Publications

Research Articles

• J Geng#, Y Tang#, Z Yu#, Y Gao, W Li, Y Lu, B Wang, H Zhou, P Li, N Liu, P Wang, Y Fan, Y Yang*, ZV Guo*, X Liu*. Chronic Ca2+ imaging of cortical neurons with long-term expression of GCaMP-X. eLife. 2022 Oct 5. Download PDF | Show Abstract
  Dynamic Ca²⁺ signals reflect acute changes in membrane excitability (e.g. responses to stimuli), and also mediate intracellular signaling cascades that normally take longer time to manifest (e.g., regulations of transcription). In both cases, chronic Ca²⁺ imaging has been often desired, but largely hindered by unexpected cytotoxicity intrinsic to GCaMP, a popular series of genetically-encoded Ca²⁺ indicators. Here, we demonstrate the performance of GCaMP-X in chronic Ca²⁺ imaging with long-term probe expression in cortical neurons, which has been designed to eliminate the unwanted interactions between conventional GCaMP indicators and endogenous (apo)calmodulin-binding proteins. By expressing in live adult mice at high levels over an extended time frame, GCaMP-X indicators showed less damage and improved performance in two-photon imaging of acute Ca²⁺ responses to whisker deflection or spontaneous Ca²⁺ fluctuations. Chronic Ca²⁺ imaging data (³1 month) were acquired from cultured cortical neurons expressing GCaMP-X, unveiling that spontaneous/local Ca²⁺ transients would progressively develop into autonomous/global Ca²⁺ oscillations. Besides the morphological indices of neurite length and soma size, the major metrics of oscillatory Ca²⁺, including rate, amplitude and synchrony were also examined along with the multiple stages (from neonatal to mature) during neural development. Dysregulations of both neuritogenesis and Ca²⁺ oscillations were observed typically in 2-3 weeks, which were exacerbated by stronger or prolonged expression of GCaMP. In comparison, neurons expressing GCaMP-X exhibited significantly less damage. By varying the timepoints of virus infection or drug induction, GCaMP-X outperformed GCaMP similarly in cultured mature neurons. These data altogether highlight the unique importance of oscillatory Ca²⁺ to morphology and health of neurons, presumably underlying the differential performance between GCaMP-X and GCaMP. In summary, GCaMP-X provides a viable option for Ca²⁺ imaging applications involving long-time and/or high-level expression of Ca²⁺ probes.

• X Yin, Y Wang, J Li, ZV Guo*. Lateralization of short-term memory in the frontal cortex. Cell Reports. 2022 Aug 16;40(7):111190. Download PDF | Show Abstract
  Despite essentially symmetric structures in mammalian brains, the left and right hemispheres do not contribute equally to certain cognitive functions. How both hemispheres interact to cause this asymmetry remains unclear. Here, we study this question in the anterior lateral motor cortex (ALM) of mice performing five versions of a tactile-based decision-making task with a short-term memory (STM) component. Unilateral inhibition of ALM produces variable behavioral deficits across tasks, with the left, right, or both ALMs playing critical roles in STM. Neural activity and its encoding capability are similar across hemispheres, despite that only one hemisphere dominates in behavior. Inhibition of the dominant ALM disrupts encoding capability in the non-dominant ALM, but not vice versa. Variable behavioral deficits are predicted by the influence on contralateral activity across sessions, mice, and tasks. Together, these results reveal that the left and right ALM interact asymmetrically, leading to their differential contributions to STM.

