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Thomas, C. J.

Publications and source records attributed to Thomas, C. J..

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USE: An integrative suite for temporally-precise psychophysical experiments in virtual environments

11.1 BackgroundThere is a growing interest in complex, active, and immersive behavioral neuroscience tasks. However, the development and control of such tasks present unique challenges.\n\n1.2 New MethodThe Unified Suite for Experiments (USE) is an integrated set of hardware and software tools for the design and control of behavioral neuroscience experiments. The software, developed using the Unity video game engine, supports both active tasks in immersive 3D environments and static 2D tasks used in more traditional visual experiments. The custom USE SyncBox hardware, based around an Arduino Mega2560 board, integrates and synchronizes multiple data streams from different pieces of experimental hardware. The suite addresses three key issues with developing cognitive neuroscience experiments in Unity: tight experimental control, accurate sub-ms timing, and accurate gaze target identification.\n\n1.3 ResultsUSE is a flexible framework to realize experiments, enabling (i) nested control over complex tasks, (ii) flexible use of 3D or 2D scenes and objects, (iii) touchscreen-, button-, joystick- and gaze-based interaction, and (v) complete offline reconstruction of experiments for post-processing and temporal alignment of data streams.\n\n1.4 Comparison with Existing MethodsMost existing experiment-creation tools are not designed to support the development of video-game-like tasks. Those that do use older or less popular video game engines as their base, and are not as feature-rich or enable as precise control over timing as USE.\n\n1.5 ConclusionsUSE provides an integrated, open source framework for a wide variety of active behavioral neuroscience experiments using human and nonhuman participants, and artificially-intelligent agents.\n\n2 GlossaryO_LIActive task: Experimental tasks which involve some combination of realistic, usually moving, stimuli, continuous opportunities for action, ecologically valid tasks, complex behaviours, etc. Here, they are contrasted with static tasks (see below)\nC_LIO_LIArduino: A multi-purpose generic micro-processor, here used to control inter-device communication and time synchronization.\nC_LIO_LIRaycast: A game-engine method that sends a vector between two points in a virtual three-dimensional environment, and returns the first object in that environment it hits. Often used to determine if a character in a game can see or shoot another character.\nC_LIO_LIState Machine (also Finite State Machine): A way of conceptualizing and implementing control in software, such that at any one moment the software is in one, and only one, state. In hierarchical state machines, as used in the present software suite, these can be organized into different levels, such that each level can only be in one state, but a state can pass control to a lower level.\nC_LIO_LIStatic task: Experimental tasks like those traditionally used in the cognitive neurosciences. Simple, usually stationary, stimuli, limited opportunities for action, simple behaviours, etc. Here, they are contrasted with active tasks (see above).\nC_LIO_LIUnity: One of the most popular video game engines. Freely available.\nC_LIO_LIVideo game engine: A software development kit designed to handle many of the common issues involved in creating video games, such as interfacing with controllers, simulating physical collisions and lighting, etc.\nC_LI

neuroscience

Targeting neuronal activity-regulated neuroligin-3 dependency for high-grade glioma therapy

Neuronal activity promotes high-grade glioma (HGG) growth. An important mechanism mediating this neural regulation of brain cancer is activity-dependent cleavage and secretion of the synaptic molecule and glioma mitogen neuroligin-3 (Nlgn3), but the therapeutic potential of targeting Nlgn3 in glioma remains to be defined. We demonstrate a striking dependence of HGG growth on microenvironmental Nlgn3 and determine a targetable mechanism of secretion. Patient-derived orthotopic xenografts of pediatric glioblastoma, diffuse intrinsic pontine glioma and adult glioblastoma fail to grow in Nlgn3 knockout mice. Glioma exposure to Nlgn3 results in numerous signaling consequences, including early focal adhesion kinase activation upstream of PI3K-mTOR. Nlgn3 is cleaved from both neurons and oligodendrocyte precursor cells via the ADAM10 sheddase. Administration of ADAM10 inhibitors robustly blocks HGG xenograft growth. This work defines the therapeutic potential of and a promising strategy for targeting Nlgn3 secretion in the glioma microenvironment, which could prove transformative for treatment of HGG.

neuroscience