Cell-type specific neuromodulation of excitatory and inhibitory neurons via muscarinic acetylcholine receptors in layer 4 of rat barrel cortex

The neuromodulator acetylcholine (ACh) plays an important role in arousal, attention, vigilance, learning and memory. ACh is released during different behavioural states and affects the brain microcircuit by regulating neuronal and synaptic properties. Here, we investigated how a low concentration of ACh (30 μM) affects the intrinsic properties of electrophysiologically and morphologically identified excitatory and inhibitory neurons in layer 4 (L4) of rat barrel cortex. ACh altered the membrane potential of L4 neurons in a heterogeneous manner. Nearly all L4 regular spiking (RS) neurons responded to bath-application of ACh with a M4 muscarinic ACh receptor-mediated hyperpolarisation. In contrast, in the majority of L4 fast spiking (FS) and non-fast spiking (nFS) interneurons 30 μM ACh induced a depolarisation while the remainder showed a hyperpolarisation or no response. The ACh-induced depolarisation of L4 FS interneurons was much weaker than that in L4 nFS interneurons. There was no clear difference in the response to ACh for three morphological subtypes of L4 FS interneurons. However, in four morpho-electrophysiological subtypes of L4 nFS interneurons, VIP+-like interneurons showed the strongest ACh-induced depolarisation; occasionally, even action potential (AP) firing was elicited. The ACh-induced depolarisation in L4 FS interneurons was exclusively mediated by M1 muscarinic ACh receptors; in L4 nFS interneurons it was mainly mediated by M1 and/or M3/5 muscarinic ACh receptors. In a subset of L4 nFS interneurons, a co-operative activation of nicotinic ACh receptors was also observed. The present study demonstrates that low-concentrations of ACh affect the different L4 neurons types in a cell-type specific way. These effects result from a specific expression of different muscarinic and/or nicotinic ACh receptors on the somatodendritic compartments of L4 neurons. This suggests that even at low concentrations ACh may tune the excitability of L4 excitatory and inhibitory neurons and their synaptic microcircuits differentially depending on the behavioural state during which ACh is released.

The Study on Feasibility and Welding Characteristics of GMAW Surfacing Remanufacturing of H13 Steel Cutter Ring of TBM Hob

As H13 steel is a common material for cutters of Tunnel Boring Machine (TBM), the research on surfacing remanufacturing performance is of great value. In this paper, the phase composition of the surfacing layer of H13 steel after gas metal arc welding (GMAW) was analyzed by exploring the precipitation of hard phase in the molten pool, and the microstructure evolution of the surfacing layer was revealed. Then, we carried out simulation modeling analysis on H13 steel surfacing remanufacturing. Results show that: (1) the surfacing layer is combined with the base metal by physical metallurgy without obvious defects such as pores, inclusions and cracks in the surfacing layer; (2) the hardness of the surfacing layer is 60 HRC, which is about 1.5 times of that of the base metal; (3) the stress is mainly concentrated in the arc starting and ending points, followed by the external constraints on both sides of the surfacing layer; (4) the deformation of surfacing layer is slight, which does not affect the forming quality of base metal, while the deformation of base metal is relatively severe. This paper verifies the feasibility of H13 steel remanufacturing from experimental and simulation, providing theoretical basis for future engineering practice.

Observational Analysis of a Wind Gust Event during the Merging of a Bow Echo and Mini-Supercell in Southeastern China

The merging of a fast-moving bow echo with a convective cell of a hook-echo signature was studied by using polarimetric radar detections. Gusts with wind speeds near 35 m s–1 were recorded by the surface station, which caused significant damage. A convective cell with a mesovortex signature, which is hereafter referred to as a mini-supercell, was observed over the northeast of the bow echo before the convective merging. It was found that the mesovortex possessed cyclonic circulation and resembled a supercell-like feature. The merging of the bow echo and the mini-supercell strengthened the updraft near the apex of the bow echo. The enhanced updraft was also demonstrated by the appearance of a differential reflectivity (ZDR) column with a topmost height of 4 km above the melting layer (~4 km). The bow was separated into northern and southern sectors after merging with the mini-supercell, leading to the gusty wind over the surface of the south sector.

