01-01

    Synapses play a critical role in establishing and maintaining neural circuits, permitting targeted information transfer throughout the brain. A large portfolio of synaptic adhesion/organizing molecules (SAMs) exists in the mammalian brain involved in synapse development and maintenance. SAMs bind protein partners, formingtrans-complexes spanning the synaptic cleft orcis-complexes attached to the same synaptic membrane. SAMs play key roles in cell adhesion and in organizing protein interaction networks; they can also provide mechanisms of recognition, generate scaffolds onto which partners can dock, and likely take part in signaling processes as well. SAMs are regulated through a portfolio of different mechanisms that affect their protein levels, precise localization, stability, and the availability of their partners at synapses. Interaction of SAMs with their partners can further be strengthened or weakened through alternative splicing, competing protein partners, ectodomain shedding, or astrocytically secreted factors. Given that numerous SAMs appear altered by synaptic activity, in vivo, these molecules may be used to dynamically scale up or scale down synaptic communication. Many SAMs, including neurexins, neuroligins, cadherins, and contactins, are now implicated in neuropsychiatric and neurodevelopmental diseases, such as autism spectrum disorder, schizophrenia, and bipolar disorder and studying their molecular mechanisms holds promise for developing novel therapeutics.

  5. Algebraic circuits

    CERN Document Server

    Lloris Ruiz, Antonio; Parrilla Roure, Luis; García Ríos, Antonio

    2014-01-01

    This book presents a complete and accurate study of algebraic circuits, digital circuits whose performance can be associated with any algebraic structure. The authors distinguish between basic algebraic circuits, such as Linear Feedback Shift Registers (LFSRs) and cellular automata, and algebraic circuits, such as finite fields or Galois fields. The book includes a comprehensive review of representation systems, of arithmetic circuits implementing basic and more complex operations, and of the residue number systems (RNS). It presents a study of basic algebraic circuits such as LFSRs and cellular automata as well as a study of circuits related to Galois fields, including two real cryptographic applications of Galois fields.

  6. A dendritic disinhibitory circuit mechanism for pathway-specific gating

    Science.gov (United States)

    Yang, Guangyu Robert; Murray, John D.; Wang, Xiao-Jing

    2016-01-01

    While reading a book in a noisy café, how does your brain ‘gate in' visual information while filtering out auditory stimuli? Here we propose a mechanism for such flexible routing of information flow in a complex brain network (pathway-specific gating), tested using a network model of pyramidal neurons and three classes of interneurons with connection probabilities constrained by data. We find that if inputs from different pathways cluster on a pyramidal neuron dendrite, a pathway can be gated-on by a disinhibitory circuit motif. The branch-specific disinhibition can be achieved despite dense interneuronal connectivity, even with random connections. Moreover, clustering of input pathways on dendrites can naturally emerge through synaptic plasticity regulated by dendritic inhibition. This gating mechanism in a neural circuit is further demonstrated by performing a context-dependent decision-making task. The model suggests that cognitive flexibility engages top-down signalling of behavioural rule or context that targets specific classes of inhibitory neurons. PMID:27649374

  7. Somatostatin-expressing inhibitory interneurons in cortical circuits

    Directory of Open Access Journals (Sweden)

    Iryna Yavorska

    2016-09-01

    Full Text Available Cortical inhibitory neurons exhibit remarkable diversity in their morphology, connectivity, and synaptic properties. Here, we review the function of somatostatin-expressing (SOM inhibitory interneurons, focusing largely on sensory cortex. SOM neurons also comprise a number of subpopulations that can be distinguished by their morphology, input and output connectivity, laminar location, firing properties, and expression of molecular markers. Several of these classes of SOM neurons show unique dynamics and characteristics, such as facilitating synapses, specific axonal projections, intralaminar input, and top-down modulation, which suggest possible computational roles. SOM cells can be differentially modulated by behavioral state depending on their class, sensory system, and behavioral paradigm. The functional effects of such modulation have been studied with optogenetic manipulation of SOM cells, which produces effects on learning and memory, task performance, and the integration of cortical activity. Different classes of SOM cells participate in distinct disinhibitory circuits with different inhibitory partners and in different cortical layers. Through these disinhibitory circuits, SOM cells help encode the behavioral relevance of sensory stimuli by regulating the activity of cortical neurons based on subcortical and intracortical modulatory input. Associative learning leads to long-term changes in the strength of connectivity of SOM cells with other neurons, often influencing the strength of inhibitory input they receive. Thus despite their heterogeneity and variability across cortical areas, current evidence shows that SOM neurons perform unique neural computations, forming not only distinct molecular but also functional subclasses of cortical inhibitory interneurons.

  8. Selective Manipulation of Neural Circuits.

    Science.gov (United States)

    Park, Hong Geun; Carmel, Jason B

    2016-04-01

    Unraveling the complex network of neural circuits that form the nervous system demands tools that can manipulate specific circuits. The recent evolution of genetic tools to target neural circuits allows an unprecedented precision in elucidating their function. Here we describe two general approaches for achieving circuit specificity. The first uses the genetic identity of a cell, such as a transcription factor unique to a circuit, to drive expression of a molecule that can manipulate cell function. The second uses the spatial connectivity of a circuit to achieve specificity: one genetic element is introduced at the origin of a circuit and the other at its termination. When the two genetic elements combine within a neuron, they can alter its function. These two general approaches can be combined to allow manipulation of neurons with a specific genetic identity by introducing a regulatory gene into the origin or termination of the circuit. We consider the advantages and disadvantages of both these general approaches with regard to specificity and efficacy of the manipulations. We also review the genetic techniques that allow gain- and loss-of-function within specific neural circuits. These approaches introduce light-sensitive channels (optogenetic) or drug sensitive channels (chemogenetic) into neurons that form specific circuits. We compare these tools with others developed for circuit-specific manipulation and describe the advantages of each. Finally, we discuss how these tools might be applied for identification of the neural circuits that mediate behavior and for repair of neural connections.

  9. Inrush Current Control Circuit

    Science.gov (United States)

    Cole, Steven W. (Inventor)

    2002-01-01

    An inrush current control circuit having an input terminal connected to a DC power supply and an output terminal connected to a load capacitor limits the inrush current that charges up the load capacitor during power up of a system. When the DC power supply applies a DC voltage to the input terminal, the inrush current control circuit produces a voltage ramp at the load capacitor instead of an abrupt DC voltage. The voltage ramp results in a constant low level current to charge up the load capacitor, greatly reducing the current drain on the DC power supply.

  10. Comparative study on glutamatergic synaptic connections in rat striatum with laser scanning confocal microscopy and electron microscopy%激光共聚焦扫描显微镜和透射电镜观察大鼠纹状体内谷氨酸能突触连接的对比观察

    Institute of Scientific and Technical Information of China (English)

    蔡青; 姬曼; 张进禄; 赵君朋

    2011-01-01

    Objective To evaluate the advantage of the use of laser scanning confocal microscopy (LSCM) for observing the glutamatergic striatal synaptic connections in comparison with the observation with transmission electron microscopy (TEM). Methods 12 normal adult rats were divided into two groups: 6 rats for LSCM or TEM each. With CM-Dil and VGluT1 immunofluorescence labeling,the distribution of the asymmetrical glutamatergic synaptic connections on the dendrites of striatal neurons was observed, and 3-D reconstruction was done. The 6 rats were studied with TEM. Results There is no significant difference in the distribution characters of the glutamatergic striatal synaptic connections obtained with either LSCM or TEM. However, the whole view of the synapses and dendrites and the three-dimensional reconstruction of synaptic connections between neurons can be obtained with LSCM but not TEM.Conclusion LSCM is an effective and quantitative technique to investigate the glutamate synaptic connections of striatal neurons.%目的 探讨使用激光共聚焦扫描显微镜 (Laser scanning confocal microscope,LSCM)观察大鼠纹状体内谷氨酸能突触连接的方法的可行性.方法 12只正常大鼠分为两组,6只大鼠进行纹状体中等棘刺神经元的CM-DiI 单细胞标记,然后Ⅰ型囊泡膜谷氨酸转运体(vesicular glutamate transporter 1,VGluT1 )免疫荧光标记,LSCM层扫后三维重建,观察VGluT1阳性位点在中等棘刺神经元树突上的分布.另外6只大鼠用TEM观察不对称性突触在纹状体神经元树突上的分布.对两种方法的结果进行比较.结果 用LSCM 和TEM方法观察到的纹状体神经元上谷氨酸能突触连接分布情况一致,没有统计学差异.但LSCM更具优越性的是,可以对图像进行三维重构,从而有利于对神经元之间突触连接的空间分布观察和定量分析.结论 神经细胞荧光标记技术结合LSCM观察是考察纹状体神经元上谷氨酸能突触连接的有效方法.

  11. Discussion on 110 kV Double-circuit Straight Tower Doubling as Single-circuit T-Connection Tower%110 kV双回路直线塔兼作单T接塔的探讨

    Institute of Scientific and Technical Information of China (English)

    王伟; 潘少良; 张文杰; 曹建伟

    2015-01-01

    With planning restrict of local government, the T-connection point of 110 kV transmission lines lo-cates at straight tower, and the straight tower doubles as T-connection tower. The paper discusses and propos-es the jumper synchronously swings with the suspension string. The single-foundation straight tower is mod-eled, which can meet the structure stress requirement of T-connection line through verification and calcula-tion. During the construction, the connection of jumper wire at the straight tower is implemented, by which the straight tower doubles as T-connection tower, greatly reducing outage duration of main lines and achieving favorable social and economic benefit.%受地方政府规划制约,110 kV输电线路T接点在直线塔塔位处,直线塔要兼作T接塔使用。讨论并解决了跳线如何和悬垂串同步摆动问题,对一基直线塔建模,经校核计算能满足T接线路结构受力要求。施工完成直线塔处跳线搭接,实现直线塔作为T接塔使用,可大量缩短主线路停电时间,取得很好的社会经济效益。

  12. Genetic dissection of GABAergic neural circuits in mouse neocortex

    Directory of Open Access Journals (Sweden)

    Hiroki eTaniguchi

    2014-01-01

    Full Text Available Diverse and flexible cortical functions rely on the ability of neural circuits to perform multiple types of neuronal computations. GABAergic inhibitory interneurons significantly contribute to this task by regulating the balance of activity, synaptic integration, spiking, synchrony, and oscillation in a neural ensemble. GABAergic interneruons display a high degree of cellular diversity in morphology, physiology, connectivity, and gene expression. A considerable number of subtypes of GABAergic interneurons diversify modes of cortical inhibition, enabling various types of information processing in the cortex. Thus, comprehensively understanding fate specification, circuit assembly and physiological function of GABAergic interneurons is a key to elucidate the principles of cortical wiring and function. Recent advances in genetically encoded molecular tools have made a breakthrough to systematically study cortical circuitry at the molecular, cellular, circuit, and whole animal levels. However, the biggest obstacle to fully applying the power of these to analysis of GABAergic circuits was that there were no efficient and reliable methods to express them in subtypes of GABAergic interneurons. Here, I first summarize cortical interneuron diversity and current understanding of mechanisms, by which distinct classes of GABAergic interneurons are generated. I then review recent development in genetically encoded molecular tools for neural circuit research, and genetic targeting of GABAergic interneuron subtypes, particulary focusing on our recent effort to develop and characterize Cre/CreER knockin lines. Finally, I highlight recent success in genetic targeting of chandelier cells (ChCs, the most unique and distinct GABAergic interneuron subtype, and discuss what kind of questions need to be addressed to understand development and function of cortical inhibitory circuits.

  13. Genetic circuit design automation.

    Science.gov (United States)

    Nielsen, Alec A K; Der, Bryan S; Shin, Jonghyeon; Vaidyanathan, Prashant; Paralanov, Vanya; Strychalski, Elizabeth A; Ross, David; Densmore, Douglas; Voigt, Christopher A

    2016-04-01

    Computation can be performed in living cells by DNA-encoded circuits that process sensory information and control biological functions. Their construction is time-intensive, requiring manual part assembly and balancing of regulator expression. We describe a design environment, Cello, in which a user writes Verilog code that is automatically transformed into a DNA sequence. Algorithms build a circuit diagram, assign and connect gates, and simulate performance. Reliable circuit design requires the insulation of gates from genetic context, so that they function identically when used in different circuits. We used Cello to design 60 circuits forEscherichia coli(880,000 base pairs of DNA), for which each DNA sequence was built as predicted by the software with no additional tuning. Of these, 45 circuits performed correctly in every output state (up to 10 regulators and 55 parts), and across all circuits 92% of the output states functioned as predicted. Design automation simplifies the incorporation of genetic circuits into biotechnology projects that require decision-making, control, sensing, or spatial organization.

  14. Synaptic Homeostasis and Restructuring across the Sleep-Wake Cycle.

    Directory of Open Access Journals (Sweden)

    Wilfredo Blanco

    2015-05-01

    Full Text Available Sleep is critical for hippocampus-dependent memory consolidation. However, the underlying mechanisms of synaptic plasticity are poorly understood. The central controversy is on whether long-term potentiation (LTP takes a role during sleep and which would be its specific effect on memory. To address this question, we used immunohistochemistry to measure phosphorylation of Ca2+/calmodulin-dependent protein kinase II (pCaMKIIα in the rat hippocampus immediately after specific sleep-wake states were interrupted. Control animals not exposed to novel objects during waking (WK showed stable pCaMKIIα levels across the sleep-wake cycle, but animals exposed to novel objects showed a decrease during subsequent slow-wave sleep (SWS followed by a rebound during rapid-eye-movement sleep (REM. The levels of pCaMKIIα during REM were proportional to cortical spindles near SWS/REM transitions. Based on these results, we modeled sleep-dependent LTP on a network of fully connected excitatory neurons fed with spikes recorded from the rat hippocampus across WK, SWS and REM. Sleep without LTP orderly rescaled synaptic weights to a narrow range of intermediate values. In contrast, LTP triggered near the SWS/REM transition led to marked swaps in synaptic weight ranking. To better understand the interaction between rescaling and restructuring during sleep, we implemented synaptic homeostasis and embossing in a detailed hippocampal-cortical model with both excitatory and inhibitory neurons. Synaptic homeostasis was implemented by weakening potentiation and strengthening depression, while synaptic embossing was simulated by evoking LTP on selected synapses. We observed that synaptic homeostasis facilitates controlled synaptic restructuring. The results imply a mechanism for a cognitive synergy between SWS and REM, and suggest that LTP at the SWS/REM transition critically influences the effect of sleep: Its lack determines synaptic homeostasis, its presence causes

  15. Cocaine exposure reorganizes cell type- and input-specific connectivity in the nucleus accumbens.

    Science.gov (United States)

    MacAskill, Andrew F; Cassel, John M; Carter, Adam G

    2014-09-01

    Repeated exposure to cocaine alters the structural and functional properties of medium spiny neurons (MSNs) in the nucleus accumbens (NAc). These changes suggest a rewiring of the NAc circuit, with an enhancement of excitatory synaptic connections onto MSNs. However, it is unknown how drug exposure alters the balance of long-range afferents onto different cell types in the NAc. Here we used whole-cell recordings, two-photon microscopy, optogenetics and pharmacogenetics to show how repeated cocaine exposure alters connectivity in the mouse NAc medial shell. Cocaine selectively enhanced amygdala innervation of MSNs expressing D1 dopamine receptors (D1-MSNs) relative to D2-MSNs. We also found that amygdala activity was required for cocaine-induced changes to behavior and connectivity. Finally, we established how heightened amygdala innervation can explain the structural and functional changes evoked by cocaine. Our findings reveal how exposure to drugs of abuse fundamentally reorganizes cell type- and input-specific connectivity in the NAc.

  16. Nonlocal mechanism for cluster synchronization in neural circuits

    Science.gov (United States)

    Kanter, I.; Kopelowitz, E.; Vardi, R.; Zigzag, M.; Kinzel, W.; Abeles, M.; Cohen, D.

    2011-03-01

    The interplay between the topology of cortical circuits and synchronized activity modes in distinct cortical areas is a key enigma in neuroscience. We present a new nonlocal mechanism governing the periodic activity mode: the greatest common divisor (GCD) of network loops. For a stimulus to one node, the network splits into GCD-clusters in which cluster neurons are in zero-lag synchronization. For complex external stimuli, the number of clusters can be any common divisor. The synchronized mode and the transients to synchronization pinpoint the type of external stimuli. The findings, supported by an information mixing argument and simulations of Hodgkin-Huxley population dynamic networks with unidirectional connectivity and synaptic noise, call for reexamining sources of correlated activity in cortex and shorter information processing time scales.

  17. Protocadherin 17 regulates presynaptic assembly in topographic corticobasal Ganglia circuits.

    Science.gov (United States)

    Hoshina, Naosuke; Tanimura, Asami; Yamasaki, Miwako; Inoue, Takeshi; Fukabori, Ryoji; Kuroda, Teiko; Yokoyama, Kazumasa; Tezuka, Tohru; Sagara, Hiroshi; Hirano, Shinji; Kiyonari, Hiroshi; Takada, Masahiko; Kobayashi, Kazuto; Watanabe, Masahiko; Kano, Masanobu; Nakazawa, Takanobu; Yamamoto, Tadashi

    2013-06-05

    Highly topographic organization of neural circuits exists for the regulation of various brain functions in corticobasal ganglia circuits. Although neural circuit-specific refinement during synapse development is essential for the execution of particular neural functions, the molecular and cellular mechanisms for synapse refinement are largely unknown. Here, we show that protocadherin 17 (PCDH17), one of the nonclustered δ2-protocadherin family members, is enriched along corticobasal ganglia synapses in a zone-specific manner during synaptogenesis and regulates presynaptic assembly in these synapses. PCDH17 deficiency in mice causes facilitated presynaptic vesicle accumulation and enhanced synaptic transmission efficacy in corticobasal ganglia circuits. Furthermore, PCDH17(-/-) mice exhibit antidepressant-like phenotypes that are known to be regulated by corticobasal ganglia circuits. Our findings demonstrate a critical role for PCDH17 in the synaptic development of specific corticobasal ganglia circuits and suggest the involvement of PCDH17 in such circuits in depressive behaviors.

  18. Superconducting Quantum Circuits

    NARCIS (Netherlands)

    Majer, J.B.

    2002-01-01

    This thesis describes a number of experiments with superconducting cir- cuits containing small Josephson junctions. The circuits are made out of aluminum islands which are interconnected with a very thin insulating alu- minum oxide layer. The connections form a Josephson junction. The current trough

  19. Visual Deprivation Causes Refinement of Intracortical Circuits in the Auditory Cortex

    Directory of Open Access Journals (Sweden)

    Xiangying Meng

    2015-08-01

    Full Text Available Loss of a sensory modality can lead to functional enhancement of the remaining senses. For example, short-term visual deprivations, or dark exposure (DE, can enhance neuronal responses in the auditory cortex to sounds. These enhancements encompass increased spiking rates and frequency selectivity as well as increased spiking reliability. Although we previously demonstrated enhanced thalamocortical transmission after DE, increased synaptic strength cannot account for increased frequency selectivity or reliability. We thus investigated whether other changes in the underlying circuitry contributed to improved neuronal responses. We show that DE can lead to refinement of intra- and inter-laminar connections in the mouse auditory cortex. Moreover, we use a computational model to show that the combination of increased transmission and circuit refinement can lead to increased firing reliability. Thus cross-modal influences can alter the spectral and temporal processing of sensory stimuli by refinement of thalamocortical and intracortical circuits.

  20. Propagation of Homeostatic Sleep Signals by Segregated Synaptic Microcircuits of the Drosophila Mushroom Body.

    Science.gov (United States)

    Sitaraman, Divya; Aso, Yoshinori; Jin, Xin; Chen, Nan; Felix, Mario; Rubin, Gerald M; Nitabach, Michael N

    2015-11-16

    The Drosophila mushroom body (MB) is a key associative memory center that has also been implicated in the control of sleep. However, the identity of MB neurons underlying homeostatic sleep regulation, as well as the types of sleep signals generated by specific classes of MB neurons, has remained poorly understood. We recently identified two MB output neuron (MBON) classes whose axons convey sleep control signals from the MB to converge in the same downstream target region: a cholinergic sleep-promoting MBON class and a glutamatergic wake-promoting MBON class. Here, we deploy a combination of neurogenetic, behavioral, and physiological approaches to identify and mechanistically dissect sleep-controlling circuits of the MB. Our studies reveal the existence of two segregated excitatory synaptic microcircuits that propagate homeostatic sleep information from different populations of intrinsic MB "Kenyon cells" (KCs) to specific sleep-regulating MBONs: sleep-promoting KCs increase sleep by preferentially activating the cholinergic MBONs, while wake-promoting KCs decrease sleep by preferentially activating the glutamatergic MBONs. Importantly, activity of the sleep-promoting MB microcircuit is increased by sleep deprivation and is necessary for homeostatic rebound sleep (i.e., the increased sleep that occurs after, and in compensation for, sleep lost during deprivation). These studies reveal for the first time specific functional connections between subsets of KCs and particular MBONs and establish the identity of synaptic microcircuits underlying transmission of homeostatic sleep signals in the MB.

  1. Optogenetics and synaptic plasticity.

    Science.gov (United States)

    Xie, Yu-feng; Jackson, Michael F; Macdonald, John F

    2013-11-01

    The intricate and complex interaction between different populations of neurons in the brain has imposed limits on our ability to gain detailed understanding of synaptic transmission and its integration when employing classical electrophysiological approaches. Indeed, electrical field stimulation delivered via traditional microelectrodes does not permit the targeted, precise and selective control of neuronal activity amongst a varied population of neurons and their inputs (eg, cholinergic, dopaminergic or glutamatergic neurons). Recently established optogenetic techniques overcome these limitations allowing precise control of the target neuron populations, which is essential for the elucidation of the neural substrates underlying complex animal behaviors. Indeed, by introducing light-activated channels (ie, microbial opsin genes) into specific neuronal populations, optogenetics enables non-invasive optical control of specific neurons with milliseconds precision. These approaches can readily be applied to freely behaving live animals. Recently there is increased interests in utilizing optogenetics tools to understand synaptic plasticity and learning/memory. Here, we summarize recent progress in applying optogenetics in in the study of synaptic plasticity.

  2. 基于IGBT串联技术的混合式高压直流断路器方案%A Hybrid High Voltage DC Circuit Breaker Design Plan With Series-Connected IGBTs

    Institute of Scientific and Technical Information of China (English)

    药韬; 温家良; 李金元; 陈中圆

    2015-01-01

    Vigorously developing renewable energy will be an inevitable choice to solve the unbalanced distribution of energy resources, ease the tension between electricity supply and demand, and achieve sustainable economic development in China. To integrate conventional DC transmission technology and flexible DC transmission technology, establishing HVDC grid would be an effective means to solve the problem of large scale grid-connected of renewable energy. In this paper the history of HVDC circuit breaker is reviewed, the latest research results are introduced, the current challenges for HVDC circuit breaker are illustrated. Also the typical topological structure, working principle, advantages and shortcomings of different types of HVDC circuit breaker are analyzed and compared. Based on this, a new hybrid HVDC circuit breaker design with series-connected insulated gate bipolar transistors (IGBTs) is presented, and the topology characteristics and its working principles are introduced in details. Zhoushan five-terminal DC transmission system is modeled and simulated in the PSCAD/EMTDC software to verify its feasibility.%大力发展可再生能源将是解决我国能源资源分布不平衡,电力供需紧张,实现经济可持续发展的必然选择.综合常规直流输电技术和柔性直流输电技术,建立高压直流电网将是解决大规模可再生能源并网问题的有效手段.回顾高压直流断路器的发展历程,介绍当前最新的研究成果,阐明现阶段高压直流断路器将要面临的挑战,分析比较不同类型高压直流断路器的典型拓扑结构、工作原理和优缺点.在此基础上提出一种基于绝缘栅双极型晶体管(insulated gate bipolar transistor,IGBT)串联技术的混合式高压直流断路器方案,详细介绍其拓扑结构、特点和工作原理,基于舟山5端直流工程在PSCAD/EMTDC软件中搭建仿真模型验证了其可行性.

  3. Achieving High-Frequency Optical Control of Synaptic Transmission

    Science.gov (United States)

    Jackman, Skyler L.; Beneduce, Brandon M.; Drew, Iain R.

    2014-01-01

    The optogenetic tool channelrhodopsin-2 (ChR2) is widely used to excite neurons to study neural circuits. Previous optogenetic studies of synapses suggest that light-evoked synaptic responses often exhibit artificial synaptic depression, which has been attributed to either the inability of ChR2 to reliably fire presynaptic axons or to ChR2 elevating the probability of release by depolarizing presynaptic boutons. Here, we compare light-evoked and electrically evoked synaptic responses for high-frequency stimulation at three synapses in the mouse brain. At synapses from Purkinje cells to deep cerebellar nuclei neurons (PC→DCN), light- and electrically evoked synaptic currents were remarkably similar for ChR2 expressed transgenically or with adeno-associated virus (AAV) expression vectors. For hippocampal CA3→CA1 synapses, AAV expression vectors of serotype 1, 5, and 8 led to light-evoked synaptic currents that depressed much more than electrically evoked currents, even though ChR2 could fire axons reliably at up to 50 Hz. The disparity between optical and electrical stimulation was eliminated when ChR2 was expressed transgenically or with AAV9. For cerebellar granule cell to stellate cell (grc→SC) synapses, AAV1 also led to artificial synaptic depression and AAV9 provided superior performance. Artificial synaptic depression also occurred when stimulating over presynaptic boutons, rather than axons, at CA3→CA1 synapses, but not at PC→DCN synapses. These findings indicate that ChR2 expression methods and light stimulation techniques influence synaptic responses in a neuron-specific manner. They also identify pitfalls associated with using ChR2 to study synapses and suggest an approach that allows optogenetics to be applied in a manner that helps to avoid potential complications. PMID:24872574

  4. Transcriptional networks in the early development of sensory-motor circuits.

    Science.gov (United States)

    Dasen, Jeremy S

    2009-01-01

    The emergence of coordinated locomotor behaviors in vertebrates relies on the establishment of selective connections between discrete populations of neurons present in the spinal cord and peripheral nervous system. The assembly of the circuits necessary for movement presumably requires the generation of many unique cell types to accommodate the intricate connections between motor neurons, sensory neurons, interneurons, and muscle. The specification of diverse neuronal subtypes is mediated largely through networks of transcription factors that operate within progenitor and postmitotic cells. Selective patterns of transcription factor expression appear to define the cell-type-specific cellular programs that govern the axonal guidance decisions and synaptic specificities of neurons, and may lay the foundation through which innate motor behaviors are genetically predetermined. Recent studies on the developmental programs that specify two highly diverse neuronal classes-spinal motor neurons and proprioceptive sensory neurons-have provided important insights into the molecular strategies used in the earliest phases of locomotor circuit assembly. This chapter reviews progress toward elucidating the early transcriptional networks that define neuronal identity in the locomotor system, focusing on the pathways controlling the specific connections of motor neurons and sensory neurons in the formation of simple reflex circuits.

  5. Multiquantal release underlies the distribution of synaptic efficacies in the neocortex

    Directory of Open Access Journals (Sweden)

    Alex Loebel

    2009-11-01

    Full Text Available Inter-pyramidal synaptic connections are characterized by a wide range of EPSP amplitudes. Although repeatedly observed at different brain regions and across layers, little is known about the synaptic characteristics that contribute to this wide range. In particular, the range could potentially be accounted for by differences in all three parameters of the quantal model of synaptic transmission, i.e. the number of release sites, release probability and quantal size. Here, we present a rigorous statistical analysis of the transmission properties of excitatory synaptic connections between layer-5 pyramidal neurons of the somatosensory cortex. Our central finding is that the EPSP amplitude is strongly correlated with the number of estimated release sites, but not with the release probability or quantal size. In addition, we found that the number of release sites can be more than an order of magnitude higher than the typical number of synaptic contacts for this type of connection. Our findings indicate that transmission at stronger synaptic connections is mediated by multiquantal release from their synaptic contacts. We propose that modulating the number of release sites could be an important mechanism in regulating neocortical synaptic transmission.

  6. New Logic Circuit with DC Parametric Excitation

    Science.gov (United States)

    Sugahara, Masanori; Kaneda, Hisayoshi

    1982-12-01

    It is shown that dc parametric excitation is possible in a circuit named JUDO, which is composed of two resistively-connected Josephson junctions. Simulation study proves that the circuit has large gain and properties suitable for the construction of small, high-speed logic circuits.

  7. The contribution of synaptic plasticity in the basal ganglia to the processing of visual information.

    Science.gov (United States)

    Sil'kis, I G

    2007-10-01

    A mechanism for the involvement of the basal ganglia in the processing of visual information, based on dopamine-dependent modulation of the efficiency of synaptic transmission in interconnected parallel associative and limbic cortex-basal ganglia-thalamus-cortex circuits, is proposed. Each circuit consists of a visual or prefrontal area of the cortex connected with the thalamic nucleus and the corresponding areas in different nuclei of the basal ganglia. The circulation of activity in these circuits is supported by the recurrent arrival of information in the thalamus and cortex. Dopamine released in response to a visual stimulus modulates the efficiencies of "strong" and "weak" corticostriatal inputs in different directions, and the subsequent reorganization of activity in the circuit leads to disinhibition (inhibition) of the activity of those cortical neurons which are "strongly" ("weakly") excited by the visual stimulus simultaneously with dopaminergic cells. The pattern in each cortical area is the neuronal reflection of the properties of the visual stimulus processed by this area. Excitation of dopaminergic cells by the visual stimulus via the superior colliculi requires parallel activation of the disinhibitory input to the superior colliculi via the thalamus and the "direct" pathway" in the basal ganglia. The prefrontal cortex, excited by the visual stimulus via the mediodorsal nucleus of the thalamus, mediates the descending influence on the activity of dopaminergic cells, simultaneously controlling dopamine release in different areas of the striatum and thus facilitating the mutual selection of neural reflections of the individual properties of the visual stimulus and their binding into an integral image.

  8. Computer simulations of stimulus dependent state switching in basic circuits of bursting neurons

    Science.gov (United States)

    Rabinovich, Mikhail; Huerta, Ramón; Bazhenov, Maxim; Kozlov, Alexander K.; Abarbanel, Henry D. I.

    1998-11-01

    We investigate the ability of oscillating neural circuits to switch between different states of oscillation in two basic neural circuits. We model two quite distinct small neural circuits. The first circuit is based on invertebrate central pattern generator (CPG) studies [A. I. Selverston and M. Moulins, The Crustacean Stomatogastric System (Springer-Verlag, Berlin, 1987)] and is composed of two neurons coupled via both gap junction and inhibitory synapses. The second consists of coupled pairs of interconnected thalamocortical relay and thalamic reticular neurons with both inhibitory and excitatory synaptic coupling. The latter is an elementary unit of the thalamic networks passing sensory information to the cerebral cortex [M. Steriade, D. A. McCormick, and T. J. Sejnowski, Science 262, 679 (1993)]. Both circuits have contradictory coupling between symmetric parts. The thalamocortical model has excitatory and inhibitory connections and the CPG has reciprocal inhibitory and electrical coupling. We describe the dynamics of the individual neurons in these circuits by conductance based ordinary differential equations of Hodgkin-Huxley type [J. Physiol. (London) 117, 500 (1952)]. Both model circuits exhibit bistability and hysteresis in a wide region of coupling strengths. The two main modes of behavior are in-phase and out-of-phase oscillations of the symmetric parts of the network. We investigate the response of these circuits, while they are operating in bistable regimes, to externally imposed excitatory spike trains with varying interspike timing and small amplitude pulses. These are meant to represent spike trains received by the basic circuits from sensory neurons. Circuits operating in a bistable region are sensitive to the frequency of these excitatory inputs. Frequency variations lead to changes from in-phase to out-of-phase coordination or vice versa. The signaling information contained in a spike train driving the network can place the circuit into one or

  9. Using Combinational Circuits for Control Purposes

    Directory of Open Access Journals (Sweden)

    Maher A. Nabulsi

    2009-01-01

    Full Text Available Problem statement: Combinational circuits are used in computers for generating binary control decisions and for providing digital components for data processing. Approach: The use of combinational circuits and logic gates to control other circuits was discussed. Different systems that use logic gates, multiplexers, decoders and encoders to control different circuits were presented. This study presented a design and implementation of some combinational circuits such as a decoder, an encoder, a multiplexer, a bus system and read/write memory operations. Results: When we connected some types of combinational circuits to the inputs/outputs of digital circuit, these combinational circuits can help us to manage and flow a different types of control signals through a large digital circuit. Conclusion: Many combinational circuits had a good function which can be used for controlling different parts of any digital system and they produce a suitable way to transfer a control signals between different digital components of any large digital system.

  10. Primer printed circuit boards

    CERN Document Server

    Argyle, Andrew

    2009-01-01

    Step-by-step instructions for making your own PCBs at home. Making your own printed circuit board (PCB) might seem a daunting task, but once you master the steps, it's easy to attain professional-looking results. Printed circuit boards, which connect chips and other components, are what make almost all modern electronic devices possible. PCBs are made from sheets of fiberglass clad with copper, usually in multiplelayers. Cut a computer motherboard in two, for instance, and you'll often see five or more differently patterned layers. Making boards at home is relatively easy

  11. Synaptic plasticity functions in an organic electrochemical transistor

    Science.gov (United States)

    Gkoupidenis, Paschalis; Schaefer, Nathan; Strakosas, Xenofon; Fairfield, Jessamyn A.; Malliaras, George G.

    2015-12-01

    Synaptic plasticity functions play a crucial role in the transmission of neural signals in the brain. Short-term plasticity is required for the transmission, encoding, and filtering of the neural signal, whereas long-term plasticity establishes more permanent changes in neural microcircuitry and thus underlies memory and learning. The realization of bioinspired circuits that can actually mimic signal processing in the brain demands the reproduction of both short- and long-term aspects of synaptic plasticity in a single device. Here, we demonstrate the implementation of neuromorphic functions similar to biological memory, such as short- to long-term memory transition, in non-volatile organic electrochemical transistors (OECTs). Depending on the training of the OECT, the device displays either short- or long-term plasticity, therefore, exhibiting non von Neumann characteristics with merged processing and storing functionalities. These results are a first step towards the implementation of organic-based neuromorphic circuits.

  12. Interplay of multiple synaptic plasticity features in filamentary memristive devices for neuromorphic computing

    Science.gov (United States)

    La Barbera, Selina; Vincent, Adrien F.; Vuillaume, Dominique; Querlioz, Damien; Alibart, Fabien

    2016-12-01

    Bio-inspired computing represents today a major challenge at different levels ranging from material science for the design of innovative devices and circuits to computer science for the understanding of the key features required for processing of natural data. In this paper, we propose a detail analysis of resistive switching dynamics in electrochemical metallization cells for synaptic plasticity implementation. We show how filament stability associated to joule effect during switching can be used to emulate key synaptic features such as short term to long term plasticity transition and spike timing dependent plasticity. Furthermore, an interplay between these different synaptic features is demonstrated for object motion detection in a spike-based neuromorphic circuit. System level simulation presents robust learning and promising synaptic operation paving the way to complex bio-inspired computing systems composed of innovative memory devices.

  13. 5-HT2C受体亚型参与易化大鼠内嗅区-海马通路的突触传递:平面微电极阵列记录技术研究%Facilitation of synaptic transmission and connections of entorhinal-hippocampal pathway by 5-HT2C receptor subtype: multi-electrode array recordings

    Institute of Scientific and Technical Information of China (English)

    许燕; 金建慧; 王燕; 王蕊蕊; 李震; 陈军

    2012-01-01

    Using 64-channels (8 × 8) multi-electrode array technique (MED-64 system), the modulatory actions of 5-hydroxytryptam-ine (5-HT) 2C receptor subtype on the entorhinal (EC)-hippocampal synaptic transmission and connections were studied. One of freshly dissociated acute hippocampal slices of rats which was placed on the MED-64 probe, was subject to constant perfusion with oxygenated artificial cerebrospinal fluid (ACSF, 95% O2 and 5% CO2). Two hours after ACSF incubation, simultaneous multi-site electrophysiological recordings were performed. One electrode was selected to be used for perforant path (PP) stimulation, and the remaining 63 electrodes were used for recordings of network field excitatory postsynaptic potentials (fEPSPs) within both CA1 and dentate gyms (DG) that have been previously proved to be mediated by glutamate non-NMDA receptors. After stability of network fEPSPs was achieved, (±)-l(2, 5-Dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI, an agonist of 5-HT2C receptor subtype), or SB242084 (6-Chloro-2,3-dihydro-5-methyl-N-[6-[(2-methyl-3-pyridinyl)oxy]-3-pyridinyl]-lH-indole-l-carboxyamide dihy-drochloride hydrate) (a selective antagonist of 5-HT2C receptor subtype) was applied for 10 min perfusion, respectively. Two-dimensional current source density (2D-CSD) analysis was also transformed by bilinear interpolation at each point of the 64 electrodes for spatial imaging of the fEPSP network responses. Based upon the polarities of fEPSP and 2D-CSD imaging, it was clearly shown that synaptic activations were evoked to occur within the molecular layer of DG and pyramidal cell layer of CA1 by the PP stimulation in which negative-going field potentials and current sink (blue) could be recorded. While, positive-going field potentials and current source (yellow) were mainly localized within the granule cell layer and hilus of DG and alveus of CA1, reflecting spread of electrical signals derived from depolarized region toward CA3 area or subiculum

  14. Resonance circuits for adiabatic circuits

    Directory of Open Access Journals (Sweden)

    C. Schlachta

    2003-01-01

    Full Text Available One of the possible techniques to reduces the power consumption in digital CMOS circuits is to slow down the charge transport. This slowdown can be achieved by introducing an inductor in the charging path. Additionally, the inductor can act as an energy storage element, conserving the energy that is normally dissipated during discharging. Together with the parasitic capacitances from the circuit a LCresonant circuit is formed.

  15. Bidirectional Synaptic Structural Plasticity after Chronic Cocaine Administration Occurs through Rap1 Small GTPase Signaling.

    Science.gov (United States)

    Cahill, Michael E; Bagot, Rosemary C; Gancarz, Amy M; Walker, Deena M; Sun, HaoSheng; Wang, Zi-Jun; Heller, Elizabeth A; Feng, Jian; Kennedy, Pamela J; Koo, Ja Wook; Cates, Hannah M; Neve, Rachael L; Shen, Li; Dietz, David M; Nestler, Eric J

    2016-02-03

    Dendritic spines are the sites of most excitatory synapses in the CNS, and opposing alterations in the synaptic structure of medium spiny neurons (MSNs) of the nucleus accumbens (NAc), a primary brain reward region, are seen at early versus late time points after cocaine administration. Here we investigate the time-dependent molecular and biochemical processes that regulate this bidirectional synaptic structural plasticity of NAc MSNs and associated changes in cocaine reward in response to chronic cocaine exposure. Our findings reveal key roles for the bidirectional synaptic expression of the Rap1b small GTPase and an associated local synaptic protein translation network in this process. The transcriptional mechanisms and pathway-specific inputs to NAc that regulate Rap1b expression are also characterized. Collectively, these findings provide a precise mechanism by which nuclear to synaptic interactions induce "metaplasticity" in NAc MSNs, and we reveal the specific effects of this plasticity on reward behavior in a brain circuit-specific manner.

  16. Distinct Subunit Domains Govern Synaptic Stability and Specificity of the Kainate Receptor

    Directory of Open Access Journals (Sweden)

    Christoph Straub

    2016-07-01

    Full Text Available Synaptic communication between neurons requires the precise localization of neurotransmitter receptors to the correct synapse type. Kainate-type glutamate receptors restrict synaptic localization that is determined by the afferent presynaptic connection. The mechanisms that govern this input-specific synaptic localization remain unclear. Here, we examine how subunit composition and specific subunit domains contribute to synaptic localization of kainate receptors. The cytoplasmic domain of the GluK2 low-affinity subunit stabilizes kainate receptors at synapses. In contrast, the extracellular domain of the GluK4/5 high-affinity subunit synergistically controls the synaptic specificity of kainate receptors through interaction with C1q-like proteins. Thus, the input-specific synaptic localization of the native kainate receptor complex involves two mechanisms that underlie specificity and stabilization of the receptor at synapses.

  17. Synaptic electronics: materials, devices and applications.

    Science.gov (United States)

    Kuzum, Duygu; Yu, Shimeng; Wong, H-S Philip

    2013-09-27

    In this paper, the recent progress of synaptic electronics is reviewed. The basics of biological synaptic plasticity and learning are described. The material properties and electrical switching characteristics of a variety of synaptic devices are discussed, with a focus on the use of synaptic devices for neuromorphic or brain-inspired computing. Performance metrics desirable for large-scale implementations of synaptic devices are illustrated. A review of recent work on targeted computing applications with synaptic devices is presented.

  18. A model of synaptic reconsolidation

    Directory of Open Access Journals (Sweden)

    David B. Kastner

    2016-05-01

    Full Text Available Reconsolidation of memories has mostly been studied at the behavioral and molecular level. Here, we put forward a simple extension of existing computational models of synaptic consolidation to capture hippocampal slice experiments that have been interpreted as reconsolidation at the synaptic level. The model implements reconsolidation through stabilization of consolidated synapses by stabilizing entities combined with an activity-dependent reservoir of stabilizing entities that are immune to protein synthesis inhibition (PSI. We derive a reduced version of our model to explore the conditions under which synaptic reconsolidation does or does not occur, often referred to as the boundary conditions of reconsolidation. We find that our computational model of synaptic reconsolidation displays complex boundary conditions. Our results suggest that a limited resource of hypothetical stabilizing molecules or complexes, which may be implemented by protein phosphorylation or different receptor subtypes, can underlie the phenomenon of synaptic reconsolidation.

  19. Mechanisms underlying autoimmune synaptic encephalitis leading to disorders of memory, behavior and cognition: insights from molecular, cellular and synaptic studies.

