Adaptive pattern recognition by mini-max neural networks as a part of an intelligent processor

In this decade and progressing into 21st Century, NASA will have missions including Space Station and the Earth related Planet Sciences. To support these missions, a high degree of sophistication in machine automation and an increasing amount of data processing throughput rate are necessary. Meeting these challenges requires intelligent machines, designed to support the necessary automations in a remote space and hazardous environment. There are two approaches to designing these intelligent machines. One of these is the knowledge-based expert system approach, namely AI. The other is a non-rule approach based on parallel and distributed computing for adaptive fault-tolerances, namely Neural or Natural Intelligence (NI). The union of AI and NI is the solution to the problem stated above. The NI segment of this unit extracts features automatically by applying Cauchy simulated annealing to a mini-max cost energy function. The feature discovered by NI can then be passed to the AI system for future processing, and vice versa. This passing increases reliability, for AI can follow the NI formulated algorithm exactly, and can provide the context knowledge base as the constraints of neurocomputing. The mini-max cost function that solves the unknown feature can furthermore give us a top-down architectural design of neural networks by means of Taylor series expansion of the cost function. A typical mini-max cost function consists of the sample variance of each class in the numerator, and separation of the center of each class in the denominator. Thus, when the total cost energy is minimized, the conflicting goals of intraclass clustering and interclass segregation are achieved simultaneously

Quantitative neuroanatomy for connectomics in Drosophila.

Neuronal circuit mapping using electron microscopy demands laborious proofreading or reconciliation of multiple independent reconstructions. Here, we describe new methods to apply quantitative arbor and network context to iteratively proofread and reconstruct circuits and create anatomically enriched wiring diagrams. We measured the morphological underpinnings of connectivity in new and existing reconstructions of Drosophila sensorimotor (larva) and visual (adult) systems. Synaptic inputs were preferentially located on numerous small, microtubule-free 'twigs' which branch off a single microtubule-containing 'backbone'. Omission of individual twigs accounted for 96% of errors. However, the synapses of highly connected neurons were distributed across multiple twigs. Thus, the robustness of a strong connection to detailed twig anatomy was associated with robustness to reconstruction error. By comparing iterative reconstruction to the consensus of multiple reconstructions, we show that our method overcomes the need for redundant effort through the discovery and application of relationships between cellular neuroanatomy and synaptic connectivity.Funding came from the HHMI Janelia Visiting Scientist program (AC), Swiss National Science Foundation grant 31003A 132969 (AC), HHMI, and the Institute of Neuroinformatics of the University of Zurich and ETH Zurich.This is the final version of the article. It first appeared from eLife via http://dx.doi.org/10.7554/eLife.12059.00

Quantitative neuroanatomy for connectomics in Drosophila

Neuronal circuit mapping using electron microscopy demands laborious proofreading or reconciliation of multiple independent reconstructions. Here, we describe new methods to apply quantitative arbor and network context to iteratively proofread and reconstruct circuits and create anatomically enriched wiring diagrams. We measured the morphological underpinnings of connectivity in new and existing reconstructions of Drosophila sensorimotor (larva) and visual (adult) systems. Synaptic inputs were preferentially located on numerous small, microtubule-free 'twigs' which branch off a single microtubule-containing 'backbone'. Omission of individual twigs accounted for 96% of errors. However, the synapses of highly connected neurons were distributed across multiple twigs. Thus, the robustness of a strong connection to detailed twig anatomy was associated with robustness to reconstruction error. By comparing iterative reconstruction to the consensus of multiple reconstructions, we show that our method overcomes the need for redundant effort through the discovery and application of relationships between cellular neuroanatomy and synaptic connectivity.Publisher PDFPeer reviewe

Acute neuroinflammation induces AIS structural plasticity in a NOX2-dependent manner

Background Chronic microglia-mediated inflammation and oxidative stress are well-characterized underlying factors in neurodegenerative disease, whereby reactive inflammatory microglia enhance ROS production and impact neuronal integrity. Recently, it has been shown that during chronic inflammation, neuronal integrity is compromised through targeted disruption of the axon initial segment (AIS), the axonal domain critical for action potential initiation. AIS disruption was associated with contact by reactive inflammatory microglia which wrap around the AIS, increasing association with disease progression. While it is clear that chronic microglial inflammation and enhanced ROS production impact neuronal integrity, little is known about how acute microglial inflammation influences AIS stability. Here, we demonstrate that acute neuroinflammation induces AIS structural plasticity in a ROS-mediated and calpain-dependent manner. Methods C57BL/6J and NOX2−/− mice were given a single injection of lipopolysaccharide (LPS; 5 mg/kg) or vehicle (0.9% saline, 10 mL/kg) and analyzed at 6 h–2 weeks post-injection. Anti-inflammatory Didox (250 mg/kg) or vehicle (0.9% saline, 10 mL/kg) was administered beginning 24 h post-LPS injection and continued for 5 days; animals were analyzed 1 week post-injection. Microglial inflammation was assessed using immunohistochemistry (IHC) and RT-qPCR, and AIS integrity was quantitatively analyzed using ankyrinG immunolabeling. Data were statistically compared by one-way or two-way ANOVA where mean differences were significant as assessed using Tukey’s post hoc analysis. Results LPS-induced neuroinflammation, characterized by enhanced microglial inflammation and increased expression of ROS-producing enzymes, altered AIS protein clustering. Importantly, inflammation-induced AIS changes were reversed following resolution of microglial inflammation. Modulation of the inflammatory response using anti-inflammatory Didox, even after significant AIS disruption occurred, increased the rate of AIS recovery. qPCR and IHC analysis revealed that expression of microglial NOX2, a ROS-producing enzyme, was significantly increased correlating with AIS disruption. Furthermore, ablation of NOX2 prevented inflammation-induced AIS plasticity, suggesting that ROS drive AIS structural plasticity. Conclusions In the presence of acute microglial inflammation, the AIS undergoes an adaptive change that is capable of spontaneous recovery. Moreover, recovery can be therapeutically accelerated. Together, these findings underscore the dynamic capabilities of this domain in the presence of a pathological insult and provide evidence that the AIS is a viable therapeutic target