• J Lu, Z Zhang, X Yin, Y Tang, R Ji, H Chen, Y Guang, X Gong, Y He, W Zhou, H Wang, K, Cheng, Y Wang, X Chen, P Xie*, ZV Guo*. An entorhinal-visual cortical circuit regulates depression-like behaviors. Molecular Psychiatry. 2022 Apr 6; 1-14. Download PDF | Supp Info | Show Abstract
  Major depressive disorder is viewed as a ‘circuitopathy’. The hippocampal-entorhinal network plays a pivotal role in regulation of depression, and its main sensory output, the visual cortex, is a promising target for stimulation therapy of depression. However, whether the entorhinal-visual cortical pathway mediates depression and the potential mechanism remains unknown. Here we report a cortical circuit linking entorhinal cortex layer Va neurons to the medial portion of secondary visual cortex (Ent→V2M) that bidirectionally regulates depression-like behaviors in mice. Analyses of brain-wide projections of Ent Va neurons and two-color retrograde tracing indicated that Ent Va→V2M projection neurons represented a unique population of neurons in Ent Va. Immunostaining of c-Fos revealed that activity in Ent Va neurons was decreased in mice under chronic social defeat stress (CSDS). Both chemogenetic inactivation of Ent→V2M projection neurons and optogenetic inactivation of the projection terminals induced social deficiency, anxiety- and despair-related behaviors in healthy mice. Chemogenetic inactivation of Ent→V2M projection neurons also aggravated these depression-like behaviors in CSDS-resilient mice. Optogenetic activation of Ent→V2M projection terminals rapidly ameliorated depression-like phenotypes. Optical recording using fiber photometry indicated that elevated neural activity in Ent→V2M projection terminals promoted antidepressant-like behaviors. Thus, the Ent→V2M circuit plays a crucial role in regulation of depression-like behaviors, and can function as a potential target for treating major depressive disorder.

• Y Tang#, H Yang#, X Chen, Z Zhang, X Yao, X Yin, ZV Guo*. Opposing regulation of short-term memory by basal ganglia direct and indirect pathways that are coactive during behavior. bioRxiv preprint. 2021 Dec 16. Download PDF | Show Abstract
  The basal ganglia direct and indirect pathways are viewed to mediate opposing functions in movement. However, this classic model is challenged by recent findings that both pathways are coactive during behavior. We examined the roles of direct (dSPNs) and indirect (iSPNs) pathway spiny projection neurons in a decision-making task with a short-term memory (STM) component. Optogenetic stimulation of cortical-input-defined dSPNs and iSPNs during STM oppositely biased upcoming licking choice, without affecting licking execution. Optogenetically identified dSPNs and iSPNs showed similar response patterns, although with quantitative difference in spatiotemporal organization. To understand how coactive dSPNs and iSPNs play opposing roles, we recorded population activity in frontal cortex and the basal ganglia output nucleus SNr. Stimulation of dSPNs and iSPNs bidirectionally regulated cortical decision variable through the differential modulation of SNr ramping activity. These results reconcile different views by demonstrating that coactive dSPNs and iSPNs precisely shape cortical activity in a push-pull balance.

• H Chen#, T Huang#, Y Yang#, X Yao, Y Huo, Y Wang, W Zhao, R Ji, H Yang, ZV Guo*. Sparse imaging and reconstruction tomography for high-speed high-resolution whole brain imaging. Cell Reports Methods. 2021 Oct 25;1(6):100089. COVER STORY | Download PDF | Show Abstract
  Understanding brain functions requires detailed knowledge of long-range connectivity through which different areas communicate. A key step towards illuminating the long-range structures is to image whole brain at synaptic resolution to trace axonal arbors of individual neurons to their termini. However, high-resolution brain-wide imaging requires continuous imaging for many days to sample over ten trillion voxels even in the mouse brain. Here we have developed a sparse imaging and reconstruction tomography system (SMART) that allows brain-wide imaging of cortical projection neurons at synaptic resolution in about 20 hours, an order of magnitude faster than previous methods. Analyses of morphological features reveal that single cortical neurons show remarkable diversity in local and long-range projections, with prefrontal, premotor and visual neurons having distinct distribution of dendritic and axonal features. The fast imaging system and diverse projection patterns of individual neurons underscore the importance of high-resolution brain-wide imaging in revealing full neuronal morphology.

• Z Zhang#, X Yao#, X Yin#, Z Ding, T Huang, Y Huo, R Ji, H Peng, ZV Guo*. Multiscale light-sheet fluorescence microscopy for fast whole brain imaging. Frontiers in Neuroanatomy. 2021 Sep 24;15:732464. Download PDF | Show Abstract
  Whole-brain imaging has become an increasingly important approach to investigate neural structures including somata distribution, dendritic morphology and axonal projection patterns. Different structures require whole-brain imaging at different resolutions. Thus it is extremely desirable to perform whole-brain imaging at multiple scales. Imaging a complete mammalian brain at synaptic resolution is challenging as it requires continuous imaging from days to weeks due to the large number of voxels to sample. And it is also difficult to acquire constant quality of imaging due to light scattering during in toto imaging. Here, we reveal that light-sheet microscopy has unique advantage over widefield microscopy in multiscale imaging due to its decoupling of illumination and detection. Based on this observation, we have developed a multiscale light-sheet microscope that combines tiling of light-sheet, automatic zooming, periodic sectioning and tissue expansion to achieve constant quality of brain wide imaging from cellular to sub-micron spatial resolution rapidly (all within a few hours). We demonstrated the strength of our system by testing it using mouse brains prepared using different clearing approaches, and were able to track electrode tracks as well as axonal projections at sub-micron resolution to trace the full morphology of single mPFC neurons that have remarkable diversity in long-range projections.