    Science.gov (United States)

    Moscato, Emilia H; Jain, Ankit; Peng, Xiaoyu; Hughes, Ethan G; Dalmau, Josep; Balice-Gordon, Rita J

    2010-07-01

    Recently, several novel, potentially lethal and treatment-responsive syndromes that affect hippocampal and cortical function have been shown to be associated with auto-antibodies against synaptic antigens, notably glutamate or GABA-B receptors. Patients with these auto-antibodies, sometimes associated with teratomas and other neoplasms, present with psychiatric symptoms, seizures, memory deficits and decreased levels of consciousness. These symptoms often improve dramatically after immunotherapy or tumor resection. Here we review studies of the cellular and synaptic effects of these antibodies in hippocampal neurons in vitro and preliminary work in rodent models. Our work suggests that patient antibodies lead to rapid and reversible removal of neurotransmitter receptors from synaptic sites, leading to changes in synaptic and circuit function that in turn are likely to lead to behavioral deficits. We also discuss several of the many questions raised by these and related disorders. Determining the mechanisms underlying these novel anti-neurotransmitter receptor encephalopathies will provide insights into the cellular and synaptic bases of the memory and cognitive deficits that are hallmarks of these disorders, and potentially suggest avenues for therapeutic intervention.

  20. Neural Circuits on a Chip

    Directory of Open Access Journals (Sweden)

    Md. Fayad Hasan

    2016-09-01

    Full Text Available Neural circuits are responsible for the brain’s ability to process and store information. Reductionist approaches to understanding the brain include isolation of individual neurons for detailed characterization. When maintained in vitro for several days or weeks, dissociated neurons self-assemble into randomly connected networks that produce synchronized activity and are capable of learning. This review focuses on efforts to control neuronal connectivity in vitro and construct living neural circuits of increasing complexity and precision. Microfabrication-based methods have been developed to guide network self-assembly, accomplishing control over in vitro circuit size and connectivity. The ability to control neural connectivity and synchronized activity led to the implementation of logic functions using living neurons. Techniques to construct and control three-dimensional circuits have also been established. Advances in multiple electrode arrays as well as genetically encoded, optical activity sensors and transducers enabled highly specific interfaces to circuits composed of thousands of neurons. Further advances in on-chip neural circuits may lead to better understanding of the brain.

  1. In Vitro Studies of Neuronal Networks and Synaptic Plasticity in Invertebrates and in Mammals Using Multielectrode Arrays

    Directory of Open Access Journals (Sweden)

    Paolo Massobrio

    2015-01-01

    Full Text Available Brain functions are strictly dependent on neural connections formed during development and modified during life. The cellular and molecular mechanisms underlying synaptogenesis and plastic changes involved in learning and memory have been analyzed in detail in simple animals such as invertebrates and in circuits of mammalian brains mainly by intracellular recordings of neuronal activity. In the last decades, the evolution of techniques such as microelectrode arrays (MEAs that allow simultaneous, long-lasting, noninvasive, extracellular recordings from a large number of neurons has proven very useful to study long-term processes in neuronal networks in vivo and in vitro. In this work, we start off by briefly reviewing the microelectrode array technology and the optimization of the coupling between neurons and microtransducers to detect subthreshold synaptic signals. Then, we report MEA studies of circuit formation and activity in invertebrate models such as Lymnaea, Aplysia, and Helix. In the following sections, we analyze plasticity and connectivity in cultures of mammalian dissociated neurons, focusing on spontaneous activity and electrical stimulation. We conclude by discussing plasticity in closed-loop experiments.

  2. In Vitro Studies of Neuronal Networks and Synaptic Plasticity in Invertebrates and in Mammals Using Multielectrode Arrays

    Science.gov (United States)

    Tessadori, Jacopo; Ghirardi, Mirella

    2015-01-01

    Brain functions are strictly dependent on neural connections formed during development and modified during life. The cellular and molecular mechanisms underlying synaptogenesis and plastic changes involved in learning and memory have been analyzed in detail in simple animals such as invertebrates and in circuits of mammalian brains mainly by intracellular recordings of neuronal activity. In the last decades, the evolution of techniques such as microelectrode arrays (MEAs) that allow simultaneous, long-lasting, noninvasive, extracellular recordings from a large number of neurons has proven very useful to study long-term processes in neuronal networks in vivo and in vitro. In this work, we start off by briefly reviewing the microelectrode array technology and the optimization of the coupling between neurons and microtransducers to detect subthreshold synaptic signals. Then, we report MEA studies of circuit formation and activity in invertebrate models such as Lymnaea, Aplysia, and Helix. In the following sections, we analyze plasticity and connectivity in cultures of mammalian dissociated neurons, focusing on spontaneous activity and electrical stimulation. We conclude by discussing plasticity in closed-loop experiments. PMID:25866681

  3. In vitro studies of neuronal networks and synaptic plasticity in invertebrates and in mammals using multielectrode arrays.

    Science.gov (United States)

    Massobrio, Paolo; Tessadori, Jacopo; Chiappalone, Michela; Ghirardi, Mirella

    2015-01-01

    Brain functions are strictly dependent on neural connections formed during development and modified during life. The cellular and molecular mechanisms underlying synaptogenesis and plastic changes involved in learning and memory have been analyzed in detail in simple animals such as invertebrates and in circuits of mammalian brains mainly by intracellular recordings of neuronal activity. In the last decades, the evolution of techniques such as microelectrode arrays (MEAs) that allow simultaneous, long-lasting, noninvasive, extracellular recordings from a large number of neurons has proven very useful to study long-term processes in neuronal networks in vivo and in vitro. In this work, we start off by briefly reviewing the microelectrode array technology and the optimization of the coupling between neurons and microtransducers to detect subthreshold synaptic signals. Then, we report MEA studies of circuit formation and activity in invertebrate models such as Lymnaea, Aplysia, and Helix. In the following sections, we analyze plasticity and connectivity in cultures of mammalian dissociated neurons, focusing on spontaneous activity and electrical stimulation. We conclude by discussing plasticity in closed-loop experiments.

  4. Fluorescence-based monitoring of in vivo neural activity using a circuit-tracing pseudorabies virus.

    Directory of Open Access Journals (Sweden)

    Andrea E Granstedt

    Full Text Available The study of coordinated activity in neuronal circuits has been challenging without a method to simultaneously report activity and connectivity. Here we present the first use of pseudorabies virus (PRV, which spreads through synaptically connected neurons, to express a fluorescent calcium indicator protein and monitor neuronal activity in a living animal. Fluorescence signals were proportional to action potential number and could reliably detect single action potentials in vitro. With two-photon imaging in vivo, we observed both spontaneous and stimulated activity in neurons of infected murine peripheral autonomic submandibular ganglia (SMG. We optically recorded the SMG response in the salivary circuit to direct electrical stimulation of the presynaptic axons and to physiologically relevant sensory stimulation of the oral cavity. During a time window of 48 hours after inoculation, few spontaneous transients occurred. By 72 hours, we identified more frequent and prolonged spontaneous calcium transients, suggestive of neuronal or tissue responses to infection that influence calcium signaling. Our work establishes in vivo investigation of physiological neuronal circuit activity and subsequent effects of infection with single cell resolution.

  5. "The developmental and functional logic of neuronal circuits": commentary on the Kavli Prize in Neuroscience.

    Science.gov (United States)

    Glover, J C

    2009-11-10

    The first Kavli Prize in Neuroscience recognizes a confluence of career achievements that together provide a fundamental understanding of how brain and spinal cord circuits are assembled during development and function in the adult. The members of the Kavli Neuroscience Prize Committee have decided to reward three scientists (Sten Grillner, Thomas Jessell, and Pasko Rakic) jointly "for discoveries on the developmental and functional logic of neuronal circuits". Pasko Rakic performed groundbreaking studies of the developing cerebral cortex, including the discovery of how radial glia guide the neuronal migration that establishes cortical layers and for the radial unit hypothesis and its implications for cortical connectivity and evolution. Thomas Jessell discovered molecular principles governing the specification and patterning of different neuron types and the development of their synaptic interconnection into sensorimotor circuits. Sten Grillner elucidated principles of network organization in the vertebrate locomotor central pattern generator, along with its command systems and sensory and higher order control. The discoveries of Rakic, Jessell and Grillner provide a framework for how neurons obtain their identities and ultimate locations, establish appropriate connections with each other, and how the resultant neuronal networks operate. Their work has significantly advanced our understanding of brain development and function and created new opportunities for the treatment of neurological disorders. Each has pioneered an important area of neuroscience research and left a legacy of exceptional scientific achievement, insight, communication, mentoring and leadership.

  6. Dissecting local circuits: parvalbumin interneurons underlie broad feedback control of olfactory bulb output.

    Science.gov (United States)

    Miyamichi, Kazunari; Shlomai-Fuchs, Yael; Shu, Marvin; Weissbourd, Brandon C; Luo, Liqun; Mizrahi, Adi

    2013-12-04

    In the mouse olfactory bulb, information from sensory neurons is extensively processed by local interneurons before being transmitted to the olfactory cortex by mitral and tufted (M/T) cells. The precise function of these local networks remains elusive because of the vast heterogeneity of interneurons, their diverse physiological properties, and their complex synaptic connectivity. Here we identified the parvalbumin interneurons (PVNs) as a prominent component of the M/T presynaptic landscape by using an improved rabies-based transsynaptic tracing method for local circuits. In vivo two-photon-targeted patch recording revealed that PVNs have exceptionally broad olfactory receptive fields and exhibit largely excitatory and persistent odor responses. Transsynaptic tracing indicated that PVNs receive direct input from widely distributed M/T cells. Both the anatomical and functional extent of this M/T→PVN→M/T circuit contrasts with the narrowly confined M/T→granule cell→M/T circuit, suggesting that olfactory information is processed by multiple local circuits operating at distinct spatial scales.

  7. HYBRID EXCITATION CLAW-POLE SYNCHRONOUS GENERATOR WITH MAGNETIC CIRCUIT SERIES CONNECTION%串联磁路混合励磁爪极发电机的研究

    Institute of Scientific and Technical Information of China (English)

    赵朝会; 秦海鸿; 严仰光

    2009-01-01

    针对电励磁爪极发电机效率低、永磁爪极发电机磁场调节困难的问题,提出了一种串联磁路混合励磁爪极同步发电机,利用磁路计算方法和三维有限元的分析研究了这种新型电机各部分的磁密大小,确定了合适的极对数和合理的磁钢厚度,探讨了这种新型电机的空载特性、外特性和调节特性.研究表明:串联磁路混合励磁爪极发电机合适的极对数为2,且磁钢厚度存在一个较为合理的优化值.相对于电励磁爪极发电机,它实现了励磁电流的双向控制;相对于永磁爪极发电机它使得输出电压可调,在更宽的负载范围内实现了输出电压的恒定.在参数相同的情况下,与电励磁爪极发电机相比,该电机具有更高的气隙磁密和功率密度.%To solve the low efficiency of electric excitation claw-pole synchronous generator(EECPSG) and regulate the magnetic field of permanent magnet (PM) claw-pole synchronous generator(PMCPSG), a novel hybrid excitation claw-pole synchronous generator(HECPSG) with magnetic circuit series connection is proposed. Through the simulation study on the generator using the calculation method for magnetic circuit and 3-D finite element method(FEA), the appropriate magnet thickness and the number of pole-pairs for the proposed generator are determined. Its off-loading characteristics, load characteristics, and regulation behaviors are investigated. The study shows that the appropriate number of pole-pairs in HECPSG with series magnetic circuits is two, and there exists an optimum magnet thickness.Compared to EECPSG, HECPSG realizes dual-directional control to the excitation current. Moreover, the generator can adjust the output voltage and keep the output voltage stable in a broad load range. Under the condition of same parametes, the motor has higer air-gap flux density and power density.

  8. A Singularity in the Kirchhoff's Circuit Equations

    CERN Document Server

    Harsha, N R Sree

    2016-01-01

    Students often have difficulty in understanding qualitatively the behaviour of simple electric circuits. In particular, as different studies have shown, they find multiple batteries connected in multiple loops difficult to analyse. In a recent paper [Phys. Educ. 50 568 (2015)], we showed such an electric circuit, which consists of ideal batteries connected in parallel, that couldn't be solved by the existing circuit analysis methods. In this paper, we shall introduce a new mathematical method of solving simple electric circuits from the solutions of more general circuits and show that the currents, in this particular circuit, take the indeterminate 0/0 form. We shall also present some of the implications of teaching the method. We believe that the description presented in this paper should help the instructors in teaching the behaviour of multiple batteries connected in parallel.

  9. 30 CFR 56.12053 - Circuits powered from trolley wires.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Circuits powered from trolley wires. 56.12053... § 56.12053 Circuits powered from trolley wires. Ground wires for lighting circuits powered from trolley wires shall be connected securely to the ground-return circuit....

  10. 46 CFR 111.75-5 - Lighting branch circuits.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Lighting branch circuits. 111.75-5 Section 111.75-5...-GENERAL REQUIREMENTS Lighting Circuits and Protection § 111.75-5 Lighting branch circuits. (a) Loads. A lighting distribution panel must not supply branch circuits rated at over 30 amperes. (b) Connected...

  11. 30 CFR 57.12053 - Circuits powered from trolley wires.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Circuits powered from trolley wires. 57.12053... Electricity Surface and Underground § 57.12053 Circuits powered from trolley wires. Ground wires for lighting circuits powered from trolley wires shall be connected securely to the ground return circuit. Surface Only...

  12. Intrinsic mechanisms stabilize encoding and retrieval circuits differentially in a hippocampal network model.

    Science.gov (United States)

    Hummos, Ali; Franklin, Charles C; Nair, Satish S

    2014-12-01

    Acetylcholine regulates memory encoding and retrieval by inducing the hippocampus to switch between pattern separation and pattern completion modes. However, both processes can introduce significant variations in the level of network activity and potentially cause a seizure-like spread of excitation. Thus, mechanisms that keep network excitation within certain bounds are necessary to prevent such instability. We developed a biologically realistic computational model of the hippocampus to investigate potential intrinsic mechanisms that might stabilize the network dynamics during encoding and retrieval. The model was developed by matching experimental data, including neuronal behavior, synaptic current dynamics, network spatial connectivity patterns, and short-term synaptic plasticity. Furthermore, it was constrained to perform pattern completion and separation under the effects of acetylcholine. The model was then used to investigate the role of short-term synaptic depression at the recurrent synapses in CA3, and inhibition by basket cell (BC) interneurons and oriens lacunosum-moleculare (OLM) interneurons in stabilizing these processes. Results showed that when CA3 was considered in isolation, inhibition solely by BCs was not sufficient to control instability. However, both inhibition by OLM cells and short-term depression at the recurrent CA3 connections stabilized the network activity. In the larger network including the dentate gyrus, the model suggested that OLM inhibition could control the network during high cholinergic levels while depressing synapses at the recurrent CA3 connections were important during low cholinergic states. Our results demonstrate that short-term plasticity is a critical property of the network that enhances its robustness. Furthermore, simulations suggested that the low and high cholinergic states can each produce runaway excitation through unique mechanisms and different pathologies. Future studies aimed at elucidating the circuit

  13. Formation and maintenance of neuronal assemblies through synaptic plasticity.

    Science.gov (United States)

    Litwin-Kumar, Ashok; Doiron, Brent

    2014-11-14

    The architecture of cortex is flexible, permitting neuronal networks to store recent sensory experiences as specific synaptic connectivity patterns. However, it is unclear how these patterns are maintained in the face of the high spike time variability associated with cortex. Here we demonstrate, using a large-scale cortical network model, that realistic synaptic plasticity rules coupled with homeostatic mechanisms lead to the formation of neuronal assemblies that reflect previously experienced stimuli. Further, reverberation of past evoked states in spontaneous spiking activity stabilizes, rather than erases, this learned architecture. Spontaneous and evoked spiking activity contains a signature of learned assembly structures, leading to testable predictions about the effect of recent sensory experience on spike train statistics. Our work outlines requirements for synaptic plasticity rules capable of modifying spontaneous dynamics and shows that this modification is beneficial for stability of learned network architectures.

  14. Defective glycinergic synaptic transmission in zebrafish motility mutants

    Directory of Open Access Journals (Sweden)

    Hiromi Hirata

    2010-01-01

    Full Text Available Glycine is a major inhibitory neurotransmitter in the spinal cord and brainstem. Recently, in vivo analysis of glycinergic synaptic transmission has been pursued in zebrafish using molecular genetics. An ENU mutagenesis screen identified two behavioral mutants that are defective in glycinergic synaptic transmission. Zebrafish bandoneon (beo mutants have a defect in glrbb, one of the duplicated glycine receptor (GlyR β subunit genes. These mutants exhibit a loss of glycinergic synaptic transmission due to a lack of synaptic aggregation of GlyRs. Due to the consequent loss of reciprocal inhibition of motor circuits between the two sides of the spinal cord, motor neurons activate simultaneously on both sides resulting in bilateral contraction of axial muscles of beo mutants, eliciting the so-called ‘accordion’ phenotype. Similar defects in GlyR subunit genes have been observed in several mammals and are the basis for human hyperekplexia/startle disease. By contrast, zebrafish shocked (sho mutants have a defect in slc6a9, encoding GlyT1, a glycine transporter that is expressed by astroglial cells surrounding the glycinergic synapse in the hindbrain and spinal cord. GlyT1 mediates rapid uptake of glycine from the synaptic cleft, terminating synaptic transmission. In zebrafish sho mutants, there appears to be elevated extracellular glycine resulting in persistent inhibition of postsynaptic neurons and subsequent reduced motility, causing the ‘twitch once’ phenotype. We review current knowledge regarding zebrafish ‘accordion’ and ‘twitch once’ mutants, including beo and sho, and report the identification of a new α2 subunit that revises the phylogeny of zebrafish GlyRs.

  15. Precise synaptic efficacy alignment suggests potentiation dominated learning

    Directory of Open Access Journals (Sweden)

    Christoph eHartmann

    2016-01-01

    Full Text Available 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 in the morning than they are after sleep depriviation.In conclusion, we show that synaptic normalization in conjunction with

  16. Depression as a Glial-Based Synaptic Dysfunction

    Directory of Open Access Journals (Sweden)

    Daniel eRial

    2016-01-01

    Full Text Available Recent studies combining pharmacological, behavioral, electrophysiological and molecular approaches indicate that depression results from maladaptive neuroplastic processing occurring in defined frontolimbic circuits responsible for emotional processing such as the prefrontal cortex, hippocampus, amygdala and ventral striatum. However, the exact mechanisms controlling synaptic plasticity that are disrupted to trigger depressive conditions have not been elucidated. Since glial cells (astrocytes and microglia tightly and dynamically interact with synapses, engaging a bi-directional communication critical for the processing of synaptic information, we now revisit the role of glial cells in the etiology of depression focusing on a dysfunction of the ‘quad-partite’ synapse. This interest is supported by the observations that depressive-like conditions are associated with a decreased density and hypofunction of astrocytes and with an increase microglia ‘activation’ in frontolimbic regions, which is expected to contribute for the synaptic dysfunction present in depression. Furthermore, the traditional culprits of depression (glucocorticoids, biogenic amines, BDNF affect glia functioning, whereas antidepressant treatments (SSRIs, electroshock, deep brain stimulation recover glia functioning. In this context of a quad-partite synapse, systems modulating glia-synapse bidirectional communication - such as the purinergic neuromodulation system operated by ATP and adenosine - emerge as promising candidates to re-normalize synaptic function by combining direct synaptic effects with an ability to also control astrocyte and microglia function. This proposed triple action of purines to control aberrant synaptic function illustrates the rationale to consider the interference with glia dysfunction as a mechanism of action driving the design of future pharmacological tools to manage depression.

  17. Circuit For Control Of Electromechanical Prosthetic Hand

    Science.gov (United States)

    Bozeman, Richard J., Jr.

    1995-01-01

    Proposed circuit for control of electromechanical prosthetic hand derives electrical control signals from shoulder movements. Updated, electronic version of prosthesis, that includes two hooklike fingers actuated via cables from shoulder harness. Circuit built around favored shoulder harness, provides more dexterous movement, without incurring complexity of computer-controlled "bionic" or hydraulically actuated devices. Additional harness and potentiometer connected to similar control circuit mounted on other shoulder. Used to control stepping motor rotating hand about prosthetic wrist to one of number of angles consistent with number of digital outputs. Finger-control signals developed by circuit connected to first shoulder harness transmitted to prosthetic hand via sliprings at prosthetic wrist joint.

  18. A neuromorphic implementation of multiple spike-timing synaptic plasticity rules for large-scale neural networks

    Science.gov (United States)

    Wang, Runchun M.; Hamilton, Tara J.; Tapson, Jonathan C.; van Schaik, André

    2015-01-01

    We present a neuromorphic implementation of multiple synaptic plasticity learning rules, which include both Spike Timing Dependent Plasticity (STDP) and Spike Timing Dependent Delay Plasticity (STDDP). We present a fully digital implementation as well as a mixed-signal implementation, both of which use a novel dynamic-assignment time-multiplexing approach and support up to 226 (64M) synaptic plasticity elements. Rather than implementing dedicated synapses for particular types of synaptic plasticity, we implemented a more generic synaptic plasticity adaptor array that is separate from the neurons in the neural network. Each adaptor performs synaptic plasticity according to the arrival times of the pre- and post-synaptic spikes assigned to it, and sends out a weighted or delayed pre-synaptic spike to the post-synaptic neuron in the neural network. This strategy provides great flexibility for building complex large-scale neural networks, as a neural network can be configured for multiple synaptic plasticity rules without changing its structure. We validate the proposed neuromorphic implementations with measurement results and illustrate that the circuits are capable of performing both STDP and STDDP. We argue that it is practical to scale the work presented here up to 236 (64G) synaptic adaptors on a current high-end FPGA platform. PMID:26041985

  19. A neuromorphic implementation of multiple spike-timing synaptic plasticity rules for large-scale neural networks.

    Science.gov (United States)

    Wang, Runchun M; Hamilton, Tara J; Tapson, Jonathan C; van Schaik, André

    2015-01-01

    We present a neuromorphic implementation of multiple synaptic plasticity learning rules, which include both Spike Timing Dependent Plasticity (STDP) and Spike Timing Dependent Delay Plasticity (STDDP). We present a fully digital implementation as well as a mixed-signal implementation, both of which use a novel dynamic-assignment time-multiplexing approach and support up to 2(26) (64M) synaptic plasticity elements. Rather than implementing dedicated synapses for particular types of synaptic plasticity, we implemented a more generic synaptic plasticity adaptor array that is separate from the neurons in the neural network. Each adaptor performs synaptic plasticity according to the arrival times of the pre- and post-synaptic spikes assigned to it, and sends out a weighted or delayed pre-synaptic spike to the post-synaptic neuron in the neural network. This strategy provides great flexibility for building complex large-scale neural networks, as a neural network can be configured for multiple synaptic plasticity rules without changing its structure. We validate the proposed neuromorphic implementations with measurement results and illustrate that the circuits are capable of performing both STDP and STDDP. We argue that it is practical to scale the work presented here up to 2(36) (64G) synaptic adaptors on a current high-end FPGA platform.

  20. Near-Perfect Synaptic Integration by Nav1.7 in Hypothalamic Neurons Regulates Body Weight.

    Science.gov (United States)

    Branco, Tiago; Tozer, Adam; Magnus, Christopher J; Sugino, Ken; Tanaka, Shinsuke; Lee, Albert K; Wood, John N; Sternson, Scott M

    2016-06-16

    Neurons are well suited for computations on millisecond timescales, but some neuronal circuits set behavioral states over long time periods, such as those involved in energy homeostasis. We found that multiple types of hypothalamic neurons, including those that oppositely regulate body weight, are specialized as near-perfect synaptic integrators that summate inputs over extended timescales. Excitatory postsynaptic potentials (EPSPs) are greatly prolonged, outlasting the neuronal membrane time-constant up to 10-fold. This is due to the voltage-gated sodium channel Nav1.7 (Scn9a), previously associated with pain-sensation but not synaptic integration. Scn9a deletion in AGRP, POMC, or paraventricular hypothalamic neurons reduced EPSP duration, synaptic integration, and altered body weight in mice. In vivo whole-cell recordings in the hypothalamus confirmed near-perfect synaptic integration. These experiments show that integration of synaptic inputs over time by Nav1.7 is critical for body weight regulation and reveal a mechanism for synaptic control of circuits regulating long term homeostatic functions.

  1. MAPK3 at the Autism-Linked Human 16p11.2 Locus Influences Precise Synaptic Target Selection at Drosophila Larval Neuromuscular Junctions

    Science.gov (United States)

    Park, Sang Mee; Park, Hae Ryoun; Lee, Ji Hye

    2017-01-01

    Proper synaptic function in neural circuits requires precise pairings between correct pre- and post-synaptic partners. Errors in this process may underlie development of neuropsychiatric disorders, such as autism spectrum disorder (ASD). Development of ASD can be influenced by genetic factors, including copy number variations (CNVs). In this study, we focused on a CNV occurring at the 16p11.2 locus in the human genome and investigated potential defects in synaptic connectivity caused by reduced activities of genes located in this region at Drosophila larval neuromuscular junctions, a well-established model synapse with stereotypic synaptic structures. A mutation of rolled, a Drosophila homolog of human mitogen-activated protein kinase 3 (MAPK3) at the 16p11.2 locus, caused ectopic innervation of axonal branches and their abnormal defasciculation. The specificity of these phenotypes was confirmed by expression of wild-type rolled in the mutant background. Albeit to a lesser extent, we also observed ectopic innervation patterns in mutants defective in Cdk2, Gαq, and Gp93, all of which were expected to interact with Rolled MAPK3. A further genetic analysis in double heterozygous combinations revealed a synergistic interaction between rolled and Gp93. In addition, results from RT-qPCR analyses indicated consistently reduced rolled mRNA levels in Cdk2, Gαq, and Gp93 mutants. Taken together, these data suggest a central role of MAPK3 in regulating the precise targeting of presynaptic axons to proper postsynaptic targets, a critical step that may be altered significantly in ASD. PMID:28196412

  2. NMDA-receptor trafficking and targeting: implications for synaptic transmission and plasticity.

    Science.gov (United States)

    Carroll, Reed C; Zukin, R Suzanne

    2002-11-01

    Dynamic regulation of synaptic efficacy is thought to play a crucial role in formation of neuronal connections and in experience-dependent modification of neural circuitry. The molecular and cellular mechanisms by which synaptic changes are triggered and expressed are the focus of intense interest. This articles reviews recent evidence that NMDA receptors undergo dynamically regulated targeting and trafficking, and that the physical transport of NMDA receptors in and out of the synaptic membrane contributes to several forms of long-lasting synaptic plasticity. The identification of targeting and internalization sequences in NMDA-receptor subunits has begun the unraveling of some mechanisms that underlie activity-dependent redistribution of NMDA receptors. Given that NMDA receptors are widely expressed throughout the CNS, regulation of NMDA-receptor trafficking provides a potentially important way to modulate efficacy of synaptic transmission.

  3. Two classes of excitatory synaptic responses in rat thalamic reticular neurons.

    Science.gov (United States)

    Deleuze, Charlotte; Huguenard, John R

    2016-09-01

    The thalamic reticular nucleus (nRt), composed of GABAergic cells providing inhibition of relay neurons in the dorsal thalamus, receives excitation from the neocortex and thalamus. The two excitatory pathways promoting feedback or feedforward inhibition of thalamocortical neurons contribute to sensory processing and rhythm generation. While synaptic inhibition within the nRt has been carefully characterized, little is known regarding the biophysics of synaptic excitation. To characterize the functional properties of thalamocortical and corticothalamic connections to the nRt, we recorded minimal electrically evoked excitatory postsynaptic currents from nRt cells in vitro. A hierarchical clustering algorithm distinguished two types of events. Type 1 events had larger amplitudes and faster kinetics, largely mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, whereas type 2 responses had more prominent N-methyl-d-aspartate (NMDA) receptor contribution. Type 1 responses showed subnormal axonal propagation and paired pulse depression, consistent with thalamocortical inputs. Furthermore, responses kinetically similar to type 1 events were evoked by glutamate-mediated activation of thalamic neurons. Type 2 responses, in contrast, likely arise from corticothalamic inputs, with larger NMDA conductance and weak Mg(2+)-dependent block, suggesting that NMDA receptors are critical for the cortical excitation of reticular neurons. The long-lasting action of NMDA receptors would promote reticular cell burst firing and produce powerful inhibitory output to relay neurons proposed to be important in triggering epilepsy. This work provides the first complete voltage-clamp analysis of the kinetics and voltage dependence of AMPA and NMDA responses of thalamocortical and corticothalamic synapses in the nRt and will be critical in optimizing biologically realistic neural network models of thalamocortical circuits relevant to sensory processing and

  4. Cross-modal synaptic plasticity in adult primary sensory cortices.

    Science.gov (United States)

    Lee, Hey-Kyoung; Whitt, Jessica L

    2015-12-01

    Sensory loss leads to widespread adaptation of brain circuits to allow an organism to navigate its environment with its remaining senses, which is broadly referred to as cross-modal plasticity. Such adaptation can be observed even in the primary sensory cortices, and falls into two distinct categories: recruitment of the deprived sensory cortex for processing the remaining senses, which we term 'cross-modal recruitment', and experience-dependent refinement of the spared sensory cortices referred to as 'compensatory plasticity.' Here we will review recent studies demonstrating that cortical adaptation to sensory loss involves LTP/LTD and homeostatic synaptic plasticity. Cross-modal synaptic plasticity is observed in adults, hence cross-modal sensory deprivation may be an effective way to promote plasticity in adult primary sensory cortices.

  5. Synaptic scaling enables dynamically distinct short- and long-term memory formation.

    Directory of Open Access Journals (Sweden)

    Christian Tetzlaff

    2013-10-01

    Full Text Available Memory storage in the brain relies on mechanisms acting on time scales from minutes, for long-term synaptic potentiation, to days, for memory consolidation. During such processes, neural circuits distinguish synapses relevant for forming a long-term storage, which are consolidated, from synapses of short-term storage, which fade. How time scale integration and synaptic differentiation is simultaneously achieved remains unclear. Here we show that synaptic scaling - a slow process usually associated with the maintenance of activity homeostasis - combined with synaptic plasticity may simultaneously achieve both, thereby providing a natural separation of short- from long-term storage. The interaction between plasticity and scaling provides also an explanation for an established paradox where memory consolidation critically depends on the exact order of learning and recall. These results indicate that scaling may be fundamental for stabilizing memories, providing a dynamic link between early and late memory formation processes.

  6. Distinct modifications of convergent excitatory and inhibitory inputs in developing olfactory circuits.

    Science.gov (United States)

    Ma, T-F; Chen, P-H; Hu, X-Q; Zhao, X-L; Tian, T; Lu, W

    2014-06-06

    The interaction between excitatory and inhibitory inputs is critical to neuronal signal processing. However, little is known about this fundamental property, largely due to the inability to clearly isolate the respective inputs. Here we took advantage of the characteristic stereotypical architecture of synaptic connections in the main olfactory bulb, which enabled us to entirely separate excitatory and inhibitory inputs. Using paired stimulation of two glomeruli located apart at different intensities, we separately elicited excitatory and inhibitory inputs and mimicked stimulation of competing mitral cells (MCs) with different odorants. We performed dual whole-cell patch recording of evoked excitatory postsynaptic responses (EPSPs) and inhibitory postsynaptic responses (IPSPs) in current-clamp mode from two competitive MCs that are connected to the two stimulated glomeruli in slices of the main olfactory bulb in 2-3-week-old rats. We deliberately held the recorded cells at a relative hyperpolarized potential. This manipulation not only suppressed action potential generation but also excluded the possible contamination of inhibitory components in excitatory inputs. We found that in weakly activated MCs repetitive EPSP-IPSP interactions (5 Hz, 180 times) induced long-term potentiation (LTP) and long-term depression (LTD) in convergent excitatory and inhibitory inputs, respectively. Unexpectedly, these forms of plasticity depend on activity of somatic (mainly non-synaptic) NMDA receptors (NMDARs). In contrast, the same repetitive stimulation induced the LTP of excitatory inputs in strongly activated MCs (MC2) that require activity of synaptic NMDARs. These distinct forms of plasticity in the developing olfactory circuit may represent a novel rule of modification in convergent inputs that leads to decorrelation of inputs and facilitates odor discrimination.

  7. Integrative functional genomic analyses implicate specific molecular pathways and circuits in autism.

    Science.gov (United States)

    Parikshak, Neelroop N; Luo, Rui; Zhang, Alice; Won, Hyejung; Lowe, Jennifer K; Chandran, Vijayendran; Horvath, Steve; Geschwind, Daniel H

    2013-11-21

    Genetic studies have identified dozens of autism spectrum disorder (ASD) susceptibility genes, raising two critical questions: (1) do these genetic loci converge on specific biological processes, and (2) where does the phenotypic specificity of ASD arise, given its genetic overlap with intellectual disability (ID)? To address this, we mapped ASD and ID risk genes onto coexpression networks representing developmental trajectories and transcriptional profiles representing fetal and adult cortical laminae. ASD genes tightly coalesce in modules that implicate distinct biological functions during human cortical development, including early transcriptional regulation and synaptic development. Bioinformatic analyses suggest that translational regulation by FMRP and transcriptional coregulation by common transcription factors connect these processes. At a circuit level, ASD genes are enriched in superficial cortical layers and glutamatergic projection neurons. Furthermore, we show that the patterns of ASD and ID risk genes are distinct, providing a biological framework for further investigating the pathophysiology of ASD.

  8. Synaptic vesicle pools and dynamics.

    Science.gov (United States)

    Alabi, AbdulRasheed A; Tsien, Richard W

    2012-08-01

    Synaptic vesicles release neurotransmitter at chemical synapses, thus initiating the flow of information in neural networks. To achieve this, vesicles undergo a dynamic cycle of fusion and retrieval to maintain the structural and functional integrity of the presynaptic terminals in which they reside. Moreover, compelling evidence indicates these vesicles differ in their availability for release and mobilization in response to stimuli, prompting classification into at least three different functional pools. Ongoing studies of the molecular and cellular bases for this heterogeneity attempt to link structure to physiology and clarify how regulation of vesicle pools influences synaptic strength and presynaptic plasticity. We discuss prevailing perspectives on vesicle pools, the role they play in shaping synaptic transmission, and the open questions that challenge current understanding.

  9. A neuromorphic implementation of multiple spike-timing synaptic plasticity rules for large-scale neural networks

    Directory of Open Access Journals (Sweden)

    Runchun Mark Wang

    2015-05-01

    Full Text Available We present a neuromorphic implementation of multiple synaptic plasticity learning rules, which include both Spike Timing Dependent Plasticity (STDP and Spike Timing Dependent Delay Plasticity (STDDP. We present a fully digital implementation as well as a mixed-signal implementation, both of which use a novel dynamic-assignment time-multiplexing approach and support up to 2^26 (64M synaptic plasticity elements. Rather than implementing dedicated synapses for particular types of synaptic plasticity, we implemented a more generic synaptic plasticity adaptor array that is separate from the neurons in the neural network. Each adaptor performs synaptic plasticity according to the arrival times of the pre- and post-synaptic spikes assigned to it, and sends out a weighted and/or delayed pre-synaptic spike to the target synapse in the neural network. This strategy provides great flexibility for building complex large-scale neural networks, as a neural network can be configured for multiple synaptic plasticity rules without changing its structure. We validate the proposed neuromorphic implementations with measurement results and illustrate that the circuits are capable of performing both STDP and STDDP. We argue that it is practical to scale the work presented here up to 2^36 (64G synaptic adaptors on a current high-end FPGA platform.

  10. Circuits in the Sun: Solar Panel Physics

    Science.gov (United States)

    Gfroerer, Tim

    2013-01-01

    Typical commercial solar panels consist of approximately 60 individual photovoltaic cells connected in series. Since the usual Kirchhoff rules apply, the current is uniform throughout the circuit, while the electric potential of the individual devices is cumulative. Hence, a solar panel is a good analog of a simple resistive series circuit, except…

  11. Identifying and tracking simulated synaptic inputs from neuronal firing: insights from in vitro experiments.

    Directory of Open Access Journals (Sweden)

    Maxim Volgushev

    2015-03-01

    Full Text Available Accurately describing synaptic interactions between neurons and how interactions change over time are key challenges for systems neuroscience. Although intracellular electrophysiology is a powerful tool for studying synaptic integration and plasticity, it is limited by the small number of neurons that can be recorded simultaneously in vitro and by the technical difficulty of intracellular recording in vivo. One way around these difficulties may be to use large-scale extracellular recording of spike trains and apply statistical methods to model and infer functional connections between neurons. These techniques have the potential to reveal large-scale connectivity structure based on the spike timing alone. However, the interpretation of functional connectivity is often approximate, since only a small fraction of presynaptic inputs are typically observed. Here we use in vitro current injection in layer 2/3 pyramidal neurons to validate methods for inferring functional connectivity in a setting where input to the neuron is controlled. In experiments with partially-defined input, we inject a single simulated input with known amplitude on a background of fluctuating noise. In a fully-defined input paradigm, we then control the synaptic weights and timing of many simulated presynaptic neurons. By analyzing the firing of neurons in response to these artificial inputs, we ask 1 How does functional connectivity inferred from spikes relate to simulated synaptic input? and 2 What are the limitations of connectivity inference? We find that individual current-based synaptic inputs are detectable over a broad range of amplitudes and conditions. Detectability depends on input amplitude and output firing rate, and excitatory inputs are detected more readily than inhibitory. Moreover, as we model increasing numbers of presynaptic inputs, we are able to estimate connection strengths more accurately and detect the presence of connections more quickly. These results

  12. Photodiode circuits for retinal prostheses.

    Science.gov (United States)

    Loudin, J D; Cogan, S F; Mathieson, K; Sher, A; Palanker, D V

    2011-10-01

    Photodiode circuits show promise for the development of high-resolution retinal prostheses. While several of these systems have been constructed and some even implanted in humans, existing descriptions of the complex optoelectronic interaction between light, photodiode, and the electrode/electrolyte load are limited. This study examines this interaction in depth with theoretical calculations and experimental measurements. Actively biased photoconductive and passive photovoltaic circuits are investigated, with the photovoltaic circuits consisting of one or more diodes connected in series, and the photoconductive circuits consisting of a single diode in series with a pulsed bias voltage. Circuit behavior and charge injection levels were markedly different for platinum and sputtered iridium-oxide film (SIROF) electrodes. Photovoltaic circuits were able to deliver 0.038 mC/cm(2) (0.75 nC/phase) per photodiode with 50- μm platinum electrodes, and 0.54-mC/cm(2) (11 nC/phase) per photodiode with 50-μ m SIROF electrodes driven with 0.5-ms pulses of light at 25 Hz. The same pulses applied to photoconductive circuits with the same electrodes were able to deliver charge injections as high as 0.38 and 7.6 mC/cm(2) (7.5 and 150 nC/phase), respectively. We demonstrate photovoltaic stimulation of rabbit retina in-vitro, with 0.5-ms pulses of 905-nm light using peak irradiance of 1 mW/mm(2). Based on the experimental data, we derive electrochemical and optical safety limits for pixel density and charge injection in various circuits. While photoconductive circuits offer smaller pixels, photovoltaic systems do not require an external bias voltage. Both classes of circuits show promise for the development of high-resolution optoelectronic retinal prostheses.

  13. Nano integrated circuit process

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Yung Sup

    2004-02-15

    This book contains nine chapters, which are introduction of manufacture of semiconductor chip, oxidation such as Dry-oxidation, wet oxidation, oxidation model and oxide film, diffusion like diffusion process, diffusion equation, diffusion coefficient and diffusion system, ion implantation, including ion distribution, channeling, multiimplantation and masking and its system, sputtering such as CVD and PVD, lithography, wet etch and dry etch, interconnection and flattening like metal-silicon connection, silicide, multiple layer metal process and flattening, an integrated circuit process, including MOSFET and CMOS.

  14. Enduring medial perforant path short-term synaptic depression at high pressure

    Directory of Open Access Journals (Sweden)

    Adolfo E Talpalar

    2010-10-01

    Full Text Available The high pressure neurological syndrome develops during deep diving (> 1.1 MPa involving impairment of cognitive functions, alteration of synaptic transmission and increased excitability in cortico-hippocampal areas. The medial perforant path (MPP, connecting entorhinal cortex with the hippocampal formation, displays synaptic frequency-dependent-depression (FDD under normal conditions. Synaptic FDD is essential for specific functions of various neuronal networks. We used rat cortico-hippocampal slices and computer simulations for studying the effects of pressure and its interaction with extracellular Ca2+ ([Ca2+]o on FDD at the MPP synapses. At atmospheric pressure, high [Ca2+]o (4-6 mM saturated single MPP field EPSP (fEPSP and increased FDD in response to short trains at 50 Hz. High pressure (HP; 10.1 MPa depressed single fEPSPs by 50 %. Increasing [Ca2+]o to 4 mM at HP saturated synaptic response at a subnormal level (only 20 % recovery of single fEPSPs, but generated a FDD similar to atmospheric pressure. Mathematical model analysis of the fractions of synaptic resources used by each fEPSP during trains (normalized to their maximum and the total fraction utilized within a train indicate that HP depresses synaptic activity also by reducing synaptic resources. This data suggest that MPP synapses may be modulated, in addition to depression of single events, by reduction of synaptic resources and then may have the ability to conserve their dynamic properties under different conditions.

  15. Biologically based neural circuit modelling for the study of fear learning and extinction

    Science.gov (United States)

    Nair, Satish S.; Paré, Denis; Vicentic, Aleksandra

    2016-11-01

    The neuronal systems that promote protective defensive behaviours have been studied extensively using Pavlovian conditioning. In this paradigm, an initially neutral-conditioned stimulus is paired with an aversive unconditioned stimulus leading the subjects to display behavioural signs of fear. Decades of research into the neural bases of this simple behavioural paradigm uncovered that the amygdala, a complex structure comprised of several interconnected nuclei, is an essential part of the neural circuits required for the acquisition, consolidation and expression of fear memory. However, emerging evidence from the confluence of electrophysiological, tract tracing, imaging, molecular, optogenetic and chemogenetic methodologies, reveals that fear learning is mediated by multiple connections between several amygdala nuclei and their distributed targets, dynamical changes in plasticity in local circuit elements as well as neuromodulatory mechanisms that promote synaptic plasticity. To uncover these complex relations and analyse multi-modal data sets acquired from these studies, we argue that biologically realistic computational modelling, in conjunction with experiments, offers an opportunity to advance our understanding of the neural circuit mechanisms of fear learning and to address how their dysfunction may lead to maladaptive fear responses in mental disorders.

