The growing threat of malware is becoming more and more difficult to ignore. In this paper, a malware feature images generation method is used to combine the static analysis of malicious code with ...the methods of recurrent neural networks (RNN) and convolutional neural networks (CNN). By using an RNN, our method considers not only the original information of malware but also the ability to associate the original code with timing characteristics; furthermore, the process reduces the dependence on category labels of malware. Then, we use minhash to generate feature images from the fusion of the original codes and the predictive codes from the RNN. Finally, we train a CNN to classify feature images. When we trained very few samples (the proportion of the sample size of training dataset to validation dataset was 1:30), we obtained accuracy over 92 percent. When we adjust the proportion to 3:1, the accuracy exceeds 99.5 percent. As shown in confusion matrices, our method obtains a good result, where the worst false positive rate of all the malware families is 0.0147 and the average false positive rate is 0.0058.
Abstract Persistence reinforces continuous action, which benefits animals in many aspects. Diverse external or internal signals may trigger animals to start a persistent movement. However, it is ...unclear how the brain decides to persist with current actions by selecting specific information. Using single-unit extracellular recordings and opto-tagging in awake mice, we demonstrated that a group of dorsal mPFC (dmPFC) motor cortex projecting (MP) neurons initiate a persistent movement by selectively encoding contextual information rather than natural valence. Inactivation of dmPFC MP neurons impairs the initiation and reduces neuronal activity in the insular and motor cortex. After the persistent movement is initiated, the dmPFC MP neurons are not required to maintain it. Finally, a computational model suggests that a successive sensory stimulus acts as an input signal for the dmPFC MP neurons to initiate a persistent movement. These results reveal a neural initiation mechanism on the persistent movement.
The way in which aberrant neural circuits contribute to epilepsy remains unclear. To elucidate this question, we dissected the circuit mechanisms underlying epileptogenesis using a mouse model of ...focal cortical malformation with spontaneous epileptiform discharges. We found that spontaneous spike-wave discharges and optogenetically induced hyperexcitable bursts in vivo were present in a cortical region distal to (>0.7 mm) freeze-lesion-induced microgyrus, instead of near the microgyrus. ChR2-assisted circuit mapping revealed ectopic inter-laminar excitatory input from infragranular layers to layers 2/3 pyramidal neurons as the key component of hyperexcitable circuitry. This hyperactivity disrupted the balance between excitation and inhibition and was more prominent in the cortical region distal to the microgyrus. Consistently, the inhibition from both parvalbumin-positive interneurons (PV) and somatostatin-positive interneurons (SOM) to pyramidal neurons were altered in a layer- and site-specific fashion. Finally, closed-loop optogenetic stimulation of SOM, but not PV, terminated spontaneous spike-wave discharges. Together, these results demonstrate the occurrence of highly site- and cell-type-specific synaptic reorganization underlying epileptic cortical circuits and provide new insights into potential treatment strategies.
•Ectopic infragranular excitatory inputs cause hyperexcitability and epileptogenesis•Disrupted E/I balance is more prominent in distal malformed cortex•SOM inhibition in the distal supragranular layers is weakened•Closed-loop optogenetic activation of SOM interneurons stops seizure in vivo
Yang et al. report key features of the circuit rewiring that contributes to epileptogenesis in a mouse model of cortical malformation. The authors further demonstrate that spontaneous spike-wave discharges can be curtailed by selectively activating somatostatin interneurons in a small cortical region distal to the microgyrus.
Recurrent neural networks (RNNs) are designed to learn sequential patterns in silico, but it is unclear whether and how an RNN forms in the native networks of the mammalian brain. Here, we report an ...innate RNN, which is formed by the unidirectional connections from three basic units: input units arriving from emotion regions, a hidden unit in the medial prefrontal cortex (mPFC), and output units located at the somatic motor cortex (sMO). Specifically, the neurons from basal lateral amygdala (BLA) and the insular cortex (IC) project to the mPFC motor-cortex-projecting (MP) neurons. These MP neurons form a local self-feedback loop and target major projecting neurons of the sMO. Within the sMO, the neurons in the infragranular layers receive stronger input than the neurons in supragranular layers. Finally, we show in vivo evidence that the communications from the emotion regions to the sMO are abolished when MP neurons are chemogenetically silenced.