• Y Wang#, X Yin#, Z Zhang, J Li, W Zhao, ZV Guo*. A cortico-basal ganglia-thalamo-cortical channel underlying short-term memory. Neuron. 2021 Nov 3; 109(21):3486-99. Download PDF | Show Abstract
  Persistent activity underlying short-term memory encodes sensory information or instructs specific future movement and, consequently, has a crucial role in cognition. Despite extensive study, how the same set of neurons respond differentially to form selective persistent activity remains unknown. Here, we report that the cortico-basal ganglia-thalamo-cortical (CBTC) circuit supports the formation of selective persistent activity in mice. Optogenetic activation or inactivation of the basal ganglia output nucleus substantia nigra pars reticulata (SNr)-to-thalamus pathway biased future licking choice, without affecting licking execution. This perturbation differentially affected persistent activity in the frontal cortex and selectively modulated neural trajectory that encodes one choice but not the other. Recording showed that SNr neurons had selective persistent activity distributed across SNr, but with a hotspot in the mediolateral region. Optogenetic inactivation of the frontal cortex also differentially affected persistent activity in the SNr. Together, these results reveal a CBTC channel functioning to produce selective persistent activity underlying short-term memory.

• J Lu#, X Gong#, X Yao, Y Guang, H Yang, R Ji, Y He, W Zhou, H Wang, W Wang, S Bai, H Guo, ZV Guo*, P Xie*. Prolonged chronic social defeat stress promotes less resilience and higher uniformity in depression-like behaviors in adult male mice. Biochemical and Biophysical Research Communications. 2021 May 14;553:107-13. Download PDF | Show Abstract
  Chronic social defeat stress (CSDS) is widely applied to study of depression in rodents. 10-day CSDS was a most commonly employed paradigm but with high resilience ratio (∼30%), producing potential variation in depression-like behavioral symptoms. Whether prolonged period (21 days) of CSDS would promote less resilience and reduce behavioral variability remains unknown. We applied 10-day and 21-day CSDS paradigms to induce mouse model of depression and compared their resilience ratio and behavioral phenotypes. Mice under 21-day CSDS had significantly lower resilience ratio and greater changes in behavioral indicators relative to mice under 10-day CSDS. Behavioral indicators from 21-day CSDS paradigm had higher correlations and better prediction for susceptibility which indicating higher uniformity in behavioral phenotypes. Furthermore, a subset of behavioral indicators in 21-day CSDS had high prediction efficacy and should be first applied to screen susceptibility of CSDS. Thus, our study demonstrates that 21-day CSDS is a more robust paradigm inducing reliable depression-like behaviors relative to 10-day CSDS, and should be preferentially used in rodent studies of depression.

• Y Huo#, H Chen#, ZV Guo*. Mapping Functional Connectivity from the Dorsal Cortex to the Thalamus. Neuron. 2020 Sep 23;107(6):1080-94. Download PDF (with supp info) | Show Abstract
  Neural activity in the corticothalamic network is crucial for sensation, memory, decision, and action. Nevertheless, a systematic characterization of corticothalamic functional connectivity has not been achieved. Here, we developed a high throughput method to systematically map functional connections from the dorsal cortex to the thalamus in awake mice by combing optogenetic inactivation with multi-channel recording. Cortical inactivation resulted in a rapid reduction of thalamic activity, revealing topographically organized corticothalamic excitatory inputs. Cluster analysis showed that groups of neurons within individual thalamic nuclei exhibited distinct dynamics. The effects of inactivation evolved with time and were modulated by behavioral states. Furthermore, we found that a subset of thalamic neurons received convergent inputs from widespread cortical regions. Our results present a framework for collecting, analyzing, and presenting large electrophysiological datasets with region-specific optogenetic perturbations and serve as a foundation for further investigation of information processing in the corticothalamic pathway.