  16. Integrated plasticity at inhibitory and excitatory synapses in the cerebellar circuit

    Directory of Open Access Journals (Sweden)

    Lisa eMapelli

    2015-05-01

    Full Text Available The way long-term potentiation (LTP and depression (LTD are integrated within the different synapses of brain neuronal circuits is poorly understood. In order to progress beyond the identification of specific molecular mechanisms, a system in which multiple forms of plasticity can be correlated with large-scale neural processing is required. In this paper we take as an example the cerebellar network , in which extensive investigations have revealed LTP and LTD at several excitatory and inhibitory synapses. Cerebellar LTP and LTD occur in all three main cerebellar subcircuits (granular layer, molecular layer, deep cerebellar nuclei and correspondingly regulate the function of their three main neurons: granule cells (GrCs, Purkinje cells (PCs and deep cerebellar nuclear (DCN cells. All these neurons, in addition to be excited, are reached by feed-forward and feed-back inhibitory connections, in which LTP and LTD may either operate synergistically or homeostatically in order to control information flow through the circuit. Although the investigation of individual synaptic plasticities in vitro is essential to prove their existence and mechanisms, it is insufficient to generate a coherent view of their impact on network functioning in vivo. Recent computational models and cell-specific genetic mutations in mice are shedding light on how plasticity at multiple excitatory and inhibitory synapses might regulate neuronal activities in the cerebellar circuit and contribute to learning and memory and behavioral control.

  17. Integrated plasticity at inhibitory and excitatory synapses in the cerebellar circuit.

    Science.gov (United States)

    Mapelli, Lisa; Pagani, Martina; Garrido, Jesus A; D'Angelo, Egidio

    2015-01-01

    The way long-term potentiation (LTP) and depression (LTD) are integrated within the different synapses of brain neuronal circuits is poorly understood. In order to progress beyond the identification of specific molecular mechanisms, a system in which multiple forms of plasticity can be correlated with large-scale neural processing is required. In this paper we take as an example the cerebellar network, in which extensive investigations have revealed LTP and LTD at several excitatory and inhibitory synapses. Cerebellar LTP and LTD occur in all three main cerebellar subcircuits (granular layer, molecular layer, deep cerebellar nuclei) and correspondingly regulate the function of their three main neurons: granule cells (GrCs), Purkinje cells (PCs) and deep cerebellar nuclear (DCN) cells. All these neurons, in addition to be excited, are reached by feed-forward and feed-back inhibitory connections, in which LTP and LTD may either operate synergistically or homeostatically in order to control information flow through the circuit. Although the investigation of individual synaptic plasticities in vitro is essential to prove their existence and mechanisms, it is insufficient to generate a coherent view of their impact on network functioning in vivo. Recent computational models and cell-specific genetic mutations in mice are shedding light on how plasticity at multiple excitatory and inhibitory synapses might regulate neuronal activities in the cerebellar circuit and contribute to learning and memory and behavioral control.

  18. Synaptic Variability Introduces State-Dependent Modulation of Excitatory Spinal Cord Synapses

    Directory of Open Access Journals (Sweden)

    David Parker

    2015-01-01

    Full Text Available The relevance of neuronal and synaptic variability remains unclear. Cellular and synaptic plasticity and neuromodulation are also variable. This could reflect state-dependent effects caused by the variable initial cellular or synaptic properties or direct variability in plasticity-inducing mechanisms. This study has examined state-dependent influences on synaptic plasticity at connections between excitatory interneurons (EIN and motor neurons in the lamprey spinal cord. State-dependent effects were examined by correlating initial synaptic properties with the substance P-mediated plasticity of low frequency-evoked EPSPs and the reduction of the EPSP depression over spike trains (metaplasticity. The low frequency EPSP potentiation reflected an interaction between the potentiation of NMDA responses and the release probability. The release probability introduced a variable state-dependent subtractive influence on the postsynaptic NMDA-dependent potentiation. The metaplasticity was also state-dependent: it was greater at connections with smaller available vesicle pools and high initial release probabilities. This was supported by the significant reduction in the number of connections showing metaplasticity when the release probability was reduced by high Mg2+ Ringer. Initial synaptic properties thus introduce state-dependent influences that affect the potential for plasticity. Understanding these conditions will be as important as understanding the subsequent changes.

  19. Synaptic Variability Introduces State-Dependent Modulation of Excitatory Spinal Cord Synapses.

    Science.gov (United States)

    Parker, David

    2015-01-01

    The relevance of neuronal and synaptic variability remains unclear. Cellular and synaptic plasticity and neuromodulation are also variable. This could reflect state-dependent effects caused by the variable initial cellular or synaptic properties or direct variability in plasticity-inducing mechanisms. This study has examined state-dependent influences on synaptic plasticity at connections between excitatory interneurons (EIN) and motor neurons in the lamprey spinal cord. State-dependent effects were examined by correlating initial synaptic properties with the substance P-mediated plasticity of low frequency-evoked EPSPs and the reduction of the EPSP depression over spike trains (metaplasticity). The low frequency EPSP potentiation reflected an interaction between the potentiation of NMDA responses and the release probability. The release probability introduced a variable state-dependent subtractive influence on the postsynaptic NMDA-dependent potentiation. The metaplasticity was also state-dependent: it was greater at connections with smaller available vesicle pools and high initial release probabilities. This was supported by the significant reduction in the number of connections showing metaplasticity when the release probability was reduced by high Mg(2+) Ringer. Initial synaptic properties thus introduce state-dependent influences that affect the potential for plasticity. Understanding these conditions will be as important as understanding the subsequent changes.

  20. Synaptic plasticity: Building memories to last.

    Science.gov (United States)

    Thompson, S M

    2000-03-23

    A series of recent studies has provided long-awaited direct evidence that enduring changes in synaptic strength, presumably underlying the formation of persistent memories, may be encoded in a lasting form as a change in synaptic structure.

  1. Beyond Optimality to Understanding Neuronal Circuits

    Science.gov (United States)

    Marder, Eve

    2010-03-01

    I will summarize recent theoretical and experimental work that shows that similar circuit outputs can be produced with highly variable circuit parameters. This work argues that the nervous system of each healthy individual has found a set of different solutions that give ``good enough'' circuit performance. I will use examples from theoretical and experimental studies using the crustacean stomatogastric nervous system to argue that synaptic and intrinsic currents can vary far more than the output of the circuit in which they are found. These data have significant implications for the mechanisms that maintain stable function over the animal's lifetime, and for the kinds of changes that allow the nervous system to recover function after injury. In this kind of complex system, merely collecting mean data from many individuals can lead to significant errors, and it becomes important to measure as many individual network parameters in each individual as possible. This work raises the question of the extent to which neuromodulation can be constant with underlying circuit parameter variation. To address this question, we construct two cell reciprocally inhibitory circuits using the dynamic clamp from biological GM neurons of the crab stomatogastric ganglion. We then describe the output of the circuits while sweeping through a range of synaptic and intrinsic conductances, first in control saline and then in the presence of serotonin. We find that serotonin extends the ranges of parameters that produce alternating bursting. Moreover, although serotonin's effects are highly robust and significant on the entire population, individual networks respond anomalously. These data demonstrate that while neuromodulation may have robust actions on a population, not all individuals may respond as do the majority. These findings have important implications for evolution.

  2. Circuit with a Switch for Charging a Battery in a Battery Capacitor Circuit

    Science.gov (United States)

    Stuart, Thomas A. (Inventor); Ashtiani, Cyrus N. (Inventor)

    2008-01-01

    A circuit for charging a battery combined with a capacitor includes a power supply adapted to be connected to the capacitor, and the battery. The circuit includes an electronic switch connected to the power supply. The electronic switch is responsive to switch between a conducting state to allow current and a non-conducting state to prevent current flow. The circuit includes a control device connected to the switch and is operable to generate a control signal to continuously switch the electronic switch between the conducting and non-conducting states to charge the battery.

  3. Mossy fiber synaptic transmission: communication from the dentate gyrus to area CA3.

    Science.gov (United States)

    Jaffe, David B; Gutiérrez, Rafael

    2007-01-01

    Communication between the dentate gyrus (DG) and area CA3 of the hippocampus proper is transmitted via axons of granule cells--the mossy fiber (MF) pathway. In this review we discuss and compare the properties of transmitter release from the MFs onto pyramidal neurons and interneurons. An examination of the anatomical connectivity from DG to CA3 reveals a surprising interplay between excitation and inhibition for this circuit. In this respect it is particularly relevant that the major targets of the MFs are interneurons and that the consequence of MF input into CA3 may be inhibitory or excitatory, conditionally dependent on the frequency of input and modulatory regulation. This is further complicated by the properties of transmitter release from the MFs where a large number of co-localized transmitters, including GABAergic inhibitory transmitter release, and the effects of presynaptic modulation finely tune transmitter release. A picture emerges that extends beyond the hypothesis that the MFs are simply "detonators" of CA3 pyramidal neurons; the properties of synaptic information flow from the DG have more subtle and complex influences on the CA3 network.

  4. Drosophila cyfip regulates synaptic development and endocytosis by suppressing filamentous actin assembly.

    Science.gov (United States)

    Zhao, Lu; Wang, Dan; Wang, Qifu; Rodal, Avital A; Zhang, Yong Q

    2013-04-01

    The formation of synapses and the proper construction of neural circuits depend on signaling pathways that regulate cytoskeletal structure and dynamics. After the mutual recognition of a growing axon and its target, multiple signaling pathways are activated that regulate cytoskeletal dynamics to determine the morphology and strength of the connection. By analyzing Drosophila mutations in the cytoplasmic FMRP interacting protein Cyfip, we demonstrate that this component of the WAVE complex inhibits the assembly of filamentous actin (F-actin) and thereby regulates key aspects of synaptogenesis. Cyfip regulates the distribution of F-actin filaments in presynaptic neuromuscular junction (NMJ) terminals. At cyfip mutant NMJs, F-actin assembly was accelerated, resulting in shorter NMJs, more numerous satellite boutons, and reduced quantal content. Increased synaptic vesicle size and failure to maintain excitatory junctional potential amplitudes under high-frequency stimulation in cyfip mutants indicated an endocytic defect. cyfip mutants exhibited upregulated bone morphogenetic protein (BMP) signaling, a major growth-promoting pathway known to be attenuated by endocytosis at the Drosophila NMJ. We propose that Cyfip regulates synapse development and endocytosis by inhibiting actin assembly.

  5. Irregular persistent activity induced by synaptic excitatory feedback

    Directory of Open Access Journals (Sweden)

    Francesca Barbieri

    2007-11-01

    Full Text Available Neurophysiological experiments on monkeys have reported highly irregular persistent activity during the performance of an oculomotor delayed-response task. These experiments show that during the delay period the coefficient of variation (CV of interspike intervals (ISI of prefrontal neurons is above 1, on average, and larger than during the fixation period. In the present paper, we show that this feature can be reproduced in a network in which persistent activity is induced by excitatory feedback, provided that (i the post-spike reset is close enough to threshold , (ii synaptic efficacies are a non-linear function of the pre-synaptic firing rate. Non-linearity between presynaptic rate and effective synaptic strength is implemented by a standard short-term depression mechanism (STD. First, we consider the simplest possible network with excitatory feedback: a fully connected homogeneous network of excitatory leaky integrate-and-fire neurons, using both numerical simulations and analytical techniques. The results are then confirmed in a network with selective excitatory neurons and inhibition. In both the cases there is a large range of values of the synaptic efficacies for which the statistics of firing of single cells is similar to experimental data.

  6. Affective Circuits

    DEFF Research Database (Denmark)

    to the intersecting streams of goods, people, ideas, and money as they circulate between African migrants and their kin who remain back home. They also show the complex ways that emotions become entangled in these exchanges. Examining how these circuits operate in domains of social life ranging from child fosterage......Moving between Africa and Europe, the book explores the many ways migrants sustain and rework family ties and intimate relationships at home and abroad. It demonstrates how their quotidian efforts—on such a mass scale—contribute to a broader process of social regeneration. The contributors point...

  7. Fast State-Space Methods for Inferring Dendritic Synaptic Connectivity

    Science.gov (United States)

    2013-08-08

    condition for the linear regression case was discussed in Efron et al. (2004). In our formulation of the LARS- lasso algorithm, the positivity can be...noisy, subsampled voltage observations we develop fast l1-penalized regression methods for Kalman state-space models of the neuron voltage dynamics...large dendritic trees. Given noisy, subsampled voltage observations we develop fast l1-penalized regression methods for Kalman state-space models of

  8. 49 CFR 236.732 - Controller, circuit; switch.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Controller, circuit; switch. 236.732 Section 236... § 236.732 Controller, circuit; switch. A device for opening and closing electric circuits, operated by a rod connected to a switch, derail or movable-point frog....

  9. Collective of mechatronics circuit

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1987-02-15

    This book is composed of three parts, which deals with mechatronics system about sensor, circuit and motor. The contents of the first part are photo sensor of collector for output, locating detection circuit with photo interrupts, photo sensor circuit with CdS cell and lamp, interface circuit with logic and LED and temperature sensor circuit. The second part deals with oscillation circuit with crystal, C-R oscillation circuit, F-V converter, timer circuit, stability power circuit, DC amp and DC-DC converter. The last part is comprised of bridge server circuit, deformation bridge server, controlling circuit of DC motor, controlling circuit with IC for PLL and driver circuit of stepping motor and driver circuit of Brushless.

  10. Polynomial threshold functions and Boolean threshold circuits

    DEFF Research Database (Denmark)

    Hansen, Kristoffer Arnsfelt; Podolskii, Vladimir V.

    2013-01-01

    of secondary interest. We show that PTFs on general Boolean domains are tightly connected to depth two threshold circuits. Our main results in regard to this connection are: PTFs of polynomial length and polynomial degree compute exactly the functions computed by THRMAJ circuits. An exponential length lower...... bound for PTFs that holds regardless of degree, thereby extending known lower bounds for THRMAJ circuits. We generalize two-party unbounded error communication complexity to the multi-party number-on-the-forehead setting, and show that communication lower bounds for 3-player protocols would yield size...... lower bounds for THRTHR circuits. We obtain several other results about PTFs. These include relationships between weight and degree of PTFs, and a degree lower bound for PTFs of constant length. We also consider a variant of PTFs over the max-plus algebra. We show that they are connected to PTFs over...

  11. Functional integrity of thalamocortical circuits differentiates normal aging from mild cognitive impairment.

    Science.gov (United States)

    Cantero, Jose L; Atienza, Mercedes; Gomez-Herrero, German; Cruz-Vadell, Abel; Gil-Neciga, Eulogio; Rodriguez-Romero, Rafael; Garcia-Solis, David

    2009-12-01

    Resonance in thalamocortical networks is critically involved in sculpting oscillatory behavior in large ensembles of neocortical cells. Neocortical oscillations provide critical information about the integrity of thalamocortical circuits and functional connectivity of cortical networks, which seem to be significantly disrupted by the neuronal death and synapse loss characterizing Alzheimer's disease (AD). By applying a novel analysis methodology to overcome volume conduction effects between scalp electroencephalographic (EEG) measurements, we were able to estimate the temporal activation of EEG-alpha sources in the thalamus and parieto-occipital regions of the cortex. We found that synaptic flow underlying the lower alpha band (7.5-10 Hz) was abnormally facilitated in patients with mild cognitive impairment (MCI) as compared to healthy elderly individuals, particularly from thalamus to cortex (approximately 38% higher). In addition, the thalamic generator of lower alpha oscillations was also abnormally activated in patients with MCI. Regarding the upper alpha subdivision (10.1-12.5 Hz), both controls and patients with MCI showed a bidirectional decrease of thalamocortical synaptic transmission, which was age-dependent only in the control group. Altogether, our results suggest that functional dynamics of thalamocortical networks differentiate individuals at high risk of developing AD from healthy elderly subjects, supporting the hypothesis that neurodegeneration mechanisms are active years before the patient is clinically diagnosed with dementia.

  12. Binocular Rivalry in a Competitive Neural Network with Synaptic Depression

    KAUST Repository

    Kilpatrick, Zachary P.

    2010-01-01

    We study binocular rivalry in a competitive neural network with synaptic depression. In particular, we consider two coupled hypercolums within primary visual cortex (V1), representing orientation selective cells responding to either left or right eye inputs. Coupling between hypercolumns is dominated by inhibition, especially for neurons with dissimilar orientation preferences. Within hypercolumns, recurrent connectivity is excitatory for similar orientations and inhibitory for different orientations. All synaptic connections are modifiable by local synaptic depression. When the hypercolumns are driven by orthogonal oriented stimuli, it is possible to induce oscillations that are representative of binocular rivalry. We first analyze the occurrence of oscillations in a space-clamped version of the model using a fast-slow analys is, taking advantage of the fact that depression evolves much slower than population activity. We th en analyze the onset of oscillations in the full spatially extended system by carrying out a piecewise smooth stability analysis of single (winner-take-all) and double (fusion) bumps within the network. Although our stability analysis takes into account only instabilities associated with real eigenvalues, it identifies points of instability that are consistent with what is found numerically. In particular, we show that, in regions of parameter space where double bumps are unstable and no single bumps exist, binocular rivalry can arise as a slow alternation between either population supporting a bump. © 2010 Society for Industrial and Applied Mathematics.

  13. Traumatic brain injury impairs synaptic plasticity in hippocampus in rats

    Institute of Scientific and Technical Information of China (English)

    ZHANG Bao-liang; CHEN Xin; TAN Tao; YANG Zhuo; CARLOS Dayao; JIANG Rong-cai; ZHANG Jian-ning

    2011-01-01

    Background Traumatic brain injury (TBl) often causes cognitive deficits and remote symptomatic epilepsy.Hippocampal regional excitability is associated with the cognitive function. However, little is known about injury-induced neuronal loss and subsequent alterations of hippocampal regional excitability. The present study was designed to determine whether TBl may impair the cellular circuit in the hippocampus.Methods Forty male Wistar rats were randomized into control (n=20) and TBl groups (n=20). Long-term potentiation,extracellular input/output curves, and hippocampal parvalbumin-immunoreactive and cholecystokinin-immunoreactive interneurons were compared between the two groups.Results TBI resulted in a significantly increased excitability in the dentate gyrus (DG), but a significantly decreased excitability in the cornu ammonis 1 (CA1) area. Using design-based stereological injury procedures, we induced interneuronal loss in the DG and CA3 subregions in the hippocampus, but not in the CA1 area.Conclusions TBl leads to the impairment of hippocampus synaptic plasticity due to the changing of interneuronal interaction. The injury-induced disruption of synaptic efficacy within the hippocampal circuit may underlie the observed cognitive deficits and symptomatic epilepsy.

  14. Development of larval motor circuits in Drosophila.

    Science.gov (United States)

    Kohsaka, Hiroshi; Okusawa, Satoko; Itakura, Yuki; Fushiki, Akira; Nose, Akinao

    2012-04-01

    How are functional neural circuits formed during development? Despite recent advances in our understanding of the development of individual neurons, little is known about how complex circuits are assembled to generate specific behaviors. Here, we describe the ways in which Drosophila motor circuits serve as an excellent model system to tackle this problem. We first summarize what has been learned during the past decades on the connectivity and development of component neurons, in particular motor neurons and sensory feedback neurons. We then review recent progress in our understanding of the development of the circuits as well as studies that apply optogenetics and other innovative techniques to dissect the circuit diagram. New approaches using Drosophila as a model system are now making it possible to search for developmental rules that regulate the construction of neural circuits.

  15. Synaptic dynamics and decision making

    Science.gov (United States)

    Deco, Gustavo; Rolls, Edmund T.; Romo, Ranulfo

    2010-01-01

    During decision making between sequential stimuli, the first stimulus must be held in memory and then compared with the second. Here, we show that in systems that encode the stimuli by their firing rate, neurons can use synaptic facilitation not only to remember the first stimulus during the delay but during the presentation of the second stimulus so that they respond to a combination of the first and second stimuli, as has been found for “partial differential” neurons recorded in the ventral premotor cortex during vibrotactile flutter frequency decision making. Moreover, we show that such partial differential neurons provide important input to a subsequent attractor decision-making network that can then compare this combination of the first and second stimuli with inputs from other neurons that respond only to the second stimulus. Thus, both synaptic facilitation and neuronal attractor dynamics can account for sequential decision making in such systems in the brain. PMID:20360555

  16. Late onset deficits in synaptic plasticity in the valproic acid rat model of autism

    Directory of Open Access Journals (Sweden)

    Henry Giles Stratten Martin

    2014-01-01

    Full Text Available Valproic acid (VPA is a frequently used drug in the treatment of epilepsy, bipolar disorders and migraines; however it is also a potent teratogen. Prenatal exposure increases the risk of childhood malformations and can result in cognitive deficits. In rodents in utero exposure to VPA also causes neurodevelopmental abnormalities and is an important model of autism. In early postnatal life VPA exposed rat pups show changes in medial prefrontal cortex (mPFC physiology and synaptic connectivity. Specifically, principal neurons show decreased excitability but increased local connectivity, coupled with an increase in long-term potentiation (LTP due to an up-regulation of NMDA receptor (NMDAR expression. However recent evidence suggests compensatory homeostatic mechanisms lead to normalization of synaptic NMDA receptors during later postnatal development. Here we have extended study of mPFC synaptic physiology into adulthood to better understand the longitudinal consequences of early developmental abnormalities in VPA exposed rats. Surprisingly in contrast to early postnatal life and adolescence, we find that adult VPA exposed rats show reduced synaptic function. Both NMDAR mediated currents and LTP are lower in adult VPA rats, although spontaneous activity and endocannabinoid dependent long-term depression are normal. We conclude that rather than correcting, synaptic abnormalities persist into adulthood in VPA exposed rats, although a quite different synaptic phenotype is present. This switch from hyper to hypo function in mPFC may be linked to some of the neurodevelopmental defects found in prenatal VPA exposure and autism spectrum disorders in general.

  17. A neuromorphic VLSI design for spike timing and rate based synaptic plasticity.

    Science.gov (United States)

    Rahimi Azghadi, Mostafa; Al-Sarawi, Said; Abbott, Derek; Iannella, Nicolangelo

    2013-09-01

    Triplet-based Spike Timing Dependent Plasticity (TSTDP) is a powerful synaptic plasticity rule that acts beyond conventional pair-based STDP (PSTDP). Here, the TSTDP is capable of reproducing the outcomes from a variety of biological experiments, while the PSTDP rule fails to reproduce them. Additionally, it has been shown that the behaviour inherent to the spike rate-based Bienenstock-Cooper-Munro (BCM) synaptic plasticity rule can also emerge from the TSTDP rule. This paper proposes an analogue implementation of the TSTDP rule. The proposed VLSI circuit has been designed using the AMS 0.35 μm CMOS process and has been simulated using design kits for Synopsys and Cadence tools. Simulation results demonstrate how well the proposed circuit can alter synaptic weights according to the timing difference amongst a set of different patterns of spikes. Furthermore, the circuit is shown to give rise to a BCM-like learning rule, which is a rate-based rule. To mimic an implementation environment, a 1000 run Monte Carlo (MC) analysis was conducted on the proposed circuit. The presented MC simulation analysis and the simulation result from fine-tuned circuits show that it is possible to mitigate the effect of process variations in the proof of concept circuit; however, a practical variation aware design technique is required to promise a high circuit performance in a large scale neural network. We believe that the proposed design can play a significant role in future VLSI implementations of both spike timing and rate based neuromorphic learning systems.

  18. Activities of nicotinic acetylcholine receptors modulate neurotransmission and synaptic architecture

    Institute of Scientific and Technical Information of China (English)

    Akira Oda; Hidekazu Tanaka

    2014-01-01

    The cholinergic system is involved in a broad spectrum of brain function, and its failure has been implicated in Alzheimer’s disease. Acetylcholine transduces signals through muscarinic and nicotinic acetylcholine receptors, both of which inlfuence synaptic plasticity and cognition. However, the mechanisms that relate the rapid gating of nicotinic acetylcholine receptors to per-sistent changes in brain function have remained elusive. Recent evidence indicates that nicotinic acetylcholine receptors activities affect synaptic morphology and density, which result in per-sistent rearrangements of neural connectivity. Further investigations of the relationships between nicotinic acetylcholine receptors and rearrangements of neural circuitry in the central nervous system may help understand the pathogenesis of Alzheimer’s disease.

  19. Random synaptic feedback weights support error backpropagation for deep learning

    Science.gov (United States)

    Lillicrap, Timothy P.; Cownden, Daniel; Tweed, Douglas B.; Akerman, Colin J.

    2016-11-01

    The brain processes information through multiple layers of neurons. This deep architecture is representationally powerful, but complicates learning because it is difficult to identify the responsible neurons when a mistake is made. In machine learning, the backpropagation algorithm assigns blame by multiplying error signals with all the synaptic weights on each neuron's axon and further downstream. However, this involves a precise, symmetric backward connectivity pattern, which is thought to be impossible in the brain. Here we demonstrate that this strong architectural constraint is not required for effective error propagation. We present a surprisingly simple mechanism that assigns blame by multiplying errors by even random synaptic weights. This mechanism can transmit teaching signals across multiple layers of neurons and performs as effectively as backpropagation on a variety of tasks. Our results help reopen questions about how the brain could use error signals and dispel long-held assumptions about algorithmic constraints on learning.

  20. Regulation of information passing by synaptic transmission: a short review.

    Science.gov (United States)

    Di Maio, Vito

    2008-08-15

    The largest part of information passed among neurons in the brain occurs by the means of chemical synapses connecting the axons of presynaptic neurons to the dendritic tree of the postsynaptic ones. In the present paper, the most relevant open problems related to the mechanisms of control of the information passing among neurons by synaptic transmission will be shortly reviewed. The "cross talking" between synapses, their mutual interactions and the control of the information flow between different areas of the dendritic tree will be also considered. The threshold mechanism based on the "reversal potential" will be considered for its role in the control of information transfer among neurons and also for its contribution to the information flow among different areas of the dendritic tree and to the computational ability of the single neuron. The concept of "competition for plasticity" will be proposed as a mechanism of competition based on the synaptic activation time.

  1. Imperfect traveling chimera states induced by local synaptic gradient coupling

    Science.gov (United States)

    Bera, Bidesh K.; Ghosh, Dibakar; Banerjee, Tanmoy

    2016-07-01

    In this paper, we report the occurrence of chimera patterns in a network of neuronal oscillators, which are coupled through local, synaptic gradient coupling. We discover a new chimera pattern, namely the imperfect traveling chimera state, where the incoherent traveling domain spreads into the coherent domain of the network. Remarkably, we also find that chimera states arise even for one-way local coupling, which is in contrast to the earlier belief that only nonlocal, global, or nearest-neighbor local coupling can give rise to chimera state; this find further relaxes the essential connectivity requirement of getting a chimera state. We choose a network of identical bursting Hindmarsh-Rose neuronal oscillators, and we show that depending upon the relative strength of the synaptic and gradient coupling, several chimera patterns emerge. We map all the spatiotemporal behaviors in parameter space and identify the transitions among several chimera patterns, an in-phase synchronized state, and a global amplitude death state.

  2. Synaptic vesicle pools: an update

    Directory of Open Access Journals (Sweden)

    Annette Denker

    2010-10-01

    Full Text Available During the last few decades synaptic vesicles have been assigned to a variety of functional and morphological classes or pools. We have argued in the past (Rizzoli SO and Betz WJ, 2005, Synaptic vesicle pools, Nat. Rev. Neurosci. 6, 57-69 that synaptic activity in several preparations is accounted for by the function of three vesicle pools: the readily releasable pool (docked at active zones and ready to go upon stimulation, the recycling pool (scattered throughout the nerve terminals and recycling upon moderate stimulation, and finally the reserve pool (occupying most of the vesicle clusters and only recycling upon strong stimulation. We discuss here the advancements in the vesicle pool field which took place in the ensuing years, focusing on the behavior of different pools under both strong stimulation and physiological activity. Several new findings have enhanced the three-pool model, with, for example, the disparity between recycling and reserve vesicles being underlined by the observation that the former are mobile, while the latter are fixed. Finally, a number of altogether new concepts have also evolved such as the current controversy on the identity of the spontaneously recycling vesicle pool.

  3. Multiscale modeling and synaptic plasticity.

    Science.gov (United States)

    Bhalla, Upinder S

    2014-01-01

    Synaptic plasticity is a major convergence point for theory and computation, and the process of plasticity engages physiology, cell, and molecular biology. In its many manifestations, plasticity is at the hub of basic neuroscience questions about memory and development, as well as more medically themed questions of neural damage and recovery. As an important cellular locus of memory, synaptic plasticity has received a huge amount of experimental and theoretical attention. If computational models have tended to pick specific aspects of plasticity, such as STDP, and reduce them to an equation, some experimental studies are equally guilty of oversimplification each time they identify a new molecule and declare it to be the last word in plasticity and learning. Multiscale modeling begins with the acknowledgment that synaptic function spans many levels of signaling, and these are so tightly coupled that we risk losing essential features of plasticity if we focus exclusively on any one level. Despite the technical challenges and gaps in data for model specification, an increasing number of multiscale modeling studies have taken on key questions in plasticity. These have provided new insights, but importantly, they have opened new avenues for questioning. This review discusses a wide range of multiscale models in plasticity, including their technical landscape and their implications.

  4. Spike timing and synaptic dynamics at the awake thalamocortical synapse.

    Science.gov (United States)

    Swadlow, Harvey A; Bezdudnaya, Tatiana; Gusev, Alexander G

    2005-01-01

    column, (b) synaptic currents elicited by TC impulses with long preceding ISIs were greatly enhanced in both of these layers, and (c) the degree of this enhancement differed reliably among neighboring TC neurons but, for a given neuron, was very similar in layers 4 and 6. Thus, results generated by both methodological approaches are consistent with the presence of a chronic depression at the awake TC synapse that is relieved by long ISIs. Since long ISIs necessarily precede TC "bursts", our results are consistent with the notion that these events powerfully activate cortical circuits.

  5. Presynaptic active zone density during development and synaptic plasticity.

    Directory of Open Access Journals (Sweden)

    Gwenaëlle L Clarke

    2012-02-01

    Full Text Available Neural circuits transmit information through synapses, and the efficiency of synaptic transmission is closely related to the density of presynaptic active zones, where synaptic vesicles are released. The goal of this review is to highlight recent insights into the molecular mechanisms that control the number of active zones per presynaptic terminal (active zone density during developmental and stimulus-dependent changes in synaptic efficacy. At the neuromuscular junctions (NMJs, the active zone density is preserved across species, remains constant during development, and is the same between synapses with different activities. However, the NMJ active zones are not always stable, as exemplified by the change in active zone density during acute experimental manipulation or as a result of aging. Therefore, a mechanism must exist to maintain its density. In the central nervous system (CNS, active zones have restricted maximal size, exist in multiple numbers in larger presynaptic terminals, and maintain a constant density during development. These findings suggest that active zone density in the CNS is also controlled. However, in contrast to the NMJ, active zone density in the CNS can also be increased, as observed in hippocampal synapses in response to synaptic plasticity. Although the numbers of known active zone proteins and protein interactions have increased, less is known about the mechanism that controls the number or spacing of active zones. The following molecules are known to control active zone density and will be discussed herein: extracellular matrix laminins and voltage-dependent calcium channels, amyloid precursor proteins, the small GTPase Rab3, an endocytosis mechanism including synaptojanin, cytoskeleton protein spectrins and β-adducin, and a presynaptic web including spectrins. The molecular mechanisms that organize the active zone density are just beginning to be elucidated.

  6. Radiation-hardened transistor and integrated circuit

    Science.gov (United States)

    Ma, Kwok K.

    2007-11-20

    A composite transistor is disclosed for use in radiation hardening a CMOS IC formed on an SOI or bulk semiconductor substrate. The composite transistor has a circuit transistor and a blocking transistor connected in series with a common gate connection. A body terminal of the blocking transistor is connected only to a source terminal thereof, and to no other connection point. The blocking transistor acts to prevent a single-event transient (SET) occurring in the circuit transistor from being coupled outside the composite transistor. Similarly, when a SET occurs in the blocking transistor, the circuit transistor prevents the SET from being coupled outside the composite transistor. N-type and P-type composite transistors can be used for each and every transistor in the CMOS IC to radiation harden the IC, and can be used to form inverters and transmission gates which are the building blocks of CMOS ICs.

  7. Analogue Square Root Calculator Circuit Designed With Logarithmic Amplifiers

    OpenAIRE

    2016-01-01

    In many applications, it has been necessary to calculate square roots of some numbers which are correspond to some voltages values. In this study such an analogue calculator has been designed and simulated in computer medium. Circuit consist of one logarithmic and one antilogarithmic amplifier connected in cascade. The component values of circuit chosen so that the output voltage of circuit is equal to square root of input voltage. The performance of designed circuit is investigated by applyi...

  8. Molecular underpinnings of synaptic vesicle pool heterogeneity.

    Science.gov (United States)

    Crawford, Devon C; Kavalali, Ege T

    2015-04-01

    Neuronal communication relies on chemical synaptic transmission for information transfer and processing. Chemical neurotransmission is initiated by synaptic vesicle fusion with the presynaptic active zone resulting in release of neurotransmitters. Classical models have assumed that all synaptic vesicles within a synapse have the same potential to fuse under different functional contexts. In this model, functional differences among synaptic vesicle populations are ascribed to their spatial distribution in the synapse with respect to the active zone. Emerging evidence suggests, however, that synaptic vesicles are not a homogenous population of organelles, and they possess intrinsic molecular differences and differential interaction partners. Recent studies have reported a diverse array of synaptic molecules that selectively regulate synaptic vesicles' ability to fuse synchronously and asynchronously in response to action potentials or spontaneously irrespective of action potentials. Here we discuss these molecular mediators of vesicle pool heterogeneity that are found on the synaptic vesicle membrane, on the presynaptic plasma membrane, or within the cytosol and consider some of the functional consequences of this diversity. This emerging molecular framework presents novel avenues to probe synaptic function and uncover how synaptic vesicle pools impact neuronal signaling.

  9. Excitatory Post-Synaptic Potential Mimicked in Indium-Zinc-Oxide Synaptic Transistors Gated by Methyl Cellulose Solid Electrolyte

    Science.gov (United States)

    Guo, Liqiang; Wen, Juan; Ding, Jianning; Wan, Changjin; Cheng, Guanggui

    2016-12-01

    The excitatory postsynaptic potential (EPSP) of biological synapses is mimicked in indium-zinc-oxide synaptic transistors gated by methyl cellulose solid electrolyte. These synaptic transistors show excellent electrical performance at an operating voltage of 0.8 V, Ion/off ratio of 2.5 × 106, and mobility of 38.4 cm2/Vs. After this device is connected to a resistance of 4 MΩ in series, it exhibits excellent characteristics as an inverter. A threshold potential of 0.3 V is achieved by changing the gate pulse amplitude, width, or number, which is analogous to biological EPSP.

  10. Analog circuit design designing dynamic circuit response

    CERN Document Server

    Feucht, Dennis

    2010-01-01

    This second volume, Designing Dynamic Circuit Response builds upon the first volume Designing Amplifier Circuits by extending coverage to include reactances and their time- and frequency-related behavioral consequences.

  11. Analog circuit design designing waveform processing circuits

    CERN Document Server

    Feucht, Dennis

    2010-01-01

    The fourth volume in the set Designing Waveform-Processing Circuits builds on the previous 3 volumes and presents a variety of analog non-amplifier circuits, including voltage references, current sources, filters, hysteresis switches and oscilloscope trigger and sweep circuitry, function generation, absolute-value circuits, and peak detectors.

  12. Sexual modulation of sex-shared neurons and circuits in Caenorhabditis elegans.

    Science.gov (United States)

    Portman, Douglas S

    2017-01-02

    Studies using the nematode C. elegans have provided unique insights into the development and function of sex differences in the nervous system. Enabled by the relative simplicity of this species, comprehensive studies have solved the complete cellular neuroanatomy of both sexes as well as the complete neural connectomes of the entire adult hermaphrodite and the adult male tail. This work, together with detailed behavioral studies, has revealed three aspects of sex differences in the nervous system: sex-specific neurons and circuits; circuits with sexually dimorphic synaptic connectivity; and sex differences in the physiology and functions of shared neurons and circuits. At all of these levels, biological sex influences neural development and function through the activity of a well-defined genetic hierarchy that acts throughout the body to translate chromosomal sex into the state of a master autosomal regulator of sexual differentiation, the transcription factor TRA-1A. This Review focuses on the role of genetic sex in implementing sex differences in shared neurons and circuits, with an emphasis on linking the sexual modulation of specific neural properties to the specification and optimization of sexually divergent and dimorphic behaviors. An important and unexpected finding from these studies is that chemosensory neurons are a primary focus of sexual modulation, with genetic sex adaptively shaping chemosensory repertoire to guide behavioral choice. Importantly, hormone-independent functions of genetic sex are the principal drivers of all of these sex differences, making nematodes an excellent model for understanding similar but poorly understood mechanisms that likely act throughout the animal kingdom. © 2016 Wiley Periodicals, Inc.

  13. Creation of defined single cell resolution neuronal circuits on microelectrode arrays

    Science.gov (United States)

    Pirlo, Russell Kirk

    2009-12-01

    The way cell-cell organization of neuronal networks influences activity and facilitates function is not well understood. Microelectrode arrays (MEAs) and advancing cell patterning technologies have enabled access to and control of in vitro neuronal networks spawning much new research in neuroscience and neuroengineering. We propose that small, simple networks of neurons with defined circuitry may serve as valuable research models where every connection can be analyzed, controlled and manipulated. Towards the goal of creating such neuronal networks we have applied microfabricated elastomeric membranes, surface modification and our unique laser cell patterning system to create defined neuronal circuits with single-cell precision on MEAs. Definition of synaptic connectivity was imposed by the 3D physical constraints of polydimethylsiloxane elastomeric membranes. The membranes had 20mum clear-through holes and 2-3mum deep channels which when applied to the surface of the MEA formed microwells to confine neurons to electrodes connected via shallow tunnels to direct neurite outgrowth. Tapering and turning of channels was used to influence neurite polarity. Biocompatibility of the membranes was increased by vacuum baking, oligomer extraction, and autoclaving. Membranes were bound to the MEA by oxygen plasma treatment and heated pressure. The MEA/membrane surface was treated with oxygen plasma, poly-D-lysine and laminin to improve neuron attachment, survival and neurite outgrowth. Prior to cell patterning the outer edge of culture area was seeded with 5x10 5 cells per cm and incubated for 2 days. Single embryonic day 7 chick forebrain neurons were then patterned into the microwells and onto the electrodes using our laser cell patterning system. Patterned neurons successfully attached to and were confined to the electrodes. Neurites extended through the interconnecting channels and connected with adjacent neurons. These results demonstrate that neuronal circuits can be

  14. Addiction therapy. Refining deep brain stimulation to emulate optogenetic treatment of synaptic pathology.

    Science.gov (United States)

    Creed, Meaghan; Pascoli, Vincent Jean; Lüscher, Christian

    2015-02-06

    Circuit remodeling driven by pathological forms of synaptic plasticity underlies several psychiatric diseases, including addiction. Deep brain stimulation (DBS) has been applied to treat a number of neurological and psychiatric conditions, although its effects are transient and mediated by largely unknown mechanisms. Recently, optogenetic protocols that restore normal transmission at identified synapses in mice have provided proof of the idea that cocaine-adaptive behavior can be reversed in vivo. The most efficient protocol relies on the activation of metabotropic glutamate receptors, mGluRs, which depotentiates excitatory synaptic inputs onto dopamine D1 receptor medium-sized spiny neurons and normalizes drug-adaptive behavior. We discovered that acute low-frequency DBS, refined by selective blockade of dopamine D1 receptors, mimics optogenetic mGluR-dependent normalization of synaptic transmission. Consequently, there was a long-lasting abolishment of behavioral sensitization.

  15. Characterization of emergent synaptic topologies in noisy neural networks

    Science.gov (United States)

    Miller, Aaron James

    Learned behaviors are one of the key contributors to an animal's ultimate survival. It is widely believed that the brain's microcircuitry undergoes structural changes when a new behavior is learned. In particular, motor learning, during which an animal learns a sequence of muscular movements, often requires precisely-timed coordination between muscles and becomes very natural once ingrained. Experiments show that neurons in the motor cortex exhibit precisely-timed spike activity when performing a learned motor behavior, and constituent stereotypical elements of the behavior can last several hundred milliseconds. The subject of this manuscript concerns how organized synaptic structures that produce stereotypical spike sequences emerge from random, dynamical networks. After a brief introduction in Chapter 1, we begin Chapter 2 by introducing a spike-timing-dependent plasticity (STDP) rule that defines how the activity of the network drives changes in network topology. The rule is then applied to idealized networks of leaky integrate-and-fire neurons (LIF). These neurons are not subjected to the variability that typically characterize neurons in vivo. In noiseless networks, synapses develop closed loops of strong connectivity that reproduce stereotypical, precisely-timed spike patterns from an initially random network. We demonstrate the characteristics of the asymptotic synaptic configuration are dependent on the statistics of the initial random network. The spike timings of the neurons simulated in Chapter 2 are generated exactly by a computationally economical, nonlinear mapping which is extended to LIF neurons injected with fluctuating current in Chapter 3. Development of an economical mapping that incorporates noise provides a practical solution to the long simulation times required to produce asymptotic synaptic topologies in networks with STDP in the presence of realistic neuronal variability. The mapping relies on generating numerical solutions to the dynamics

  16. Strategies for mapping synaptic inputs on dendrites in vivo by combining two-photon microscopy, sharp intracellular recording and pharmacology

    Directory of Open Access Journals (Sweden)

    Manuel eLevy

    2012-12-01

    Full Text Available Uncovering the functional properties of individual synaptic inputs on single neurons is critical for understanding the computational role of synapses and dendrites. Previous studies combined whole-cell patch recording to load neurons with a fluorescent calcium indicator and two-photon imaging to map subcellular changes in fluorescence upon sensory stimulation. By hyperpolarizing the neuron below spike threshold, the patch electrode ensured that changes in fluorescence associated with synaptic events were isolated from those caused by back-propagating action potentials. This technique holds promise for determining whether the existence of unique cortical feature maps across different species may be associated with distinct wiring diagrams. However, the use of whole-cell patch for mapping inputs on dendrites is challenging in large mammals, due to brain pulsations and the accumulation of fluorescent dye in the extracellular milieu. Alternatively, sharp intracellular electrodes have been used to label neurons with fluorescent dyes, but the current passing capabilities of these high impedance electrodes may be insufficient to prevent spiking. In this study, we tested whether sharp electrode recording is suitable for mapping functional inputs on dendrites in the cat visual cortex. We compared three different strategies for suppressing visually evoked spikes: (1 hyperpolarization by intracellular current injection, (2 pharmacological blockade of voltage-gated sodium channels by intracellular QX-314, and (3 GABA iontophoresis from a perisomatic electrode glued to the intracellular electrode. We found that functional inputs on dendrites could be successfully imaged using all three strategies. However, the best method for preventing spikes was GABA iontophoresis with low currents (5 to 10 nA, which minimally affected the local circuit. Our methods advance the possibility of determining functional connectivity in preparations where whole-cell patch may be

  17. Physiological expression of olfactory discrimination rule learning balances whole-population modulation and circuit stability in the piriform cortex network.

