Biology subjects

Stanis, N.

Publications and source records attributed to Stanis, N..

4 recordsLinked to original sources

bioRxiv2025

Multimodal optical imaging and modulation through Smart Dura in non-human primates

Multimodal neural interfaces that integrate electrical and optical functionalities are promising tools for neuroscientific and clinical applications that involve recording and manipulating neuronal activity. However, most technologies for multimodal implementation are largely restricted to small animal models and lack the ability to translate to the larger brains of non-human primates (NHPs). Smart Dura, a recently developed large-scale neural interface for NHPs, enables high-density electrophysiological recordings and broad optical accessibility, providing multiscale information with enhanced spatiotemporal resolution. In this paper, the multimodal capabilities of Smart Dura are demonstrated through integration with multiphoton imaging, optical coherence tomography angiography (OCTA), and intrinsic signal optical imaging (ISOI), as well as optical manipulations such as photothrombotic lesioning and optogenetics. Through the transparent Smart Dura, in vivo fluorescence vascular imaging is achieved down to depths of 200 and 550 m using two-photon and three-photon microscopy, respectively. When combined with simultaneous electrophysiology, Smart Dura also enables assessment of vascular and neural dynamics via OCTA and ISOI, the induction of ischemic stroke, and the application of optogenetic neuromodulation across a wide cortical area of 20 mm in diameter. These capabilities support comprehensive investigations of brain dynamics in NHPs, advancing translational neurotechnology for human applications.

neuroscience↗

bioRxiv2025

Smart Dura: a functional artificial dura for multimodal neural recording and modulation

A multi-modal neural interface capable of long-term recording and stimulation is essential for advancing brain monitoring and developing targeted therapeutics. Among the traditional electrophysiological methods, micro-electrocorticography (ECoG) is appealing for chronic applications because it provides a good compromise between invasiveness and high-resolution neural recording. When combining ECoG with optical technologies, such as calcium imaging and optogenetics, this multi-modal approach enables the simultaneous collection of neural activity from individual neurons and the ability to perform cell-specific manipulation. While previous efforts have focused on multi-modal interfaces for small animal models, scaling these technologies to larger brains, of primates, remains challenging. In this paper, we present a multi-modal neural interface, named Smart Dura, a functional version of the commonly used artificial dura with integrated electrophysiological electrodes for large cortical area coverage for the NHP brain. The Smart Dura is fabricated using a thin-film microfabrication process to monolithically integrate a micron-scale electrode array into a soft, flexible, and transparent substrate with high-density electrodes (up to 256 electrodes) while providing matched mechanical compliance with the native tissue and achieving high optical transparency (exceeding 97%). Our in vivo experiments demonstrate electrophysiological recording capabilities combined with neuromodulation, as well as optical transparency via multiphoton imaging. This work paves the way toward a chronic neural interface that can provide large-scale, bidirectional interfacing for multimodal and closed-loop neuromodulation capabilities to study cortical brain activity in non-human primates, with the potential for translation to humans.

neuroscience↗

bioRxiv2024

A large-scale optogenetic neurophysiology platform for improving accessibility in NHP behavioral experiments

Optogenetics has been a powerful scientific tool for two decades, yet its integration with non-human primate (NHP) electrophysiology has been limited due to several technical challenges. These include a lack of electrode arrays capable of supporting large-scale and long-term optical access, inaccessible viral vector delivery methods for transfection of large regions of cortex, a paucity of hardware designed for large-scale patterned cortical illumination, and limited designs for multi-modal experimentation. To address these gaps, we introduce a highly accessible platform integrating optogenetics and electrophysiology for behavioral and neural modulation with neurophysiological recording in NHPs. We employed this platform in two rhesus macaques and showcased its capability of optogenetically disrupting reaches, while simultaneously monitoring ongoing electrocorticography activity underlying the stimulation-induced behavioral changes. The platform exhibits long-term stability and functionality, thereby facilitating large-scale electrophysiology, optical imaging, and optogenetics over months, which is crucial for translationally relevant multi-modal studies of neurological and neuropsychiatric disorders. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/600719v2_ufig1.gif" ALT="Figure 1"> View larger version (67K): org.highwire.dtl.DTLVardef@179542eorg.highwire.dtl.DTLVardef@85ab3aorg.highwire.dtl.DTLVardef@1ac8deeorg.highwire.dtl.DTLVardef@19a0831_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2024

Healthy human induced pluripotent stem cell-derived cardiomyocytes exhibit sex dimorphism even without the addition of hormones

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are a valuable cell type for studying human cardiac health and disease in vitro. However, it is not known whether hiPSC-CM display sex dimorphism and therefore whether sex should be incorporated as a biological variable in in vitro studies that include this cell type. To date, the vast majority of studies that utilize hiPSC-CM do not include both male and female sex nor stratify results based on sex because it is challenging to amass such a cohort of cells. Here we generated three female and three male hiPSC-lines from adult left ventricular cardiac fibroblasts as a resource for studying sex differences in in vitro cardiac models. We used this resource to generate hiPSC-CM and maintained them in basal media without exogenous hormones. Functional assessment of CM showed enhanced calcium handling in female-derived hiPSC-CM relative to male. Bulk RNA sequencing revealed over 300 differentially expressed genes (DEG) between male and female hiPSC-CM. Some of the DEG are X and Y-linked genes and many are implicated in cardiac health and disease including potassium channels which could account for net differences in calcium handling shown here. Gene ontology analysis of DEG showed distinct differences in pathways related to cardiac pathology including cell-cell adhesion, metabolic processes, and response to ischemic stress. These findings highlight the importance of considering sex as a variable when conducting studies to evaluate aspects of human cardiac health and disease related to cardiomyocyte function.

cell biology↗