Experimental Study of Gangue Layer Weakening with Deep-Hole Presplitting Blasting

Advances in coal mining technology and an increase in coal output are resulting in increasingly challenging conditions being encountered at coal seams. This is particularly so at thin coal seams, where a large number of hard rock layers known as gangue are often present, which seriously affect the normal operation of the shearer and reduce coal output. Therefore, the effective weakening of hard gangue layers in a coal seam is crucial to ensure that the shearer operates effectively and that coal output is maximized. In this paper, the weakening effect of deep-hole presplitting blasting technology on the hard gangue layer in a coal seam is studied via a similar simulation. Four test schemes are designed: (1) A blasting hole spacing of 200 mm with the holes offset vertically. (2) A blast hole spacing of 300 mm with the holes offset vertically. (3) A blast hole spacing of 200 mm with the holes parallel to the gangue layer. (4) A blasting hole spacing of 200 mm with the holes offset vertically and initiation of interval blasting. The effect of the different blasting hole spacings and arrangements and different detonation methods on the weakening of coal seam clamping by gangue is studied, and the best configuration is identified. This improves the effect of weakening the coal gangue layer by deep-hole presplitting blasting.

Weak Coupling Between Spontaneous Local Cortical Activity State Switches Under Anesthesia Leads to Strongly Correlated Global Cortical States

Under anesthesia, neural dynamics deviate dramatically from those seen during wakefulness. During recovery from this perturbation, thalamocortical activity abruptly switches among a small set of metastable intermediate states. These metastable states and structured transitions among them form a scaffold that guides the brain back to the waking state. Here, we investigate the mechanisms that constrain cortical activity to discrete states and give rise to abrupt transitions among them. If state transitions were imposed onto the thalamocortical system by changes in the subcortical modulation, different cortical sites should exhibit near-synchronous state transitions. To test this hypothesis, we quantified state synchrony at different cortical sites in anesthetized rats. States were defined by compressing spectra of layer-specific local field potentials (LFPs) in visual and motor cortices. Transition synchrony, mutual information, and canonical correlations all demonstrate that most state transitions in the cortex are local and that coupling between sites is weak. Fluctuations in the LFP in the thalamic input layer 4 were particularly dissimilar from those in supra- and infra-granular layers. Thus, our results suggest that the discrete global cortical states are not imposed by the ascending modulatory pathways but emerge from the multitude of weak pairwise interactions within the cortex.

Thalamus gates active dendritic computations in cortex during sensory processing

Perception is causally linked to a calcium-dependent spiking mechanism that is built into the distal dendrites of layer 5 pyramidal tract neurons – the major output cell type of the cerebral cortex. It is yet unclear which circuits activate this cellular mechanism upon sensory stimulation. Here we found that the same thalamocortical axons that relay sensory signals to layer 4 also densely target the dendritic domain by which pyramidal tract neurons initiate calcium spikes. Distal dendritic inputs, which normally appear greatly attenuated at the cell body, thereby generate bursts of action potentials in cortical output during sensory processing. Our findings indicate that thalamus gates an active dendritic mechanism to facilitate the combination of sensory signals with top-down information streams into cortical output. Thus, in addition to being the central hub for sensory signals, thalamus is also likely to ensure that the signals it relays to cortex are perceived by the animal.

The Expression Patterns of Cytochrome Oxidase and Immediate-Early Genes Show Absence of Ocular Dominance Columns in the Striate Cortex of Squirrel Monkeys Following Monocular Inactivation