    Science.gov (United States)

    Jammal, Luna; Whalley, Ben; Ghosh, Sourav; Lamrecht, Raphael; Barkai, Edi

    2016-07-01

    Once trained, rats are able to execute particularly difficult olfactory discrimination tasks with exceptional accuracy. Such skill acquisition, termed "rule learning", is accompanied by a series of long-lasting modifications to three cellular properties which modulate pyramidal neuron activity in piriform cortex; intrinsic excitability, synaptic excitation, and synaptic inhibition. Here, we explore how these changes, which are seemingly contradictory at the single-cell level in terms of their effect on neuronal excitation, are manifested within the piriform cortical neuronal network to store the memory of the rule, while maintaining network stability. To this end, we monitored network activity via multisite extracellular recordings of field postsynaptic potentials (fPSPS) and with single-cell recordings of miniature inhibitory and excitatory synaptic events in piriform cortex slices. We show that although 5 days after rule learning the cortical network maintains its basic activity patterns, synaptic connectivity is strengthened specifically between spatially proximal cells. Moreover, while the enhancement of inhibitory and excitatory synaptic connectivity is nearly identical, strengthening of synaptic inhibition is equally distributed between neurons while synaptic excitation is particularly strengthened within a specific subgroup of cells. We suggest that memory for the acquired rule is stored mainly by strengthening excitatory synaptic connection between close pyramidal neurons and runaway synaptic activity arising from this change is prevented by a nonspecific enhancement of synaptic inhibition.

  18. A singularity in Kirchhoff’s circuit equations

    Science.gov (United States)

    Sree Harsha, N. R.

    2016-09-01

    Students often have difficulty in understanding qualitatively the behavior of simple electric circuits. In particular, as different studies have shown, they find multiple batteries connected in multiple loops difficult to analyze. In a recent paper, Sree Harsha et al (2015 Phys. Educ. 50 568), we showed such an electric circuit, which consists of ideal batteries connected in parallel, that could not be solved by the existing circuit analysis methods. In this paper, we shall introduce a new mathematical method for solving simple electric circuits from the solutions of more general circuits and show that the currents, in this particular circuit, take the indeterminate 0/0 form. We shall also present some of the implications of teaching the method. We believe that the description presented in this paper should help instructors in teaching the behavior of multiple batteries connected in parallel.

  19. Defining inhibitory neurone function in respiratory circuits: opportunities with optogenetics?

    Science.gov (United States)

    Abdala, Ana Paula; Paton, Julian F R; Smith, Jeffrey C

    2015-07-15

    Pharmacological and mathematical modelling studies support the view that synaptic inhibition in mammalian brainstem respiratory circuits is essential for generating normal and stable breathing movements. GABAergic and glycinergic neurones are known components of these circuits but their precise functional roles have not been established, especially within key microcircuits of the respiratory pre-Bötzinger (pre-BötC) and Bötzinger (BötC) complexes involved in phasic control of respiratory pump and airway muscles. Here, we review briefly current concepts of relevant complexities of inhibitory synapses and the importance of synaptic inhibition in the operation of these microcircuits. We highlight results and limitations of classical pharmacological studies that have suggested critical functions of synaptic inhibition. We then explore the potential opportunities for optogenetic strategies that represent a promising new approach for interrogating function of inhibitory circuits, including a hypothetical wish list for optogenetic approaches to allow expedient application of this technology. We conclude that recent technical advances in optogenetics should provide a means to understand the role of functionally select and regionally confined subsets of inhibitory neurones in key respiratory circuits such as those in the pre-BötC and BötC.

  20. Wnts in adult brain: from synaptic plasticity to cognitive deficiencies

    Science.gov (United States)

    Oliva, Carolina A.; Vargas, Jessica Y.; Inestrosa, Nibaldo C.

    2013-01-01

    During development of the central nervous system the Wnt signaling pathway has been implicated in a wide spectrum of physiological processes, including neuronal connectivity and synapse formation. Wnt proteins and components of the Wnt pathway are expressed in the brain since early development to the adult life, however, little is known about its role in mature synapses. Here, we review evidences indicating that Wnt proteins participate in the remodeling of pre- and post-synaptic regions, thus modulating synaptic function. We include the most recent data in the literature showing that Wnts are constantly released in the brain to maintain the basal neural activity. Also, we review the evidences that involve components of the Wnt pathway in the development of neurological and mental disorders, including a special emphasis on in vivo studies that relate behavioral abnormalities to deficiencies in Wnt signaling. Finally, we include the evidences that support a neuroprotective role of Wnt proteins in Alzheimer’s disease. We postulate that deregulation in Wnt signaling might have a fundamental role in the origin of neurological diseases, by altering the synaptic function at stages where the phenotype is not yet established but when the cognitive decline starts. PMID:24348327

  1. Grounding and shielding circuits and interference

    CERN Document Server

    Morrison, Ralph

    2016-01-01

    Applies basic field behavior in circuit design and demonstrates how it relates to grounding and shielding requirements and techniques in circuit design This book connects the fundamentals of electromagnetic theory to the problems of interference in all types of electronic design. The text covers power distribution in facilities, mixing of analog and digital circuitry, circuit board layout at high clock rates, and meeting radiation and susceptibility standards. The author examines the grounding and shielding requirements and techniques in circuit design and applies basic physics to circuit behavior. The sixth edition of this book has been updated with new material added throughout the chapters where appropriate. The presentation of the book has also been rearranged in order to reflect the current trends in the field.

  2. Solid-state circuits

    CERN Document Server

    Pridham, G J

    2013-01-01

    Solid-State Circuits provides an introduction to the theory and practice underlying solid-state circuits, laying particular emphasis on field effect transistors and integrated circuits. Topics range from construction and characteristics of semiconductor devices to rectification and power supplies, low-frequency amplifiers, sine- and square-wave oscillators, and high-frequency effects and circuits. Black-box equivalent circuits of bipolar transistors, physical equivalent circuits of bipolar transistors, and equivalent circuits of field effect transistors are also covered. This volume is divided

  3. Simple Autonomous Chaotic Circuits

    Science.gov (United States)

    Piper, Jessica; Sprott, J.

    2010-03-01

    Over the last several decades, numerous electronic circuits exhibiting chaos have been proposed. Non-autonomous circuits with as few as two components have been developed. However, the operation of such circuits relies on the non-ideal behavior of the devices used, and therefore the circuit equations can be quite complex. In this paper, we present two simple autonomous chaotic circuits using only opamps and linear passive components. The circuits each use one opamp as a comparator, to provide a signum nonlinearity. The chaotic behavior is robust, and independent of nonlinearities in the passive components. Moreover, the circuit equations are among the algebraically simplest chaotic systems yet constructed.

  4. Circuit analysis for dummies

    CERN Document Server

    Santiago, John

    2013-01-01

    Circuits overloaded from electric circuit analysis? Many universities require that students pursuing a degree in electrical or computer engineering take an Electric Circuit Analysis course to determine who will ""make the cut"" and continue in the degree program. Circuit Analysis For Dummies will help these students to better understand electric circuit analysis by presenting the information in an effective and straightforward manner. Circuit Analysis For Dummies gives you clear-cut information about the topics covered in an electric circuit analysis courses to help

  5. The kinase activity of EphA4 mediates homeostatic scaling-down of synaptic strength via activation of Cdk5.

    Science.gov (United States)

    Peng, Yi-Rong; Hou, Zai-Hua; Yu, Xiang

    2013-02-01

    Neurons within a network have the ability to homeostatically scale-down their excitatory synaptic strength under conditions of persistent neuronal activity elevation, a process pivotal to neural circuit stability. How this homeostatic regulation is achieved at the molecular level in developing neural circuits, which face gradually elevated neuronal activity as part of circuit wiring, is not well-understood. Using dissociated hippocampal neuronal cultures, we identified a critical and cell autonomous role for the receptor tyrosine kinase EphA4 in mediating activity-induced homeostatic down-regulation of excitatory synaptic strength. Reducing the endogenous level of EphA4 in individual neurons by RNAi effectively blocked activity-induced scaling-down of excitatory synaptic strength, while co-transfection of RNAi resistant EphA4 rescued this effect. Furthermore, interfering with EphA4 forward signaling using EphA4-Fc blocked activity-induced homeostatic synaptic scaling-down, while direct activation of EphA4 with its ligand EphrinA1 weakened excitatory synaptic strength. Up- or down-regulating EphA4 function in individual neurons also did not affect the density of excitatory synapses. The kinase activities of EphA4 and its downstream effector Cdk5 were both required for homeostatic synaptic scaling, as overexpression of EphA4 with constitutively active kinase activity reduced excitatory synaptic strength, while interfering with either the kinase activity of EphA4 or Cdk5 blocked activity-induced synaptic scaling. Consistently, the activities of EphA4 and Cdk5 increased significantly during global and persistent activity elevation. Together, our work demonstrated that the kinase activity of EphA4, via activation of downstream Cdk5 activity, mediates the scaling-down of excitatory synaptic strength under conditions of global activity elevation.

  6. Starting Circuit For Erasable Programmable Logic Device

    Science.gov (United States)

    Cole, Steven W.

    1990-01-01

    Voltage regulator bypassed to supply starting current. Starting or "pullup" circuit supplies large inrush of current required by erasable programmable logic device (EPLD) while being turned on. Operates only during such intervals of high demand for current and has little effect any other time. Performs needed bypass, acting as current-dependent shunt connecting battery or other source of power more nearly directly to EPLD. Input capacitor of regulator removed when starting circuit installed, reducing probability of damage to transistor in event of short circuit in or across load.

  7. Synaptic and Cellular Organization of Layer 1 of the Developing Rat Somatosensory Cortex

    Directory of Open Access Journals (Sweden)

    Shruti eMuralidhar

    2014-01-01

    Full Text Available We have performed a systematic and quantitative study of the neuronal and synaptic organisation of neocortical layer 1 in the somatosensory cortex in juvenile rats (P13 – P16 using multi-neuron patch-clamp and 3D morphology reconstructions. We used both subjective expert based and objective classification to establish distinct morphological groups. According to expert based subjective classification, the neurons were classified into six morphological types: (1 the dense axon neurogliaform cell (NGC-DA and (2 a sparse axon neurogliaform cell (NGC-SA, (3 the horizontal axon cell (HAC and (4 those with descending axonal colaterals (DAC, (5 the large axon cell (LAC and (6 the small axon cell (SAC. We also used objective supervised and unsupervised analyses that confirmed 4 out of the 6 expert proposed groups, namely, DAC, HAC, LAC and a combined NGC. The cells were also classified into 5 electrophysiological types based on the Petilla convention; classical non-adapting (cNAC, burst non-adapting (bNAC, classical adapting (cAC, classical stuttering (cSTUT and classical irregular spiking (cIR. The most common electrophysiological type was the cNAC type (40% and the most commonly encountered morpho-electrical type of neuron was the NGC-DA - cNAC. Layer 1 cells are connected by GABAergic inhibitory synaptic connections with a 7.9% connection probability, as well gap junctions with 5.2% connection probability. Most synaptic connections were mediated by both GABAA and GABAB receptors (62.6%, as observed from the response characteristics to single pulse and train stimulations. A smaller fraction of synaptic connections were mediated exclusively by GABAA (15.4% or GABAB (21.8% receptors. Based on the morphological reconstructions, we found multi-synapse connections with an average of 9 putative synapses per connection. These putative touches were widely distributed with 39% on somata and 61% on dendrites.

  8. Solenoid-Simulation Circuit

    Science.gov (United States)

    Simon, R. A.

    1986-01-01

    Electrical properties of solenoids imitated for tests of control circuits. Simulation circuit imitates voltage and current responses of two engine-controlling solenoids. Used in tests of programs of digital engine-control circuits, also provides electronic interface with circuits imitating electrical properties of pressure sensors and linear variable-differential transformers. Produces voltages, currents, delays, and discrete turnon and turnoff signals representing operation of solenoid in engine-control relay. Many such circuits used simulating overall engine circuitry.

  9. Spontaneous Vesicle Recycling in the Synaptic Bouton

    Directory of Open Access Journals (Sweden)

    Sven eTruckenbrodt

    2014-12-01

    Full Text Available The trigger for synaptic vesicle exocytosis is Ca2+, which enters the synaptic bouton following action potential stimulation. However, spontaneous release of neurotransmitter also occurs in the absence of stimulation in virtually all synaptic boutons. It has long been thought that this represents exocytosis driven by fluctuations in local Ca2+ levels. The vesicles responding to these fluctuations are thought to be the same ones that release upon stimulation, albeit potentially triggered by different Ca2+ sensors. This view has been challenged by several recent works, which have suggested that spontaneous release is driven by a separate pool of synaptic vesicles. Numerous articles appeared during the last few years in support of each of these hypotheses, and it has been challenging to bring them into accord. We speculate here on the origins of this controversy, and propose a solution that is related to developmental effects. Constitutive membrane traffic, needed for the biogenesis of vesicles and synapses, is responsible for high levels of spontaneous membrane fusion in young neurons, probably independent of Ca2+. The vesicles releasing spontaneously in such neurons are not related to other synaptic vesicle pools and may represent constitutively releasing vesicles (CRVs rather than bona fide synaptic vesicles. In mature neurons, constitutive traffic is much dampened, and the few remaining spontaneous release events probably represent bona fide spontaneously releasing synaptic vesicles (SRSVs responding to Ca2+ fluctuations, along with a handful of CRVs that participate in synaptic vesicle turnover.

  10. Spontaneous vesicle recycling in the synaptic bouton.

    Science.gov (United States)

    Truckenbrodt, Sven; Rizzoli, Silvio O

    2014-01-01

    The trigger for synaptic vesicle exocytosis is Ca(2+), which enters the synaptic bouton following action potential stimulation. However, spontaneous release of neurotransmitter also occurs in the absence of stimulation in virtually all synaptic boutons. It has long been thought that this represents exocytosis driven by fluctuations in local Ca(2+) levels. The vesicles responding to these fluctuations are thought to be the same ones that release upon stimulation, albeit potentially triggered by different Ca(2+) sensors. This view has been challenged by several recent works, which have suggested that spontaneous release is driven by a separate pool of synaptic vesicles. Numerous articles appeared during the last few years in support of each of these hypotheses, and it has been challenging to bring them into accord. We speculate here on the origins of this controversy, and propose a solution that is related to developmental effects. Constitutive membrane traffic, needed for the biogenesis of vesicles and synapses, is responsible for high levels of spontaneous membrane fusion in young neurons, probably independent of Ca(2+). The vesicles releasing spontaneously in such neurons are not related to other synaptic vesicle pools and may represent constitutively releasing vesicles (CRVs) rather than bona fide synaptic vesicles. In mature neurons, constitutive traffic is much dampened, and the few remaining spontaneous release events probably represent bona fide spontaneously releasing synaptic vesicles (SRSVs) responding to Ca(2+) fluctuations, along with a handful of CRVs that participate in synaptic vesicle turnover.

  11. Polynomial threshold functions and Boolean threshold circuits

    DEFF Research Database (Denmark)

    Hansen, Kristoffer Arnsfelt; Podolskii, Vladimir V.

    2013-01-01

    We study the complexity of computing Boolean functions on general Boolean domains by polynomial threshold functions (PTFs). A typical example of a general Boolean domain is 12n . We are mainly interested in the length (the number of monomials) of PTFs, with their degree and weight being...... of secondary interest. We show that PTFs on general Boolean domains are tightly connected to depth two threshold circuits. Our main results in regard to this connection are: PTFs of polynomial length and polynomial degree compute exactly the functions computed by THRMAJ circuits. An exponential length lower...

  12. Connected Traveler

    Energy Technology Data Exchange (ETDEWEB)

    Schroeder, Alex

    2015-11-01

    The Connected Traveler project is a multi-disciplinary undertaking that seeks to validate potential for transformative transportation system energy savings by incentivizing efficient traveler behavior. This poster outlines various aspects of the Connected Traveler project, including market opportunity, understanding traveler behavior and decision-making, automation and connectivity, and a projected timeline for Connected Traveler's key milestones.

  13. An optogenetics- and imaging-assisted simultaneous multiple patch-clamp recording system for decoding complex neural circuits.

    Science.gov (United States)

    Wang, Guangfu; Wyskiel, Daniel R; Yang, Weiguo; Wang, Yiqing; Milbern, Lana C; Lalanne, Txomin; Jiang, Xiaolong; Shen, Ying; Sun, Qian-Quan; Zhu, J Julius

    2015-03-01

    Deciphering neuronal circuitry is central to understanding brain function and dysfunction, yet it remains a daunting task. To facilitate the dissection of neuronal circuits, a process requiring functional analysis of synaptic connections and morphological identification of interconnected neurons, we present here a method for stable simultaneous octuple patch-clamp recordings. This method allows physiological analysis of synaptic interconnections among 4-8 simultaneously recorded neurons and/or 10-30 sequentially recorded neurons, and it allows anatomical identification of >85% of recorded interneurons and >99% of recorded principal neurons. We describe how to apply the method to rodent tissue slices; however, it can be used on other model organisms. We also describe the latest refinements and optimizations of mechanics, electronics, optics and software programs that are central to the realization of a combined single- and two-photon microscopy-based, optogenetics- and imaging-assisted, stable, simultaneous quadruple-viguple patch-clamp recording system. Setting up the system, from the beginning of instrument assembly and software installation to full operation, can be completed in 3-4 d.

  14. Cannabinoids modulate spontaneous synaptic activity in retinal ganglion cells.

    Science.gov (United States)

    Middleton, T P; Protti, D A

    2011-09-01

    The endocannabinoid (ECB) system has been found throughout the central nervous system and modulates cell excitability in various forms of short-term plasticity. ECBs and their receptors have also been localized to all retinal cells, and cannabinoid receptor activation has been shown to alter voltage-dependent conductances in several different retinal cell types, suggesting a possible role for cannabinoids in retinal processing. Their effects on synaptic transmission in the mammalian retina, however, have not been previously investigated. Here, we show that exogenous cannabinoids alter spontaneous synaptic transmission onto retinal ganglion cells (RGCs). Using whole-cell voltage-clamp recordings in whole-mount retinas, we measured spontaneous postsynaptic currents (SPSCs) in RGCs in adult and young (P14-P21) mice. We found that the addition of an exogenous cannabinoid agonist, WIN55212-2 (5 μM), caused a significant reversible reduction in the frequency of SPSCs. This change, however, did not alter the kinetics of the SPSCs, indicating a presynaptic locus of action. Using blockers to isolate inhibitory or excitatory currents, we found that cannabinoids significantly reduced the release probability of both GABA and glutamate, respectively. While the addition of cannabinoids reduced the frequency of both GABAergic and glutamatergic SPSCs in both young and adult mice, we found that the largest effect was on GABA-mediated currents in young mice. These results suggest that the ECB system may potentially be involved in the modulation of signal transmission in the retina. Furthermore, they suggest that it might play a role in the developmental maturation of synaptic circuits, and that exogenous cannabinoids are likely able to disrupt retinal processing and consequently alter vision.

  15. Synaptic control of motoneuronal excitability

    DEFF Research Database (Denmark)

    Rekling, J C; Funk, G D; Bayliss, D A

    2000-01-01

    Movement, the fundamental component of behavior and the principal extrinsic action of the brain, is produced when skeletal muscles contract and relax in response to patterns of action potentials generated by motoneurons. The processes that determine the firing behavior of motoneurons are therefore......, and membrane properties, both passive and active. We then describe the general anatomical organization of synaptic input to motoneurons, followed by a description of the major transmitter systems that affect motoneuronal excitability, including ligands, receptor distribution, pre- and postsynaptic actions...... and norepinephrine, and neuropeptides, as well as the glutamate and GABA acting at metabotropic receptors, modulate motoneuronal excitability through pre- and postsynaptic actions. Acting principally via second messenger systems, their actions converge on common effectors, e.g., leak K(+) current, cationic inward...

  16. Microglia and Spinal Cord Synaptic Plasticity in Persistent Pain

    Directory of Open Access Journals (Sweden)

    Sarah Taves

    2013-01-01

    Full Text Available Microglia are regarded as macrophages in the central nervous system (CNS and play an important role in neuroinflammation in the CNS. Microglial activation has been strongly implicated in neurodegeneration in the brain. Increasing evidence also suggests an important role of spinal cord microglia in the genesis of persistent pain, by releasing the proinflammatory cytokines tumor necrosis factor-alpha (TNFα, Interleukine-1beta (IL-1β, and brain derived neurotrophic factor (BDNF. In this review, we discuss the recent findings illustrating the importance of microglial mediators in regulating synaptic plasticity of the excitatory and inhibitory pain circuits in the spinal cord, leading to enhanced pain states. Insights into microglial-neuronal interactions in the spinal cord dorsal horn will not only further our understanding of neural plasticity but may also lead to novel therapeutics for chronic pain management.

  17. Memristor-based neural networks: Synaptic versus neuronal stochasticity

    KAUST Repository

    Naous, Rawan

    2016-11-02

    In neuromorphic circuits, stochasticity in the cortex can be mapped into the synaptic or neuronal components. The hardware emulation of these stochastic neural networks are currently being extensively studied using resistive memories or memristors. The ionic process involved in the underlying switching behavior of the memristive elements is considered as the main source of stochasticity of its operation. Building on its inherent variability, the memristor is incorporated into abstract models of stochastic neurons and synapses. Two approaches of stochastic neural networks are investigated. Aside from the size and area perspective, the impact on the system performance, in terms of accuracy, recognition rates, and learning, among these two approaches and where the memristor would fall into place are the main comparison points to be considered.

  18. Hidden circuits and argumentation

    Science.gov (United States)

    Leinonen, Risto; Kesonen, Mikko H. P.; Hirvonen, Pekka E.

    2016-11-01

    Despite the relevance of DC circuits in everyday life and schools, they have been shown to cause numerous learning difficulties at various school levels. In the course of this article, we present a flexible method for teaching DC circuits at lower secondary level. The method is labelled as hidden circuits, and the essential idea underlying hidden circuits is in hiding the actual wiring of DC circuits, but to make their behaviour evident for pupils. Pupils are expected to find out the wiring of the circuit which should enhance their learning of DC circuits. We present two possible ways to utilise hidden circuits in a classroom. First, they can be used to test and enhance pupils’ conceptual understanding when pupils are expected to find out which one of the offered circuit diagram options corresponds to the actual circuit shown. This method aims to get pupils to evaluate the circuits holistically rather than locally, and as a part of that aim this method highlights any learning difficulties of pupils. Second, hidden circuits can be used to enhance pupils’ argumentation skills with the aid of argumentation sheet that illustrates the main elements of an argument. Based on the findings from our co-operating teachers and our own experiences, hidden circuits offer a flexible and motivating way to supplement teaching of DC circuits.

  19. Synaptic mechanisms underlying sparse coding of active touch.

    Science.gov (United States)

    Crochet, Sylvain; Poulet, James F A; Kremer, Yves; Petersen, Carl C H

    2011-03-24

    Sensory information is actively gathered by animals, but the synaptic mechanisms driving neuronal circuit function during active sensory processing are poorly understood. Here, we investigated the synaptically driven membrane potential dynamics during active whisker sensation using whole-cell recordings from layer 2/3 pyramidal neurons in the primary somatosensory barrel cortex of behaving mice. Although whisker contact with an object evoked rapid depolarization in all neurons, these touch responses only drove action potentials in ∼10% of the cells. Such sparse coding was ensured by cell-specific reversal potentials of the touch-evoked response that were hyperpolarized relative to action potential threshold for most neurons. Intercontact interval profoundly influenced touch-evoked postsynaptic potentials, interestingly without affecting the peak membrane potential of the touch response. Dual whole-cell recordings indicated highly correlated membrane potential dynamics during active touch. Sparse action potential firing within synchronized cortical layer 2/3 microcircuits therefore appears to robustly signal each active touch response.

  20. Compensating for thalamocortical synaptic loss in Alzheimer's disease.

    Science.gov (United States)

    Abuhassan, Kamal; Coyle, Damien; Maguire, Liam

    2014-01-01

    The study presents a thalamocortical network model which oscillates within the alpha frequency band (8-13 Hz) as recorded in the wakeful relaxed state with closed eyes to study the neural causes of abnormal oscillatory activity in Alzheimer's disease (AD). Incorporated within the model are various types of cortical excitatory and inhibitory neurons, recurrently connected to thalamic and reticular thalamic regions with the ratios and distances derived from the mammalian thalamocortical system. The model is utilized to study the impacts of four types of connectivity loss on the model's spectral dynamics. The study focuses on investigating degeneration of corticocortical, thalamocortical, corticothalamic, and corticoreticular couplings, with an emphasis on the influence of each modeled case on the spectral output of the model. Synaptic compensation has been included in each model to examine the interplay between synaptic deletion and compensation mechanisms, and the oscillatory activity of the network. The results of power spectra and event related desynchronization/synchronization (ERD/S) analyses show that the dynamics of the thalamic and cortical oscillations are significantly influenced by corticocortical synaptic loss. Interestingly, the patterns of changes in thalamic spectral activity are correlated with those in the cortical model. Similarly, the thalamic oscillatory activity is diminished after partial corticothalamic denervation. The results suggest that thalamic atrophy is a secondary pathology to cortical shrinkage in Alzheimer's disease. In addition, this study finds that the inhibition from neurons in the thalamic reticular nucleus (RTN) to thalamic relay (TCR) neurons plays a key role in regulating thalamic oscillations; disinhibition disrupts thalamic oscillatory activity even though TCR neurons are more depolarized after being released from RTN inhibition. This study provides information that can be explored experimentally to further our understanding

  1. Compensating for Thalamocortical Synaptic Loss in Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Kamal eAbuhassan

    2014-06-01

    Full Text Available The study presents a thalamocortical network model which oscillates within the alpha frequency band (8-13 Hz as recorded in the wakeful relaxed state with closed eyes to study the neural causes of abnormal oscillatory activity in Alzheimer’s disease (AD. Incorporated within the model are various types of cortical excitatory and inhibitory neurons, recurrently connected to thalamic and reticular thalamic regions with the ratios and distances derived from the mammalian thalamocortical system. The model is utilized to study the impacts of four types of connectivity loss on the model’s spectral dynamics. The study focuses on investigating degeneration of corticocortical, thalamocortical, corticothalamic and corticoreticular couplings, with an emphasis on the influence of each modelled case on the spectral output of the model. Synaptic compensation has been included in each model to examine the interplay between synaptic deletion and compensation mechanisms, and the oscillatory activity of the network. The results of power spectra and event related desynchronisation/synchronisation (ERD/S analyses show that the dynamics of the thalamic and cortical oscillations are significantly influenced by corticocortical synaptic loss. Interestingly, the patterns of changes in thalamic spectral activity are correlated with those in the cortical model. Similarly, the thalamic oscillatory activity is diminished after partial corticothalamic denervation. The results suggest that thalamic atrophy is a secondary pathology to cortical shrinkage in Alzheimer’s disease. In addition, this study finds that the inhibition from neurons in the thalamic reticular nucleus (RTN to thalamic relay (TCR neurons plays a key role in regulating thalamic oscillations; disinhibition disrupts thalamic oscillatory activity even though TCR neurons are more depolarized after being released from RTN inhibition. This study provides information that can be explored experimentally to

  2. Design of drive circuit of laser diode

    Science.gov (United States)

    Ran, Yingying; Huang, Xuegong; Xu, Xiaobin

    2016-10-01

    Aiming at the difficult problem of high precision frequency stabilization of semiconductor laser diode, the laser frequency control is realized through the design of the semiconductor drive system. Above all, the relationship between the emission frequency and the temperature of LD is derived theoretically. Then the temperature corresponding to the stable frequency is obtained. According to the desired temperature stability of LD, temperature control system is designed, which is composed of a temperature setting circuit, temperature gathering circuit, the temperature display circuit, analog PID control circuit and a semiconductor refrigerator control circuit module. By sampling technology, voltage of platinum resistance is acquired, and the converted temperature is display on liquid crystal display. PID analog control circuit controls speed stability and precision of temperature control. The constant current source circuit is designed to provide the reference voltage by a voltage stabilizing chip, which is buffered by an operational amplifier. It is connected with the MOSFET to drive the semiconductor laser to provide stable current for the semiconductor laser. PCB circuit board was finished and the experimental was justified. The experimental results show that: the design of the temperature control system could achieve the goal of temperature monitoring. Meanwhile, temperature can be stabilized at 40°C +/- 0.1°C. The output voltage of the constant current source is 2 V. The current is 35 mA.

  3. Special requisites for ground switch operation of parallel circuits of strongly connected transmission lines; Requisitos especiais de manobra para chaves de terra de circuitos paralelos de linhas de transmissao fortemente acoplados

    Energy Technology Data Exchange (ETDEWEB)

    Amon Filho, J.; Kastrup Filho, O.; Franca, W.J. [FURNAS, Rio de Janeiro, RJ (Brazil)

    1993-12-31

    This work aims to present results of a qualitative and quantitative analysis of the problem concerning the ground switch turn off operation of transmission lines parallel circuits involving computer simulations and field tests, being such tests compared to standards and constant criteria of the technical specifications of such ground switches. The so far achieved conclusions indicate that the arc resistors installed in the ground switches have been satisfactory solving the problem of the interruption of induced currents by those ground switches. 7 refs., 2 figs., 3 tabs.

  4. The circuit designer's companion

    CERN Document Server

    Williams, Tim

    2013-01-01

    The Circuit Designer's Companion covers the theoretical aspects and practices in analogue and digital circuit design. Electronic circuit design involves designing a circuit that will fulfill its specified function and designing the same circuit so that every production model of it will fulfill its specified function, and no other undesired and unspecified function.This book is composed of nine chapters and starts with a review of the concept of grounding, wiring, and printed circuits. The subsequent chapters deal with the passive and active components of circuitry design. These topics are foll

  5. Intuitive analog circuit design

    CERN Document Server

    Thompson, Marc

    2013-01-01

    Intuitive Analog Circuit Design outlines ways of thinking about analog circuits and systems that let you develop a feel for what a good, working analog circuit design should be. This book reflects author Marc Thompson's 30 years of experience designing analog and power electronics circuits and teaching graduate-level analog circuit design, and is the ideal reference for anyone who needs a straightforward introduction to the subject. In this book, Dr. Thompson describes intuitive and ""back-of-the-envelope"" techniques for designing and analyzing analog circuits, including transistor amplifi

  6. Diode-quad bridge circuit means

    Science.gov (United States)

    Harrison, D. R.; Dimeff, J. (Inventor)

    1975-01-01

    A transducer and frequency discriminator circuit is described including a four-terminal circulating diode bridge, a first pair of capacitors connected in series across two terminals of the bridge, and a second pair of capacitors, or other impedance elements, connected in series across the other two terminals of the bridge. A source of balanced alternating electrical energy for energizing the circuit is coupled between the commonly connected plates of the first pair of capacitors and the commonly connected plates of the second pair of capacitors. Due to the operation of the diode bridge, the sum of the resultant charges developed on the first pair of capacitors is proportional to the relationship between the respective capacitors of the second pair, and consequently, an output voltage taken across the first pair of capacitors will be proportional to that relationship.

  7. The NG2 Protein Is Not Required for Glutamatergic Neuron-NG2 Cell Synaptic Signaling.

    Science.gov (United States)

    Passlick, Stefan; Trotter, Jacqueline; Seifert, Gerald; Steinhäuser, Christian; Jabs, Ronald

    2016-01-01

    NG2 glial cells (as from now NG2 cells) are unique in receiving synaptic input from neurons. However, the components regulating formation and maintenance of these neuron-glia synapses remain elusive. The transmembrane protein NG2 has been considered a potential mediator of synapse formation and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) clustering, because it contains 2 extracellular Laminin G/Neurexin/Sex Hormone-Binding Globulin domains, which in neurons are crucial for formation of transsynaptic neuroligin-neurexin complexes. NG2 is connected via Glutamate Receptor-Interacting Protein with GluA2/3-containing AMPARs, thereby possibly mediating receptor clustering in glial postsynaptic density. To elucidate the role of NG2 in neuron-glia communication, we investigated glutamatergic synaptic transmission in juvenile and aged hippocampal NG2 cells of heterozygous and homozygous NG2 knockout mice. Neuron-NG2 cell synapses readily formed in the absence of NG2. Short-term plasticity, synaptic connectivity, postsynaptic AMPAR current kinetics, and density were not affected by NG2 deletion. During development, an NG2-independent acceleration of AMPAR current kinetics and decreased synaptic connectivity were observed. Our results indicate that the lack of NG2 does not interfere with genesis and basic properties of neuron-glia synapses. In addition, we demonstrate frequent expression of neuroligins 1-3 in juvenile and aged NG2 cells, suggesting a role of these molecules in synapse formation between NG2 glia and neurons.

  8. Analog VLSI Circuits for Short-Term Dynamic Synapses

    Directory of Open Access Journals (Sweden)

    Shih-Chii Liu

    2003-06-01

    Full Text Available Short-term dynamical synapses increase the computational power of neuronal networks. These synapses act as additional filters to the inputs of a neuron before the subsequent integration of these signals at its cell body. In this work, we describe a model of depressing and facilitating synapses derived from a hardware circuit implementation. This model is equivalent to theoretical models of short-term synaptic dynamics in network simulations. These circuits have been added to a network of leaky integrate-and-fire neurons. A cortical model of direction-selectivity that uses short-term dynamic synapses has been implemented with this network.

  9. Single pulse responses in cultured neuronal networks to describe connectivity

    NARCIS (Netherlands)

    Feber, le Joost; Corner, Michael

    2011-01-01

    Synaptic connections between neurons play a crucial role in cognitive processes like learning and memory. In recent work we developed a method, using conditional firing probability (CFP analysis), to estimate functional connectivity in terms of strength and latency, and here we further explored on t

  10. Design and implementation of a hybrid circuit system for micro sensor signal processing

    Energy Technology Data Exchange (ETDEWEB)

    Wang Zhuping; Chen Jing; Liu Ruqing, E-mail: wangzhuping169@163.com [School of Information and Electronics, Beijing Institute of Technology, Beijing 100081 (China)

    2011-04-15

    This paper covers a micro sensor analog signal processing circuit system (MASPS) chip with low power and a digital signal processing circuit board implementation including hardware connection and software design. Attention has been paid to incorporate the MASPS chip into the digital circuit board. The ultimate aim is to form a hybrid circuit used for mixed-signal processing, which can be applied to a micro sensor flow monitoring system. (semiconductor integrated circuits)

  11. Midbrain local circuits shape sound intensity codes.

    Science.gov (United States)

    Grimsley, Calum Alex; Sanchez, Jason Tait; Sivaramakrishnan, Shobhana

    2013-01-01

    Hierarchical processing of sensory information requires interaction at multiple levels along the peripheral to central pathway. Recent evidence suggests that interaction between driving and modulating components can shape both top down and bottom up processing of sensory information. Here we show that a component inherited from extrinsic sources combines with local components to code sound intensity. By applying high concentrations of divalent cations to neurons in the nucleus of the inferior colliculus in the auditory midbrain, we show that as sound intensity increases, the source of synaptic efficacy changes from inherited inputs to local circuits. In neurons with a wide dynamic range response to intensity, inherited inputs increase firing rates at low sound intensities but saturate at mid-to-high intensities. Local circuits activate at high sound intensities and widen dynamic range by continuously increasing their output gain with intensity. Inherited inputs are necessary and sufficient to evoke tuned responses, however local circuits change peak output. Push-pull driving inhibition and excitation create net excitatory drive to intensity-variant neurons and tune neurons to intensity. Our results reveal that dynamic range and tuning re-emerge in the auditory midbrain through local circuits that are themselves variable or tuned.

  12. Electrophysiological Data and the Biophysical Modelling of Local Cortical Circuits

    Directory of Open Access Journals (Sweden)

    Dimitris Pinotsis

    2014-03-01

    Full Text Available This paper shows how recordings of gamma oscillations – under different experimental conditions or from different subjects – can be combined with a class of population models called neural fields and dynamic causal modeling (DCM to distinguish among alternative hypotheses regarding cortical structure and function. This approach exploits inter-subject variability and trial-specific effects associated with modulations in the peak frequency of gamma oscillations. It draws on the computational power of Bayesian model inversion, when applied to neural field models of cortical dynamics. Bayesian model comparison allows one to adjudicate among different mechanistic hypotheses about cortical excitability, synaptic kinetics and the cardinal topographic features of local cortical circuits. It also provides optimal parameter estimates that quantify neuromodulation and the spatial dispersion of axonal connections or summation of receptive fields in the visual cortex. This paper provides an overview of a family of neural field models that have been recently implemented using the DCM toolbox of the academic freeware Statistical Parametric Mapping (SPM. The SPM software is a popular platform for analyzing neuroimaging data, used by several neuroscience communities worldwide. DCM allows for a formal (Bayesian statistical analysis of cortical network connectivity, based upon realistic biophysical models of brain responses. It is this particular feature of DCM – the unique combination of generative models with optimization techniques based upon (variational Bayesian principles – that furnishes a novel way to characterize functional brain architectures. In particular, it provides answers to questions about how the brain is wired and how it responds to different experimental manipulations. For a review of the general role of neural fields in SPM the reader can consult e.g. see [1]. Neural fields have a long and illustrious history in mathematical

  13. Engaging cognitive circuits to promote motor recovery in degenerative disorders. exercise as a learning modality

    Directory of Open Access Journals (Sweden)

    Jakowec Michael W.

    2016-09-01

    Full Text Available Exercise and physical activity are fundamental components of a lifestyle essential in maintaining a healthy brain. This is primarily due to the fact that the adult brain maintains a high degree of plasticity and activity is essential for homeostasis throughout life. Plasticity is not lost even in the context of a neurodegenerative disorder, but could be maladaptive thus promoting disease onset and progression. A major breakthrough in treating brain disorders such as Parkinson’s disease is to drive neuroplasticity in a direction to improve motor and cognitive dysfunction. The purpose of this short review is to present the evidence from our laboratories that supports neuroplasticity as a potential therapeutic target in treating brain disorders. We consider that the enhancement of motor recovery in both animal models of dopamine depletion and in patients with Parkinson’s disease is optimized when cognitive circuits are engaged; in other words, the brain is engaged in a learning modality. Therefore, we propose that to be effective in treating Parkinson’s disease, physical therapy must employ both skill-based exercise (to drive specific circuits and aerobic exercise (to drive the expression of molecules required to strengthen synaptic connections components to select those neuronal circuits, such as the corticostriatal pathway, necessary to restore proper motor and cognitive behaviors. In the wide spectrum of different forms of exercise, learning as the fundamental modality likely links interventions used to treat patients with Parkinson’s disease and may be necessary to drive beneficial neuroplasticity resulting in symptomatic improvement and possible disease modification.

  14. Impaired activity-dependent neural circuit assembly and refinement in autism spectrum disorder genetic models

    Directory of Open Access Journals (Sweden)

    Caleb Andrew Doll

    2014-02-01

    Full Text Available Early-use activity during circuit-specific critical periods refines brain circuitry by the coupled processes of eliminating inappropriate synapses and strengthening maintained synapses. We theorize these activity-dependent developmental processes are specifically impaired in autism spectrum disorders (ASDs. ASD genetic models in both mouse and Drosophila have pioneered our insights into normal activity-dependent neural circuit assembly and consolidation, and how these developmental mechanisms go awry in specific genetic conditions. The monogenic Fragile X syndrome (FXS, a common cause of heritable ASD and intellectual disability, has been particularly well linked to defects in activity-dependent critical period processes. The Fragile X Mental Retardation Protein (FMRP is positively activity-regulated in expression and function, in turn regulates excitability and activity in a negative feedback loop, and appears to be required for the activity-dependent remodeling of synaptic connectivity during early-use critical periods. The Drosophila FXS model has been shown to functionally conserve the roles of human FMRP in synaptogenesis, and has been centrally important in generating our current mechanistic understanding of the FXS disease state. Recent advances in Drosophila optogenetics, transgenic calcium reporters, highly-targeted transgenic drivers for individually-identified neurons, and a vastly improved connectome of the brain are now being combined to provide unparalleled opportunities to both manipulate and monitor activity-dependent processes during critical period brain development in defined neural circuits. The field is now poised to exploit this new Drosophila transgenic toolbox for the systematic dissection of activity-dependent mechanisms in normal versus ASD brain development, particularly utilizing the well-established Drosophila FXS disease model.