• N Li*, S Chen, ZV Guo, H Chen, Y Huo, HK Inagaki, G Chen, C Davis, D Hansel, C Guo, K Svoboda*.  Spatiotemporal constraints on optogenetic inactivation in cortical circuits. Elife. 2019 Nov 18;8:e48622. Download PDF | Show Abstract
  Optogenetics allows manipulations of genetically and spatially defined neuronal populations with excellent temporal control. However, neurons are coupled with other neurons over multiple length scales, and the effects of localized manipulations thus spread beyond the targeted neurons. We benchmarked several optogenetic methods to inactivate small regions of neocortex. Optogenetic excitation of GABAergic neurons produced more effective inactivation than light-gated ion pumps. Transgenic mice expressing the light-dependent chloride channel GtACR1 produced the most potent inactivation. Generally, inactivation spread substantially beyond the photostimulation light, caused by strong coupling between cortical neurons. Over some range of light intensity, optogenetic excitation of inhibitory neurons reduced activity in these neurons, together with pyramidal neurons, a signature of inhibition-stabilized neural networks (‘paradoxical effect’). The offset of optogenetic inactivation was followed by rebound excitation in a light dose-dependent manner, limiting temporal resolution. Our data offer guidance for the design of in vivo optogenetics experiments.

• ZV Guo#, HK Inagaki#, K Daie, S Druckmann, CR Gerfen and K Svoboda*. Maintenance of persistent activity in a frontal thalamocortical loop. Nature. 2017 May;545(7653):181-6. Download PDF | Supp Info | Show Abstract
  Persistent neural activity maintains information that connects past and future events. Models of persistent activity often invoke reverberations within local cortical circuits, but long-range circuits could also contribute. Neurons in the mouse anterior lateral motor cortex (ALM) have been shown to have selective persistent activity that instructs future actions. The ALM is connected bidirectionally with parts of the thalamus, including the ventral medial and ventral anterior–lateral nuclei. We recorded spikes from the ALM and thalamus during tactile discrimination with a delayed directional response. Here we show that, similar to ALM neurons, thalamic neurons exhibited selective persistent delay activity that predicted movement direction. Unilateral photoinhibition of delay activity in the ALM or thalamus produced contralesional neglect. Photoinhibition of the thalamus caused a short-latency and near-complete collapse of ALM activity. Similarly, photoinhibition of the ALM diminished thalamic activity. Our results show that the thalamus is a circuit hub in motor preparation and suggest that persistent activity requires reciprocal excitation across multiple brain areas.

• N Li, T Chen, ZV Guo, CR Gerfen and K Svoboda*. A motor cortex circuit for motor planning and movement. Nature. 2015 Mar;519(7541):51-6. Download PDF | Show Abstract
  Activity in motor cortex predicts specific movements seconds before they occur, but how this preparatory activity relates to upcoming movements is obscure. We dissected the conversion of preparatory activity to movement within a structured motor cortex circuit. An anterior lateral region of the mouse cortex (a possible homologue of premotor cortex in primates) contains equal proportions of intermingled neurons predicting ipsi- or contralateral movements, yet unilateral inactivation of this cortical region during movement planning disrupts contralateral movements. Using cell-type-specific electrophysiology, cellular imaging and optogenetic perturbation, we show that layer 5 neurons projecting within the cortex have unbiased laterality. Activity with a contralateral population bias arises specifically in layer 5 neurons projecting to the brainstem, and only late during movement planning. These results reveal the transformation of distributed preparatory activity into movement commands within hierarchically organized cortical circuits.

