Ultrastructural features and synaptic connections of hilar ectopic granule cells in the rat dentate gyrus are different from those of granule cells in the granule cell layer.

Several investigators have shown the existence of dentate granule cells in ectopic locations within the hilus and molecular layer using both Golgi and retrograde tracing studies but the ultrastructural features and synaptic connections of ectopic granule cells were not previously examined. In the present study, the biocytin retrograde tracing technique was used to label ectopic granule cells following injections into stratum lucidum of CA3b of hippocampal slices obtained from epileptic rats. Electron microscopy was used to study hilar ectopic granule cells that were located 20-40 microm from the granule cell layer (GCL). They had ultrastructural features similar to those of granule cells in the GCL but showed differences, including nuclei that often displayed infoldings and thicker apical dendrites. At their origin, these dendrites were 6 microm in diameter and they tapered down to 2 microm at the border with the GCL. Both biocytin-labeled and unlabeled axon terminals formed exclusively asymmetric synapses with the somata and proximal dendrites of hilar ectopic granule cells. The mean number of axosomatic synapses for these cells was three times that for granule cells in the GCL. Together, these data indicate that hilar ectopic granule cells are postsynaptic to mossy fibers and have less inhibitory input on their somata and proximal dendrites than granule cells in the GCL. This finding is consistent with recent physiological results showing that hilar ectopic granule cells from epileptic rats are more hyperexcitable than granule cells in the GCL

Suppression of hippocampal neurogenesis is associated with developmental stage, number of perinatal seizure episodes, and glucocorticosteroid level.

Seizures increase dentate granule cell proliferation in adult rats but decrease proliferation in young pups. The particular period and number of perinatal seizures required to cause newborn granule cell suppression in development are unknown. Therefore, we examined cell proliferation with bromodeoxyuridine (BrdU) immunohistochemistry during the peak of neurogenesis (e.g., P6 and P9) and at later postnatal ages (e.g., P13, P20, or P30) following single and multiple episodes of perinatal status epilepticus induced by kainate (KA). Because an inverse relationship exists between glucocorticosteroids (CORT) levels and granule cell proliferation, plasma CORT levels and electroencephalographic (EEG) activity were simultaneously monitored to elucidate underlying mechanisms that inhibit cell proliferation. In control animals, the number of BrdU-labeled cells increased then declined with maturation. After 1x KA or 2x KA administered on P6 and P9, the numbers of BrdU-labeled cells were not different from age-matched controls. However, rat pups with 3x KA (on P6, P9, and P13) had marked suppression of BrdU-labeled cells 48-72 h after the last seizure (43 +/- 6.5% of control). Cell proliferation was also significantly inhibited on P20 after 2x KA (to 56 +/- 6.9%) or 3x KA (to 54 +/- 7.9%) and on P30 with 3x KA (to 74.5 +/- 8.2% of age-matched controls). Cell death was not apparent as chromatin stains showed increased basophilia of only inner cells lining the granule cell layers, in the absence of eosinophilia, argyrophilia, or terminal deoxynucleotidyl dUTP nick endlabeling (TUNEL) labeling at times examined. In P13 pups with 3x KA, electron microscopy revealed an increased number of immature granule cells and putative stem cells with irregular shape, condensed cytoplasm, and electron dense nuclei, and they were also BrdU positive. The EEG showed no relationship between neurogenesis and duration of high-synchronous ictal activity. However, endocrine studies showed a correlation with BrdU number and age, sustained increases in circulating CORT levels following 1x KA on P6 (0.7 +/- 0.1 to 2.40 +/- 0.86 microg/dl), and cumulative increases that exceeded 10 microg/dl at 4-8 h after 3x KA on P13 or P20. In conclusion, a history of only one or two perinatal seizure(s) can suppress neurogenesis if a second or third seizure recurs after a critical developmental period associated with a marked surge in CORT. During the first 2 weeks of postnatal life sustained increases in postictal circulating CORT levels but not duration or intensity of ictal activity has long-term consequences on neurogenesis. The occurrence of an increased proportion of immature granule cells and putative stem cells with irregular morphology in the absence of neurodegeneration suggests that progenitors may not differentiate properly and remain in an immature state

Statistical analysis driven optimized deep learning system for intrusion detection

Attackers have developed ever more sophisticated and intelligent ways to hack information and communication technology systems. The extent of damage an individual hacker can carry out upon infiltrating a system is well understood. A potentially catastrophic scenario can be envisaged where a nation-state intercepting encrypted financial data gets hacked. Thus, intelligent cybersecurity systems have become inevitably important for improved protection against malicious threats. However, as malware attacks continue to dramatically increase in volume and complexity, it has become ever more challenging for traditional analytic tools to detect and mitigate threat. Furthermore, a huge amount of data produced by large networks has made the recognition task even more complicated and challenging. In this work, we propose an innovative statistical analysis driven optimized deep learning system for intrusion detection. The proposed intrusion detection system (IDS) extracts optimized and more correlated features using big data visualization and statistical analysis methods (human-in-the-loop), followed by a deep autoencoder for potential threat detection. Specifically, a pre-processing module eliminates the outliers and converts categorical variables into one-hot-encoded vectors. The feature extraction module discard features with null values and selects the most significant features as input to the deep autoencoder model (trained in a greedy-wise manner). The NSL-KDD dataset from the Canadian Institute for Cybersecurity is used as a benchmark to evaluate the feasibility and effectiveness of the proposed architecture. Simulation results demonstrate the potential of our proposed system and its outperformance as compared to existing state-of-the-art methods and recently published novel approaches. Ongoing work includes further optimization and real-time evaluation of our proposed IDS.Comment: To appear in the 9th International Conference on Brain Inspired Cognitive Systems (BICS 2018

Temporal profile of hilar basal dendrite formation on dentate granule cells after status epilepticus.

Granule cells with hilar basal dendrites (HBDs) are found after status epilepticus (SE) in three rat models of temporal lobe epilepsy. These granule cells are commonly located at the hilar border and could be newly born granule cells based on their location. The aim of this study was to determine how long it takes for HBDs to form on granule cells after SE. Pilocarpine was injected to induce SE and rats were killed at different times: 3 days, 1, 2, and 3 weeks after SE. Biocytin was injected into CA3 stratum lucidum of hippocampal slices to label granule cells with HBDs. The number, morphology, and length of HBDs were analyzed at the different time points. Basal processes of granule cells from rats killed 3 days after pilocarpine injection were judged not to be HBDs because they were short in length and did not ramify in the hilus. "True" HBDs were detected as early as 7 and 8 days after pilocarpine-induced SE. Similar frequencies of granule cells with HBDs were observed at the later time points. This study shows that HBDs can form on granule cells as early as 1 week following SE. These results are consistent with the hypothesis that HBDs on granule cells may be generated from seizure-induced, de novo granule cells, however, alternative explanations that some or all HBDs arise from pre-SE generated granule cells cannot be ruled out at this time and will require further examination