  15. 基于偏最小二乘法的3/2接线方式下开关回路电阻在线评估方法%On-line Evaluation of Switchgear Circuit Resistance Under 3/2 Connection Mode Based on Partial Least Squares Method

    Institute of Scientific and Technical Information of China (English)

    侯洋; 吉晓筱; 卜京; 夏方涛

    2016-01-01

    Switchgear circuit resistance is one of the most important parameters to evaluate the status of switch equipment. Aiming at the online evaluation problem of switchgear circuit resistance under 3/2 connection mode, a kind of online calculation method based on partial least squares is proposed. The mathematical model of switchgear circuit resistance is established according to the data of current flowing through switch equipment and Kirchhoff’s law. To reduce the error caused by the high linear correlation of current condition at different time, partial least squares method is used to calculate the switchgear circuit resistance. Lastly,using a 500 kV substation which uses 3/2 connection mode as an example to do simulation calculation. The result shows that partial least squares method can reduce the error caused by the high linear correlation of current condition obviously. Compared with least squares method, partial least squares method is more accurate.%开关回路电阻是评价开关设备状态的重要参数之一,针对3/2接线方式变电站开关回路电阻在线评估问题,提出一种基于偏最小二乘法的在线计算方法。根据变电站开关电流数据和基尔霍夫定律,建立开关回路电阻的数学模型。为减小不同时刻电流工况线性相关性带来的误差,采用偏最小二乘法求解开关回路电阻。最后,以采用3/2接线方式的某500 kV变电站为例,进行仿真计算。结果表明,采用偏最小二乘法能显著减小电流工况线性相关性带来的误差,相比于最小二乘法,精度更高。

  16. Electrical Circuits and Water Analogies

    Science.gov (United States)

    Smith, Frederick A.; Wilson, Jerry D.

    1974-01-01

    Briefly describes water analogies for electrical circuits and presents plans for the construction of apparatus to demonstrate these analogies. Demonstrations include series circuits, parallel circuits, and capacitors. (GS)

  17. Analysis of Short-circuit Characteristics and Calculation of Steady-state Short-circuit Current for DFIG Wind Turbine

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    Large-scale doubly-fed induction generator (DFIG) wind turbines are connected to the grid and required to remain grid-connection during faults, the short-circuit current contributed by the generation has become a significant issue. However, the traditional calculation methods aiming at synchronous generators cannot be directly applied to the DFIG wind turbines. A new method is needed to calculate the short-circuit current required by the planning, protection and control of the power grid. The short-circuit transition of DFIG under symmetrical and asymmetric short-circuit conditions are mathematically deduced, and the short-circuit characteristics of DFIG are analyzed. A new method is proposed to calculate the steady-state short-circuit current of DFIG based on the derived expressions. The time-domain simulations are conducted to verify the accuracy of the proposed method.

  18. POSSIBILITIES FOR OPTIMIZATION OF CIRCUIT ACCELERATING OPERATION OF ELECTROMAGNETS

    Directory of Open Access Journals (Sweden)

    S. S. Stoyanova

    2005-01-01

    Full Text Available The paper reveals an accelerating circuit for electromagnet operation with the help of an additional resistor R that is shunted with a capacitor C. Resistor R is connected in series with the electromagnet winding. The possibility of the circuit optimization has been substantiated with the purpose to limit the final speed with which a movable part of the electromagnet reaches a limiter. Such circuit may find its application in relay protection.

  19. Circuits on Cylinders

    DEFF Research Database (Denmark)

    Hansen, Kristoffer Arnsfelt; Miltersen, Peter Bro; Vinay, V

    2006-01-01

    We consider the computational power of constant width polynomial size cylindrical circuits and nondeterministic branching programs. We show that every function computed by a Pi2 o MOD o AC0 circuit can also be computed by a constant width polynomial size cylindrical nondeterministic branching...... program (or cylindrical circuit) and that every function computed by a constant width polynomial size cylindrical circuit belongs to ACC0....

  20. Electric circuits essentials

    CERN Document Server

    REA, Editors of

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Electric Circuits I includes units, notation, resistive circuits, experimental laws, transient circuits, network theorems, techniques of circuit analysis, sinusoidal analysis, polyph

  1. Local connections of layer 5 GABAergic interneurons to corticospinal neurons

    Directory of Open Access Journals (Sweden)

    Yasuyo H Tanaka

    2011-09-01

    Full Text Available In the local circuit of the cerebral cortex, GABAergic inhibitory interneurons are considered to work in collaboration with excitatory neurons. Although many interneuron subgroups have been described in the cortex, local inhibitory connections of each interneuron subgroup are only partially understood with respect to the functional neuron groups that receive these inhibitory connections. In the present study, we morphologically examined local inhibitory inputs to corticospinal neurons (CSNs in motor areas using transgenic rats in which GABAergic neurons expressed fluorescent protein Venus. By analysis of biocytin-filled axons obtained with whole-cell recording/staining in cortical slices, we classified fast-spiking (FS neurons in layer (L 5 into two types, FS1 and FS2, by their high and low densities of axonal arborization, respectively. We then investigated the connections of FS1, FS2, somatostatin-immunopositive (SOM and other (non-FS/non-SOM interneurons to CSNs that were retrogradely labeled in a Golgi-like manner in motor areas. When close appositions between the axon boutons of the intracellularly labeled interneurons and the somata/dendrites of the retrogradely labeled CSNs were examined electron-microscopically, 74% of these appositions made symmetric synaptic contacts. The axon boutons of single FS1 neurons were 2–4-fold more frequent in appositions to the somata/dendrites of CSNs than those of FS2, SOM and non-FS/non-SOM neurons. Axosomatic appositions were most frequently formed with axon boutons of FS1 and FS2 neurons (approximately 30% and least frequently formed with those of SOM neurons (7%. In contrast, SOM neurons most extensively sent axon boutons to the apical dendrites of CSNs. These results might suggest that motor outputs are controlled differentially by the subgroups of L5 GABAergic interneurons in cortical motor areas. 

  2. Compact SCR trigger circuit for ignitron switch operates efficiently

    Science.gov (United States)

    Foster, L. E.

    1965-01-01

    Trigger circuit with two series-connected SCR triggers an ignitron switch used to discharge high-energy capacitor banks. It does not require a warmup period and operates at relatively high efficiency.

  3. Piezoelectric drive circuit

    Science.gov (United States)

    Treu, Jr., Charles A.

    1999-08-31

    A piezoelectric motor drive circuit is provided which utilizes the piezoelectric elements as oscillators and a Meacham half-bridge approach to develop feedback from the motor ground circuit to produce a signal to drive amplifiers to power the motor. The circuit automatically compensates for shifts in harmonic frequency of the piezoelectric elements due to pressure and temperature changes.

  4. A lock circuit for a multi-core processor

    DEFF Research Database (Denmark)

    2015-01-01

    An integrated circuit comprising a multiple processor cores and a lock circuit that comprises a queue register with respective bits set or reset via respective, connections dedicated to respective processor cores, whereby the queue register identifies those among the multiple processor cores that...

  5. An Unsolved Electric Circuit: A Common Misconception

    Science.gov (United States)

    Harsha, N. R. Sree; Sreedevi, A.; Prakash, Anupama

    2015-01-01

    Despite a number of theories in circuit analysis, little is known about the behaviour of ideal equal voltage sources in parallel, connected across a resistive load. We neither have any theory that can predict the voltage source that provides the load current, nor is there any method to test it experimentally. In a series of experiments performed…

  6. Switchable Ultrastrong Coupling in Circuit QED

    NARCIS (Netherlands)

    Peropadre, B.; Forn-Diaz, P.; Solano, E.; Garcia-Ripoll, J.J.

    2010-01-01

    We propose different designs of switchable coupling between a superconducting flux qubit and a microwave transmission line. They are based on two or more loops of Josephson junctions which are directly connected to a closed (cavity) or open transmission line. In both cases the circuit induces a coup

  7. Learning Structure of Sensory Inputs with Synaptic Plasticity Leads to Interference

    Directory of Open Access Journals (Sweden)

    Joseph eChrol-Cannon

    2015-08-01

    Full Text Available Synaptic plasticity is often explored as a form of unsupervised adaptationin cortical microcircuits to learn the structure of complex sensoryinputs and thereby improve performance of classification and prediction. The question of whether the specific structure of the input patterns is encoded in the structure of neural networks has been largely neglected. Existing studies that have analyzed input-specific structural adaptation have used simplified, synthetic inputs in contrast to complex and noisy patterns found in real-world sensory data.In this work, input-specific structural changes are analyzed forthree empirically derived models of plasticity applied to three temporal sensory classification tasks that include complex, real-world visual and auditory data. Two forms of spike-timing dependent plasticity (STDP and the Bienenstock-Cooper-Munro (BCM plasticity rule are used to adapt the recurrent network structure during the training process before performance is tested on the pattern recognition tasks.It is shown that synaptic adaptation is highly sensitive to specific classes of input pattern. However, plasticity does not improve the performance on sensory pattern recognition tasks, partly due to synaptic interference between consecutively presented input samples. The changes in synaptic strength produced by one stimulus are reversed by thepresentation of another, thus largely preventing input-specific synaptic changes from being retained in the structure of the network.To solve the problem of interference, we suggest that models of plasticitybe extended to restrict neural activity and synaptic modification to a subset of the neural circuit, which is increasingly found to be the casein experimental neuroscience.

  8. Effects of active conductance distribution over dendrites on the synaptic integration in an identified nonspiking interneuron.

    Directory of Open Access Journals (Sweden)

    Akira Takashima

    Full Text Available The synaptic integration in individual central neuron is critically affected by how active conductances are distributed over dendrites. It has been well known that the dendrites of central neurons are richly endowed with voltage- and ligand-regulated ion conductances. Nonspiking interneurons (NSIs, almost exclusively characteristic to arthropod central nervous systems, do not generate action potentials and hence lack voltage-regulated sodium channels, yet having a variety of voltage-regulated potassium conductances on their dendritic membrane including the one similar to the delayed-rectifier type potassium conductance. It remains unknown, however, how the active conductances are distributed over dendrites and how the synaptic integration is affected by those conductances in NSIs and other invertebrate neurons where the cell body is not included in the signal pathway from input synapses to output sites. In the present study, we quantitatively investigated the functional significance of active conductance distribution pattern in the spatio-temporal spread of synaptic potentials over dendrites of an identified NSI in the crayfish central nervous system by computer simulation. We systematically changed the distribution pattern of active conductances in the neuron's multicompartment model and examined how the synaptic potential waveform was affected by each distribution pattern. It was revealed that specific patterns of nonuniform distribution of potassium conductances were consistent, while other patterns were not, with the waveform of compound synaptic potentials recorded physiologically in the major input-output pathway of the cell, suggesting that the possibility of nonuniform distribution of potassium conductances over the dendrite cannot be excluded as well as the possibility of uniform distribution. Local synaptic circuits involving input and output synapses on the same branch or on the same side were found to be potentially affected under

  9. AMPA receptor inhibition by synaptically released zinc.

    Science.gov (United States)

    Kalappa, Bopanna I; Anderson, Charles T; Goldberg, Jacob M; Lippard, Stephen J; Tzounopoulos, Thanos

    2015-12-22

    The vast amount of fast excitatory neurotransmission in the mammalian central nervous system is mediated by AMPA-subtype glutamate receptors (AMPARs). As a result, AMPAR-mediated synaptic transmission is implicated in nearly all aspects of brain development, function, and plasticity. Despite the central role of AMPARs in neurobiology, the fine-tuning of synaptic AMPA responses by endogenous modulators remains poorly understood. Here we provide evidence that endogenous zinc, released by single presynaptic action potentials, inhibits synaptic AMPA currents in the dorsal cochlear nucleus (DCN) and hippocampus. Exposure to loud sound reduces presynaptic zinc levels in the DCN and abolishes zinc inhibition, implicating zinc in experience-dependent AMPAR synaptic plasticity. Our results establish zinc as an activity-dependent, endogenous modulator of AMPARs that tunes fast excitatory neurotransmission and plasticity in glutamatergic synapses.

  10. Constructing circuit codes by permuting initial sequences

    CERN Document Server

    Wynn, Ed

    2012-01-01

    Two new constructions are presented for coils and snakes in the hypercube. Improvements are made on the best known results for snake-in-the-box coils of dimensions 9, 10 and 11, and for some other circuit codes of dimensions between 8 and 13. In the first construction, circuit codes are generated from permuted copies of an initial transition sequence; the multiple copies constrain the search, so that long codes can be found relatively efficiently. In the second construction, two lower-dimensional paths are joined together with only one or two changes in the highest dimension; this requires a search for a permutation of the second sequence to fit around the first. It is possible to investigate sequences of vertices of the hypercube, including circuit codes, by connecting the corresponding vertices in an extended graph related to the hypercube. As an example of this, invertible circuit codes are briefly discussed.

  11. Effects of Chronic Sleep Restriction during Early Adolescence on the Adult Pattern of Connectivity of Mouse Secondary Motor Cortex123

    Science.gov (United States)

    Billeh, Yazan N.; Bernard, Amy; de Vivo, Luisa; Honjoh, Sakiko; Mihalas, Stefan; Ng, Lydia; Koch, Christof

    2016-01-01

    Abstract Cortical circuits mature in stages, from early synaptogenesis and synaptic pruning to late synaptic refinement, resulting in the adult anatomical connection matrix. Because the mature matrix is largely fixed, genetic or environmental factors interfering with its establishment can have irreversible effects. Sleep disruption is rarely considered among those factors, and previous studies have focused on very young animals and the acute effects of sleep deprivation on neuronal morphology and cortical plasticity. Adolescence is a sensitive time for brain remodeling, yet whether chronic sleep restriction (CSR) during adolescence has long-term effects on brain connectivity remains unclear. We used viral-mediated axonal labeling and serial two-photon tomography to measure brain-wide projections from secondary motor cortex (MOs), a high-order area with diffuse projections. For each MOs target, we calculated the projection fraction, a combined measure of passing fibers and axonal terminals normalized for the size of each target. We found no homogeneous differences in MOs projection fraction between mice subjected to 5 days of CSR during early adolescence (P25–P30, ≥50% decrease in daily sleep, n=14) and siblings that slept undisturbed (n=14). Machine learning algorithms, however, classified animals at significantly above chance levels, indicating that differences between the two groups exist, but are subtle and heterogeneous. Thus, sleep disruption in early adolescence may affect adult brain connectivity. However, because our method relies on a global measure of projection density and was not previously used to measure connectivity changes due to behavioral manipulations, definitive conclusions on the long-term structural effects of early CSR require additional experiments. PMID:27351022

  12. THE SYNAPTIC CONNECTIONS BETWEEN PV-LI TERMINALS AND THALAMIC PROJECTION NEURONS IN THE THIRD-ORDER NUCLEI OF CENTRAL PATHWAY OF TRIGEMINAL PROPRIOCEPTIVE SENSATION OF THE RAT%大鼠三叉神经本体觉中枢通路上第三级核团内PV样阳性终末与丘脑投射神经元的突触联系

    Institute of Scientific and Technical Information of China (English)

    董玉琳; 李金莲

    2004-01-01

    Objective To examine if axonal varicosities with parvalbumin-like immunoreactivity(PV-LI) might make synaptic connections with thalamic projection neurons in the third-order nuclei of central pathway of trigeminal proprioceptive sensation of the rat. Methods The HRP-retrograde tracing method combined with immuno-electron microscopy was used.Projection neurons were retrogradely labeled with wheat germ agglutinin-horseradish peroxidase(WGA-HRP) which was injected into the ventral posteromedial nucleus(VPM) of the thalamus. Results After injection,a number of WGA-HRP-labeled neurons were observed mainly in the principal sensory trigeminal nucleus(Vp),the caudolateral part of supratrigeminal nucleus (Vsup-CL),the area ventral to the motor trigeminal nucleus(AVM) and the area dorsal to the superior olivary nucleus(ADO).Electron microscopy confirmed that axon terminals with PV-LI made synaptic contact on somatic and dendritic profiles which were labeled with WGA-HRP.In addition,some PV-negative axon terminals made synapses with WGA-HRP-labeled somatic or dendritic profiles occasionally showed PV-LI.Conclusion It was indicated that some of PV-containing projection neurons might be involved in the transmission of the trigeminal proprioceptive information from the third-order nuclei to the VPM of thalamus through the mechanism of synaptic transmission.%目的观察大鼠三叉神经本体觉中枢通路上第三级核团内Parvalbumin样阳性轴突终末与丘脑投射神经元之间是否存在突触联系. 方法用HRP逆行追踪和包埋前免疫电镜相结合的双重标记法.将WGA-HRP注入丘脑腹后内侧核逆行标记投射神经元. 结果 WGA-HRP注入丘脑腹后内侧核(VPM)后,WGA-HRP标记神经元主要分布在感觉主核背内侧部(Vpdm)、三叉上核尾外侧部(Vsup-CL)以及三叉神经运动核腹侧区(AVM)和上橄榄核背侧区(ADO).电镜下可见PV样阳性神经元的轴突终末与WGA-HRP标记的胞体或者树突形成突触联系.

  13. 基于关键因子和辨识技术的光伏并网系统短路电流建模%Modeling of short circuit current for photovoltaic connected-grid system based on the key factors and identification technology

    Institute of Scientific and Technical Information of China (English)

    张尧; 晁勤; 李育强; 王一波

    2016-01-01

    为了提高光伏并网点短路时光伏系统输出短路电流计算准确性,提出以电压跌落程度 n 和光伏并网逆变器输出有功 p 及电网电压正序分量 u+三个特征量为关键因子,分析推导三个关键因子与光伏并网逆变器输出电流峰值 Imax 的关系。采用光伏并网逆变器输出对称三相正弦交流电流为控制目标的电压功率控制策略,基于系统辨识技术,建立光伏并网逆变器输出短路电流模型并辨识其相关参数。运用求和算法,获得近似的光伏并网发电系统输出短路电流模型。基于 MATLAB 编程软件验证了所建模型的正确性。同时与 PSCAD/EMTDC 搭建的恒功率控制仿真模型对比分析论证了该模型能较准确反映光伏并网发电系统输出短路电流的大小。%In order to improve the accuracy of the calculation of photovoltaic system short circuit current, this paper proposes that voltage drop degree, the output active of photovoltaic connected-grid inverter, and the positive sequence component of the grid voltage are the key factors, and the relationship between the three key factors and the peak value of the output current of PV connected-grid inverter is analyzed. The voltage power control strategy for the control objective of the output symmetrical three-phase sinusoidal AC current of photovoltaic connected-grid inverter is adopted. The output current model of the PV connected-grid inverter is established and the relevant parameters are identified based on system identification technology. Using the sum algorithm, the output short circuit current model of photovoltaic connected-grid system is obtained. The built model can be verified by MATLAB programming software. At the same time, compared with the constant power control simulation model built by PSCAD/EMTDC, the model can accurately reflect the output short circuit current of PV grid connected power generation system.

  14. Electrostimulation to reduce synaptic scaling driven progression of Alzheimer's disease.

    Science.gov (United States)

    Rowan, Mark S; Neymotin, Samuel A; Lytton, William W

    2014-01-01

    Cell death and synapse dysfunction are two likely causes of cognitive decline in AD. As cells die and synapses lose their drive, remaining cells suffer an initial decrease in activity. Neuronal homeostatic synaptic scaling then provides a feedback mechanism to restore activity. This homeostatic mechanism is believed to sense levels of activity-dependent cytosolic calcium within the cell and to adjust neuronal firing activity by increasing the density of AMPA synapses at remaining synapses to achieve balance. The scaling mechanism increases the firing rates of remaining cells in the network to compensate for decreases in network activity. However, this effect can itself become a pathology, as it produces increased imbalance between excitatory and inhibitory circuits, leading to greater susceptibility to further cell loss via calcium-mediated excitotoxicity. Here, we present a mechanistic explanation of how directed brain stimulation might be expected to slow AD progression based on computational simulations in a 470-neuron biomimetic model of a neocortical column. The simulations demonstrate that the addition of low-intensity electrostimulation (neuroprosthesis) to a network undergoing AD-like cell death can raise global activity and break this homeostatic-excitotoxic cascade. The increase in activity within the remaining cells in the column results in lower scaling-driven AMPAR upregulation, reduced imbalances in excitatory and inhibitory circuits, and lower susceptibility to ongoing damage.

  15. Electrostimulation to reduce synaptic scaling driven progression of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Mark eRowan

    2014-04-01

    Full Text Available Cell death and synapse dysfunction are two likely causes of cognitive decline in AD. As cells die and synapses lose their drive, remaining cells suffer an initial decrease in activity. Neuronal homeostatic synaptic scaling then provides a feedback mechanism to restore activity. This homeostatic mechanism is believed to sense levels of activity-dependent cytosolic calcium within the cell and to adjust neuronal firing activity by increasing the density of AMPA synapses at remaining synapses to achieve balance. The scaling mechanism increases the firing rates of remaining cells in the network to compensate for decreases in network activity. However, this effect can itself become a pathology, as it produces increased imbalance between excitatory and inhibitory circuits, leading to greater susceptibility to further cell loss via calcium-mediated excitotoxicity.Here, we present a mechanistic explanation of how directed brain stimulation might be expected to slow AD progression based on computational simulations in a 470-neuron biomimetic model of a neocortical column. The simulations demonstrate that the addition of low-intensity electrostimulation (neuroprosthesis to a network undergoing AD-like cell death can raise global activity and break this homeostatic-excitotoxic cascade. The increase in activity within the remaining cells in the column results in lower scaling-driven AMPAR upregulation, reduced imbalances in excitatory and inhibitory circuits, and lower susceptibility to ongoing damage.

  16. Reversible Logic Circuit Synthesis

    CERN Document Server

    Shende, V V; Markov, I L; Prasad, A K; Hayes, John P.; Markov, Igor L.; Prasad, Aditya K.; Shende, Vivek V.

    2002-01-01

    Reversible, or information-lossless, circuits have applications in digital signal processing, communication, computer graphics and cryptography. They are also a fundamental requirement for quantum computation. We investigate the synthesis of reversible circuits that employ a minimum number of gates and contain no redundant input-output line-pairs (temporary storage channels). We propose new constructions for reversible circuits composed of NOT, Controlled-NOT, and TOFFOLI gates (the CNT gate library) based on permutation theory. A new algorithm is given to synthesize optimal reversible circuits using an arbitrary gate library. We also describe much faster heuristic algorithms. We also pursue applications of the proposed techniques to the synthesis of quantum circuits.

  17. Synaptic gating at axonal branches, and sharp-wave ripples with replay: a simulation study.

    Science.gov (United States)

    Vladimirov, Nikita; Tu, Yuhai; Traub, Roger D

    2013-11-01

    Mechanisms of place cell replay occurring during sharp-wave ripples (SPW-Rs) remain obscure due to the fact that ripples in vitro depend on non-synaptic mechanisms, presumably via axo-axonal gap junctions between pyramidal cells. We suggest a model of in vivo SPW-Rs in which synaptic excitatory post-synaptic potentials (EPSPs) control the axonal spiking of cells in SPW-Rs: ripple activity remains hidden in the network of axonal collaterals (connected by gap junctions) due to conduction failures, unless there is a sufficient dendritic EPSP. The EPSP brings the axonal branching point to threshold, and action potentials from the collateral start to propagate to the soma and to the distal axon. The model coherently explains multiple experimental data on SPW-Rs, both in vitro and in vivo. The mechanism of synaptic gating leads to the following implication: a sequence of pyramidal cells can be replayed at ripple frequency by the superposition of subthreshold dendritic EPSPs and ripple activity in the axonal plexus. Replay is demonstrated in both forward and reverse directions. We discuss several testable predictions. In general, the mechanism of synaptic gating suggests that pyramidal cells under certain conditions can act like a transistor.

  18. Effects of axonal topology on the somatic modulation of synaptic outputs.

    Science.gov (United States)

    Sasaki, Takuya; Matsuki, Norio; Ikegaya, Yuji

    2012-02-22

    Depolarization of the neuronal soma augments synaptic output onto postsynaptic neurons via long-range, axonal cable properties. Here, we report that the range of this somatic influence is spatially restricted by not only axonal path length but also a branching-dependent decrease in axon diameter. Cell-attached recordings of action potentials (APs) from multiple axon branches of a rat hippocampal CA3 pyramidal cell revealed that an AP was broadened following a 20 mV depolarization of the soma and reverted to a normal width during propagation down the axon. The narrowing of the AP depended on the distance traveled by the AP and on the number of axon branch points through which the AP passed. These findings were confirmed by optical imaging of AP-induced calcium elevations in presynaptic boutons, suggesting that the somatic membrane potential modifies synaptic outputs near the soma but not long-projection outputs. Consistent with this prediction, whole-cell recordings from synaptically connected neurons revealed that depolarization of presynaptic CA3 pyramidal cells facilitated synaptic transmission to nearby CA3 pyramidal cells, but not to distant pyramidal cells in CA3 or CA1. Therefore, axonal geometry enables the differential modulation of synaptic output depending on target location.

  19. A method for the three-dimensional reconstruction of Neurobiotin™-filled neurons and the location of their synaptic inputs

    Directory of Open Access Journals (Sweden)

    Matthew Joseph Fogarty

    2013-10-01

    Full Text Available Here, we describe a robust method for mapping the number and type of neuro-chemically distinct synaptic inputs that a single reconstructed neuron receives. We have used individual hypoglossal motor neurons filled with Neurobiotin by semi-loose seal electroporation in thick brainstem slices. These filled motor neurons were then processed for excitatory and inhibitory synaptic inputs, using immunohistochemical-labeling procedures. For excitatory synapses, we used anti-VGLUT2 to locate glutamatergic pre-synaptic terminals and anti-PSD-95 to locate post-synaptic specializations on and within the surface of these filled motor neurons. For inhibitory synapses, we used anti-VGAT to locate GABAergic pre-synaptic terminals and anti-GABA-A receptor subunit α1 to locate the post-synaptic domain. The Neurobiotin-filled and immuno-labeled motor neuron was then processed for optical sectioning using confocal microscopy. The morphology of the motor neuron including its dendritic tree and the distribution of excitatory and inhibitory synapses were then determined by three-dimensional reconstruction using IMARIS software (Bitplane. Using surface rendering, fluorescence thresholding, and masking of unwanted immuno-labeling, tools found in IMARIS, we were able to obtain an accurate 3D structure of an individual neuron including the number and location of its glutamatergic and GABAergic synaptic inputs. The power of this method allows for a rapid morphological confirmation of the post-synaptic responses recorded by patch-clamp prior to Neurobiotin filling. Finally, we show that this method can be adapted to super-resolution microscopy techniques, which will enhance its applicability to the study of neural circuits at the level of synapses.

  20. Low phase noise oscillator using two parallel connected amplifiers

    Science.gov (United States)

    Kleinberg, Leonard L.

    1987-01-01

    A high frequency oscillator is provided by connecting two amplifier circuits in parallel where each amplifier circuit provides the other amplifier circuit with the conditions necessary for oscillation. The inherent noise present in both amplifier circuits causes the quiescent current, and in turn, the generated frequency, to change. The changes in quiescent current cause the transconductance and the load impedance of each amplifier circuit to vary, and this in turn results in opposing changes in the input susceptance of each amplifier circuit. Because the changes in input susceptance oppose each other, the changes in quiescent current also oppose each other. The net result is that frequency stability is enhanced.

  1. Microglial Intracellular Ca2+ Signaling in Synaptic Development and its Alterations in Neurodevelopmental Disorders

    Science.gov (United States)

    Mizoguchi, Yoshito; Monji, Akira

    2017-01-01

    Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by deficits in social interaction, difficulties with language and repetitive/restricted behaviors. Microglia are resident innate immune cells which release many factors including proinflammatory cytokines, nitric oxide (NO) and brain-derived neurotrophic factor (BDNF) when they are activated in response to immunological stimuli. Recent in vivo imaging has shown that microglia sculpt and refine the synaptic circuitry by removing excess and unwanted synapses and be involved in the development of neural circuits or synaptic plasticity thereby maintaining the brain homeostasis. BDNF, one of the neurotrophins, has various important roles in cell survival, neurite outgrowth, neuronal differentiation, synaptic plasticity and the maintenance of neural circuits in the CNS. Intracellular Ca2+ signaling is important for microglial functions including ramification, de-ramification, migration, phagocytosis and release of cytokines, NO and BDNF. BDNF induces a sustained intracellular Ca2+ elevation through the upregulation of the surface expression of canonical transient receptor potential 3 (TRPC3) channels in rodent microglia. BDNF might have an anti-inflammatory effect through the inhibition of microglial activation and TRPC3 could play important roles in not only inflammatory processes but also formation of synapse through the modulation of microglial phagocytic activity in the brain. This review article summarizes recent findings on emerging dual, inflammatory and non-inflammatory, roles of microglia in the brain and reinforces the importance of intracellular Ca2+ signaling for microglial functions in both normal neurodevelopment and their potential contributing to neurodevelopmental disorders such as ASDs. PMID:28367116

  2. Circadian clocks, rhythmic synaptic plasticity and the sleep-wake cycle in zebrafish.

    Science.gov (United States)

    Elbaz, Idan; Foulkes, Nicholas S; Gothilf, Yoav; Appelbaum, Lior

    2013-01-01

    The circadian clock and homeostatic processes are fundamental mechanisms that regulate sleep. Surprisingly, despite decades of research, we still do not know why we sleep. Intriguing hypotheses suggest that sleep regulates synaptic plasticity and consequently has a beneficial role in learning and memory. However, direct evidence is still limited and the molecular regulatory mechanisms remain unclear. The zebrafish provides a powerful vertebrate model system that enables simple genetic manipulation, imaging of neuronal circuits and synapses in living animals, and the monitoring of behavioral performance during day and night. Thus, the zebrafish has become an attractive model to study circadian and homeostatic processes that regulate sleep. Zebrafish clock- and sleep-related genes have been cloned, neuronal circuits that exhibit circadian rhythms of activity and synaptic plasticity have been studied, and rhythmic behavioral outputs have been characterized. Integration of this data could lead to a better understanding of sleep regulation. Here, we review the progress of circadian clock and sleep studies in zebrafish with special emphasis on the genetic and neuroendocrine mechanisms that regulate rhythms of melatonin secretion, structural synaptic plasticity, locomotor activity and sleep.

  3. Compensating Level-Dependent Frequency Representation in Auditory Cortex by Synaptic Integration of Corticocortical Input

    Science.gov (United States)

    Happel, Max F. K.; Ohl, Frank W.

    2017-01-01

    Robust perception of auditory objects over a large range of sound intensities is a fundamental feature of the auditory system. However, firing characteristics of single neurons across the entire auditory system, like the frequency tuning, can change significantly with stimulus intensity. Physiological correlates of level-constancy of auditory representations hence should be manifested on the level of larger neuronal assemblies or population patterns. In this study we have investigated how information of frequency and sound level is integrated on the circuit-level in the primary auditory cortex (AI) of the Mongolian gerbil. We used a combination of pharmacological silencing of corticocortically relayed activity and laminar current source density (CSD) analysis. Our data demonstrate that with increasing stimulus intensities progressively lower frequencies lead to the maximal impulse response within cortical input layers at a given cortical site inherited from thalamocortical synaptic inputs. We further identified a temporally precise intercolumnar synaptic convergence of early thalamocortical and horizontal corticocortical inputs. Later tone-evoked activity in upper layers showed a preservation of broad tonotopic tuning across sound levels without shifts towards lower frequencies. Synaptic integration within corticocortical circuits may hence contribute to a level-robust representation of auditory information on a neuronal population level in the auditory cortex. PMID:28046062

  4. Feedback in analog circuits

    CERN Document Server

    Ochoa, Agustin

    2016-01-01

    This book describes a consistent and direct methodology to the analysis and design of analog circuits with particular application to circuits containing feedback. The analysis and design of circuits containing feedback is generally presented by either following a series of examples where each circuit is simplified through the use of insight or experience (someone else’s), or a complete nodal-matrix analysis generating lots of algebra. Neither of these approaches leads to gaining insight into the design process easily. The author develops a systematic approach to circuit analysis, the Driving Point Impedance and Signal Flow Graphs (DPI/SFG) method that does not require a-priori insight to the circuit being considered and results in factored analysis supporting the design function. This approach enables designers to account fully for loading and the bi-directional nature of elements both in the feedback path and in the amplifier itself, properties many times assumed negligible and ignored. Feedback circuits a...

  5. Exact Threshold Circuits

    DEFF Research Database (Denmark)

    Hansen, Kristoffer Arnsfelt; Podolskii, Vladimir V.

    2010-01-01

    We initiate a systematic study of constant depth Boolean circuits built using exact threshold gates. We consider both unweighted and weighted exact threshold gates and introduce corresponding circuit classes. We next show that this gives a hierarchy of classes that seamlessly interleave with the ......We initiate a systematic study of constant depth Boolean circuits built using exact threshold gates. We consider both unweighted and weighted exact threshold gates and introduce corresponding circuit classes. We next show that this gives a hierarchy of classes that seamlessly interleave...... with the well-studied corresponding hierarchies defined using ordinary threshold gates. A major open problem in Boolean circuit complexity is to provide an explicit super-polynomial lower bound for depth two threshold circuits. We identify the class of depth two exact threshold circuits as a natural subclass...

  6. TIME CALIBRATED OSCILLOSCOPE SWEEP CIRCUIT

    Science.gov (United States)

    Smith, V.L.; Carstensen, H.K.

    1959-11-24

    An improved time calibrated sweep circuit is presented, which extends the range of usefulness of conventional oscilloscopes as utilized for time calibrated display applications in accordance with U. S. Patent No. 2,832,002. Principal novelty resides in the provision of a pair of separate signal paths, each of which is phase and amplitude adjustable, to connect a high-frequency calibration oscillator to the output of a sawtooth generator also connected to the respective horizontal deflection plates of an oscilloscope cathode ray tube. The amplitude and phase of the calibration oscillator signals in the two signal paths are adjusted to balance out feedthrough currents capacitively coupled at high frequencies of the calibration oscillator from each horizontal deflection plate to the vertical plates of the cathode ray tube.

  7. Short-term synaptic depression is topographically distributed in the cochlear nucleus of the chicken.

    Science.gov (United States)

    Oline, Stefan N; Burger, R Michael

    2014-01-22

    In the auditory system, sounds are processed in parallel frequency-tuned circuits, beginning in the cochlea. Activity of auditory nerve fibers reflects this frequency-specific topographic pattern, known as tonotopy, and imparts frequency tuning onto their postsynaptic target neurons in the cochlear nucleus. In birds, cochlear nucleus magnocellularis (NM) neurons encode the temporal properties of acoustic stimuli by "locking" discharges to a particular phase of the input signal. Physiological specializations exist in gradients corresponding to the tonotopic axis in NM that reflect the characteristic frequency (CF) of their auditory nerve fiber inputs. One feature of NM neurons that has not been investigated across the tonotopic axis is short-term synaptic plasticity. NM offers a rather homogeneous population of neurons with a distinct topographical distribution of synaptic properties that is ideal for the investigation of specialized synaptic plasticity. Here we demonstrate for the first time that short-term synaptic depression (STD) is expressed topographically, where unitary high CF synapses are more robust with repeated stimulation. Correspondingly, high CF synapses drive spiking more reliably than their low CF counterparts. We show that postsynaptic AMPA receptor desensitization does not contribute to the observed difference in STD. Further, rate of recovery from depression, a presynaptic property, does not differ tonotopically. Rather, we show that another presynaptic feature, readily releasable pool (RRP) size, is tonotopically distributed and inversely correlated with vesicle release probability. Mathematical model results demonstrate that these properties of vesicle dynamics are sufficient to explain the observed tonotopic distribution of STD.

  8. Coordinated Regulation of Synaptic Plasticity at Striatopallidal and Striatonigral Neurons Orchestrates Motor Control

    Directory of Open Access Journals (Sweden)

    Massimo Trusel

    2015-11-01

    Full Text Available The basal ganglia play a critical role in shaping motor behavior. For this function, the activity of medium spiny neurons (MSNs of the striatonigral and striatopallidal pathways must be integrated. It remains unclear whether the activity of the two pathways is primarily coordinated by synaptic plasticity mechanisms. Using a model of Parkinson’s disease, we determined the circuit and behavioral effects of concurrently regulating cell-type-specific forms of corticostriatal long-term synaptic depression (LTD by inhibiting small-conductance Ca2+-activated K+ channels (SKs of the dorsolateral striatum. At striatopallidal synapses, SK channel inhibition rescued the disease-linked deficits in endocannabinoid (eCB-dependent LTD. At striatonigral cells, inhibition of these channels counteracted a form of adenosine-mediated LTD by activating the ERK cascade. Interfering with eCB-, adenosine-, and ERK signaling in vivo alleviated motor abnormalities, which supports that synaptic modulation of striatal pathways affects behavior. Thus, our results establish a central role of coordinated synaptic plasticity at MSN subpopulations in motor control.

  9. INVOLVEMENT OF SYNAPTIC GENES IN THE PATHOGENESIS OF AUTISM SPECTRUM DISORDERS: THE CASE OF SYNAPSINS

    Directory of Open Access Journals (Sweden)

    Silvia eGiovedi

    2014-09-01

    Full Text Available Autism spectrum disorders (ASDs are heterogeneous neurodevelopmental disorders characterized by deficits in social interaction and social communication, restricted interests and repetitive behaviors. Many synaptic protein genes are linked to the pathogenesis of ASDs, making them prototypical synaptopathies. An array of mutations in the synapsin (Syn genes in humans have been recently associated with ASD and epilepsy, diseases that display a frequent comorbidity. Synapsins are presynaptic proteins regulating synaptic vesicle traffic, neurotransmitter release and short-term synaptic plasticity. In doing so, Syn isoforms control the tone of activity of neural circuits and the balance between excitation and inhibition. As ASD pathogenesis is believed to result from dysfunctions in the balance between excitatory and inhibitory transmissions in neocortical areas, Syns are novel ASD candidate genes. Accordingly, deletion of single Syn genes in mice, in addition to epilepsy, causes core symptoms of ASD by affecting social behavior, social communication and repetitive behaviors. Thus, Syn knockout mice represent a good experimental model to define synaptic alterations involved in the pathogenesis of ASD and epilepsy.

  10. Birth order dependent growth cone segregation determines synaptic layer identity in the Drosophila visual system.

    Science.gov (United States)

    Kulkarni, Abhishek; Ertekin, Deniz; Lee, Chi-Hon; Hummel, Thomas

    2016-03-17

    The precise recognition of appropriate synaptic partner neurons is a critical step during neural circuit assembly. However, little is known about the developmental context in which recognition specificity is important to establish synaptic contacts. We show that in the Drosophila visual system, sequential segregation of photoreceptor afferents, reflecting their birth order, lead to differential positioning of their growth cones in the early target region. By combining loss- and gain-of-function analyses we demonstrate that relative differences in the expression of the transcription factor Sequoia regulate R cell growth cone segregation. This initial growth cone positioning is consolidated via cell-adhesion molecule Capricious in R8 axons. Further, we show that the initial growth cone positioning determines synaptic layer selection through proximity-based axon-target interactions. Taken together, we demonstrate that birth order dependent pre-patterning of afferent growth cones is an essential pre-requisite for the identification of synaptic partner neurons during visual map formation in Drosophila.

  11. Implementing dynamic clamp with synaptic and artificial conductances in mouse retinal ganglion cells.

    Science.gov (United States)

    Huang, Jin Y; Stiefel, Klaus M; Protti, Dario A

    2013-05-16

    Ganglion cells are the output neurons of the retina and their activity reflects the integration of multiple synaptic inputs arising from specific neural circuits. Patch clamp techniques, in voltage clamp and current clamp configurations, are commonly used to study the physiological properties of neurons and to characterize their synaptic inputs. Although the application of these techniques is highly informative, they pose various limitations. For example, it is difficult to quantify how the precise interactions of excitatory and inhibitory inputs determine response output. To address this issue, we used a modified current clamp technique, dynamic clamp, also called conductance clamp (1, 2, 3) and examined the impact of excitatory and inhibitory synaptic inputs on neuronal excitability. This technique requires the injection of current into the cell and is dependent on the real-time feedback of its membrane potential at that time. The injected current is calculated from predetermined excitatory and inhibitory synaptic conductances, their reversal potentials and the cell's instantaneous membrane potential. Details on the experimental procedures, patch clamping cells to achieve a whole-cell configuration and employment of the dynamic clamp technique are illustrated in this video article. Here, we show the responses of mouse retinal ganglion cells to various conductance waveforms obtained from physiological experiments in control conditions or in the presence of drugs. Furthermore, we show the use of artificial excitatory and inhibitory conductances generated using alpha functions to investigate the responses of the cells.

  12. Settings Calculation and Comparison of Unbalanced Current Protection of High Voltage Filter Capacitor Banks Connected as H and∏Circuits%H和Π接线高压滤波电容器组不平衡电流保护的定值计算及比较

    Institute of Scientific and Technical Information of China (English)

    肖遥; 夏谷林; 张楠

    2014-01-01

    提出了高压滤波电容器组不平衡电流保护的整定原则,从两方面通过数学逻辑分析了H型和∏型接线高压电容器组及其不平衡电流保护的优缺点:其一是部分电容器单元失效后滤波器所允许的失谐度,其二是余下完好电容器单元所承受的端电压。文中给出了不同电容器单元短路方式下的不平衡保护定值计算公式和整定值,得出了∏型接线优于H型接线的结论。为改进∏型接线电容器组的差电流检测精度,给出了差值电流检测电路的改进方案。%The paper proposed principles for calculating the settings of unbalanced current protection of high voltage filter capacitor banks, and analyzed the merits and demerits of“H-type” and “∏-type” connections of capacitor banks from perspective of mathematic logic in two ways. Of which one involved the permitted detuning of the filters after failure of some units, the other involved the withstand voltages on remaining perfect capacitor units. The formulations were deducted to calculate the settings of unbalanced current protection in cases when short circuit of some capacitor units occurred. It is concluded that ∏-type connection is better than the H-type connection. To improve the accuracy for detecting differential currents of ∏-type connection, a new unbalanced current transformer and its application are suggested.

  13. Pattern classification by memristive crossbar circuits using ex situ and in situ training

    Science.gov (United States)

    Alibart, Fabien; Zamanidoost, Elham; Strukov, Dmitri B.