• ZV Guo, SA Hires, N Li, DH, O’Connor, T Komiyama, E. Ophir, D Huber, C Bonardi, K Morandell, D Gutnisky, S Peron, N Xu, J Cox, K Svoboda*. Procedures for behavioral experiments in head-fixed mice. Plos one. 2014 Feb 10;9(2):e88678. Download PDF | Show Abstract
  The mouse is an increasingly prominent model for the analysis of mammalian neuronal circuits. Neural circuits ultimately have to be probed during behaviors that engage the circuits. Linking circuit dynamics to behavior requires precise control of sensory stimuli and measurement of body movements. Head-fixation has been used for behavioral research, particularly in non-human primates, to facilitate precise stimulus control, behavioral monitoring and neural recording. However, choice-based, perceptual decision tasks by head-fixed mice have only recently been introduced. Training mice relies on motivating mice using water restriction. Here we describe procedures for head-fixation, water restriction and behavioral training for head-fixed mice, with a focus on active, whisker-based tactile behaviors. In these experiments mice had restricted access to water (typically 1 ml/day). After ten days of water restriction, body weight stabilized at approximately 80% of initial weight. At that point mice were trained to discriminate sensory stimuli using operant conditioning. Head-fixed mice reported stimuli by licking in go/no-go tasks and also using a forced choice paradigm using a dual lickport. In some cases mice learned to discriminate sensory stimuli in a few trials within the first behavioral session. Delay epochs lasting a second or more were used to separate sensation (e.g. tactile exploration) and action (i.e. licking). Mice performed a variety of perceptual decision tasks with high performance for hundreds of trials per behavioral session. Up to four months of continuous water restriction showed no adverse health effects. Behavioral performance correlated with the degree of water restriction, supporting the importance of controlling access to water. These behavioral paradigms can be combined with cellular resolution imaging, random access photostimulation, and whole cell recordings.

• ZV Guo#, N Li#, D Huber, E Ophir, D Gutnisky, JT Ting, G Feng and K Svoboda*. Flow of cortical activity underlying a tactile decision in mice. Neuron. 2014 Jan 8;81(1):179-94. Download PDF | Show Abstract
  Perceptual decisions involve distributed cortical activity. Does information flow sequentially from one cortical area to another, or do networks of interconnected areas contribute at the same time? Here we delineate when and how activity in specific areas drives a whisker-based decision in mice. A short-term memory component temporally separated tactile “sensation” and “action” (licking). Using optogenetic inhibition (spatial resolution, 2 mm; temporal resolution, 100 ms), we surveyed the neocortex for regions driving behavior during specific behavioral epochs. Barrel cortex was critical for sensation. During the short-term memory, unilateral inhibition of anterior lateral motor cortex biased responses to the ipsilateral side. Consistently, barrel cortex showed stimulus-specific activity during sensation, whereas motor cortex showed choice-specific preparatory activity and movement-related activity, consistent with roles in motor planning and movement. These results suggest serial information flow from sensory to motor areas during perceptual decision making.

• DH O’Connor#, SA Hires#, ZV Guo, N Li, J Yu, Q Sun, D Huber and K Svoboda*. Neural coding during active somatosensation revealed using illusory touch. Nature Neuroscience. 2013 Jul;16(7):958-65. Download PDF | Supp Info | Show Abstract
  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.

• Z Wei, ZV Guo, L Dudte, H Liang and L Mahadevan*. Geometric mechanics of periodic pleated origami. Physical Review Letters. 2013 May 21;110(21):215501. Download PDF | Show Abstract
  Origami structures are mechanical metamaterials with properties that arise almost exclusively from the geometry of the constituent folds and the constraint of piecewise isometric deformations. Here we characterize the geometry and planar and nonplanar effective elastic response of a simple periodically folded Miura-ori structure, which is composed of identical unit cells of mountain and valley folds with four-coordinated ridges, defined completely by two angles and two lengths. We show that the in-plane and out-of-plane Poisson’s ratios are equal in magnitude, but opposite in sign, independent of material properties. Furthermore, we show that effective bending stiffness of the unit cell is singular, allowing us to characterize the two-dimensional deformation of a plate in terms of a one-dimensional theory. Finally, we solve the inverse design problem of determining the geometric parameters for the optimal geometric and mechanical response of these extreme structures.