Targeting Oxidative Stress and Aberrant Critical Period Plasticity in the Developmental Trajectory to Schizophrenia

Schizophrenia is a neurodevelopmental disorder reflecting a convergence of genetic risk and early life stress. The slow progression to first psychotic episode represents both a window of vulnerability as well as opportunity for therapeutic intervention. Here, we consider recent neurobiological insight into the cellular and molecular components of developmental critical periods and their vulnerability to redox dysregulation. In particular, the consistent loss of parvalbumin-positive interneuron (PVI) function and their surrounding perineuronal nets (PNNs) as well as myelination in patient brains is consistent with a delayed or extended period of circuit instability. This linkage to critical period triggers (PVI) and brakes (PNN, myelin) implicates mistimed trajectories of brain development in mental illness. Strategically introduced antioxidant treatment or later reinforcement of molecular brakes may then offer a novel prophylactic psychiatr

Monosynaptic targets of utricular afferents in the larval zebrafish

The larval zebrafish acquires a repertoire of vestibular-driven behaviors that aid survival early in development. These behaviors rely mostly on the utricular otolith, which senses inertial (tilt and translational) head movements. We previously characterized the known central brainstem targets of utricular afferents using serial-section electron microscopy of a larval zebrafish brain. Here we describe the rest of the central targets of utricular afferents, focusing on the neurons whose identities are less certain in our dataset. We find that central neurons with commissural projections have a wide range of predicted directional tuning, just as in other vertebrates. In addition, somata of central neurons with inferred responses to contralateral tilt are located more laterally than those with inferred responses to ipsilateral tilt. Many dorsally located central utricular neurons are unipolar, with an ipsilateral dendritic ramification and commissurally projecting axon emerging from a shared process. Ventrally located central utricular neurons tended to receive otolith afferent synaptic input at a shorter distance from the soma than in dorsally located neurons. Finally, we observe an unexpected synaptic target of utricular afferents: afferents from the medial (horizontal) semicircular canal. Collectively, these data provide a better picture of the gravity-sensing circuit. Furthermore, we suggest that vestibular circuits important for survival behaviors develop first, followed by the circuits that refine these behaviors

Altered Excitatory-Inhibitory Balance in the NMDA-Hypofunction Model of Schizophrenia

Schizophrenia is a common psychiatric disorder of high incidence, affecting approximately 1% of the world population. The essential neurotransmitter pathology of schizophrenia remains poorly defined, despite huge advances over the past half-century in identifying neurochemical and pathological abnormalities in the disease. The dopamine/serotonin hypothesis has originally provided much of the momentum for neurochemical research in schizophrenia. In recent years, the attention has, however, shifted to the glutamate system, the major excitatory neurotransmitter in the CNS and towards a concept of functional imbalance between excitatory and inhibitory transmission at the network level in various brain regions in schizophrenia. The evidence indicating a central role for the NMDA-receptor subtype in the aetiology of schizophrenia has led to the NMDA-hypofunction model of this disease and the use of phencyclidines as a means to induce the NMDA-hypofunction state in animal models. The purpose of this review is to discuss recent findings highlighting the importance of the NMDA-hypofunction model of schizophrenia, both from a clinical perspective, as well as in opening a line of research, which enables electrophysiological studies at the cellular and network level in vitro. In particular, changes in excitation–inhibition (E/I) balance in the NMDA-hypofunction model of the disease and the resulting changes in network behaviours, particularly in gamma frequency oscillatory activity, will be discussed

Microglia regulate chandelier cell axo-axonic synaptogenesis

SignificanceChandelier cells (ChCs) are a unique type of GABAergic interneuron that form axo-axonic synapses exclusively on the axon initial segment (AIS) of neocortical pyramidal neurons (PyNs), allowing them to exert powerful yet precise control over PyN firing and population output. The importance of proper ChC function is further underscored by the association of ChC connectivity defects with various neurological conditions. Despite this, the cellular mechanisms governing ChC axo-axonic synapse formation remain poorly understood. Here, we identify microglia as key regulators of ChC axonal morphogenesis and AIS synaptogenesis, and show that disease-induced aberrant microglial activation perturbs proper ChC synaptic development/connectivity in the neocortex. In doing so, such findings highlight the therapeutic potential of manipulating microglia to ensure proper brain wiring

The brain's polymath: Emerging roles of microglia throughout brain development

Microglia, the resident brain immune cells, have garnered a reputation as major effectors of circuit wiring due to their ability to prune synapses. Other roles of microglia in regulating neuronal circuit development have so far received comparatively less attention. Here, we review the latest studies that have contributed to our increased understanding of how microglia regulate brain wiring beyond their role in synapse pruning. We summarize recent findings showing that microglia regulate neuronal numbers and influence neuronal connectivity through a bidirectional communication between microglia and neurons, processes regulated by neuronal activity and the remodeling of the extracellular matrix. Finally, we speculate on the potential contribution of microglia to the development of functional networks and propose an integrative view of microglia as active elements of neural circuits