    2013-06-01

    Memristors are memory resistors that promise the efficient implementation of synaptic weights in artificial neural networks. Whereas demonstrations of the synaptic operation of memristors already exist, the implementation of even simple networks is more challenging and has yet to be reported. Here we demonstrate pattern classification using a single-layer perceptron network implemented with a memrisitive crossbar circuit and trained using the perceptron learning rule by ex situ and in situ methods. In the first case, synaptic weights, which are realized as conductances of titanium dioxide memristors, are calculated on a precursor software-based network and then imported sequentially into the crossbar circuit. In the second case, training is implemented in situ, so the weights are adjusted in parallel. Both methods work satisfactorily despite significant variations in the switching behaviour of the memristors. These results give hope for the anticipated efficient implementation of artificial neuromorphic networks and pave the way for dense, high-performance information processing systems.

  14. Robust network oscillations during mammalian respiratory rhythm generation driven by synaptic dynamics.

    Science.gov (United States)

    Guerrier, Claire; Hayes, John A; Fortin, Gilles; Holcman, David

    2015-08-04

    How might synaptic dynamics generate synchronous oscillations in neuronal networks? We address this question in the preBötzinger complex (preBötC), a brainstem neural network that paces robust, yet labile, inspiration in mammals. The preBötC is composed of a few hundred neurons that alternate bursting activity with silent periods, but the mechanism underlying this vital rhythm remains elusive. Using a computational approach to model a randomly connected neuronal network that relies on short-term synaptic facilitation (SF) and depression (SD), we show that synaptic fluctuations can initiate population activities through recurrent excitation. We also show that a two-step SD process allows activity in the network to synchronize (bursts) and generate a population refractory period (silence). The model was validated against an array of experimental conditions, which recapitulate several processes the preBötC may experience. Consistent with the modeling assumptions, we reveal, by electrophysiological recordings, that SF/SD can occur at preBötC synapses on timescales that influence rhythmic population activity. We conclude that nondeterministic neuronal spiking and dynamic synaptic strengths in a randomly connected network are sufficient to give rise to regular respiratory-like rhythmic network activity and lability, which may play an important role in generating the rhythm for breathing and other coordinated motor activities in mammals.

  15. Treatment with Piribedil and Memantine Reduces Noise-Induced Loss of Inner Hair Cell Synaptic Ribbons

    Science.gov (United States)

    Altschuler, Richard A.; Wys, Noel; Prieskorn, Diane; Martin, Cathy; DeRemer, Susan; Bledsoe, Sanford; Miller, Josef M.

    2016-01-01

    Noise overstimulation can induce loss of synaptic ribbons associated with loss of Inner Hair Cell – Auditory Nerve synaptic connections. This study examined if systemic administration of Piribedil, a dopamine agonist that reduces the sound evoked auditory nerve compound action potential and/or Memantine, an NMDA receptor open channel blocker, would reduce noise-induced loss of Inner Hair Cell ribbons. Rats received systemic Memantine and/or Piribedil for 3 days before and 3 days after a 3 hour 4 kHz octave band noise at 117 dB (SPL). At 21 days following the noise there was a 26% and 38% loss of synaptic ribbons in regions 5.5 and 6.5 mm from apex, respectively, elevations in 4-, 8- and 20 kHz tonal ABR thresholds and reduced dynamic output at higher intensities of stimulation. Combined treatment with Piribedil and Memantine produced a significant reduction in the noise-induced loss of ribbons in both regions and changes in ABR sensitivity and dynamic responsiveness. Piribedil alone gave significant reduction in only the 5.5 mm region and Memantine alone did not reach significance in either region. Results identify treatments that could prevent the hearing loss and hearing disorders that result from noise-induced loss of Inner Hair Cell – Auditory Nerve synaptic connections. PMID:27686418

  16. Differential modifications of synaptic weights during odor rule learning: dynamics of interaction between the piriform cortex with lower and higher brain areas.

    Science.gov (United States)

    Cohen, Yaniv; Wilson, Donald A; Barkai, Edi

    2015-01-01

    Learning of a complex olfactory discrimination (OD) task results in acquisition of rule learning after prolonged training. Previously, we demonstrated enhanced synaptic connectivity between the piriform cortex (PC) and its ascending and descending inputs from the olfactory bulb (OB) and orbitofrontal cortex (OFC) following OD rule learning. Here, using recordings of evoked field postsynaptic potentials in behaving animals, we examined the dynamics by which these synaptic pathways are modified during rule acquisition. We show profound differences in synaptic connectivity modulation between the 2 input sources. During rule acquisition, the ascending synaptic connectivity from the OB to the anterior and posterior PC is simultaneously enhanced. Furthermore, post-training stimulation of the OB enhanced learning rate dramatically. In sharp contrast, the synaptic input in the descending pathway from the OFC was significantly reduced until training completion. Once rule learning was established, the strength of synaptic connectivity in the 2 pathways resumed its pretraining values. We suggest that acquisition of olfactory rule learning requires a transient enhancement of ascending inputs to the PC, synchronized with a parallel decrease in the descending inputs. This combined short-lived modulation enables the PC network to reorganize in a manner that enables it to first acquire and then maintain the rule.

  17. Short term synaptic depression imposes a frequency dependent filter on synaptic information transfer.

    Science.gov (United States)

    Rosenbaum, Robert; Rubin, Jonathan; Doiron, Brent

    2012-01-01

    Depletion of synaptic neurotransmitter vesicles induces a form of short term depression in synapses throughout the nervous system. This plasticity affects how synapses filter presynaptic spike trains. The filtering properties of short term depression are often studied using a deterministic synapse model that predicts the mean synaptic response to a presynaptic spike train, but ignores variability introduced by the probabilistic nature of vesicle release and stochasticity in synaptic recovery time. We show that this additional variability has important consequences for the synaptic filtering of presynaptic information. In particular, a synapse model with stochastic vesicle dynamics suppresses information encoded at lower frequencies more than information encoded at higher frequencies, while a model that ignores this stochasticity transfers information encoded at any frequency equally well. This distinction between the two models persists even when large numbers of synaptic contacts are considered. Our study provides strong evidence that the stochastic nature neurotransmitter vesicle dynamics must be considered when analyzing the information flow across a synapse.

  18. Synaptic Ribbons Require Ribeye for Electron Density, Proper Synaptic Localization, and Recruitment of Calcium Channels

    Directory of Open Access Journals (Sweden)

    Caixia Lv

    2016-06-01

    Full Text Available Synaptic ribbons are structures made largely of the protein Ribeye that hold synaptic vesicles near release sites in non-spiking cells in some sensory systems. Here, we introduce frameshift mutations in the two zebrafish genes encoding for Ribeye and thus remove Ribeye protein from neuromast hair cells. Despite Ribeye depletion, vesicles collect around ribbon-like structures that lack electron density, which we term “ghost ribbons.” Ghost ribbons are smaller in size but possess a similar number of smaller vesicles and are poorly localized to synapses and calcium channels. These hair cells exhibit enhanced exocytosis, as measured by capacitance, and recordings from afferent neurons post-synaptic to hair cells show no significant difference in spike rates. Our results suggest that Ribeye makes up most of the synaptic ribbon density in neuromast hair cells and is necessary for proper localization of calcium channels and synaptic ribbons.

  19. Cntnap4 differentially contributes to GABAergic and dopaminergic synaptic transmission.

    Science.gov (United States)

    Karayannis, T; Au, E; Patel, J C; Kruglikov, I; Markx, S; Delorme, R; Héron, D; Salomon, D; Glessner, J; Restituito, S; Gordon, A; Rodriguez-Murillo, L; Roy, N C; Gogos, J A; Rudy, B; Rice, M E; Karayiorgou, M; Hakonarson, H; Keren, B; Huguet, G; Bourgeron, T; Hoeffer, C; Tsien, R W; Peles, E; Fishell, G

    2014-07-10

    Although considerable evidence suggests that the chemical synapse is a lynchpin underlying affective disorders, how molecular insults differentially affect specific synaptic connections remains poorly understood. For instance, Neurexin 1a and 2 (NRXN1 and NRXN2) and CNTNAP2 (also known as CASPR2), all members of the neurexin superfamily of transmembrane molecules, have been implicated in neuropsychiatric disorders. However, their loss leads to deficits that have been best characterized with regard to their effect on excitatory cells. Notably, other disease-associated genes such as BDNF and ERBB4 implicate specific interneuron synapses in psychiatric disorders. Consistent with this, cortical interneuron dysfunction has been linked to epilepsy, schizophrenia and autism. Using a microarray screen that focused upon synapse-associated molecules, we identified Cntnap4 (contactin associated protein-like 4, also known as Caspr4) as highly enriched in developing murine interneurons. In this study we show that Cntnap4 is localized presynaptically and its loss leads to a reduction in the output of cortical parvalbumin (PV)-positive GABAergic (γ-aminobutyric acid producing) basket cells. Paradoxically, the loss of Cntnap4 augments midbrain dopaminergic release in the nucleus accumbens. In Cntnap4 mutant mice, synaptic defects in these disease-relevant neuronal populations are mirrored by sensory-motor gating and grooming endophenotypes; these symptoms could be pharmacologically reversed, providing promise for therapeutic intervention in psychiatric disorders.

  20. Integrated differential high-voltage transmitting circuit for CMUTs

    DEFF Research Database (Denmark)

    Llimos Muntal, Pere; Larsen, Dennis Øland; Farch, Kjartan;

    2015-01-01

    In this paper an integrated differential high-voltage transmitting circuit for capacitive micromachined ultrasonic transducers (CMUTs) used in portable ultrasound scanners is designed and implemented in a 0.35 μm high-voltage process. Measurements are performed on the integrated circuit in order...... to assess its performance. The circuit generates pulses at differential voltage levels of 60V, 80V and 100 V, a frequency up to 5MHz and a measured driving strength of 1.75 V/ns with the CMUT connected. The total on-chip area occupied by the transmitting circuit is 0.18 mm2 and the power consumption...

  1. P2Y Receptors in Synaptic Transmission and Plasticity: Therapeutic Potential in Cognitive Dysfunction

    Directory of Open Access Journals (Sweden)

    Segundo J. Guzman

    2016-01-01

    Full Text Available ATP released from neurons and astrocytes during neuronal activity or under pathophysiological circumstances is able to influence information flow in neuronal circuits by activation of ionotropic P2X and metabotropic P2Y receptors and subsequent modulation of cellular excitability, synaptic strength, and plasticity. In the present paper we review cellular and network effects of P2Y receptors in the brain. We show that P2Y receptors inhibit the release of neurotransmitters, modulate voltage- and ligand-gated ion channels, and differentially influence the induction of synaptic plasticity in the prefrontal cortex, hippocampus, and cerebellum. The findings discussed here may explain how P2Y1 receptor activation during brain injury, hypoxia, inflammation, schizophrenia, or Alzheimer’s disease leads to an impairment of cognitive processes. Hence, it is suggested that the blockade of P2Y1 receptors may have therapeutic potential against cognitive disturbances in these states.

  2. Axon initial segment Kv1 channels control axonal action potential waveform and synaptic efficacy.

    Science.gov (United States)

    Kole, Maarten H P; Letzkus, Johannes J; Stuart, Greg J

    2007-08-16

    Action potentials are binary signals that transmit information via their rate and temporal pattern. In this context, the axon is thought of as a transmission line, devoid of a role in neuronal computation. Here, we show a highly localized role of axonal Kv1 potassium channels in shaping the action potential waveform in the axon initial segment (AIS) of layer 5 pyramidal neurons independent of the soma. Cell-attached recordings revealed a 10-fold increase in Kv1 channel density over the first 50 microm of the AIS. Inactivation of AIS and proximal axonal Kv1 channels, as occurs during slow subthreshold somatodendritic depolarizations, led to a distance-dependent broadening of axonal action potentials, as well as an increase in synaptic strength at proximal axonal terminals. Thus, Kv1 channels are strategically positioned to integrate slow subthreshold signals, providing control of the presynaptic action potential waveform and synaptic coupling in local cortical circuits.

  3. An On-line Identification of Equipment Risk for 3/2 Circuit Breaker Connections%针对电网3/2接线方式的设备风险在线辨识方法

    Institute of Scientific and Technical Information of China (English)

    闪鑫; 戴则梅; 曹路; 汪德星

    2012-01-01

    3/2接线方式由于具有供电可靠性高、运行调度灵活、倒闸操作方便等优点,在500kV厂站和部分220kV枢纽变电站得到了广泛应用。但是,该接线方式在一次设备或开关处于检修方式下时,某些故障模式可能会造成多个设备的停电。基于网络拓扑分析和保护动作逻辑的设备风险在线辨识技术,能够针对3/2接线方式下的一次设备或开关检修,自动识别出具有N-2以上停电设备的潜在故障模式,提醒调度运行人员;同时,结合静态安全分析、动态安全分析以及检修计划,实现大电网的设备风险在线防控。%Owing to lots of advantages such as high reliability for power supply,flexible operating and dispatching mechanism and convenient transfer switching,etc,the 3/2 connection mode has been widely put into operation in 500 kV power stations and some 200 kV load-center substations.However,many equipments may be subjected to power cut caused by some fault modes as long as the connection mode is linked with primary equipment or the breaker under prophylactic overhaul.Using on-line identification technology of equipment risk based on network topology analysis and operation logic for protection,it is able to automatically identify the latent fault mode concerning N-2 or more power-failure equipments for primary equipment or breaker overhaul under 3/2 connection mode,and reminds relevant dispatching working staff.In the meantime,through the combination of static and dynamic security analysis and maintenance schedule,it will achieve on-line prevention and control mechanism for equipment risk in large power grid.

  4. 电网短路状态下并网逆变器的谐振控制%Resonant controlling grid-connected converter under grid short-circuit fault

    Institute of Scientific and Technical Information of China (English)

    包广清; 王兴贵

    2012-01-01

    To improve the performance of directly driven wind turbine system with permanent magnet synchronous generator (DWT-PMSG) under grid short-circuit fault, a resonant control (RC) strategy was introduced into coordinate direct power control (DPC) scheme of grid side converter. Two RC controllers were developed based on the proportional-resonant regulator, which are tuned at the doub- le fundamental frequency and grid frequency respectively to eliminate the direct current (DC) link voltage ripples and power pulsations produced by transient unbalanced grid faults. The quasi unity power factor was obtained without any necessity of grid voltage phase detecting, decoupling control or rotating transformation and diminishment of the overall control bandwidth of whole system, which in- dicates RC has better control precision and adaptability than traditional proportional integral (PI) con- trol in wind energy conversion system. A 1.5 MW DWT-PMSG with back-to-back converter during grid single-phase short-circuit fault was simulated in the PSCAD/EMTDC environment. By adding an energy consumption crowbar, the redundant energy at DC side during grid faults will be consumed, which demonstrates the validity of the model and its analysis. The generator-converter arrangement and switching strategy are also verified by the 10 kV ·A laboratory experiment.%为了改善电网短路故障情况下直驱式永磁风电系统的并网逆变器控制性能,提出基于比例积分谐振控制器的并网逆变器直接功率控制算法,通过设置基频谐振控制器实现网侧变流器输出电压、电流信号的无静差跟踪,同时在直流母线侧通过2倍工频谐振控制器可以抑制电网故障状态下直流母线的电压波动.与传统网侧逆变器的交直轴电流双闭环PI控制相比,该算法无须分离正负序电流分量,从而避免了电流滤波环节带来的系统带宽减小的弊端.在PSCAD/EMTDC环境下建

  5. Analysis and design of a charge pump circuit for high output current applications

    NARCIS (Netherlands)

    Steenwijk, van Gijs; Hoen, Klaas; Wallinga, Hans

    1993-01-01

    A charge pump circuit has been developed that can deliver high currents even for a system supply voltage of 3 V. The circuit consists of capacitances, connected by MOS switches. The influence of the on-resistance of the switches on the circuit's output resistance has been analysed. The switches are

  6. 30 CFR 57.6404 - Separation of blasting circuits from power source.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Separation of blasting circuits from power... NONMETAL MINES Explosives Electric Blasting-Surface and Underground § 57.6404 Separation of blasting circuits from power source. (a) Switches used to connect the power source to a blasting circuit shall...

  7. 30 CFR 56.6404 - Separation of blasting circuits from power source.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Separation of blasting circuits from power... MINES Explosives Electric Blasting § 56.6404 Separation of blasting circuits from power source. (a) Switches used to connect the power source to a blasting circuit shall be locked in the open position...

  8. Analog circuit design

    CERN Document Server

    Dobkin, Bob

    2012-01-01

    Analog circuit and system design today is more essential than ever before. With the growth of digital systems, wireless communications, complex industrial and automotive systems, designers are being challenged to develop sophisticated analog solutions. This comprehensive source book of circuit design solutions aids engineers with elegant and practical design techniques that focus on common analog challenges. The book's in-depth application examples provide insight into circuit design and application solutions that you can apply in today's demanding designs. <

  9. Parallelizing quantum circuit synthesis

    OpenAIRE

    Di Matteo, Olivia; Mosca, Michele

    2016-01-01

    Quantum circuit synthesis is the process in which an arbitrary unitary operation is decomposed into a sequence of gates from a universal set, typically one which a quantum computer can implement both efficiently and fault-tolerantly. As physical implementations of quantum computers improve, the need is growing for tools which can effectively synthesize components of the circuits and algorithms they will run. Existing algorithms for exact, multi-qubit circuit synthesis scale exponentially in t...

  10. Regenerative feedback resonant circuit

    Science.gov (United States)

    Jones, A. Mark; Kelly, James F.; McCloy, John S.; McMakin, Douglas L.

    2014-09-02

    A regenerative feedback resonant circuit for measuring a transient response in a loop is disclosed. The circuit includes an amplifier for generating a signal in the loop. The circuit further includes a resonator having a resonant cavity and a material located within the cavity. The signal sent into the resonator produces a resonant frequency. A variation of the resonant frequency due to perturbations in electromagnetic properties of the material is measured.

  11. Analog circuits cookbook

    CERN Document Server

    Hickman, Ian

    2013-01-01

    Analog Circuits Cookbook presents articles about advanced circuit techniques, components and concepts, useful IC for analog signal processing in the audio range, direct digital synthesis, and ingenious video op-amp. The book also includes articles about amplitude measurements on RF signals, linear optical imager, power supplies and devices, and RF circuits and techniques. Professionals and students of electrical engineering will find the book informative and useful.

  12. Input-specific maturation of synaptic dynamics of parvalbumin interneurons in primary visual cortex.

    Science.gov (United States)

    Lu, Jiangteng; Tucciarone, Jason; Lin, Ying; Huang, Z Josh

    2014-11-25

    Cortical networks consist of local recurrent circuits and long-range pathways from other brain areas. Parvalbumin-positive interneurons (PVNs) regulate the dynamic operation of local ensembles as well as the temporal precision of afferent signals. The synaptic recruitment of PVNs that support these circuit operations is not well-understood. Here we demonstrate that the synaptic dynamics of PVN recruitment in mouse visual cortex are customized according to input source with distinct maturation profiles. Whereas the long-range inputs to PVNs show strong short-term depression throughout postnatal maturation, local inputs from nearby pyramidal neurons progressively lose such depression. This enhanced local recruitment depends on PVN-mediated reciprocal inhibition and results from both pre- and postsynaptic mechanisms, including calcium-permeable AMPA receptors at PVN postsynaptic sites. Although short-term depression of long-range inputs is well-suited for afferent signal detection, the robust dynamics of local inputs may facilitate rapid and proportional PVN recruitment in regulating local circuit operations.

  13. Antagonism of Muscarinic Acetylcholine Receptors Alters Synaptic ERK Phosphorylation in the Rat Forebrain.

    Science.gov (United States)

    Mao, Li-Min; Wang, Henry H; Wang, John Q

    2016-12-28

    Acetylcholine (ACh) is a key transmitter in the mesocorticolimbic circuit. By interacting with muscarinic ACh receptors (mAChR) enriched in the circuit, ACh actively regulates various neuronal and synaptic activities. The extracellular signal-regulated kinase (ERK) is one of members of the mitogen-activated protein kinase family and is subject to the regulation by dopamine receptors, although the regulation of ERKs by limbic mAChRs is poorly understood. In this study, we investigated the role of mAChRs in the regulation of ERK phosphorylation (activation) in the mesocorticolimbic system of adult rat brains in vivo. We targeted a sub-pool of ERKs at synaptic sites. We found that a systemic injection of the mAChR antagonist scopolamine increased phosphorylation of synaptic ERKs in the striatum (caudate putamen and nucleus accumbens) and medial prefrontal cortex (mPFC). Increases in ERK phosphorylation in both forebrain regions were rapid and transient. Notably, pretreatment with a dopamine D1 receptor (D1R) antagonist SCH23390 blocked the scopolamine-stimulated ERK phosphorylation in these brain regions, while a dopamine D2 receptor antagonist eticlopride did not. Scopolamine and SCH23390 did not change the amount of total ERK proteins. These results demonstrate that mAChRs inhibit synaptic ERK phosphorylation in striatal and mPFC neurons under normal conditions. Blockade of this inhibitory mAChR tone leads to the upregulation of ERK phosphorylation likely through a mechanism involving the level of D1R activity.

  14. Timergenerator circuits manual

    CERN Document Server

    Marston, R M

    2013-01-01

    Timer/Generator Circuits Manual is an 11-chapter text that deals mainly with waveform generator techniques and circuits. Each chapter starts with an explanation of the basic principles of its subject followed by a wide range of practical circuit designs. This work presents a total of over 300 practical circuits, diagrams, and tables.Chapter 1 outlines the basic principles and the different types of generator. Chapters 2 to 9 deal with a specific type of waveform generator, including sine, square, triangular, sawtooth, and special waveform generators pulse. These chapters also include pulse gen

  15. CMOS circuits manual

    CERN Document Server

    Marston, R M

    1995-01-01

    CMOS Circuits Manual is a user's guide for CMOS. The book emphasizes the practical aspects of CMOS and provides circuits, tables, and graphs to further relate the fundamentals with the applications. The text first discusses the basic principles and characteristics of the CMOS devices. The succeeding chapters detail the types of CMOS IC, including simple inverter, gate and logic ICs and circuits, and complex counters and decoders. The last chapter presents a miscellaneous collection of two dozen useful CMOS circuits. The book will be useful to researchers and professionals who employ CMOS circu

  16. Electronic devices and circuits

    CERN Document Server

    Pridham, Gordon John

    1968-01-01

    Electronic Devices and Circuits, Volume 1 deals with the design and applications of electronic devices and circuits such as passive components, diodes, triodes and transistors, rectification and power supplies, amplifying circuits, electronic instruments, and oscillators. These topics are supported with introductory network theory and physics. This volume is comprised of nine chapters and begins by explaining the operation of resistive, inductive, and capacitive elements in direct and alternating current circuits. The theory for some of the expressions quoted in later chapters is presented. Th

  17. Circuits and filters handbook

    CERN Document Server

    Chen, Wai-Kai

    2003-01-01

    A bestseller in its first edition, The Circuits and Filters Handbook has been thoroughly updated to provide the most current, most comprehensive information available in both the classical and emerging fields of circuits and filters, both analog and digital. This edition contains 29 new chapters, with significant additions in the areas of computer-aided design, circuit simulation, VLSI circuits, design automation, and active and digital filters. It will undoubtedly take its place as the engineer's first choice in looking for solutions to problems encountered in the design, analysis, and behavi

  18. MOS integrated circuit design

    CERN Document Server

    Wolfendale, E

    2013-01-01

    MOS Integral Circuit Design aims to help in the design of integrated circuits, especially large-scale ones, using MOS Technology through teaching of techniques, practical applications, and examples. The book covers topics such as design equation and process parameters; MOS static and dynamic circuits; logic design techniques, system partitioning, and layout techniques. Also featured are computer aids such as logic simulation and mask layout, as well as examples on simple MOS design. The text is recommended for electrical engineers who would like to know how to use MOS for integral circuit desi

  19. Security electronics circuits manual

    CERN Document Server

    MARSTON, R M

    1998-01-01

    Security Electronics Circuits Manual is an invaluable guide for engineers and technicians in the security industry. It will also prove to be a useful guide for students and experimenters, as well as providing experienced amateurs and DIY enthusiasts with numerous ideas to protect their homes, businesses and properties.As with all Ray Marston's Circuits Manuals, the style is easy-to-read and non-mathematical, with the emphasis firmly on practical applications, circuits and design ideas. The ICs and other devices used in the practical circuits are modestly priced and readily available ty

  20. Hybrid high direct current circuit interrupter

    Science.gov (United States)

    Rockot, J.H.; Mikesell, H.E.; Jha, K.N.

    1998-08-11

    A device and a method are disclosed for interrupting very high direct currents (greater than 100,000 amperes) and simultaneously blocking high voltages (greater than 600 volts). The device utilizes a mechanical switch to carry very high currents continuously with low loss and a silicon controlled rectifier (SCR) to bypass the current around the mechanical switch while its contacts are separating. A commutation circuit, connected in parallel with the SCR, turns off the SCR by utilizing a resonant circuit to divert the SCR current after the switch opens. 7 figs.

  1. Disruption of an Evolutionarily Novel Synaptic Expression Pattern in Autism

    Science.gov (United States)

    Jiang, Xi; Hu, Haiyang; Guijarro, Patricia; Mitchell, Amanda; Ely, John J.; Sherwood, Chet C.; Hof, Patrick R.; Qiu, Zilong; Pääbo, Svante; Akbarian, Schahram; Khaitovich, Philipp

    2016-01-01

    Cognitive defects in autism spectrum disorder (ASD) include socialization and communication: key behavioral capacities that separate humans from other species. Here, we analyze gene expression in the prefrontal cortex of 63 autism patients and control individuals, as well as 62 chimpanzees and macaques, from natal to adult age. We show that among all aberrant expression changes seen in ASD brains, a single aberrant expression pattern overrepresented in genes involved synaptic-related pathways is enriched in nucleotide variants linked to autism. Furthermore, only this pattern contains an excess of developmental expression features unique to humans, thus resulting in the disruption of human-specific developmental programs in autism. Several members of the early growth response (EGR) transcription factor family can be implicated in regulation of this aberrant developmental change. Our study draws a connection between the genetic risk architecture of autism and molecular features of cortical development unique to humans. PMID:27685936

  2. Fractal Electronic Circuits Assembled From Nanoclusters

    Science.gov (United States)

    Fairbanks, M. S.; McCarthy, D.; Taylor, R. P.; Brown, S. A.

    2009-07-01

    Many patterns in nature can be described using fractal geometry. The effect of this fractal character is an array of properties that can include high internal connectivity, high dispersivity, and enhanced surface area to volume ratios. These properties are often desirable in applications and, consequently, fractal geometry is increasingly employed in technologies ranging from antenna to storm barriers. In this paper, we explore the application of fractal geometry to electrical circuits, inspired by the pervasive fractal structure of neurons in the brain. We show that, under appropriate growth conditions, nanoclusters of Sb form into islands on atomically flat substrates via a process close to diffusion-limited aggregation (DLA), establishing fractal islands that will form the basis of our fractal circuits. We perform fractal analysis of the islands to determine the spatial scaling properties (characterized by the fractal dimension, D) of the proposed circuits and demonstrate how varying growth conditions can affect D. We discuss fabrication approaches for establishing electrical contact to the fractal islands. Finally, we present fractal circuit simulations, which show that the fractal character of the circuit translates into novel, non-linear conduction properties determined by the circuit's D value.

  3. Ciliary Neurotrophic Factor Cell-Based Delivery Prevents Synaptic Impairment and Improves Memory in Mouse Models of Alzheimer's Disease

    NARCIS (Netherlands)

    Garcia, Pierre; Youssef, Ihsen; Utvik, Jo K.; Florent-Bechard, Sabrina; Barthelemy, Vanassa; Malaplate-Armand, Catherine; Kriem, Badreddine; Stenger, Christophe; Koziel, Violette; Olivier, Jean-Luc; Escanye, Marie-Christine; Hanse, Marine; Allouche, Ahmad; Desbene, Cedric; Yen, Frances T.; Bjerkvig, Rolf; Oster, Thierry; Niclou, Simone P.; Pillot, Thierry

    2010-01-01

    The development of novel therapeutic strategies for Alzheimer's disease (AD) represents one of the biggest unmet medical needs today. Application of neurotrophic factors able to modulate neuronal survival and synaptic connectivity is a promising therapeutic approach for AD. We aimed to determine whe

  4. A High-Voltage Level Tolerant Transistor Circuit

    NARCIS (Netherlands)

    Annema, Anne Johan; Geelen, Godefridus Johannes Gertrudis Maria

    2001-01-01

    A high-voltage level tolerant transistor circuit, comprising a plurality of cascoded transistors, including a first transistor (T1) operatively connected to a high-voltage level node (3) and a second transistor (T2) operatively connected to a low-voltage level node (2). The first transistor (T1) con

  5. Connectomics of synaptic microcircuits: lessons from the outer retina.

    Science.gov (United States)

    Rogerson, Luke Edward; Behrens, Christian; Euler, Thomas; Berens, Philipp; Schubert, Timm

    2017-03-10

    Photoreceptors form a sophisticated synaptic complex with bipolar and horizontal cells, transmitting the signals generated by the phototransduction cascade to downstream retinal circuitry. The cone photoreceptor synapse shows several characteristic anatomical connectivity motifs that shape signal transfer: Typically, ON-cone bipolar cells receive photoreceptor input through invaginating synapses; OFF-cone bipolar cells form basal synapses with photoreceptors. Both ON- and OFF-cone bipolar cells are believed to sample from all cone photoreceptors within their dendritic span. Electron microscopy and immunolabelling studies have established the robustness of these motifs, but have been limited by trade-offs in sample size and spatial resolution, respectively, constraining precise quantitative investigation to few individual cells. 3D-serial electron microscopy overcomes these limitations and has permitted complete sets of neurons to be reconstructed over a comparatively large section of retinal tissue (Helmstaedter et al. 2013). Although the mouse dataset published by Helmstaedter and co-workers lacks labels for synaptic structures, the characteristic anatomical motifs at the photoreceptor synapse can be exploited to identify functional contacts, enabling Behrens, Schubert et al. (2016) to develop a quantitative description of outer retinal connectivity. This revealed unexpected exceptions to classical motifs, including substantial interaction between rod and cone pathways at the photoreceptor synapse, sparse photoreceptor sampling and atypical contacts. Here, we summarize what was learned from this study in a more general context: We consider both the implications and limitations of the study and identify promising avenues for future research. This article is protected by copyright. All rights reserved.

  6. Imaging synaptic zinc: promises and perils.

    Science.gov (United States)

    Kay, Alan R

    2006-04-01

    It is well established that some excitatory nerve terminals have high concentrations of Zn(2+) in their synaptic vesicles. For some time, it has been believed that synaptic Zn(2+) is released during neurotransmission and acts as a neuromodulator. Fluorescent Zn(2+) indicators that do not penetrate membranes offer the prospect of rendering the release of Zn(2+) visible. Here, I take a critical look at fluorimetric imaging experiments devised to determine whether Zn(2+) is released and show that they are particularly susceptible to artifacts. Moreover, I will argue that recent experiments suggest that, rather than being released, Zn(2+) is presented to the extracellular space firmly coordinated to presynaptic macromolecules.

  7. Spike timing regulation on the millisecond scale by distributed synaptic plasticity at the cerebellum input stage: a simulation study

    Directory of Open Access Journals (Sweden)

    Jesus A Garrido

    2013-05-01

    Full Text Available The way long-term synaptic plasticity regulates neuronal spike patterns is not completely understood. This issue is especially relevant for the cerebellum, which is endowed with several forms of long-term synaptic plasticity and has been predicted to operate as a timing and a learning machine. Here we have used a computational model to simulate the impact of multiple distributed synaptic weights in the cerebellar granular layer network. In response to mossy fiber bursts, synaptic weights at multiple connections played a crucial role to regulate spike number and positioning in granule cells. The weight at mossy fiber to granule cell synapses regulated the delay of the first spike and the weight at mossy fiber and parallel fiber to Golgi cell synapses regulated the duration of the time-window during which the first-spike could be emitted. Moreover, the weights of synapses controlling Golgi cell activation regulated the intensity of granule cell inhibition and therefore the number of spikes that could be emitted. First spike timing was regulated with millisecond precision and the number of spikes ranged from 0 to 3. Interestingly, different combinations of synaptic weights optimized either first-spike timing precision or spike number, efficiently controlling transmission and filtering properties. These results predict that distributed synaptic plasticity regulates the emission of quasi-digital spike patterns on the millisecond time scale and allows the cerebellar granular layer to flexibly control burst transmission along the mossy fiber pathway.

  8. About Connections

    Directory of Open Access Journals (Sweden)

    Kathleen S Rockland

    2015-05-01

    Full Text Available Despite the attention attracted by connectomics, one can lose sight of the very real questions concerning What are connections? In the neuroimaging community, structural connectivity is ground truth and underlying constraint on functional or effective connectivity. It is referenced to underlying anatomy; but, as increasingly remarked, there is a large gap between the wealth of human brain mapping and the relatively scant data on actual anatomical connectivity. Moreover, connections have typically been discussed as pairwise, point x projecting to point y (or: to points y and z, or more recently, in graph theoretical terms, as nodes or regions and the interconnecting edges. This is a convenient shorthand, but tends not to capture the richness and nuance of basic anatomical properties as identified in the classic tradition of tracer studies. The present short review accordingly revisits connectional weights, heterogeneity, reciprocity, topography, and hierarchical organization, drawing on concrete examples. The emphasis is on presynaptic long-distance connections, motivated by the intention to probe current assumptions and promote discussions about further progress and synthesis.

  9. Extracellular ATP hydrolysis inhibits synaptic transmission by increasing ph buffering in the synaptic cleft.

    Directory of Open Access Journals (Sweden)

    Rozan Vroman

    2014-05-01

    Full Text Available Neuronal computations strongly depend on inhibitory interactions. One such example occurs at the first retinal synapse, where horizontal cells inhibit photoreceptors. This interaction generates the center/surround organization of bipolar cell receptive fields and is crucial for contrast enhancement. Despite its essential role in vision, the underlying synaptic mechanism has puzzled the neuroscience community for decades. Two competing hypotheses are currently considered: an ephaptic and a proton-mediated mechanism. Here we show that horizontal cells feed back to photoreceptors via an unexpected synthesis of the two. The first one is a very fast ephaptic mechanism that has no synaptic delay, making it one of the fastest inhibitory synapses known. The second one is a relatively slow (τ≈200 ms, highly intriguing mechanism. It depends on ATP release via Pannexin 1 channels located on horizontal cell dendrites invaginating the cone synaptic terminal. The ecto-ATPase NTPDase1 hydrolyses extracellular ATP to AMP, phosphate groups, and protons. The phosphate groups and protons form a pH buffer with a pKa of 7.2, which keeps the pH in the synaptic cleft relatively acidic. This inhibits the cone Ca²⁺ channels and consequently reduces the glutamate release by the cones. When horizontal cells hyperpolarize, the pannexin 1 channels decrease their conductance, the ATP release decreases, and the formation of the pH buffer reduces. The resulting alkalization in the synaptic cleft consequently increases cone glutamate release. Surprisingly, the hydrolysis of ATP instead of ATP itself mediates the synaptic modulation. Our results not only solve longstanding issues regarding horizontal cell to photoreceptor feedback, they also demonstrate a new form of synaptic modulation. Because pannexin 1 channels and ecto-ATPases are strongly expressed in the nervous system and pannexin 1 function is implicated in synaptic plasticity, we anticipate that this novel form

  10. Neural circuit dysfunction in schizophrenia: Insights from animal models.

    Science.gov (United States)

    Sigurdsson, T

    2016-05-03

    Despite decades of research, the neural circuit abnormalities underlying schizophrenia remain elusive. Although studies on schizophrenia patients have yielded important insights they have not been able to fully reveal the details of how neural circuits are disrupted in the disease, which is essential for understanding its pathophysiology and developing new treatment strategies. Animal models of schizophrenia are likely to play an important role in this effort. Such models allow neural circuit dysfunction to be investigated in detail and the role of risk factors and pathophysiological mechanisms to be experimentally assessed. The goal of this review is to summarize what we have learned from electrophysiological studies that have examined neural circuit function in animal models of schizophrenia. Although these studies have revealed diverse manifestations of neural circuit dysfunction spanning multiple levels of analysis, common themes have nevertheless emerged across different studies and animal models, revealing a core set of neural circuit abnormalities. These include an imbalance between excitation and inhibition, deficits in synaptic plasticity, disruptions in local and long-range synchrony and abnormalities in dopaminergic signaling. The relevance of these findings to the pathophysiology of the disease is discussed, as well as outstanding questions for future research.

  11. Visual experience modulates spatio-temporal dynamics of circuit activation

    Directory of Open Access Journals (Sweden)

    Lang eWang

    2011-06-01

    Full Text Available Persistent reduction in sensory drive in early development results in multiple plastic changes of different cortical synapses. How these experience-dependent modifications affect the spatio-temporal dynamics of signal propagation in neocortical circuits is poorly understood. Here we demonstrate that brief visual deprivation significantly affects the propagation of electrical signals in the primary visual cortex. The spatio-temporal spread of circuit activation upon direct stimulation of its input layer (Layer 4 is reduced, as is the activation of Layer 2/3 – the main recipient of the output from Layer 4. Our data suggest that the decrease in spatio-temporal activation of L2/3 depends on reduced L4 output, and is not intrinsically generated within L2/3. The data shown here suggest that changes in the synaptic components of the visual cortical circuit result not only in alteration of local integration of excitatory and inhibitory inputs, but also in a significant decrease in overall circuit activation. Furthermore, our data indicate a differential effect of visual deprivation on L4 and L2/3, suggesting that while feedforward activation of L2/3 is reduced, its activation by long range, within layer inputs is unaltered. Thus, brief visual deprivation induces experience-dependent circuit re-organization by modulating not only circuit excitability, but also the spatio-temporal patterns of cortical activation within and between layers.

  12. Gendered Connections

    DEFF Research Database (Denmark)

    Jensen, Steffen Bo

    2009-01-01

    This article explores the gendered nature of urban politics in Cape Town by focusing on a group of female, township politicians. Employing the Deleuzian concept of `wild connectivity', it argues that these politically entrepreneurial women were able to negotiate a highly volatile urban landscape...... space also drew on quite traditional notions of female respectability. Furthermore, the article argues, the form of wild connectivity to an extent was a function of the political transition, which destabilized formal structures of gendered authority. It remains a question whether this form...... of connectivity might endure, as Capetonian politics assumes a post-apartheid structure....

  13. Neuromodulatory state and sex specify alternative behaviors through antagonistic synaptic pathways in C. elegans.

    Science.gov (United States)

    Jang, Heeun; Kim, Kyuhyung; Neal, Scott J; Macosko, Evan; Kim, Dongshin; Butcher, Rebecca A; Zeiger, Danna M; Bargmann, Cornelia I; Sengupta, Piali

    2012-08-23

    Pheromone responses are highly context dependent. For example, the C. elegans pheromone ascaroside C9 (ascr#3) is repulsive to wild-type hermaphrodites, attractive to wild-type males, and usually neutral to "social" hermaphrodites with reduced activity of the npr-1 neuropeptide receptor gene. We show here that these distinct behavioral responses arise from overlapping push-pull circuits driven by two classes of pheromone-sensing neurons. The ADL sensory neurons detect C9 and, in wild-type hermaphrodites, drive C9 repulsion through their chemical synapses. In npr-1 mutant hermaphrodites, C9 repulsion is reduced by the recruitment of a gap junction circuit that antagonizes ADL chemical synapses. In males, ADL sensory responses are diminished; in addition, a second pheromone-sensing neuron, ASK, antagonizes C9 repulsion. The additive effects of these antagonistic circuit elements generate attractive, repulsive, or neutral pheromone responses. Neuronal modulation by circuit state and sex, and flexibility in synaptic output pathways, may permit small circuits to maximize their adaptive behavioral outputs.

  14. Synchronizing Hyperchaotic Circuits

    DEFF Research Database (Denmark)

    Tamasevicius, Arunas; Cenys, Antanas; Namajunas, Audrius;

    1997-01-01

    Regarding possible applications to secure communications the technique of synchronizing hyperchaotic circuits with a single dynamical variable is discussed. Several specific examples including the fourth-order circuits with two positive Lyapunov exponents as well as the oscillator with a delay line...

  15. A Virtual Circuits Lab

    Science.gov (United States)

    Vick, Matthew E.

    2010-01-01

    The University of Colorado's Physics Education Technology (PhET) website offers free, high-quality simulations of many physics experiments that can be used in the classroom. The Circuit Construction Kit, for example, allows students to safely and constructively play with circuit components while learning the mathematics behind many circuit…

  16. Synaptic plasticity can produce and enhance direction selectivity.

    Directory of Open Access Journals (Sweden)

    Sean Carver

    2008-02-01

    Full Text Available The discrimination of the direction of movement of sensory images is critical to the control of many animal behaviors. We propose a parsimonious model of motion processing that generates direction selective responses using short-term synaptic depression and can reproduce salient features of direction selectivity found in a population of neurons in the midbrain of the weakly electric fish Eigenmannia virescens. The model achieves direction selectivity with an elementary Reichardt motion detector: information from spatially separated receptive fields converges onto a neuron via dynamically different pathways. In the model, these differences arise from convergence of information through distinct synapses that either exhibit or do not exhibit short-term synaptic depression--short-term depression produces phase-advances relative to nondepressing synapses. Short-term depression is modeled using two state-variables, a fast process with a time constant on the order of tens to hundreds of milliseconds, and a slow process with a time constant on the order of seconds to tens of seconds. These processes correspond to naturally occurring time constants observed at synapses that exhibit short-term depression. Inclusion of the fast process is sufficient for the generation of temporal disparities that are necessary for direction selectivity in the elementary Reichardt circuit. The addition of the slow process can enhance direction selectivity over time for stimuli that are sustained for periods of seconds or more. Transient (i.e., short-duration stimuli do not evoke the slow process and therefore do not elicit enhanced direction selectivity. The addition of a sustained global, synchronous oscillation in the gamma frequency range can, however, drive the slow process and enhance direction selectivity to transient stimuli. This enhancement effect does not, however, occur for all combinations of model parameters. The ratio of depressing and nondepressing synapses

  17. Promoter-Specific Effects of DREADD Modulation on Hippocampal Synaptic Plasticity and Memory Formation

    OpenAIRE

    Lopez, AJ; Kramar, E; Matheos, DP; White, AO; Kwapis, J; Vogel-Ciernia, A; Sakata, K.; Espinoza, M; Wood, MA

    2016-01-01

    Designer receptors exclusively activated by designer drug (DREADDs) are a novel tool with the potential to bidirectionally drive cellular, circuit, and ultimately, behavioral changes. We used DREADDs to evaluate memory formation in a hippocampus-dependent task in mice and effects on synaptic physiology in the dorsal hippocampus. We expressed neuron-specific (hSyn promoter) DREADDs that were either excitatory (HM3D) or inhibitory (HM4D) in the dorsal hippocampus. As predicted, hSyn–HM3D was ab...