Because at least some squirrel monkeys lack ocular dominance columns (ODCs) in the striate cortex (V1) that are detectable by cytochrome oxidase (CO) histochemistry, the functional importance of ODCs on stereoscopic 3-D vision has been questioned. However, conventional CO histochemistry or trans-synaptic tracer study has limited capacity to reveal cortical functional architecture, whereas the expression of immediate-early genes (IEGs), c-FOS and ZIF268, is more directly responsive to neuronal activity of cortical neurons to demonstrate ocular dominance (OD)-related domains in V1 following monocular inactivation. Thus, we wondered whether IEG expression would reveal ODCs in the squirrel monkey V1. In this study, we first examined CO histochemistry in V1 of five squirrel monkeys that were subjected to monocular enucleation or tetrodotoxin (TTX) treatment to address whether there is substantial cross-individual variation as reported previously. Then, we examined the IEG expression of the same V1 tissue to address whether OD-related domains are revealed. As a result, staining patterns of CO histochemistry were relatively homogeneous throughout layer 4 of V1. IEG expression was also moderate and homogeneous throughout layer 4 of V1 in all cases. On the other hand, the IEG expression was patchy in accordance with CO blobs outside layer 4, particularly in infragranular layers, although they may not directly represent OD clusters. Squirrel monkeys remain an exceptional species among anthropoid primates with regard to OD organization, and thus are potentially good subjects to study the development and function of ODCs.

Contribution of Interneuron Subtype-Specific GABAergic Signaling to Emergent Sensory Processing in Mouse Somatosensory Whisker Barrel Cortex

Mammalian neocortex is important for conscious processing of sensory information with balanced glutamatergic and GABAergic signaling fundamental to this function. Yet little is known about how this interaction arises despite increasing insight into early GABAergic interneuron (IN) circuits. To study this, we assessed the contribution of specific INs to the development of sensory processing in the mouse whisker barrel cortex, specifically the role of INs in early speed coding and sensory adaptation. In wild-type animals, both speed processing and adaptation were present as early as the layer 4 critical period of plasticity and showed refinement over the period leading to active whisking onset. To test the contribution of IN subtypes, we conditionally silenced action-potential-dependent GABA release in either somatostatin (SST) or vasoactive intestinal peptide (VIP) INs. These genetic manipulations influenced both spontaneous and sensory-evoked cortical activity in an age- and layer-dependent manner. Silencing SST + INs reduced early spontaneous activity and abolished facilitation in sensory adaptation observed in control pups. In contrast, VIP + IN silencing had an effect towards the onset of active whisking. Silencing either IN subtype had no effect on speed coding. Our results show that these IN subtypes contribute to early sensory processing over the first few postnatal weeks.

Layer-4 Load Balancer for Flow Size Prediction with TCP/UDP Separation Using P4

Nowadays, datacenters become more complicated and handle many more users’ requests. Custom protocols are becoming more demanded, and an advanced load balancer to distribute the requests among servers is essential to serve the users quickly and efficiently. P4 introduced a new way to manipulate all packet headers. Therefore, by making use of the P4 ability to decapsulate the transport layer header, a new algorithm of load balancing is proposed. The algorithm has three main parts. First, a TCP/UDP separation is used to separate the flows based on the network layer information about the used protocol in the transport layer. Second, a flow size prediction technique is adopted, which relies on the service port number of the transport layer. Lastly, a probing system is considered to detect and solve the failure of the link and server. The proposed load balancer enhances response time of both resources usage and packet processing of the datacenter. Also, our load balancer improves link failure detection by developing a custom probing protocol.

Transformation of Primary Sensory Cortical Representations from Layer 4 to Layer 2

Sensory input arrives from thalamus in cortical layer (L) 4, from which it flows predominantly to superficial layers, so that L4 to L2 constitutes one of the earliest cortical feedforward networks. Despite extensive study, the transformation performed by this network remains poorly understood. We use two-photon calcium imaging in L2-4 of primary vibrissal somatosensory cortex (vS1) to record neural activity as mice perform an object localization task with two whiskers. We find that touch responses sparsen but become more reliable from L4 to L2, with superficial neurons responding to a broader range of touches. Decoding of sensory features either improves from L4 to L2 or remains unchanged. Pairwise correlations increase superficially, with L2/3 containing ensembles of mostly broadly tuned neurons responding robustly to touch. Thus, from L4 to L2, cortex transitions from a dense probabilistic code to a sparse and robust ensemble-based code that improves stimulus decoding, facilitating perception.