Physiological synaptic signals initiate sequential spikes at soma of cortical pyramidal neurons

The neurons in the brain produce sequential spikes as the digital codes whose various patterns manage well-organized cognitions and behaviors. A source for the physiologically integrated synaptic signals to initiate digital spikes remains unknown, which we studied at pyramidal neurons of cortical slices. In dual recordings from the soma vs. axon, the signals recorded in vivo induce somatic spikes with higher capacity, which is associated with lower somatic thresholds and shorter refractory periods mediated by voltage-gated sodium channels. The introduction of these parameters from the soma and axon into NEURON model simulates sequential spikes being somatic in origin. Physiological signals integrated from synaptic inputs primarily trigger the soma to encode neuronal digital spikes

Immunogenomic Landscape in Breast Cancer Reveals Immunotherapeutically Relevant Gene Signatures

Breast cancer is characterized by some types of heterogeneity, high aggressive behaviour, and low immunotherapeutic efficiency. Detailed immune stratification is a prerequisite for interpreting resistance to treatment and escape from immune control. Hence, the immune landscape of breast cancer needs further understanding. We systematically clustered breast cancer into six immune subtypes based on the mRNA expression patterns of immune signatures and comprehensively depicted their characteristics. The immunotherapeutic benefit score (ITBscore) was validated to be a superior predictor of the response to immunotherapy in cohorts from various datasets. Six distinct immune subtypes related to divergences in biological functions, signatures of immune or stromal cells, extent of the adaptive immune response, genomic events, and clinical prognostication were identified. These six subtypes were characterized as immunologically quiet, chemokine dominant, lymphocyte depleted, wounding dominant, innate immune dominant, and IFN-γ dominant and exhibited features of the tumor microenvironment (TME). The high ITBscore subgroup, characterized by a high proportion of M1 macrophages:M2 macrophages, an activated inflammatory response, and increased mutational burden (such as mutations in TP53, CDH1 and CENPE), indicated better immunotherapeutic benefits. A low proportion of tumor-infiltrating lymphocytes (TILs) and an inadequate response to immune treatment were associated with the low ITBscore subgroup, which was also associated with poor survival. Analyses of four cohorts treated with immune checkpoint inhibitors (ICIs) suggested that patients with a high ITBscore received significant therapeutic advantages and clinical benefits. Our work may facilitate the understanding of immune phenotypes in shaping different TME landscapes and guide precision immuno-oncology and immunotherapy strategies

Axons Amplify Somatic Incomplete Spikes into Uniform Amplitudes in Mouse Cortical Pyramidal Neurons

BACKGROUND: Action potentials are the essential unit of neuronal encoding. Somatic sequential spikes in the central nervous system appear various in amplitudes. To be effective neuronal codes, these spikes should be propagated to axonal terminals where they activate the synapses and drive postsynaptic neurons. It remains unclear whether these effective neuronal codes are based on spike timing orders and/or amplitudes. METHODOLOGY/PRINCIPAL FINDINGS: We investigated this fundamental issue by simultaneously recording the axon versus soma of identical neurons and presynaptic vs. postsynaptic neurons in the cortical slices. The axons enable somatic spikes in low amplitude be enlarged, which activate synaptic transmission in consistent patterns. This facilitation in the propagation of sequential spikes through the axons is mechanistically founded by the short refractory periods, large currents and high opening probability of axonal voltage-gated sodium channels. CONCLUSION/SIGNIFICANCE: An amplification of somatic incomplete spikes into axonal complete ones makes sequential spikes to activate consistent synaptic transmission. Therefore, neuronal encoding is likely based on spike timing order, instead of graded analogues

An End-to-End Steel Surface Classification Approach Based on EDCGAN and MobileNet V2

In the production process of steel products, it is very important to find defects, which can not only reduce the failure rate of industrial production but also can reduce economic losses. All deep learning-based methods need many labeled samples for training. However, in the industrial field, there is a lack of sufficient training samples, especially in steel surface defects. It is almost impossible to collect enough samples that can be used for training. To solve this kind of problem, different from traditional data enhancement methods, this paper constructed a data enhancement model dependent on GAN, using our designed EDCGAN to generate abundant samples that can be used for training. Finally, we mixed different proportions of the generated samples with the original samples and tested them through the MobileNet V2 classification model. The test results showed that if we added the samples generated by EDCGAN to the original samples, the classification results would gradually improve. When the ratio reaches 80%, the overall classification result reaches the highest, achieving an accuracy rate of more than 99%. The experimental process proves the effectiveness of this method and can improve the quality of steel processing

Associative Memory Extinction Is Accompanied by Decayed Plasticity at Motor Cortical Neurons and Persistent Plasticity at Sensory Cortical Neurons

Associative memory is essential for cognition, in which associative memory cells and their plasticity presumably play important roles. The mechanism underlying associative memory extinction vs. maintenance remains unclear, which we have studied in a mouse model of cross-modal associative learning. Paired whisker and olfaction stimulations lead to a full establishment of odorant-induced whisker motion in training day 10, which almost disappears if paired stimulations are not given in a week, and then recovers after paired stimulation for an additional day. In mice that show associative memory, extinction and recovery, we have analyzed the dynamical plasticity of glutamatergic neurons in layers II–III of the barrel cortex and layers IV–V of the motor cortex. Compared with control mice, the rate of evoked spikes as well as the amplitude and frequency of excitatory postsynaptic currents increase, whereas the amplitude and frequency of inhibitory postsynaptic currents (IPSC) decrease at training day 10 in associative memory mice. Without paired training for a week, these plastic changes are persistent in the barrel cortex and decayed in the motor cortex. If paired training is given for an additional day to revoke associative memory, neuronal plasticity recovers in the motor cortex. Our study indicates persistent neuronal plasticity in the barrel cortex for cross-modal memory maintenance as well as the dynamical change of neuronal plasticity in the motor cortex for memory retrieval and extinction. In other words, the sensory cortices are essential for long-term memory while the behavior-related cortices with the inability of memory retrieval are correlated to memory extinction