  18. Design and implementation of a hybrid circuit system for micro sensor signal processing*

    Institute of Scientific and Technical Information of China (English)

    Wang Zhuping; Chen Jing; Liu Ruqing

    2011-01-01

    This paper covers a micro sensor analog signal processing circuit system (MASPS) chip with low power and a digital signal processing circuit board implementation including hardware connection and software design.Attention has been paid to incorporate the MASPS chip into the digital circuit board. The ultimate aim is to form a hybrid circuit used for mixed-signal processing, which can be applied to a micro sensor flow monitoring system.

  19. HR Connect

    Data.gov (United States)

    US Agency for International Development — HR Connect is the USAID HR personnel system which allows HR professionals to process HR actions related to employee's personal and position information. This system...

  20. Logarithmic circuit with wide dynamic range

    Science.gov (United States)

    Wiley, P. H.; Manus, E. A. (Inventor)

    1978-01-01

    A circuit deriving an output voltage that is proportional to the logarithm of a dc input voltage susceptible to wide variations in amplitude includes a constant current source which forward biases a diode so that the diode operates in the exponential portion of its voltage versus current characteristic, above its saturation current. The constant current source includes first and second, cascaded feedback, dc operational amplifiers connected in negative feedback circuit. An input terminal of the first amplifier is responsive to the input voltage. A circuit shunting the first amplifier output terminal includes a resistor in series with the diode. The voltage across the resistor is sensed at the input of the second dc operational feedback amplifier. The current flowing through the resistor is proportional to the input voltage over the wide range of variations in amplitude of the input voltage.

  1. Thermodynamics of squeezed states in mesoscopic circuits

    Institute of Scientific and Technical Information of China (English)

    Ji Ying-Hua; Luo Hai-Mei; Liu Qing; Lei Min-Sheng

    2005-01-01

    Based on the information theory, we present a density matrix to discuss coherent and squeezed states in a mesoscopic LC circuit with time-dependent frequency. With the relevant operators included in the density matrix, a connection between the appearance of coherent and squeezed states is established, i.e., the quantum state evolution of the system is closely related to the initial state. Generally speaking, due to the effect of environment temperature, the mesoscopic LC circuit will evolve to a squeezed state when it initially lies in an excited state. In particular, at a low temperature, step changes of circuit parameters will result in a squeezed minimum uncertainty state if the resonance frequency remains the same after the change.

  2. Synaptic plasticity in a recurrent neural network for versatile and adaptive behaviors of a walking robot

    DEFF Research Database (Denmark)

    Grinke, Eduard; Tetzlaff, Christian; Wörgötter, Florentin

    2015-01-01

    mechanisms with plasticity, exteroceptive sensory feedback, and biomechanics. The neural mechanisms consist of adaptive neural sensory processing and modular neural locomotion control. The sensory processing is based on a small recurrent neural network consisting of two fully connected neurons. Online...... correlation-based learning with synaptic scaling is applied to adequately change the connections of the network. By doing so, we can effectively exploit neural dynamics (i.e., hysteresis effects and single attractors) in the network to generate different turning angles with short-term memory for a walking...

  3. Molecular mechanisms of synaptic plasticity and memory.

    Science.gov (United States)

    Elgersma, Y; Silva, A J

    1999-04-01

    To unravel the molecular and cellular bases of learning and memory is one of the most ambitious goals of modern science. The progress of recent years has not only brought us closer to understanding the molecular mechanisms underlying stable, long-lasting changes in synaptic strength, but it has also provided further evidence that these mechanisms are required for memory formation.

  4. Targeting synaptic dysfunction in Alzheimer's disease therapy.

    Science.gov (United States)

    Nisticò, Robert; Pignatelli, Marco; Piccinin, Sonia; Mercuri, Nicola B; Collingridge, Graham

    2012-12-01

    In the past years, major efforts have been made to understand the genetics and molecular pathogenesis of Alzheimer's disease (AD), which has been translated into extensive experimental approaches aimed at slowing down or halting disease progression. Advances in transgenic (Tg) technologies allowed the engineering of different mouse models of AD recapitulating a range of AD-like features. These Tg models provided excellent opportunities to analyze the bases for the temporal evolution of the disease. Several lines of evidence point to synaptic dysfunction as a cause of AD and that synapse loss is a pathological correlate associated with cognitive decline. Therefore, the phenotypic characterization of these animals has included electrophysiological studies to analyze hippocampal synaptic transmission and long-term potentiation, a widely recognized cellular model for learning and memory. Transgenic mice, along with non-Tg models derived mainly from exogenous application of Aβ, have also been useful experimental tools to test the various therapeutic approaches. As a result, numerous pharmacological interventions have been reported to attenuate synaptic dysfunction and improve behavior in the different AD models. To date, however, very few of these findings have resulted in target validation or successful translation into disease-modifying compounds in humans. Here, we will briefly review the synaptic alterations across the different animal models and we will recapitulate the pharmacological strategies aimed at rescuing hippocampal plasticity phenotypes. Finally, we will highlight intrinsic limitations in the use of experimental systems and related challenges in translating preclinical studies into human clinical trials.

  5. Synaptic plasticity and the warburg effect

    KAUST Repository

    Magistretti, Pierre J.

    2014-01-01

    Functional brain imaging studies show that in certain brain regions glucose utilization exceeds oxygen consumption, indicating the predominance of aerobic glycolysis. In this issue, Goyal et al. (2014) report that this metabolic profile is associated with an enrichment in the expression of genes involved in synaptic plasticity and remodeling processes. © 2014 Elsevier Inc.

  6. Approximate circuits for increased reliability

    Energy Technology Data Exchange (ETDEWEB)

    Hamlet, Jason R.; Mayo, Jackson R.

    2015-12-22

    Embodiments of the invention describe a Boolean circuit having a voter circuit and a plurality of approximate circuits each based, at least in part, on a reference circuit. The approximate circuits are each to generate one or more output signals based on values of received input signals. The voter circuit is to receive the one or more output signals generated by each of the approximate circuits, and is to output one or more signals corresponding to a majority value of the received signals. At least some of the approximate circuits are to generate an output value different than the reference circuit for one or more input signal values; however, for each possible input signal value, the majority values of the one or more output signals generated by the approximate circuits and received by the voter circuit correspond to output signal result values of the reference circuit.

  7. Approximate circuits for increased reliability

    Energy Technology Data Exchange (ETDEWEB)

    Hamlet, Jason R.; Mayo, Jackson R.

    2015-08-18

    Embodiments of the invention describe a Boolean circuit having a voter circuit and a plurality of approximate circuits each based, at least in part, on a reference circuit. The approximate circuits are each to generate one or more output signals based on values of received input signals. The voter circuit is to receive the one or more output signals generated by each of the approximate circuits, and is to output one or more signals corresponding to a majority value of the received signals. At least some of the approximate circuits are to generate an output value different than the reference circuit for one or more input signal values; however, for each possible input signal value, the majority values of the one or more output signals generated by the approximate circuits and received by the voter circuit correspond to output signal result values of the reference circuit.

  8. Synaptic Plasticity, Dementia and Alzheimer Disease.

    Science.gov (United States)

    Skaper, Stephen D; Facci, Laura; Zusso, Morena; Giusti, Pietro

    2017-01-13

    Neuroplasticity is not only shaped by learning and memory but is also a mediator of responses to neuron attrition and injury (compensatory plasticity). As an ongoing process it reacts to neuronal cell activity and injury, death, and genesis, which encompasses the modulation of structural and functional processes of axons, dendrites, and synapses. The range of structural elements that comprise plasticity includes long-term potentiation (a cellular correlate of learning and memory), synaptic efficacy and remodelling, synaptogenesis, axonal sprouting and dendritic remodelling, and neurogenesis and recruitment. Degenerative diseases of the human brain continue to pose one of biomedicine's most intractable problems. Research on human neurodegeneration is now moving from descriptive to mechanistic analyses. At the same time, it is increasing apparent that morphological lesions traditionally used by neuropathologists to confirm post-mortem clinical diagnosis might furnish us with an experimentally tractable handle to understand causative pathways. Consider the aging-dependent neurodegenerative disorder Alzheimer's disease (AD) which is characterised at the neuropathological level by deposits of insoluble amyloid b-peptide (Ab) in extracellular plaques and aggregated tau protein, which is found largely in the intracellular neurofibrillary tangles. We now appreciate that mild cognitive impairment in early AD may be due to synaptic dysfunction caused by accumulation of non-fibrillar, oligomeric Ab, occurring well in advance of evident widespread synaptic loss and neurodegeneration. Soluble Ab oligomers can adversely affect synaptic structure and plasticity at extremely low concentrations, although the molecular substrates by which synaptic memory mechanisms are disrupted remain to be fully elucidated. The dendritic spine constitutes a primary locus of excitatory synaptic transmission in the mammalian central nervous system. These structures protruding from dendritic shafts

  9. Numerical approach of the quantum circuit theory

    Science.gov (United States)

    Silva, J. J. B.; Duarte-Filho, G. C.; Almeida, F. A. G.

    2017-03-01

    In this paper we develop a numerical method based on the quantum circuit theory to approach the coherent electronic transport in a network of quantum dots connected with arbitrary topology. The algorithm was employed in a circuit formed by quantum dots connected each other in a shape of a linear chain (associations in series), and of a ring (associations in series, and in parallel). For both systems we compute two current observables: conductance and shot noise power. We find an excellent agreement between our numerical results and the ones found in the literature. Moreover, we analyze the algorithm efficiency for a chain of quantum dots, where the mean processing time exhibits a linear dependence with the number of quantum dots in the array.

  10. Optimal and Local Connectivity Between Neuron and Synapse Array in the Quantum Dot/Silicon Brain

    Science.gov (United States)

    Duong, Tuan A.; Assad, Christopher; Thakoor, Anikumar P.

    2010-01-01

    This innovation is used to connect between synapse and neuron arrays using nanowire in quantum dot and metal in CMOS (complementary metal oxide semiconductor) technology to enable the density of a brain-like connection in hardware. The hardware implementation combines three technologies: 1. Quantum dot and nanowire-based compact synaptic cell (50x50 sq nm) with inherently low parasitic capacitance (hence, low dynamic power approx.l0(exp -11) watts/synapse), 2. Neuron and learning circuits implemented in 50-nm CMOS technology, to be integrated with quantum dot and nanowire synapse, and 3. 3D stacking approach to achieve the overall numbers of high density O(10(exp 12)) synapses and O(10(exp 8)) neurons in the overall system. In a 1-sq cm of quantum dot layer sitting on a 50-nm CMOS layer, innovators were able to pack a 10(exp 6)-neuron and 10(exp 10)-synapse array; however, the constraint for the connection scheme is that each neuron will receive a non-identical 10(exp 4)-synapse set, including itself, via its efficacy of the connection. This is not a fully connected system where the 100x100 synapse array only has a 100-input data bus and 100-output data bus. Due to the data bus sharing, it poses a great challenge to have a complete connected system, and its constraint within the quantum dot and silicon wafer layer. For an effective connection scheme, there are three conditions to be met: 1. Local connection. 2. The nanowire should be connected locally, not globally from which it helps to maximize the data flow by sharing the same wire space location. 3. Each synapse can have an alternate summation line if needed (this option is doable based on the simple mask creation). The 10(exp 3)x10(exp 3)-neuron array was partitioned into a 10-block, 10(exp 2)x10(exp 3)-neuron array. This building block can be completely mapped within itself (10,000 synapses to a neuron).

  11. The Roles of Protein Expression in Synaptic Plasticity and Memory Consolidation

    Directory of Open Access Journals (Sweden)

    Tali eRosenberg

    2014-11-01

    Full Text Available The amount and availability of proteins are regulated by their synthesis, degradation, and transport. These processes can specifically, locally, and temporally regulate a protein or a population of proteins, thus affecting numerous biological processes in health and disease states. Accordingly, malfunction in the processes of protein turnover and localization underlies different neuronal diseases. However, as early as a century ago, it was recognized that there is a specific need for normal macromolecular synthesis in a specific fragment of the learning process, memory consolidation, which takes place minutes to hours following acquisition. Memory consolidation is the process by which fragile short-term memory is converted into stable long-term memory. It is accepted today that synaptic plasticity is a cellular mechanism of learning and memory processes. Interestingly, similar molecular mechanisms subserve both memory and synaptic plasticity consolidation. In this review, we survey the current view on the connection between memory consolidation processes and proteostasis, i.e., maintaining the protein contents at the neuron and the synapse. In addition, we describe the technical obstacles and possible new methods to determine neuronal proteostasis of synaptic function and better explain the process of memory and synaptic plasticity consolidation.

  12. Age-related synaptic loss of the medial olivocochlear efferent innervation

    Directory of Open Access Journals (Sweden)

    Schrader Angela

    2010-11-01

    Full Text Available Abstract Age-related functional decline of the nervous system is consistently observed, though cellular and molecular events responsible for this decline remain largely unknown. One of the most prevalent age-related functional declines is age-related hearing loss (presbycusis, a major cause of which is the loss of outer hair cells (OHCs and spiral ganglion neurons. Previous studies have also identified an age-related functional decline in the medial olivocochlear (MOC efferent system prior to age-related loss of OHCs. The present study evaluated the hypothesis that this functional decline of the MOC efferent system is due to age-related synaptic loss of the efferent innervation of the OHCs. To this end, we used a recently-identified transgenic mouse line in which the expression of yellow fluorescent protein (YFP, under the control of neuron-specific elements from the thy1 gene, permits the visualization of the synaptic connections between MOC efferent fibers and OHCs. In this model, there was a dramatic synaptic loss between the MOC efferent fibers and the OHCs in older mice. However, age-related loss of efferent synapses was independent of OHC status. These data demonstrate for the first time that age-related loss of efferent synapses may contribute to the functional decline of the MOC efferent system and that this synaptic loss is not necessary for age-related loss of OHCs.

  13. A computational study of the role of spike broadening in synaptic facilitation of Hermissenda.

    Science.gov (United States)

    Flynn, Mark; Cai, Yidao; Baxter, Douglas A; Crow, Terry

    2003-01-01

    Pavlovian conditioning in Hermissenda produces a decrease in voltage-dependent (I(K,A) and I(Ca)) and Ca2+-dependent (I(K,Ca)) currents, and an increase in the action potential (AP) duration in type B-photoreceptors. In addition, synaptic connections between B and A photoreceptors and B photoreceptor and type I interneurons are facilitated. The increase in AP duration, produced by decreasing one or more K+ currents, may account for synaptic facilitation. The present study examined this issue by using a mathematical model of the B-photoreceptor and the neurosimulator SNNAP. In the model, decreasing g(K,A) by 70% increased the duration of the AP in the terminal by 41% and Ca2+ influx by 30%. However, if the decrease in g(K,A) was combined with a decrease in g(Ca), similar to what has been reported experimentally, the Ca2+ influx decreased by 54%. Therefore, the concomitant change in I(Ca) counter-acted the broadening-induced increase in Ca2+ influx in the synaptic terminal. This result suggests that a spike-duration independent process must contribute to the synaptic facilitation observed following Pavlovian conditioning.

  14. A Single Aplysia Neurotrophin Mediates Synaptic Facilitation via Differentially Processed Isoforms

    Directory of Open Access Journals (Sweden)

    Stefan R. Kassabov

    2013-04-01

    Full Text Available Neurotrophins control the development and adult plasticity of the vertebrate nervous system. Failure to identify invertebrate neurotrophin orthologs, however, has precluded studies in invertebrate models, limiting our understanding of fundamental aspects of neurotrophin biology and function. We identified a neurotrophin (ApNT and Trk receptor (ApTrk in the mollusk Aplysia and found that they play a central role in learning-related synaptic plasticity. Blocking ApTrk signaling impairs long-term facilitation, whereas augmenting ApNT expression enhances it and induces the growth of new synaptic varicosities at the monosynaptic connection between sensory and motor neurons of the gill-withdrawal reflex. Unlike vertebrate neurotrophins, ApNT has multiple coding exons and exerts distinct synaptic effects through differentially processed and secreted splice isoforms. Our findings demonstrate the existence of bona fide neurotrophin signaling in invertebrates and reveal a posttranscriptional mechanism that regulates neurotrophin processing and the release of proneurotrophins and mature neurotrophins that differentially modulate synaptic plasticity.

  15. Interneurons and oligodendrocyte progenitors form a structured synaptic network in the developing neocortex.

    Science.gov (United States)

    Orduz, David; Maldonado, Paloma P; Balia, Maddalena; Vélez-Fort, Mateo; de Sars, Vincent; Yanagawa, Yuchio; Emiliani, Valentina; Angulo, Maria Cecilia

    2015-04-22

    NG2 cells, oligodendrocyte progenitors, receive a major synaptic input from interneurons in the developing neocortex. It is presumed that these precursors integrate cortical networks where they act as sensors of neuronal activity. We show that NG2 cells of the developing somatosensory cortex form a transient and structured synaptic network with interneurons that follows its own rules of connectivity. Fast-spiking interneurons, highly connected to NG2 cells, target proximal subcellular domains containing GABAA receptors with γ2 subunits. Conversely, non-fast-spiking interneurons, poorly connected with these progenitors, target distal sites lacking this subunit. In the network, interneuron-NG2 cell connectivity maps exhibit a local spatial arrangement reflecting innervation only by the nearest interneurons. This microcircuit architecture shows a connectivity peak at PN10, coinciding with a switch to massive oligodendrocyte differentiation. Hence, GABAergic innervation of NG2 cells is temporally and spatially regulated from the subcellular to the network level in coordination with the onset of oligodendrogenesis.

  16. Interaction of baseline synaptic noise and Ia EPSPs: evidence for appreciable negative correlation under physiological conditions.

    Science.gov (United States)

    Solodkin, M; Jiménez, I; Collins, W F; Mendell, L M; Rudomin, P

    1991-04-01

    1. In the anesthetized cat, simultaneous intracellular recordings from pairs of spinal motoneurons were undertaken to see whether the amplitude of single-fiber excitatory postsynaptic potentials (EPSPs) in both cells fluctuated in a coordinated manner that would indicate correlative mechanisms at either pre- or post-synaptic level. Although these recordings revealed correlated fluctuations in the baseline, the single-fiber Ia/EPSPs recorded with the spike-triggered averaging technique exhibited no correlated fluctuations and, unexpectedly, virtually no increase in baseline variance associated with the EPSP. However, the fact that these experiments were carried out under conditions of high baseline synaptic noise (i.e., with muscle stretch) may have influenced the outcome because of interaction between EPSP and synaptic noise, and this possibility was evaluated explicitly. 2. A given connection was studied under low noise by electrically stimulating a single Ia fiber in the absence of muscle stretch. The same connection was analyzed under conditions of high noise by activating the fiber and all other stretch receptor afferents with muscle stretch and by using spike-triggered averaging to extract the EPSP. The differences in mean EPSP amplitude at a given connection under conditions of low noise and high noise were minimal. 3. Fluctuations in EPSP amplitude were then determined to see whether these were influenced by presence of baseline synaptic noise and whether the interaction was nonlinear. Two methods were used to measure EPSP fluctuations: measurement of the variance associated with the EPSP, and determination by the use of deconvolution methods of the discrete amplitude components associated with the EPSP. 4. An increase in baseline variance was observed during the EPSP evoked under low noise conditions at all six connections studied in this way. This increase disappeared at two of these connections when examined under high noise. This may help to explain the

  17. Bilinearity in spatiotemporal integration of synaptic inputs.

    Directory of Open Access Journals (Sweden)

    Songting Li

    2014-12-01

    Full Text Available Neurons process information via integration of synaptic inputs from dendrites. Many experimental results demonstrate dendritic integration could be highly nonlinear, yet few theoretical analyses have been performed to obtain a precise quantitative characterization analytically. Based on asymptotic analysis of a two-compartment passive cable model, given a pair of time-dependent synaptic conductance inputs, we derive a bilinear spatiotemporal dendritic integration rule. The summed somatic potential can be well approximated by the linear summation of the two postsynaptic potentials elicited separately, plus a third additional bilinear term proportional to their product with a proportionality coefficient [Formula: see text]. The rule is valid for a pair of synaptic inputs of all types, including excitation-inhibition, excitation-excitation, and inhibition-inhibition. In addition, the rule is valid during the whole dendritic integration process for a pair of synaptic inputs with arbitrary input time differences and input locations. The coefficient [Formula: see text] is demonstrated to be nearly independent of the input strengths but is dependent on input times and input locations. This rule is then verified through simulation of a realistic pyramidal neuron model and in electrophysiological experiments of rat hippocampal CA1 neurons. The rule is further generalized to describe the spatiotemporal dendritic integration of multiple excitatory and inhibitory synaptic inputs. The integration of multiple inputs can be decomposed into the sum of all possible pairwise integration, where each paired integration obeys the bilinear rule. This decomposition leads to a graph representation of dendritic integration, which can be viewed as functionally sparse.

  18. Four-gate transistor analog multiplier circuit

    Science.gov (United States)

    Mojarradi, Mohammad M. (Inventor); Blalock, Benjamin (Inventor); Cristoloveanu, Sorin (Inventor); Chen, Suheng (Inventor); Akarvardar, Kerem (Inventor)

    2011-01-01

    A differential output analog multiplier circuit utilizing four G.sup.4-FETs, each source connected to a current source. The four G.sup.4-FETs may be grouped into two pairs of two G.sup.4-FETs each, where one pair has its drains connected to a load, and the other par has its drains connected to another load. The differential output voltage is taken at the two loads. In one embodiment, for each G.sup.4-FET, the first and second junction gates are each connected together, where a first input voltage is applied to the front gates of each pair, and a second input voltage is applied to the first junction gates of each pair. Other embodiments are described and claimed.

  19. The Synaptic and Morphological Basis of Orientation Selectivity in a Polyaxonal Amacrine Cell of the Rabbit Retina.

    Science.gov (United States)

    Murphy-Baum, Benjamin L; Taylor, W Rowland

    2015-09-30

    Much of the computational power of the retina derives from the activity of amacrine cells, a large and diverse group of GABAergic and glycinergic inhibitory interneurons. Here, we identify an ON-type orientation-selective, wide-field, polyaxonal amacrine cell (PAC) in the rabbit retina and demonstrate how its orientation selectivity arises from the structure of the dendritic arbor and the pattern of excitatory and inhibitory inputs. Excitation from ON bipolar cells and inhibition arising from the OFF pathway converge to generate a quasi-linear integration of visual signals in the receptive field center. This serves to suppress responses to high spatial frequencies, thereby improving sensitivity to larger objects and enhancing orientation selectivity. Inhibition also regulates the magnitude and time course of excitatory inputs to this PAC through serial inhibitory connections onto the presynaptic terminals of ON bipolar cells. This presynaptic inhibition is driven by graded potentials within local microcircuits, similar in extent to the size of single bipolar cell receptive fields. Additional presynaptic inhibition is generated by spiking amacrine cells on a larger spatial scale covering several hundred microns. The orientation selectivity of this PAC may be a substrate for the inhibition that mediates orientation selectivity in some types of ganglion cells. Significance statement: The retina comprises numerous excitatory and inhibitory circuits that encode specific features in the visual scene, such as orientation, contrast, or motion. Here, we identify a wide-field inhibitory neuron that responds to visual stimuli of a particular orientation, a feature selectivity that is primarily due to the elongated shape of the dendritic arbor. Integration of convergent excitatory and inhibitory inputs from the ON and OFF visual pathways suppress responses to small objects and fine textures, thus enhancing selectivity for larger objects. Feedback inhibition regulates the

  20. Composite behaviors of dual meminductor circuits

    Institute of Scientific and Technical Information of China (English)

    郑辞晏; 于东升; 梁燕; 陈孟科

    2015-01-01

    This paper focuses on analyzing the composite dynamic behaviors of two meminductors in serial and parallel connec-tions with different polarities. Based on the constitutive relations, two time-integral-of-flux (TIF) controlled meminductors are adopted to theoretically demonstrate the variation of memductance in terms of TIF, charge, flux, and current. By uti-lizing a floating memristor-less meminductor emulator, the theoretical analysis reported in this paper is confirmed via a PSPICE simulation study and hardware experiment. Good agreement among theoretical analysis, simulation, and hardware validation confirms that dual meminductor circuits in composite connections behave as a new meminductor with higher complexity.

  1. Cognitive control network connectivity in adolescent women with and without a parental history of depression

    Directory of Open Access Journals (Sweden)

    Peter C. Clasen

    2014-01-01

    Conclusions: Depressed parents may transmit depression vulnerability to their adolescent daughters via alterations in functional connectivity within neural circuits that underlie cognitive control of emotional information.

  2. Troubleshooting analog circuits

    CERN Document Server

    Pease, Robert A

    1991-01-01

    Troubleshooting Analog Circuits is a guidebook for solving product or process related problems in analog circuits. The book also provides advice in selecting equipment, preventing problems, and general tips. The coverage of the book includes the philosophy of troubleshooting; the modes of failure of various components; and preventive measures. The text also deals with the active components of analog circuits, including diodes and rectifiers, optically coupled devices, solar cells, and batteries. The book will be of great use to both students and practitioners of electronics engineering. Other

  3. Modern TTL circuits manual

    CERN Document Server

    Marston, R M

    2013-01-01

    Modern TTL Circuits Manual provides an introduction to the basic principles of Transistor-Transistor Logic (TTL). This book outlines the major features of the 74 series of integrated circuits (ICs) and introduces the various sub-groups of the TTL family.Organized into seven chapters, this book begins with an overview of the basics of digital ICs. This text then examines the symbology and mathematics of digital logic. Other chapters consider a variety of topics, including waveform generator circuitry, clocked flip-flop and counter circuits, special counter/dividers, registers, data latches, com

  4. Plasmonic Nanoguides and Circuits

    CERN Document Server

    Bozhevolnyi, Sergey

    2008-01-01

    Modern communication systems dealing with huge amounts of data at ever increasing speed try to utilize the best aspects of electronic and optical circuits. Electronic circuits are tiny but their operation speed is limited, whereas optical circuits are extremely fast but their sizes are limited by diffraction. Waveguide components utilizing surface plasmon (SP) modes were found to combine the huge optical bandwidth and compactness of electronics, and plasmonics thereby began to be considered as the next chip-scale technology. In this book, the authors concentrate on the SP waveguide configurati

  5. Pragmatic circuits frequency domain

    CERN Document Server

    Eccles, William

    2006-01-01

    Pragmatic Circuits: Frequency Domain goes through the Laplace transform to get from the time domain to topics that include the s-plane, Bode diagrams, and the sinusoidal steady state. This second of three volumes ends with a-c power, which, although it is just a special case of the sinusoidal steady state, is an important topic with unique techniques and terminology. Pragmatic Circuits: Frequency Domain is focused on the frequency domain. In other words, time will no longer be the independent variable in our analysis. The two other volumes in the Pragmatic Circuits series include titles on DC

  6. Optoelectronics circuits manual

    CERN Document Server

    Marston, R M

    2013-01-01

    Optoelectronics Circuits Manual covers the basic principles and characteristics of the best known types of optoelectronic devices, as well as the practical applications of many of these optoelectronic devices. The book describes LED display circuits and LED dot- and bar-graph circuits and discusses the applications of seven-segment displays, light-sensitive devices, optocouplers, and a variety of brightness control techniques. The text also tackles infrared light-beam alarms and multichannel remote control systems. The book provides practical user information and circuitry and illustrations.

  7. Circuit analysis with Multisim

    CERN Document Server

    Baez-Lopez, David

    2011-01-01

    This book is concerned with circuit simulation using National Instruments Multisim. It focuses on the use and comprehension of the working techniques for electrical and electronic circuit simulation. The first chapters are devoted to basic circuit analysis.It starts by describing in detail how to perform a DC analysis using only resistors and independent and controlled sources. Then, it introduces capacitors and inductors to make a transient analysis. In the case of transient analysis, it is possible to have an initial condition either in the capacitor voltage or in the inductor current, or bo

  8. Monolithic microwave integrated circuits

    Science.gov (United States)

    Pucel, R. A.

    Monolithic microwave integrated circuits (MMICs), a new microwave technology which is expected to exert a profound influence on microwave circuit designs for future military systems as well as for the commercial and consumer markets, is discussed. The book contains an historical discussion followed by a comprehensive review presenting the current status in the field. The general topics of the volume are: design considerations, materials and processing considerations, monolithic circuit applications, and CAD, measurement, and packaging techniques. All phases of MMIC technology are covered, from design to testing.

  9. Attachment method for stacked integrated circuit (IC) chips

    Energy Technology Data Exchange (ETDEWEB)

    Bernhardt, Anthony F. (Berkeley, CA); Malba, Vincent (Livermore, CA)

    1999-01-01

    An attachment method for stacked integrated circuit (IC) chips. The method involves connecting stacked chips, such as DRAM memory chips, to each other and/or to a circuit board. Pads on the individual chips are rerouted to form pads on the side of the chip, after which the chips are stacked on top of each other whereby desired interconnections to other chips or a circuit board can be accomplished via the side-located pads. The pads on the side of a chip are connected to metal lines on a flexible plastic tape (flex) by anisotropically conductive adhesive (ACA). Metal lines on the flex are likewise connected to other pads on chips and/or to pads on a circuit board. In the case of a stack of DRAM chips, pads to corresponding address lines on the various chips may be connected to the same metal line on the flex to form an address bus. This method has the advantage of reducing the number of connections required to be made to the circuit board due to bussing; the flex can accommodate dimensional variation in the alignment of chips in the stack; bonding of the ACA is accomplished at low temperature and is otherwise simpler and less expensive than solder bonding; chips can be bonded to the ACA all at once if the sides of the chips are substantially coplanar, as in the case for stacks of identical chips, such as DRAM.

  10. Attachment method for stacked integrated circuit (IC) chips

    Energy Technology Data Exchange (ETDEWEB)

    Bernhardt, A.F.; Malba, V.

    1999-08-03

    An attachment method for stacked integrated circuit (IC) chips is disclosed. The method involves connecting stacked chips, such as DRAM memory chips, to each other and/or to a circuit board. Pads on the individual chips are rerouted to form pads on the side of the chip, after which the chips are stacked on top of each other whereby desired interconnections to other chips or a circuit board can be accomplished via the side-located pads. The pads on the side of a chip are connected to metal lines on a flexible plastic tape (flex) by anisotropically conductive adhesive (ACA). Metal lines on the flex are likewise connected to other pads on chips and/or to pads on a circuit board. In the case of a stack of DRAM chips, pads to corresponding address lines on the various chips may be connected to the same metal line on the flex to form an address bus. This method has the advantage of reducing the number of connections required to be made to the circuit board due to bussing; the flex can accommodate dimensional variation in the alignment of chips in the stack; bonding of the ACA is accomplished at low temperature and is otherwise simpler and less expensive than solder bonding; chips can be bonded to the ACA all at once if the sides of the chips are substantially coplanar, as in the case for stacks of identical chips, such as DRAM. 12 figs.

  11. Dynamic spike threshold and nonlinear dendritic computation for coincidence detection in neuromorphic circuits.

    Science.gov (United States)

    Hsu, Chih-Chieh; Parker, Alice C

    2014-01-01

    We present an electronic cortical neuron incorporating dynamic spike threshold and active dendritic properties. The circuit is simulated using a carbon nanotube field-effect transistor SPICE model. We demonstrate that our neuron has lower spike threshold for coincident synaptic inputs; however when the synaptic inputs are not in synchrony, it requires larger depolarization to evoke the neuron to fire. We also demonstrate that a dendritic spike is key to precisely-timed input-output transformation, produces reliable firing and results in more resilience to input jitter within an individual neuron.

  12. Intrinsic variability in Pv, RRP size, Ca2+ channel repertoire and presynaptic potentiation in individual synaptic boutons

    Directory of Open Access Journals (Sweden)

    Pablo eAriel

    2013-01-01

    Full Text Available The strength of individual synaptic contacts is considered a key modulator of information flow across circuits. Presynaptically the strength can be parsed into two key parameters: the size of the readily-releasable pool (RRP and the probability that a vesicle in that pool will undergo exocytosis when an action potential fires (Pv. How these variables are controlled and the degree to which they vary across individual nerve terminals is crucial to understand synaptic plasticity within neural circuits. Here we report robust measurements of these parameters in rat hippocampal neurons and their variability across populations of individual synapses. We explore the diversity of presynaptic Ca2+ channel repertoires and evaluate their effect on synaptic strength at single boutons. Finally, we study the degree to which synapses can be differentially modified by a known potentiator of presynaptic function, forskolin. Our experiments revealed that both Pv and RRP spanned a large range, even for synapses made by the same axon, demonstrating that presynaptic efficacy is governed locally at the single synapse level. Synapses varied greatly in their dependence on N or P/Q type Ca2+ channels for neurotransmission, but there was no association between specific channel repertoires and synaptic efficacy. Increasing cAMP concentration using forskolin enhanced synaptic transmission in a Ca2+-independent manner that was inversely related with a synapse’s initial Pv, and independent of its RRP size. We propose a simple model based on the relationship between Pv and calcium entry that can account for the variable potentiation of synapses based on initial probability of vesicle fusion.

  13. Synchronization and long-time memory in neural networks with inhibitory hubs and synaptic plasticity

    Science.gov (United States)

    Bertolotti, Elena; Burioni, Raffaella; di Volo, Matteo; Vezzani, Alessandro

    2017-01-01

    We investigate the dynamical role of inhibitory and highly connected nodes (hub) in synchronization and input processing of leaky-integrate-and-fire neural networks with short term synaptic plasticity. We take advantage of a heterogeneous mean-field approximation to encode the role of network structure and we tune the fraction of inhibitory neurons fI and their connectivity level to investigate the cooperation between hub features and inhibition. We show that, depending on fI, highly connected inhibitory nodes strongly drive the synchronization properties of the overall network through dynamical transitions from synchronous to asynchronous regimes. Furthermore, a metastable regime with long memory of external inputs emerges for a specific fraction of hub inhibitory neurons, underlining the role of inhibition and connectivity also for input processing in neural networks.

  14. Connected Traveler

    Energy Technology Data Exchange (ETDEWEB)

    2016-06-01

    The Connected Traveler framework seeks to boost the energy efficiency of personal travel and the overall transportation system by maximizing the accuracy of predicted traveler behavior in response to real-time feedback and incentives. It is anticipated that this approach will establish a feedback loop that 'learns' traveler preferences and customizes incentives to meet or exceed energy efficiency targets by empowering individual travelers with information needed to make energy-efficient choices and reducing the complexity required to validate transportation system energy savings. This handout provides an overview of NREL's Connected Traveler project, including graphics, milestones, and contact information.

  15. Latching overcurrent circuit breaker

    Science.gov (United States)

    Moore, M. L.

    1970-01-01

    Circuit breaker consists of a preset current amplitude sensor, and a lamp-photo-resistor combination in a feedback arrangement which energizes a power switching relay. The ac input power is removed from the load at predetermined current amplitudes.

  16. High temperature circuit breaker

    Science.gov (United States)

    Edwards, R. N.; Travis, E. F.

    1970-01-01

    Alternating current circuit breaker is suitable for reliable long-term service at 1000 deg F in the vacuum conditions of outer space. Construction materials are resistant to nuclear radiation and vacuum welding. Service test conditions and results are given.

  17. Alteration in synaptic junction proteins following traumatic brain injury.

    Science.gov (United States)

    Merlo, Lucia; Cimino, Francesco; Angileri, Filippo Flavio; La Torre, Domenico; Conti, Alfredo; Cardali, Salvatore Massimiliano; Saija, Antonella; Germanò, Antonino

    2014-08-15

    Extensive research and scientific efforts have been focused on the elucidation of the pathobiology of cellular and axonal damage following traumatic brain injury (TBI). Conversely, few studies have specifically addressed the issue of synaptic dysfunction. Synaptic junction proteins may be involved in post-TBI alterations, leading to synaptic loss or disrupted plasticity. A Synapse Protein Database on synapse ontology identified 109 domains implicated in synaptic activities and over 5000 proteins, but few of these demonstrated to play a role in the synaptic dysfunction after TBI. These proteins are involved in neuroplasticity and neuromodulation and, most importantly, may be used as novel neuronal markers of TBI for specific intervention.

  18. Stochastic single-molecule dynamics of synaptic membrane protein domains

    CERN Document Server

    Kahraman, Osman; Haselwandter, Christoph A

    2016-01-01

    Motivated by single-molecule experiments on synaptic membrane protein domains, we use a stochastic lattice model to study protein reaction and diffusion processes in crowded membranes. We find that the stochastic reaction-diffusion dynamics of synaptic proteins provide a simple physical mechanism for collective fluctuations in synaptic domains, the molecular turnover observed at synaptic domains, key features of the single-molecule trajectories observed for synaptic proteins, and spatially inhomogeneous protein lifetimes at the cell membrane. Our results suggest that central aspects of the single-molecule and collective dynamics observed for membrane protein domains can be understood in terms of stochastic reaction-diffusion processes at the cell membrane.

  19. Short-term synaptic depression and stochastic vesicle dynamics reduce and shape neuronal correlations.

    Science.gov (United States)

    Rosenbaum, Robert; Rubin, Jonathan E; Doiron, Brent

    2013-01-01

    Correlated neuronal activity is an important feature in many neural codes, a neural correlate of a variety of cognitive states, as well as a signature of several disease states in the nervous system. The cellular and circuit mechanics of neural correlations is a vibrant area of research. Synapses throughout the cortex exhibit a form of short-term depression where increased presynaptic firing rates deplete neurotransmitter vesicles, which transiently reduces synaptic efficacy. The release and recovery of these vesicles are inherently stochastic, and this stochasticity introduces variability into the conductance elicited by depressing synapses. The impact of spiking and subthreshold membrane dynamics on the transfer of neuronal correlations has been studied intensively, but an investigation of the impact of short-term synaptic depression and stochastic vesicle dynamics on correlation transfer is lacking. We find that short-term synaptic depression and stochastic vesicle dynamics can substantially reduce correlations, shape the timescale over which these correlations occur, and alter the dependence of spiking correlations on firing rate. Our results show that short-term depression and stochastic vesicle dynamics need to be taken into account when modeling correlations in neuronal populations.

  20. Overriding Faulty Circuit Breakers

    Science.gov (United States)

    Robbins, Richard L.; Pierson, Thomas E.

    1987-01-01

    Retainer keeps power on in emergency. Simple mechanical device attaches to failed aircraft-type push/pull circuit breaker to restore electrical power temporarily until breaker replaced. Device holds push/pull button in closed position; unnecessary for crewmember to hold button in position by continual finger pressure. Sleeve and plug hold button in, overriding mechanical failure in circuit breaker. Windows in sleeve show button position.

  1. Multiple personalities: synaptic target cells as introverts and extroverts.

    Science.gov (United States)

    Ritzenthaler, S; Chiba, A

    2001-10-01

    The intricate process of wiring a neuronetwork requires a high degree of accuracy in the communication between pre- and post-synaptic cells. While presynaptic cells have been widely recognized for their dynamic role in synaptic matchmaking, post-synaptic cells have historically been overlooked as passive targets. Recent studies in the Drosophila embryonic neuromuscular system provide compelling evidence that post-synaptic cells participate actively in the synaptogenic process. Endocytosis allows them to quickly modify the array of molecular cues they provide on their surfaces and the extension of dynamic filopodia allows post-synaptic cells to engage in direct long-distance communication. By making use of familiar cellular mechanisms such as endocytosis and filopodia formation, post-synaptic cells may be able to communicate more effectively with potential synaptic partners.

  2. Learning Connections

    Science.gov (United States)

    Royer, Regina D.; Richards, Patricia O.

    2005-01-01

    In this edition of Learning Connections, the authors show how technology can enhance study of weather patterns, reading comprehension, real-world training, critical thinking, health education, and art criticism. The following sections are included: (1) Social Studies; (2) Language Arts; (3) Computer Science and ICT; (4) Art; and (5) Health.…

  3. Getting Connected

    Science.gov (United States)

    Larkin, Patrick

    2011-01-01

    That the world outside schools is changing faster than ever is old news. Unfortunately, that the world "inside" schools is changing at a glacial pace is even older news. As school leaders, principals have an important choice to make as they move into the second decade of the 21st century. School leaders have a moral obligation to connect and…

  4. Light microscopy mapping of connections in the intact brain.

    Science.gov (United States)

    Kim, Sung-Yon; Chung, Kwanghun; Deisseroth, Karl

    2013-12-01

    Mapping of neural connectivity across the mammalian brain is a daunting and exciting prospect. Current approaches can be divided into three classes: macroscale, focusing on coarse inter-regional connectivity; mesoscale, involving a finer focus on neurons and projections; and microscale, reconstructing full details of all synaptic contacts. It remains to be determined how to bridge the datasets or insights from the different levels of study. Here we review recent light-microscopy-based approaches that may help in integration across scales.

  5. Order-theoretical connectivity

    Directory of Open Access Journals (Sweden)

    T. A. Richmond

    1990-01-01

    Full Text Available Order-theoretically connected posets are introduced and applied to create the notion of T-connectivity in ordered topological spaces. As special cases T-connectivity contains classical connectivity, order-connectivity, and link-connectivity.

  6. A tool for errors detection in printed circuit boards production

    OpenAIRE

    A. de Luca Pennacchia; L. G. de la Fraga; U. Martínez Hernández

    2009-01-01

    The progressive implementation of software functions in Integrated Circuits (ICs) has considerably increased the number of transistors and pin connections of ICs. For that reason, Printed Circuit Boards (PCBs) are fabricated with the Surface Mount Technology (SMT) nowadays and IC mounting on PCB is a crucial process that requires high precision. An Automatic Mechanical Montage (AMM) system is used to mount ICs on the sockets using a couple of reference points for every IC in order to find the...