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•mPFC MP neurons consist of L2/3 CC neurons and L5 PT-CStr neurons•MP neurons form a local, monosynaptic self-feedback loop in the mPFC•mPFC MP neurons are necessary for communication from emotion regions to the sMO•MP-PT-CStr neurons are the functional subtype in contacting emotion regions with the sMO
Wang and Sun show that the unidirectional, recurrent neuronal network, linking with the emotion regions and the somatic motor cortex, is formed by three basic units: input units arriving from the emotion regions, a hidden unit composed of self-feedback connected medial prefrontal cortex (mPFC) neurons, and output units located at the somatic motor cortex (sMO).
Active sensation requires the convergence of external stimuli with representations of body movements. We used mouse behavior, electrophysiology and optogenetics to dissect the temporal interactions ...among whisker movement, neural activity and sensation of touch. We photostimulated layer 4 activity in single barrels in a closed loop with whisking. Mimicking touch-related neural activity caused illusory perception of an object at a particular location, but scrambling the timing of the spikes over one whisking cycle (tens of milliseconds) did not abolish the illusion, indicating that knowledge of instantaneous whisker position is unnecessary for discriminating object locations. The illusions were induced only during bouts of directed whisking, when mice expected touch, and in the relevant barrel. Reducing activity biased behavior, consistent with a spike count code for object detection at a particular location. Our results show that mice integrate coding of touch with movement over timescales of a whisking bout to produce perception of active touch.
It is unclear whether intrinsic excitabilities of specific interneurons are modulated by sensory experiences. Here, I examined the intrinsic excitabilities of interneurons in "sensory-spared" and ..."sensory-deprived" cortices of GAD67-GFP mice. The results showed that whisker trimming, begun at postnatal day 7 for 3 wk, induced significant changes in intrinsic and firing properties of fast-spiking (FS) but not regular spiking nonpyramidal (RSNP) cells. Firing threshold, spike frequency, spike adaptation index, and input resistance of FS cells were significantly altered by sensory deprivation such that FS cells became less excitable. An up-regulation of IA currents in FS cells appeared to be responsible. Along with changes in the intrinsic properties of FS cells, whisker trimming also induced a robust reduction in the number of vesicular glutamate transporter 2 positive varicosities and parvalbumin expression and the strength of thalamocortical (TC) excitatory postsynaptic currents in FS cells in the "sensory-deprived barrels." The probability of spike induction by TC stimulus was reduced by 30% and the spike jitter was increased in sensory-deprived FS cells. These results suggest that the FS networks are selectively inhibited by sensory deprivation. The concurrent changes of intrinsic properties and expression of parvalbumin in FS but not RSNP cells with TC synapses support a contribution from the TC pathway and glutamate to sensory-induced activity-dependent intrinsic plasticity of inhibitory networks in barrel cortex.
Summary
Objective
To examine if mice with focal cortical dysplasia (FCD) develop spontaneous epileptic seizures and, if so, determine the key electroencephalography (EEG) features.
Methods
Unilateral ...single freeze lesions to the S1 region (SFLS1R) were made in postnatal day 0–1 pups to induce a neocortical microgyrus in the right cortical hemisphere. Continuous 24‐h recordings with intracranial EEG electrodes and behavioral tests were performed in adult SFLS1R and sham‐control mice to assess neurologic status.
Results
A high percentage of adult SFLS1R animals (89%, 40/45) exhibited at least one or more spontaneous nonconvulsive seizure events over the course of 24 h. Of these animals, 60% (27/45) presented with a chronic seizure state that was persistent throughout the recording session, consisting of bursts of rhythmic high‐amplitude spike‐wave activities and primarily occurring during periods of slow‐wave sleep. In comparison, none of the control, age‐matched, mice (0/12) developed seizures. The epileptic discharge pattern closely resembled a pattern of continuous spike‐waves during slow‐wave sleep (CSWS) of the human syndrome described as an electrical status epilepticus during slow‐wave sleep (ESES). Key findings in the SFLS1R model indicated that the observed CSWS (1) were more prevalent in female (18/23) versus male (9/22, p < 0.05), (2) were strongest in the right S1 region although generalized to other brain regions, (3) were associated with significant cognitive and behavioral deficits, (4) were temporarily alleviated by ethosuximide treatment or optogenetic activation of cortical γ‐aminobutyric acid (GABA)ergic neurons, and (5) theta and alpha band rhythms may play a key role in the generalization of spike‐wave activities.
