Project description:Loss of nervous system tissue after severe brain injury is a main determinant of poor functional recovery. Cell transplantation is a promising method to restore lost tissue and function, yet it remains unclear if transplanted neurons can demonstrate the population level dynamics important for movement control. Here we present a comprehensive approach for long-term single neuron monitoring and manipulation of transplanted embryonic cortical neurons after cortical injury in adult male mice performing a prehension task. The observed patterns of population activity in the transplanted network strongly resembled that of healthy networks. Specifically, the task-related spatiotemporal activity patterns of transplanted neurons could be represented by latent factors that evolve within a low dimensional manifold. We also demonstrate reliable modulation of the transplanted networks using minimally invasive epidural stimulation. Our approach may allow greater insight into how restoration of cell-type specific network dynamics in vivo can restore motor function.
Project description:Traction force against the substrate is required for neuronal migration, but how it is generated and regulated remains controversial. Using traction force microscopy, we showed in cultured granule cells the coexistence of three distinct contraction centers (CCs) that are located at the distal and proximal regions of the leading process as well as at the trailing process, regions exhibiting high-level myosin-II activities. The CC activities depended on myosin-II, actin filaments, and microtubules, as well as substrate adhesion, and exhibited apparently independent fluctuation. The difference of strain energies associated with CC activities between leading versus trailing processes tightly correlated with the displacement of the soma at any given time. Application of brain-derived neurotrophic factor (BDNF) and Slit2, factors known to guide neuronal migration, at the leading process altered CC activities by regulating the small GTPases Cdc42 and RhoA, respectively, leading to forward and rearward soma translocation. These results delineate the multiple origins and spatiotemporal dynamics of the traction force underlying neuronal migration.
Project description:As a key building block of biological cortex, neurons are powerful information processing units and can achieve highly complex nonlinear computations even in individual cells. Hardware implementation of artificial neurons with similar capability is of great significance for the construction of intelligent, neuromorphic systems. Here, we demonstrate an artificial neuron based on NbOx volatile memristor that not only realizes traditional all-or-nothing, threshold-driven spiking and spatiotemporal integration, but also enables dynamic logic including XOR function that is not linearly separable and multiplicative gain modulation among different dendritic inputs, therefore surpassing neuronal functions described by a simple point neuron model. A monolithically integrated 4 × 4 fully memristive neural network consisting of volatile NbOx memristor based neurons and nonvolatile TaOx memristor based synapses in a single crossbar array is experimentally demonstrated, showing capability in pattern recognition through online learning using a simplified δ-rule and coincidence detection, which paves the way for bio-inspired intelligent systems.
Project description:Rhodamine-phalloidin-labeled actin filaments were visualized gliding over a skeletal heavy meromyosin (HMM)-coated surface. Experiments at low filament densities showed that when two filaments collided, their paths were affected in a manner that depended on collision angle. Some collisions resulted in complete alignment of the filament paths; in others, the filaments crossed over one another. Filament crossover or alignment was equally probable at ?40° contact angle. Filaments often underwent significant bending during collision and analysis of filament shape indicated an energy requirement of ?13 kBT. Experiments were performed over a wide range of HMM surface density and actin filament bulk concentration. Actin filament gliding speed and path persistence plateaued above a critical HMM surface density, and at high (micromolar) actin filament concentrations, filament motion became dramatically aligned in a common direction. Spatiotemporal features of alignment behavior were determined by correlation analysis, supported by simulations. The thermal drift of individual filament tracks was suppressed as the population became more oriented. Spatial correlation analysis revealed that long-range alignment was due to incremental recruitment rather than fusion of locally ordered seed domains. The global alignment of filament movement, described by an "order parameter," peaked at optimal actin concentrations and myosin surface densities, in contrast to previous predictions of a critical phase transition. Either hydrodynamic coupling or exchange of filaments between the surface bound and adjacent bulk phase layers might degrade order at high actin filament concentration, and high HMM surface densities might decrease alignment probability during collisions. Our results are compatible with generation of long-range order from mechanical interaction between individual actin filaments. Furthermore, we show that randomly oriented myosin motors align relatively short, submicrometer actin filaments into motile surface domains that extend over many tens of micrometers and these patterns persist for several minutes.
Project description:We report the use of matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry combined with capillary electrophoresis (CE) mass spectrometry to visualize energy metabolism in the mouse hippocampus by imaging energy-related metabolites. We show the distribution patterns of ATP, ADP, and AMP in the hippocampus as well as changes in their amounts and distribution patterns in a murine model of limbic, kainate-induced seizure. As an acute response to kainate administration, we found massive and moderate reductions in ATP and ADP levels, respectively, but no significant changes in AMP levels--especially in cells of the CA3 layer. The results suggest the existence of CA3 neuron-selective energy metabolism at the anhydride bonds of ATP and ADP in the hippocampal neurons during seizure. In addition, metabolome analysis of energy synthesis pathways indicates accelerated glycolysis and possibly TCA cycle activity during seizure, presumably due to the depletion of ATP. Consistent with this result, the observed energy depletion significantly recovered up to 180 min after kainate administration. However, the recovery rate was remarkably low in part of the data-pixel population in the CA3 cell layer region, which likely reflects acute and CA3-selective neural death. Taken together, the present approach successfully revealed the spatiotemporal energy metabolism of the mouse hippocampus at a cellular resolution--both quantitatively and qualitatively. We aim to further elucidate various metabolic processes in the neural system.