  7. Structured Connectivity Shapes Microcircuit Function in the Prefrontal Cortex.

    Directory of Open Access Journals (Sweden)

    Stefanos Stefanou - Stamatiadis

    2014-03-01

    Full Text Available The application of new experimental techniques in vivo has shed light on the wiring diagram of cortical networks, revealing the highly non-random connectivity of pyramidal neurons. This structured connectivity is characterized by distance-dependent formation of neuronal clusters and over-represented structural ‘motifs’ (Perin 2011, Ko 2013. In the prefrontal cortex (PFC in particular, pyramidal neurons were shown to form hyper-clusters, compared to other sensory regions. Yet, very little is known about the functional properties of these microcircuits and their role in Persistent Activity (PA, a well known function of the PFC. PA is the spiking activity that persists beyond the stimulus presentation and is considered to be the cellular correlate of working memory. Although, PA was traditionally assumed to emerge in large scale networks, recent in vivo data in the PFC suggest that small microcircuits mediate its functional output (Durstwitz, 2010. Motivated by the above findings this work probes the role of realistic connectivity constraints in shaping the functional output of PFC, through simulations of biophysically and morphologically detailed PFC circuits. Towards this goal, we used a compartmental modeling approach, whereby layer 5 PFC pyramidal neurons are modeled with detailed morphological and biophysical properties. Three different types of interneurons were also implemented; the Fast-spiking (FS, Regular-spiking (RS, and Irregular-spiking (IS. These were biophysically detailed, yet morphologically simplified. Microcircuits consisted of 75 pyramidal neurons, 13 FS, 6 RS and 6 IS. Properties (location /number /amplitude /kinetics of both excitatory and inhibitory synapses were extensively validated against experimental data. The network model was used to investigate the effect of connectivity on the emergence of persistent activity. Two different connectivity profiles of pyramidal cells were implemented: one highly non

  8. TNFα in synaptic function: switching gears.

    Science.gov (United States)

    Santello, Mirko; Volterra, Andrea

    2012-10-01

    Pathological brain states are known to induce massive production of proinflammatory cytokines, including tumor necrosis factor alpha (TNFα). At much lower levels, these cytokines are also present in the healthy brain, where it is increasingly being recognized that they exert regulatory influences. Recent studies suggest that TNFα plays important roles in controlling synaptic transmission and plasticity. Here, we discuss the evidence in support of synaptic regulation by TNFα and the underlying cellular mechanisms, including control of AMPA receptor trafficking and glutamate release from astrocytes. These findings suggest that increases in TNFα levels (caused by nervous system infection, injury, or disease) transform the physiological actions of the cytokine into deleterious ones. This functional switch may contribute to cognitive alterations in several brain pathologies.

  9. Filamentary Switching: Synaptic Plasticity through Device Volatility

    CERN Document Server

    La Barbera, Selina; Alibart, Fabien

    2015-01-01

    Replicating the computational functionalities and performances of the brain remains one of the biggest challenges for the future of information and communication technologies. Such an ambitious goal requires research efforts from the architecture level to the basic device level (i.e., investigating the opportunities offered by emerging nanotechnologies to build such systems). Nanodevices, or, more precisely, memory or memristive devices, have been proposed for the implementation of synaptic functions, offering the required features and integration in a single component. In this paper, we demonstrate that the basic physics involved in the filamentary switching of electrochemical metallization cells can reproduce important biological synaptic functions that are key mechanisms for information processing and storage. The transition from short- to long-term plasticity has been reported as a direct consequence of filament growth (i.e., increased conductance) in filamentary memory devices. In this paper, we show tha...

  10. Linking neuronal ensembles by associative synaptic plasticity.

    Directory of Open Access Journals (Sweden)

    Qi Yuan

    Full Text Available Synchronized activity in ensembles of neurons recruited by excitatory afferents is thought to contribute to the coding information in the brain. However, the mechanisms by which neuronal ensembles are generated and modified are not known. Here we show that in rat hippocampal slices associative synaptic plasticity enables ensembles of neurons to change by incorporating neurons belonging to different ensembles. Associative synaptic plasticity redistributes the composition of different ensembles recruited by distinct inputs such as to specifically increase the similarity between the ensembles. These results show that in the hippocampus, the ensemble of neurons recruited by a given afferent projection is fluid and can be rapidly and persistently modified to specifically include neurons from different ensembles. This linking of ensembles may contribute to the formation of associative memories.

  11. Synaptic devices based on purely electronic memristors

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Ruobing [Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201 (China); Institute of Materials Science, School of Materials Science and Engineering, Shanghai University, Shanghai 200072 (China); Li, Jun; Zhuge, Fei, E-mail: zhugefei@nimte.ac.cn, E-mail: h-cao@nimte.ac.cn; Zhu, Liqiang; Liang, Lingyan; Zhang, Hongliang; Gao, Junhua; Cao, Hongtao, E-mail: zhugefei@nimte.ac.cn, E-mail: h-cao@nimte.ac.cn; Fu, Bing; Li, Kang [Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201 (China)

    2016-01-04

    Memristive devices have been widely employed to emulate biological synaptic behavior. In these cases, the memristive switching generally originates from electrical field induced ion migration or Joule heating induced phase change. In this letter, the Ti/ZnO/Pt structure was found to show memristive switching ascribed to a carrier trapping/detrapping of the trap sites (e.g., oxygen vacancies or zinc interstitials) in ZnO. The carrier trapping/detrapping level can be controllably adjusted by regulating the current compliance level or voltage amplitude. Multi-level conductance states can, therefore, be realized in such memristive device. The spike-timing-dependent plasticity, an important Hebbian learning rule, has been implemented in this type of synaptic device. Compared with filamentary-type memristive devices, purely electronic memristors have potential to reduce their energy consumption and work more stably and reliably, since no structural distortion occurs.

  12. Superconducting Optoelectronic Circuits for Neuromorphic Computing

    Science.gov (United States)

    Shainline, Jeffrey M.; Buckley, Sonia M.; Mirin, Richard P.; Nam, Sae Woo

    2017-03-01

    Neural networks have proven effective for solving many difficult computational problems, yet implementing complex neural networks in software is computationally expensive. To explore the limits of information processing, it is necessary to implement new hardware platforms with large numbers of neurons, each with a large number of connections to other neurons. Here we propose a hybrid semiconductor-superconductor hardware platform for the implementation of neural networks and large-scale neuromorphic computing. The platform combines semiconducting few-photon light-emitting diodes with superconducting-nanowire single-photon detectors to behave as spiking neurons. These processing units are connected via a network of optical waveguides, and variable weights of connection can be implemented using several approaches. The use of light as a signaling mechanism overcomes fanout and parasitic constraints on electrical signals while simultaneously introducing physical degrees of freedom which can be employed for computation. The use of supercurrents achieves the low power density (1 mW /cm2 at 20-MHz firing rate) necessary to scale to systems with enormous entropy. Estimates comparing the proposed hardware platform to a human brain show that with the same number of neurons (1 011) and 700 independent connections per neuron, the hardware presented here may achieve an order of magnitude improvement in synaptic events per second per watt.

  13. Strain-dependent variations in spatial learning and in hippocampal synaptic plasticity in the dentate gyrus of freely behaving rats

    Directory of Open Access Journals (Sweden)

    Denise eManahan-Vaughan

    2011-03-01

    Full Text Available Hippocampal synaptic plasticity is believed to comprise the cellular basis for spatial learning. Strain-dependent differences in synaptic plasticity in the CA1 region have been reported. However, it is not known whether these differences extend to other synapses within the trisynaptic circuit, although there is evidence for morphological variations within that path. We investigated whether Wistar and Hooded Lister (HL rat strains express differences in synaptic plasticity in the dentate gyrus in vivo. We also explored whether they exhibit differences in the ability to engage in spatial learning in an 8-arm radial maze. Basal synaptic transmission was stable over a 24h period in both rat strains, and the input-output relationship of both strains was not significantly different. Paired-pulse analysis revealed significantly less paired-pulse facilitation in the Hooded Lister strain when pulses were given 40-100 msec apart. Low frequency stimulation at 1Hz evoked long-term depression (>24h in Wistar and short-term depression (<2h in HL rats; 200Hz stimulation induced long-term potentiation (>24h in Wistar, and a transient, significantly smaller potentiation (<1h in HL rats, suggesting that HL rats have higher thresholds for expression of persistent synaptic plasticity. Training for 10d in an 8-arm radial maze revealed that HL rats master the working memory task faster than Wistar rats, although both strains show an equivalent performance by the end of the trial period. HL rats also perform more efficiently in a double working and reference memory task. On the other hand, Wistar rats show better reference memory performance on the final (8-10 days of training. Wistar rats were less active and more anxious than HL rats.These data suggest that strain-dependent variations in hippocampal synaptic plasticity occur in different hippocampal synapses. A clear correlation with differences in spatial learning is not evident however.

  14. Experience-driven axon retraction in the pharmacologically inactivated visual cortex does not require synaptic transmission.

    Directory of Open Access Journals (Sweden)

    Kana Watanabe

    Full Text Available BACKGROUND: Experience during early postnatal development plays an important role in the refinement of specific neural connections in the brain. In the mammalian visual system, altered visual experiences induce plastic adaptation of visual cortical responses and guide rearrangements of afferent axons from the lateral geniculate nucleus. Previous studies using visual deprivation demonstrated that the afferents serving an open eye significantly retract when cortical neurons are pharmacologically inhibited by applying a gamma-aminobutyric acid type A receptor agonist, muscimol, whereas those serving a deprived eye are rescued from retraction, suggesting that presynaptic activity can lead to the retraction of geniculocortical axons in the absence of postsynaptic activity. Because muscimol application suppresses the spike activity of cortical neurons leaving transmitter release intact at geniculocortical synapses, local synaptic interaction may underlie the retraction of active axons in the inhibited cortex. METHOD AND FINDINGS: New studies reported here determined whether experience-driven axon retraction can occur in the visual cortex inactivated by blocking synaptic inputs. We inactivated the primary visual cortex of kittens by suppressing synaptic transmission with cortical injections of botulinum neurotoxin type E, which cleaves a synaptic protein, SNAP-25, and blocks transmitter release, and examined the geniculocortical axon morphology in the animals with normal vision and those deprived of vision binocularly. We found that afferent axons in the animals with normal vision showed a significant retraction in the inactivated cortex, as similarly observed in the muscimol-treated cortex, whereas the axons in the binocularly deprived animals were preserved. CONCLUSIONS: Therefore, the experience-driven axon retraction in the inactivated cortex can proceed in the absence of synaptic transmission. These results suggest that presynaptic mechanisms play

  15. Targeting synaptic dysfunction in Alzheimer's disease by administering a specific nutrient combination.

    Science.gov (United States)

    van Wijk, Nick; Broersen, Laus M; de Wilde, Martijn C; Hageman, Robert J J; Groenendijk, Martine; Sijben, John W C; Kamphuis, Patrick J G H

    2014-01-01

    Synapse loss and synaptic dysfunction are pathological processes already involved in the early stages of Alzheimer's disease (AD). Synapses consist principally of neuronal membranes, and the neuronal and synaptic losses observed in AD have been linked to the degeneration and altered composition and structure of these membranes. Consequently, synapse loss and membrane-related pathology provide viable targets for intervention in AD. The specific nutrient combination Fortasyn Connect (FC) is designed to ameliorate synapse loss and synaptic dysfunction in AD by addressing distinct nutritional needs believed to be present in these patients. This nutrient combination comprises uridine, docosahexaenoic acid, eicosapentaenoic acid, choline, phospholipids, folic acid, vitamins B12, B6, C, and E, and selenium, and is present in Souvenaid, a medical food intended for use in early AD. It has been hypothesized that FC counteracts synaptic loss and reduces membrane-related pathology in AD by providing nutritional precursors and cofactors that act together to support neuronal membrane formation and function. Preclinical studies formed the basis of this hypothesis which is being validated in a broad clinical study program investigating the potential of this nutrient combination in AD. Memory dysfunction is one key early manifestation in AD and is associated with synapse loss. The clinical studies to date show that the FC-containing medical food improves memory function and preserves functional brain network organization in mild AD compared with controls, supporting the hypothesis that this intervention counteracts synaptic dysfunction. This review provides a comprehensive overview of basic scientific studies that led to the creation of FC and of its effects in various preclinical models.

  16. DESIGN OF TERNARY COUNTER BASED ON ADIABATIC DOMINO CIRCUIT

    Institute of Scientific and Technical Information of China (English)

    Yang Qiankun; Wang Pengjun; Zheng Xuesong

    2013-01-01

    By researching the ternary counter and low power circuit design method,a novel design of low power ternary Domino counter on switch-level is proposed.Firstly,the switch-level structure expression of ternary loop operation circuit with enable pin is derived according to the switch-signal theory,and the one bit ternary counter is obtained combining the ternary adiabatic Domino literal operation circuit and buffer.Then the switch-level structure expression of enable signal circuit is derived,and the four bits ternary counter is obtained by cascade connection.Finally,the circuit is simulated by Spice tool and the output waveforms transform in proper order indicating that the logic function is correct.The energy consumption of the four bits ternary adiabatic Domino counter is 63% less than the conventional Domino counterpart.

  17. Circuit simulation: some humbling thoughts

    Energy Technology Data Exchange (ETDEWEB)

    Wendt, Manfred; /Fermilab

    2006-01-01

    A short, very personal note on circuit simulation is presented. It does neither include theoretical background on circuit simulation, nor offers an overview of available software, but just gives some general remarks for a discussion on circuit simulator needs in context to the design and development of accelerator beam instrumentation circuits and systems.

  18. Caenorhabditis elegans glutamate transporters influence synaptic function and behavior at sites distant from the synapse.

    Science.gov (United States)

    Mano, Itzhak; Straud, Sarah; Driscoll, Monica

    2007-11-23

    To ensure precise neurotransmission and prevent neurotoxic accumulation, l-glutamate (Glu), the major excitatory neurotransmitter in the brain, is cleared from the synapse by glutamate transporters (GluTs). The molecular components of Glu synapses are highly conserved between Caenorhabditis elegans and mammals, yet the absence of synaptic insulation in C. elegans raises fundamental questions about Glu clearance strategies in the nematode nervous system. To gain insight into how Glu clearance is accomplished and how GluTs impact neurotransmission, we probed expression and function of all 6 GluTs found in the C. elegans genome. Disruption of each GluT impacts multiple Glu-dependent behaviors, with GluT combinations commonly increasing the severity of behavioral deficits. Interestingly, the sole GluT that we find expressed in neurons is localized predominantly in presynaptic neurons, in contrast to the postsynaptic concentration of neuronal GluTs typical in mammals. Moreover, 3 of the 6 GluT genes appear strongly expressed on the capillary excretory canal cell, where they affect Glu-dependent behaviors from positions distal to glutamatergic circuits. Indeed, our focused study of GLT-3, one of the distally expressed GluTs, shows that despite this distance, GLT-3 function can balance the activity mediated by synaptic release and synaptic receptors. The effects of distal GluTs on glutamatergic circuits support that Glu diffusion outside the vicinity of the synapse is a critical factor in C. elegans neurotransmission. Together with the presynaptic localization of neuronal GluTs, these observations suggest an unusual strategy for Glu clearance in C. elegans.

  19. Muscles innervated by a single motor neuron exhibit divergent synaptic properties on multiple time scales.

    Science.gov (United States)

    Blitz, Dawn M; Pritchard, Amy E; Latimer, John K; Wakefield, Andrew T

    2017-01-19

    Adaptive changes in the output of neural circuits underlying rhythmic behaviors are relayed to muscles via motor neuron activity. Pre- and postsynaptic properties of neuromuscular junctions can impact the transformation from motor neuron activity to muscle response. Further, synaptic plasticity occurring on the time scale of inter-spike intervals can differ between multiple muscles innervated by the same motor neuron. In rhythmic behaviors, motor neuron bursts can elicit additional synaptic plasticity. However, it is unknown if plasticity regulated by the longer time scale of inter-burst intervals also differs between synapses from the same neuron, and whether any such distinctions occur across a physiological activity range. To address these issues, we measured electrical responses in muscles innervated by a chewing circuit neuron, the lateral gastric (LG) motor neuron, in a well-characterized small motor system, the stomatogastric nervous system (STNS) of the Jonah crab, Cancer borealis In vitro and in vivo, sensory, hormonal and modulatory inputs elicit LG bursting consisting of inter-spike intervals of 50-250 ms and inter-burst intervals of 2-24 s. Muscles expressed similar facilitation measured with paired stimuli except at the shortest inter-spike interval. However distinct decay time constants resulted in differences in temporal summation. In response to bursting activity, augmentation occurred to different extents and saturated at different inter-burst intervals in the three muscles. Further, augmentation interacted with facilitation, resulting in distinct intra-burst facilitation between muscles. Thus, responses of multiple target muscles diverge across a physiological activity range due to distinct synaptic properties sensitive to multiple time scales.

  20. Justification of equivalent substitution circuits used to optimize the dissipative properties of electroelastic bodies with external electric circuits

    Science.gov (United States)

    Ivanov, A. S.; Matvienko, V. P.; Oshmarin, D. A.; Sevodina, N. V.; Yurlov, M. A.; Yurlova, N. A.

    2016-05-01

    We consider elastoplastic systems which are piecewise homogeneous bodies composed of piezoelectric elements some of which have piezoelectrical properties. Electric series circuits consisting of resistors, capacitors, and inductance coils are applied to piezoelectric elements through the electrode coating on the body surface. The goal of the study is to develop efficient methods of mathematical modelling for determining the parameters of elements of the external electric circuit, which ensure, at prescribed resonance frequencies, the maximum damping properties of electroelastic bodies with external electric circuits. To choose effective circuits for solving the problem posed above, we suggest to pose the problem of natural vibrations of elastic bodies whose elements exhibit piezoeffect and have external electric circuits.As the most efficient approaches for calculating the electric circuit parameters necessary for the maximal damping, we propose some versions of equivalent circuits, which can be used to substitute elastic systems with piezoelectric elements. The most reliable equivalent substitution circuits are justified on the basis of the proposed problem of natural vibrations. Numerical results are obtained for a cantilever plate with a piezoelement connected through the electrode coated surface with a series electric circuit consisting of resistors, capacitors and inductance coils.

  1. Glutamic acid decarboxylase 65: a link between GABAergic synaptic plasticity in the lateral amygdala and conditioned fear generalization.

    Science.gov (United States)

    Lange, Maren D; Jüngling, Kay; Paulukat, Linda; Vieler, Marc; Gaburro, Stefano; Sosulina, Ludmila; Blaesse, Peter; Sreepathi, Hari K; Ferraguti, Francesco; Pape, Hans-Christian

    2014-08-01

    An imbalance of the gamma-aminobutyric acid (GABA) system is considered a major neurobiological pathomechanism of anxiety, and the amygdala is a key brain region involved. Reduced GABA levels have been found in anxiety patients, and genetic variations of glutamic acid decarboxylase (GAD), the rate-limiting enzyme of GABA synthesis, have been associated with anxiety phenotypes in both humans and mice. These findings prompted us to hypothesize that a deficiency of GAD65, the GAD isoform controlling the availability of GABA as a transmitter, affects synaptic transmission and plasticity in the lateral amygdala (LA), and thereby interferes with fear responsiveness. Results indicate that genetically determined GAD65 deficiency in mice is associated with (1) increased synaptic length and release at GABAergic connections, (2) impaired efficacy of GABAergic synaptic transmission and plasticity, and (3) reduced spillover of GABA to presynaptic GABAB receptors, resulting in a loss of the associative nature of long-term synaptic plasticity at cortical inputs to LA principal neurons. (4) In addition, training with high shock intensities in wild-type mice mimicked the phenotype of GAD65 deficiency at both the behavioral and synaptic level, indicated by generalization of conditioned fear and a loss of the associative nature of synaptic plasticity in the LA. In conclusion, GAD65 is required for efficient GABAergic synaptic transmission and plasticity, and for maintaining extracellular GABA at a level needed for associative plasticity at cortical inputs in the LA, which, if disturbed, results in an impairment of the cue specificity of conditioned fear responses typifying anxiety disorders.

  2. Endocannabinoids and synaptic function in the CNS.

    Science.gov (United States)

    Hashimotodani, Yuki; Ohno-Shosaku, Takako; Kano, Masanobu

    2007-04-01

    Marijuana affects neural functions through the binding of its active component (Delta(9)-THC) to cannabinoid receptors in the CNS. Recent studies have elucidated that endogenous ligands for cannabinoid receptors, endocannabinoids, serve as retrograde messengers at central synapses. Endocannabinoids are produced on demand in activity-dependent manners and released from postsynaptic neurons. The released endocannabinoids travel backward across the synapse, activate presynaptic CB1 cannabinoid receptors, and modulate presynaptic functions. Retrograde endocannabinoid signaling is crucial for certain forms of short-term and long-term synaptic plasticity at excitatory or inhibitory synapses in many brain regions, and thereby contributes to various aspects of brain function including learning and memory. Molecular identities of the CB1 receptor and enzymes involved in production and degradation of endocannabinoids have been elucidated. Anatomical studies have demonstrated unique distributions of these molecules around synapses, which provide morphological bases for the roles of endocannabinoids as retrograde messengers. CB1-knockout mice exhibit various behavioral abnormalities and multiple defects in synaptic plasticity, supporting the notion that endocannabinoid signaling is involved in various aspects of neural function. In this review article, the authors describe molecular mechanisms of the endocannabinoid-mediated synaptic modulation and its possible physiological significance.

  3. Characterization and extraction of the synaptic apposition surface for synaptic geometry analysis

    Science.gov (United States)

    Morales, Juan; Rodríguez, Angel; Rodríguez, José-Rodrigo; DeFelipe, Javier; Merchán-Pérez, Angel

    2013-01-01

    Geometrical features of chemical synapses are relevant to their function. Two critical components of the synaptic junction are the active zone (AZ) and the postsynaptic density (PSD), as they are related to the probability of synaptic release and the number of postsynaptic receptors, respectively. Morphological studies of these structures are greatly facilitated by the use of recent electron microscopy techniques, such as combined focused ion beam milling and scanning electron microscopy (FIB/SEM), and software tools that permit reconstruction of large numbers of synapses in three dimensions. Since the AZ and the PSD are in close apposition and have a similar surface area, they can be represented by a single surface—the synaptic apposition surface (SAS). We have developed an efficient computational technique to automatically extract this surface from synaptic junctions that have previously been three-dimensionally reconstructed from actual tissue samples imaged by automated FIB/SEM. Given its relationship with the release probability and the number of postsynaptic receptors, the surface area of the SAS is a functionally relevant measure of the size of a synapse that can complement other geometrical features like the volume of the reconstructed synaptic junction, the equivalent ellipsoid size and the Feret's diameter. PMID:23847474

  4. Short term synaptic depression imposes a frequency dependent filter on synaptic information transfer.

    Directory of Open Access Journals (Sweden)

    Robert Rosenbaum

    Full Text Available Depletion of synaptic neurotransmitter vesicles induces a form of short term depression in synapses throughout the nervous system. This plasticity affects how synapses filter presynaptic spike trains. The filtering properties of short term depression are often studied using a deterministic synapse model that predicts the mean synaptic response to a presynaptic spike train, but ignores variability introduced by the probabilistic nature of vesicle release and stochasticity in synaptic recovery time. We show that this additional variability has important consequences for the synaptic filtering of presynaptic information. In particular, a synapse model with stochastic vesicle dynamics suppresses information encoded at lower frequencies more than information encoded at higher frequencies, while a model that ignores this stochasticity transfers information encoded at any frequency equally well. This distinction between the two models persists even when large numbers of synaptic contacts are considered. Our study provides strong evidence that the stochastic nature neurotransmitter vesicle dynamics must be considered when analyzing the information flow across a synapse.

  5. Developmental α₂-adrenergic regulation of noradrenergic synaptic facilitation at cerebellar GABAergic synapses.

    Science.gov (United States)

    Hirono, M; Nagao, S; Obata, K

    2014-01-03

    In the central nervous system, the normal development of neuronal circuits requires adequate temporal activation of receptors for individual neurotransmitters. Previous studies have demonstrated that α₂-adrenoceptor (α₂-AR) activation eliminates spontaneous action potentials of interneurons in the cerebellar molecular layer (MLIs) and subsequently reduces the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) in Purkinje cells (PCs) after the second postnatal week. The magnitude of the α₂-adrenergic reduction in sIPSC frequency is enhanced during the third postnatal week because of an increase in firing-derived sIPSCs. However, little is known about the effects of α₂-AR activation by noradrenaline (NA) on cerebellar GABAergic synaptic transmission that is accompanied by the activation of other AR subtypes, α₁- and β-ARs. Here, we developmentally examined the roles of α₂-AR activation in the noradrenergic facilitation of sIPSCs in cerebellar PCs. Until the second postnatal week, when substantial inhibitory effects of α₂-ARs are absent, NA potentiated sIPSCs and maintained the increased sIPSC frequency, suggesting that NA causes long-lasting facilitation of GABAergic synaptic transmission through α₁- and β-AR activation. After the second postnatal week, NA transiently increased the sIPSC frequency, whereas blocking α₂-ARs sustained the noradrenergic sIPSC facilitation and increase in the firing rate of MLIs, suggesting that α₂-AR activation suppresses the noradrenergic facilitation of GABAergic synaptic transmission. The simultaneous activation of α₁- and β-ARs by their specific agonists mimicked the persistent facilitation of sIPSC frequency, which required extracellular signal-regulated kinase 1/2 activation. These findings indicate that NA acts as a neurotrophic factor that strengthens GABAergic synaptic transmission in the developing cerebellar cortex and that α₂-ARs temporally restrain the noradrenergic

  6. Differences in chloride gradients allow for three distinct types of synaptic modulation by endocannabinoids.

    Science.gov (United States)

    Wang, Yanqing; Burrell, Brian D

    2016-08-01

    Endocannabinoids can elicit persistent depression of excitatory and inhibitory synapses, reducing or enhancing (disinhibiting) neural circuit output, respectively. In this study, we examined whether differences in Cl(-) gradients can regulate which synapses undergo endocannabinoid-mediated synaptic depression vs. disinhibition using the well-characterized central nervous system (CNS) of the medicinal leech, Hirudo verbana Exogenous application of endocannabinoids or capsaicin elicits potentiation of pressure (P) cell synapses and depression of both polymodal (Npoly) and mechanical (Nmech) nociceptive synapses. In P synapses, blocking Cl(-) export prevented endocannabinoid-mediated potentiation, consistent with a disinhibition process that has been indicated by previous experiments. In Nmech neurons, which are depolarized by GABA due to an elevated Cl(-) equilibrium potentials (ECl), endocannabinoid-mediated depression was prevented by blocking Cl(-) import, indicating that this decrease in synaptic signaling was due to depression of excitatory GABAergic input (disexcitation). Npoly neurons are also depolarized by GABA, but endocannabinoids elicit depression in these synapses directly and were only weakly affected by disruption of Cl(-) import. Consequently, the primary role of elevated ECl may be to protect Npoly synapses from disinhibition. All forms of endocannabinoid-mediated plasticity required activation of transient potential receptor vanilloid (TRPV) channels. Endocannabinoid/TRPV-dependent synaptic plasticity could also be elicited by distinct patterns of afferent stimulation with low-frequency stimulation (LFS) eliciting endocannabinoid-mediated depression of Npoly synapses and high-frequency stimulus (HFS) eliciting endocannabinoid-mediated potentiation of P synapses and depression of Nmech synapses. These findings demonstrate a critical role of differences in Cl(-) gradients between neurons in determining the sign, potentiation vs. depression, of

  7. Striking differences in synaptic facilitation along the dorsoventral axis of the hippocampus.

    Science.gov (United States)

    Papatheodoropoulos, C

    2015-08-20

    Hippocampus displays functional heterogeneity along its long axis which has been interpreted in terms of segregation of inputs. Recent evidence has shown that there are also important differences in the organization of the local neuronal circuitry between the dorsal (DH) and the ventral hippocampus (VH). Synaptic plasticity is a crucial factor for the function of the hippocampal circuit. In this study I compared the synaptic facilitation of the CA1 excitatory postsynaptic potential (EPSP) between dorsal and ventral rat hippocampal slices using field recordings and paired-pulse stimulation delivered at varying inter-pulse intervals (IPIs). The facilitation of the EPSP-slope displayed an exponential decline with increasing stimulation strength or IPI. Furthermore, the facilitation of threshold EPSP-slope was significantly higher in DH than in VH at all IPIs. Most remarkably, the facilitation of the area of EPSP displayed a prominent peak at around 200ms in DH but not VH. This optimal facilitation declined abruptly at a position located two thirds of the way along the dorsoventral axis. N-methyl-d-aspartic acid receptors (NMDARs) contributed to the facilitation of EPSP-area in an IPI-selective manner in DH but not VH. Furthermore, NMDARs participated to the single-pulse-evoked EPSP-area more in VH than in DH. Blockade of GABAB receptors (GABABRs) eliminated the prominent facilitation at around 200ms and abolished the large dorsoventral difference in the facilitation of EPSP-area. Blockade of GABAA receptors (GABAARs) increased the maximum area of EPSP more in VH than in DH and reversed facilitation into GABABR-dependent depression that was more robust in DH than in VH. I conclude that interactions between the synaptic actions of GABABR, GABAAR, and NMDAR contribute to diversifying short-term synaptic plasticity along the dorsoventral axis of the hippocampus. It is hypothesized that this diversification has important implications for the information processing

  8. Synaptic profiles during neurite extension, refinement and retraction in the developing cochlea

    Directory of Open Access Journals (Sweden)

    Huang Lin-Chien

    2012-12-01

    Full Text Available Abstract Background During development, excess synapses form between the central and peripheral nervous systems that are then eliminated to achieve correct connectivity. In the peripheral auditory system, the developing type I spiral ganglion afferent fibres undergo a dramatic re-organisation, initially forming connections with both sensory inner hair cells (IHCs and outer hair cells (OHCs. The OHC connections are then selectively eliminated, leaving sparse innervation by type II afferent fibres, whilst the type I afferent synapses with IHCs are consolidated. Results We examined the molecular makeup of the synaptic contacts formed onto the IHCs and OHCs during this period of afferent fibre remodelling. We observed that presynaptic ribbons initially form at all the afferent neurite contacts, i.e. not only at the expected developing IHC-type I fibre synapses but also at OHCs where type I fibres temporarily contact. Moreover, the transient contacts forming onto OHCs possess a broad set of pre- and postsynaptic proteins, suggesting that functional synaptic connections are formed prior to the removal of type I fibre innervation. AMPA-type glutamate receptor subunits were transiently observed at the base of the OHCs, with their downregulation occurring in parallel with the withdrawal of type I fibres, dispersal of presynaptic ribbons, and downregulation of the anchoring proteins Bassoon and Shank. Conversely, at developing type I afferent IHC synapses, the presence of pre- and postsynaptic scaffold proteins was maintained, with differential plasticity in AMPA receptor subunits observed and AMPA receptor subunit composition changing around hearing onset. Conclusions Overall our data show a differential balance in the patterns of synaptic proteins at developing afferent IHC versus OHC synapses that likely reflect their stable versus transient fates.

  9. Learning probabilistic models of connectivity from multiple spike train data

    OpenAIRE

    2010-01-01

    Neuronal circuits or cell assemblies carry out brain function through complex coordinated firing patterns [1]. Inferring topology of neuronal circuits from simultaneously recorded spike train data is a challenging problem in neuroscience. In this work we present a new class of dynamic Bayesian networks to infer polysynaptic excitatory connectivity between spiking cortical neurons [2]. The emphasis on excitatory networks allows us to learn connectivity models by exploiting fast data mining alg...

  10. A semiconductor laser excitation circuit

    Energy Technology Data Exchange (ETDEWEB)

    Kaadzunari, O.; Masaty, K.

    1984-03-27

    A semiconductor laser excitation circuit is patented that is designed for operation in a pulsed mode with a high pulse repetition frequency. This circuit includes, in addition to a semiconductor laser, a high speed photodetector, a reference voltage source, a comparator, and a pulse oscillator and modulator. If the circuit is built using standard silicon integrated circuits, its speed amounts to several hundred megahertz, if it is constructed using gallium arsenide integrated circuits, its speed is several gigahertz.

  11. Zone heated diesel particulate filter electrical connection

    Science.gov (United States)

    Gonze, Eugene V.; Paratore, Jr., Michael J.

    2010-03-30

    An electrical connection system for a particulate filter is provided. The system includes: a particulate filter (PF) disposed within an outer shell wherein the PF is segmented into a plurality of heating zones; an outer mat disposed between the particulate filter and the outer shell; an electrical connector coupled to the outer shell of the PF; and a plurality of printed circuit connections that extend along the outer surface of the PF from the electrical connector to the plurality of heating zones.

  12. The Mind Grows Circuits

    CERN Document Server

    Panigrahy, Rina

    2012-01-01

    There is a vast supply of prior art that study models for mental processes. Some studies in psychology and philosophy approach it from an inner perspective in terms of experiences and percepts. Others such as neurobiology or connectionist-machines approach it externally by viewing the mind as complex circuit of neurons where each neuron is a primitive binary circuit. In this paper, we also model the mind as a place where a circuit grows, starting as a collection of primitive components at birth and then builds up incrementally in a bottom up fashion. A new node is formed by a simple composition of prior nodes when we undergo a repeated experience that can be described by that composition. Unlike neural networks, however, these circuits take "concepts" or "percepts" as inputs and outputs. Thus the growing circuits can be likened to a growing collection of lambda expressions that are built on top of one another in an attempt to compress the sensory input as a heuristic to bound its Kolmogorov Complexity.

  13. Sleep-dependent synaptic down-selection (I): modeling the benefits of sleep on memory consolidation and integration.

    Science.gov (United States)

    Nere, Andrew; Hashmi, Atif; Cirelli, Chiara; Tononi, Giulio

    2013-01-01

    Sleep can favor the consolidation of both procedural and declarative memories, promote gist extraction, help the integration of new with old memories, and desaturate the ability to learn. It is often assumed that such beneficial effects are due to the reactivation of neural circuits in sleep to further strengthen the synapses modified during wake or transfer memories to different parts of the brain. A different possibility is that sleep may benefit memory not by further strengthening synapses, but rather by renormalizing synaptic strength to restore cellular homeostasis after net synaptic potentiation in wake. In this way, the sleep-dependent reactivation of neural circuits could result in the competitive down-selection of synapses that are activated infrequently and fit less well with the overall organization of memories. By using computer simulations, we show here that synaptic down-selection is in principle sufficient to explain the beneficial effects of sleep on the consolidation of procedural and declarative memories, on gist extraction, and on the integration of new with old memories, thereby addressing the plasticity-stability dilemma.

  14. TGF-β Signaling in Dopaminergic Neurons Regulates Dendritic Growth, Excitatory-Inhibitory Synaptic Balance, and Reversal Learning

    Directory of Open Access Journals (Sweden)

    Sarah X. Luo

    2016-12-01

    Full Text Available Neural circuits involving midbrain dopaminergic (DA neurons regulate reward and goal-directed behaviors. Although local GABAergic input is known to modulate DA circuits, the mechanism that controls excitatory/inhibitory synaptic balance in DA neurons remains unclear. Here, we show that DA neurons use autocrine transforming growth factor β (TGF-β signaling to promote the growth of axons and dendrites. Surprisingly, removing TGF-β type II receptor in DA neurons also disrupts the balance in TGF-β1 expression in DA neurons and neighboring GABAergic neurons, which increases inhibitory input, reduces excitatory synaptic input, and alters phasic firing patterns in DA neurons. Mice lacking TGF-β signaling in DA neurons are hyperactive and exhibit inflexibility in relinquishing learned behaviors and re-establishing new stimulus-reward associations. These results support a role for TGF-β in regulating the delicate balance of excitatory/inhibitory synaptic input in local microcircuits involving DA and GABAergic neurons and its potential contributions to neuropsychiatric disorders.

  15. Cellular and molecular bases of memory: synaptic and neuronal plasticity.

    Science.gov (United States)

    Wang, J H; Ko, G Y; Kelly, P T

    1997-07-01

    Discoveries made during the past decade have greatly improved our understanding of how the nervous system functions. This review article examines the relation between memory and the cellular mechanisms of neuronal and synaptic plasticity in the central nervous system. Evidence indicating that activity-dependent short- and long-term changes in strength of synaptic transmission are important for memory processes is examined. Focus is placed on one model of synaptic plasticity called long-term potentiation, and its similarities with memory processes are illustrated. Recent studies show that the regulation of synaptic strength is bidirectional (e.g., synaptic potentiation or depression). Mechanisms involving intracellular signaling pathways that regulate synaptic strength are described, and the specific roles of calcium, protein kinases, protein phosphatases, and retrograde messengers are emphasized. Evidence suggests that changes in synaptic ultrastructure, dendritic ultrastructure, and neuronal gene expression may also contribute to mechanisms of synaptic plasticity. Also discussed are recent findings about postsynaptic mechanisms that regulate short-term synaptic facilitation and neuronal burst-pattern activity, as well as evidence about the subcellular location (presynaptic or postsynaptic) of mechanisms involved in long-term synaptic plasticity.

  16. Photonic gene circuits by optically addressable siRNA-Au nanoantennas.

    Science.gov (United States)

    Lee, Somin Eunice; Sasaki, Darryl Y; Park, Younggeun; Xu, Ren; Brennan, James S; Bissell, Mina J; Lee, Luke P

    2012-09-25

    The precise perturbation of gene circuits and the direct observation of signaling pathways in living cells are essential for both fundamental biology and translational medicine. Current optogenetic technology offers a new paradigm of optical control for cells; however, this technology relies on permanent genomic modifications with light-responsive genes, thus limiting dynamic reconfiguration of gene circuits. Here, we report precise control of perturbation and reconfiguration of gene circuits in living cells by optically addressable siRNA-Au nanoantennas. The siRNA-Au nanoantennas fulfill dual functions as selectively addressable optical receivers and biomolecular emitters of small interfering RNA (siRNA). Using siRNA-Au nanoantennas as optical inputs to existing circuit connections, photonic gene circuits are constructed in living cells. We show that photonic gene circuits are modular, enabling subcircuits to be combined on-demand. Photonic gene circuits open new avenues for engineering functional gene circuits useful for fundamental bioscience, bioengineering, and medical applications.

  17. Equivalent circuit with complex physical constants and equivalent-parameters-expressed dissipation factors of piezoelectric materials

    Institute of Scientific and Technical Information of China (English)

    Chen Yu; Wen Yu-Mei; Li Ping

    2006-01-01

    The equivalent circuit with complex physical constants for a piezoelectric ceramic in thickness mode is established.In the equivalent circuit, electric components (equivalent circuit parameters) are connected to real and imaginary parts of complex physical coefficients of piezoelectric materials. Based on definitions of dissipation factors, three of them (dielectric, elastic and piezoelectric dissipation factors) are represented by equivalent circuit parameters. Since the equivalent circuit parameters are detectable, the dissipation factors can be easily obtained. In the experiments, the temperature and the stress responses of the three dissipation factors are measured.

  18. Coupling Two Different Nucleic Acid Circuits in an Enzyme-Free Amplifier

    Directory of Open Access Journals (Sweden)

    Andrew D. Ellington

    2012-11-01

    Full Text Available DNA circuits have proven to be useful amplifiers for diagnostic applications, in part because of their modularity and programmability. In order to determine whether different circuits could be modularly stacked, we used a catalytic hairpin assembly (CHA circuit to initiate a hybridization chain reaction (HCR circuit. In response to an input nucleic acid sequence, the CHA reaction accumulates immobilized duplexes and HCR elongates these duplexes. With fluorescein as a reporter each of these processes yielded 10-fold signal amplification in a convenient 96-well format. The modular circuit connections also allowed the output reporter to be readily modified to a G-quadruplex-DNAzyme that yielded a fluorescent signal.

  19. Chaotic memristive circuit: equivalent circuit realization and dynamical analysis

    Institute of Scientific and Technical Information of China (English)

    Bao Bo-Cheng; Xu Jian-Ping; Zhou Guo-Hua; Ma Zheng-Hua; Zou Ling

    2011-01-01

    In this paper,a practical equivalent circuit of an active flux-controlled memristor characterized by smooth piecewise-quadratic nonlinearity is designed and an experimental chaotic memristive circuit is implemented.The chaotic memristive circuit has an equilibrium set and its stability is dependent on the initial state of the memristor.The initial state-dependent and the circuit parameter-dependent dynamics of the chaotic memristive circuit are investigated via phase portraits,bifurcation diagrams and Lyapunov exponents.Both experimental and simulation results validate the proposed equivalent circuit realization of the active flux-controlled memristor.

  20. A morpho-density approach to estimating neural connectivity.

    Directory of Open Access Journals (Sweden)

    Michael P McAssey

    Full Text Available Neuronal signal integration and information processing in cortical neuronal networks critically depend on the organization of synaptic connectivity. Because of the challenges involved in measuring a large number of neurons, synaptic connectivity is difficult to determine experimentally. Current computational methods for estimating connectivity typically rely on the juxtaposition of experimentally available neurons and applying mathematical techniques to compute estimates of neural connectivity. However, since the number of available neurons is very limited, these connectivity estimates may be subject to large uncertainties. We use a morpho-density field approach applied to a vast ensemble of model-generated neurons. A morpho-density field (MDF describes the distribution of neural mass in the space around the neural soma. The estimated axonal and dendritic MDFs are derived from 100,000 model neurons that are generated by a stochastic phenomenological model of neurite outgrowth. These MDFs are then used to estimate the connectivity between pairs of neurons as a function of their inter-soma displacement. Compared with other density-field methods, our approach to estimating synaptic connectivity uses fewer restricting assumptions and produces connectivity estimates with a lower standard deviation. An important requirement is that the model-generated neurons reflect accurately the morphology and variation in morphology of the experimental neurons used for optimizing the model parameters. As such, the method remains subject to the uncertainties caused by the limited number of neurons in the experimental data set and by the quality of the model and the assumptions used in creating the MDFs and in calculating estimating connectivity. In summary, MDFs are a powerful tool for visualizing the spatial distribution of axonal and dendritic densities, for estimating the number of potential synapses between neurons with low standard deviation, and for obtaining