• K Askin#*, C Shen#, ZV Guo and S Ramanathan*. Controlling interneuron activity in Caenorhabditis elegans to evoke chemotactic behavior. Nature. 2012 Oct;490(7419):273-7. Download PDF | Supp Info | Show Abstract
  Animals locate and track chemoattractive gradients in the environment to find food. With its small nervous system, Caenorhabditis elegans is a good model system in which to understand how the dynamics of neural activity control this search behaviour. Extensive work on the nematode has identified the neurons that are necessary for the different locomotory behaviours underlying chemotaxis through the use of laser ablation, activity recording in immobilized animals and the study of mutants. However, we do not know the neural activity patterns in C. elegans that are sufficient to control its complex chemotactic behaviour. To understand how the activity in its interneurons coordinate different motor programs to lead the animal to food, here we used optogenetics and new optical tools to manipulate neural activity directly in freely moving animals to evoke chemotactic behaviour. By deducing the classes of activity patterns triggered during chemotaxis and exciting individual neurons with these patterns, we identified interneurons that control the essential locomotory programs for this behaviour. Notably, we discovered that controlling the dynamics of activity in just one interneuron pair (AIY) was sufficient to force the animal to locate, turn towards and track virtual light gradients. Two distinct activity patterns triggered in AIY as the animal moved through the gradient controlled reversals and gradual turns to drive chemotactic behaviour. Because AIY neurons are post-synaptic to most chemosensory and thermosensory neurons, it is probable that these activity patterns in AIY have an important role in controlling and coordinating different taxis behaviours of the animal.

• ZV Guo, AC Hart and S Ramanathan*. Optical interrogation of neural circuits in Caenorhabditis elegans. Nature Methods. 2009 Dec;6(12):891-6. Download PDF | Supp Info | Show Abstract
  The nematode Caenorhabditis elegans has a compact nervous system with only 302 neurons. Whereas most of the synaptic connections between these neurons have been identified by electron microscopy serial reconstructions, functional connections have been inferred between only a few neurons through combinations of electrophysiology, cell ablation, in vivo calcium imaging and genetic analysis. To map functional connections between neurons, we combined in vivo optical stimulation with simultaneous calcium imaging. We analyzed the connections from the ASH sensory neurons and RIM interneurons to the command interneurons AVA and AVD. Stimulation of ASH or RIM neurons using channelrhodopsin-2 (ChR2) resulted in activation of AVA neurons, evoking an avoidance behavior. Our results demonstrate that we can excite specific neurons expressing ChR2 while simultaneously monitoring G-CaMP fluorescence in several other neurons, making it possible to rapidly decipher functional connections in C. elegans neural circuits.

• ZV Guo and L Mahadevan*. Limbless undulatory propulsion on land. Proceedings of the National Academy of Sciences. 2008 Mar 4;105(9):3179-84. Download PDF | Show Abstract
  We analyze the lateral undulatory motion of a natural or artificial snake or other slender organism that “swims” on land by propagating retrograde flexural waves. The governing equations for the planar lateral undulation of a thin filament that interacts frictionally with its environment lead to an incomplete system. Closures accounting for the forces generated by the internal muscles and the interaction of the filament with its environment lead to a nonlinear boundary value problem, which we solve using a combination of analytical and numerical methods. We find that the primary determinant of the shape of the organism is its interaction with the external environment, whereas the speed of the organism is determined primarily by the internal muscular forces, consistent with prior qualitative observations. Our model also allows us to pose and solve a variety of optimization problems such as those associated with maximum speed and mechanical efficiency, thus defining the performance envelope of this mode of locomotion.

• ZV Guo and W Yang*. MPM/MD handshaking method for multiscale simulation and its application to high energy cluster impacts. International Journal of Mechanical Sciences. 2006 Feb 1;48(2):145-59. Download PDF | Show Abstract
  We propose a new multiscale simulation method which seamlessly combines the conventional molecular dynamics (MD) with the continuum mechanics formulated under the material point method (MPM). In MPM, modified interpolation shape functions are adopted to reduce artificial forces on the hierarchical background grids. The multiscale method is validated using the examples of step-like wave and wave packet propagations within a bar. The method is applicable to several kinds of potentials including the Lennard–Jones, EAM and a bonding-angle related potential for silicon. Examples of high energy Cu–Cu and Si–Si cluster impacts are presented. The evolution of displaced atoms is found to depend on the underlying lattice structures. For the case of Cu–Cu cluster impacts, stacking faults play an important role. The displaced atoms, visualized in the method of “local crystalline order”, propagate in an anisotropic manner. This implies the anisotropy in energy transformation process through multi-interactions among cluster and surface atoms.