Significance
This is the first report of an in vivo animal FCD model that induces chronic spontaneous electrographic brain seizures. Further characterization of the abnormal oscillations in this mouse model may lead to a better understanding of the mechanisms of CSWS/ESES.
Abstract To facilitate the study of the CaMKIIα function in vivo , a CaMKIIα-GFP transgenic mouse line was generated. Here, our goal is to provide the first neuroanatomical characterization of GFP ...expression in the CNS of this line of mouse. Overall, CaMKIIα-GFP expression is strong and highly heterogeneous, with the dentate gyrus of the hippocampus as the most abundantly expressed region. In the hippocampus, around 70% of granule and pyramidal neurons expressed strong GFP. In the neocortex, presumed pyramidal neurons were GFP positive: around 32% of layer II/III and 35% of layer VI neurons expressed GFP, and a lower expression rate was found in other layers. In the thalamus and hypothalamus, strong GFP signals were detected in the neuropil. GFP-positive cells were also found in many other regions such as the spinal trigeminal nucleus, cerebellum and basal ganglia. We further compared the GFP expression with specific antibody staining for CaMKIIα and GABA. We found that GFP+ neurons were mostly positive for CaMKIIα-IR throughout the brain, with some exceptions throughout the brain, especially in the deeper layers of neocortex. GFP and GABA-IR marked distinct neuronal populations in most brain regions with the exception of granule cells in the olfactory bulb, purkinje cells in the cerebellar, and some layer I cells in neocortex. In conclusion, GFP expression in the CaMKIIα-GFP mice is similar to the endogenous expression of CaMKIIα protein, thus these mice can be used in in vivo and in vitro physiological studies in which visualization of CaMKIIα- neuronal populations is required.
We used ChR2-assisted circuit mapping (CRACM) to examine neuronal/compartmental excitatory and inhibitory synaptic balance (E-I balance) in pyramidal cells (PCs) located in several brain regions ...(including both neocortices and paleocortices). Within the vS1, different inputs on the same neurons, or the same inputs formed on different targets, induced different E/I ratios. E/I ratios in PCs from different regions were largely different. Chemogenetic silencing of somatostatin (SOM)- or parvalbumin (PV)-containing interneurons (INs) while optogenetically activating long-range M1 inputs demonstrated differential contribution of PV and SOM INs to the E/I ratios in a layer-specific manner in S1. Our results thus demonstrate that there are both universal subcellular-wide E-I balance within single PC and high specificity in the value of E/I ratios across different circuits (i.e. visual, somatosensory, piriform and hippocampal). Specificity of E/I balance are likely caused by unique glutamatergic innervation of interneurons. The dichotomy of high specificity and generalization of subcellular E-I balance in different circuits forms the basis for further understanding of neuronal computation under physiological conditions and various neuro-psychiatric disease-states.
Parvalbumin interneurons (PVIs) are affected in many psychiatric disorders including schizophrenia (SCZ), however the mechanism remains unclear. FXR1, a high confident risk gene for SCZ, is ...indispensable but its role in the brain is largely unknown. We show that deleting FXR1 from PVIs of medial prefrontal cortex (mPFC) leads to reduced PVI excitability, impaired mPFC gamma oscillation, and SCZ-like behaviors. PVI-specific translational profiling reveals that FXR1 regulates the expression of Cacna1h/Cav3.2 a T-type calcium channel implicated in autism and epilepsy. Inhibition of Cav3.2 in PVIs of mPFC phenocopies whereas elevation of Cav3.2 in PVIs of mPFC rescues behavioral deficits resulted from FXR1 deficiency. Stimulation of PVIs using a gamma oscillation-enhancing light flicker rescues behavioral abnormalities caused by FXR1 deficiency in PVIs. This work unveils the function of a newly identified SCZ risk gene in SCZ-relevant neurons and identifies a therapeutic target and a potential noninvasive treatment for psychiatric disorders.
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