Project description:We analyse theoretically the spatiotemporal dynamics of two incoherent counterpropagating Airy beams interacting in a photorefractive crystal under focusing conditions. For a large enough nonlinearity strength the interaction between the two Airy beams leads to light-induced waveguiding. The stability of the waveguide is determined by the crystal length, the nonlinearity strength and the beam's intensities and is improved when comparing to the situation using Gaussian beams. We further identify the threshold above which the waveguide is no longer static but evolves dynamically either time-periodically or even chaotically. Above the stability threshold, each Airy-soliton moves erratically between privileged output positions that correspond to the spatial positions of the lobes of the counterpropagating Airy beam. These results suggest new ways of creating dynamically varying waveguides, optical logic gates and chaos-based computing.
Project description:Time is a fundamental dimension, but millisecond-level judgments sometimes lead to perceptual illusions. We previously introduced a "time-shrinking illusion" using a psychological paradigm that induces auditory temporal assimilation (ATA). In ATA, the duration of two successive intervals (T1 and T2), marked by three auditory stimuli, can be perceived as equal when they are not. Here, we investigate the spatiotemporal profile of human temporal judgments using magnetoencephalography (MEG). Behavioural results showed typical ATA: participants judged T1 and T2 as equal when T2 - T1???+80 ms. MEG source-localisation analysis demonstrated that regional activity differences between judgment and no-judgment conditions emerged in the temporoparietal junction (TPJ) during T2. This observation in the TPJ may indicate its involvement in the encoding process when T1???T2. Activation in the inferior frontal gyrus (IFG) was enhanced irrespective of the stimulus patterns when participants engaged in temporal judgment. Furthermore, just after the final marker, activity in the IFG was enhanced specifically for the time-shrinking pattern. This indicates that activity in the IFG is also related to the illusory perception of time-interval equality. Based on these observations, we propose neural signatures for judgments of temporal equality in the human brain.
Project description:It is generally accepted that visual perception results from the activation of a feed-forward hierarchy of areas, leading to increasingly complex representations. Here we present evidence for a fundamental role of backward projections to the occipito-temporal region for understanding conceptual object properties. The evidence is based on two studies. In the first study, using high-density EEG, we showed that during the observation of how objects are used there is an early activation of occipital and temporal areas, subsequently reaching the pole of the temporal lobe, and a late reactivation of the visual areas. In the second study, using transcranial magnetic stimulation over the occipital lobe, we showed a clear impairment in the accuracy of recognition of how objects are used during both early activation and, most importantly, late occipital reactivation. These findings represent strong neurophysiological evidence that a top-down mechanism is fundamental for understanding conceptual object properties, and suggest that a similar mechanism might be also present for other higher-order cognitive functions.
Project description:Longitudinal single cell RNA-expression analysis of tumor cells along the metastatic cascade. AKTP MTOs were implanted in the caecum and left to metastasize into the liver. Mice with different metastatic burden were collected and GFP+ CD45- cells were sorted in 96-well smart-seq plates. Tumor cells were collected at four stages (Primary tumors, micrometastases, small metastases and big metastases) and each Smart-seq2 plate contained cells from all conditions to avoid batch effects. Primary tumor samples were matched with micro, small or big metastases samples.
Project description:Working memory is capacity-limited. In everyday life we rarely notice this limitation, in part because we develop behavioral strategies that help mitigate the capacity limitation. How behavioral strategies are mediated at the neural level is unclear, but a likely locus is lateral prefrontal cortex (LPFC). Neurons in LPFC play a prominent role in working memory and have been shown to encode behavioral strategies. To examine the role of LPFC in overcoming working-memory limitations, we recorded the activity of LPFC neurons in animals trained to perform a serial self-ordered search task. This task measured the ability to prospectively plan the selection of unchosen spatial search targets while retrospectively tracking which targets were previously visited. We found that individual LPFC neurons encoded the spatial location of the current search target but also encoded the spatial location of targets up to several steps away in the search sequence. Neurons were more likely to encode prospective than retrospective targets. When subjects used a behavioral strategy of stereotyped target selection, mitigating the working-memory requirements of the task, not only did the number of selection errors decrease but there was a significant reduction in the strength of spatial encoding in LFPC. These results show that LPFC neurons have spatiotemporal mnemonic fields, in that their firing rates are modulated both by the spatial location of future selection behaviors and the temporal organization of that behavior. Furthermore, the strength of this tuning can be dynamically modulated by the demands of the task.