In search of problems.

With early training in physics, my career was marked by continuous learning and searching for interesting problems in biology. Here, I recount some key events that influenced my choices of research topics. The diversity of topics could be attributed to my own lack of a particular focus and the interests of students and postdocs who happened to join my laboratory.

Assessing the impact of Arctic shipping routes on the global container shipping network's connectivity.

Amidst the intensifying impact of climate change, the extension of navigable periods along Arctic Shipping Routes (ASRs) has garnered attention as a maritime route for container vessels. The urgency to comprehend the reverberations of ASRs on the global container shipping network (GCSN) led to the development of the Latitudinal Centrality Index (LCI), which integrates latitude and centrality in maritime analysis. This index evaluates ASRs' influence across 968 port nodes within the GCSN.

Live birth of chimeric monkey with high contribution from embryonic stem cells.

A formal demonstration that mammalian pluripotent stem cells possess preimplantation embryonic cell-like (naive) pluripotency is the generation of chimeric animals through early embryo complementation with homologous cells. Whereas such naive pluripotency has been well demonstrated in rodents, poor chimerism has been achieved in other species including non-human primates due to the inability of the donor cells to match the developmental state of the host embryos. Here, we have systematically tested various culture conditions for establishing monkey naive embryonic stem cells and optimized the procedures for chimeric embryo culture.

A brain-inspired algorithm that mitigates catastrophic forgetting of artificial and spiking neural networks with low computational cost.

Neuromodulators in the brain act globally at many forms of synaptic plasticity, represented as metaplasticity, which is rarely considered by existing spiking (SNNs) and nonspiking artificial neural networks (ANNs). Here, we report an efficient brain-inspired computing algorithm for SNNs and ANNs, referred to here as neuromodulation-assisted credit assignment (NACA), which uses expectation signals to induce defined levels of neuromodulators to selective synapses, whereby the long-term synaptic potentiation and depression are modified in a nonlinear manner depending on the neuromodulator level. The NACA algorithm achieved high recognition accuracy with substantially reduced computational cost in learning spatial and temporal classification tasks.

Enhanced Beta2-band Oscillations Denote Auditory Hallucination in Schizophrenia Patients and a Monkey Model of Psychosis.

An electroencephalographic (EEG) signature of auditory hallucinations (AHs) is important for facilitating the diagnosis and treatment of AHs in schizophrenia. We recorded EEG from 25 schizophrenia patients with recurrent AHs. During the period of AHs, EEG recordings exhibited significantly elevated beta2-band power in the temporal region, as compared to those recorded in the absence of AHs or during stimulation with verbal sounds.

Single-cell spatial transcriptome reveals cell-type organization in the macaque cortex.

Elucidating the cellular organization of the cerebral cortex is critical for understanding brain structure and function. Using large-scale single-nucleus RNA sequencing and spatial transcriptomic analysis of 143 macaque cortical regions, we obtained a comprehensive atlas of 264 transcriptome-defined cortical cell types and mapped their spatial distribution across the entire cortex. We characterized the cortical layer and region preferences of glutamatergic, GABAergic, and non-neuronal cell types, as well as regional differences in cell-type composition and neighborhood complexity.

Reduction of Intracellular Tension and Cell Adhesion Promotes Open Chromatin Structure and Enhances Cell Reprogramming.

The role of transcription factors and biomolecules in cell type conversion has been widely studied. Yet, it remains unclear whether and how intracellular mechanotransduction through focal adhesions (FAs) and the cytoskeleton regulates the epigenetic state and cell reprogramming. Here, it is shown that cytoskeletal structures and the mechanical properties of cells are modulated during the early phase of induced neuronal (iN) reprogramming, with an increase in actin cytoskeleton assembly induced by Ascl1 transgene.

Origin of the efficiency of spike timing-based neural computation for processing temporal information.

Although the advantage of spike timing-based over rate-based network computation has been recognized, the underlying mechanism remains unclear. Using Tempotron and Perceptron as elementary neural models, we examined the intrinsic difference between spike timing-based and rate-based computations. For more direct comparison, we modified Tempotron computation into rate-based computation with the retention of some temporal information.

Visualizing advances in the future of primate neuroscience research.

Future neuroscience and biomedical projects involving non-human primates (NHPs) remain essential in our endeavors to understand the complexities and functioning of the mammalian central nervous system. In so doing, the NHP neuroscience researcher must be allowed to incorporate state-of-the-art technologies, including the use of novel viral vectors, gene therapy and transgenic approaches to answer continuing and emerging research questions that can only be addressed in NHP research models. This perspective piece captures these emerging technologies and some specific research questions they can address.

Stability and dynamics of dendritic spines in macaque prefrontal cortex.

Formation and elimination of synapses reflect structural plasticity of neuronal connectivity. Here we performed high-resolution two-photon imaging of dendritic spines in the prefrontal cortex of four macaque monkeys and found that spines were in general highly stable, with low percentages undergoing synaptic turnover. By observing the same spines at weekly intervals, we found that newly formed spines were more susceptible to elimination, with only 40% persisting over a period of months.

Neural Mechanism Underlying Task-Specific Enhancement of Motor Learning by Concurrent Transcranial Direct Current Stimulation.

The optimal protocol for neuromodulation by transcranial direct current stimulation (tDCS) remains unclear. Using the rotarod paradigm, we found that mouse motor learning was enhanced by anodal tDCS (3.2 mA/cm) during but not before or after the performance of a task.

Transcriptome, connectome and neuromodulation of the primate brain.

Single-cell transcriptomic analysis has facilitated cell type identification in the brain and mapping of cell type-specific connectomes, helping to elucidate neural circuits underlying brain functions and to treat brain disorders by neuromodulation. Yet, we lack a consensual definition of neuronal types/subtypes and clear distinction between cause and effect within interconnected networks.

A call for international research on COVID-19-induced brain dysfunctions.

COVID-19-induced brain dysfunction (CIBD) will put a strain on world health systems complicated by the heterogeneity of manifestations, which is higher than any other aspect of human biology. Neural, psychological and social causes must be disentangled for effective population-level management of CIBD. International cooperation is required in order to discover neurotechnologies appropriate for health systems.