The Initiative on Neurosciences is pleased to announce the winners of the Inspiration Awards for Neuroscience and Technology. These awards were made directly to graduate students and postdoctoral research associates for research projects that intersect neuroscience with either computer science or engineering technology.
Twenty proposals were submitted from applicants in ten departments across four colleges. The three main criteria used in judging were creativity, feasibility, and integration of neuroscience with either computer science or engineering. We are hopeful that the winning proposals will lead to larger projects and continued collaboration in the future of merging neuroscience and technology. We are thrilled to announce the winners below, along with the abstracts accompanying their proposals. All awardees were recognized at the 3rd annual IONs Interdisciplinary Neurosciences Conference on May 26.
Carey Dougan, PhD student, Chemical Engineering, Advisor: Shelly Peyton
Brandon Roberts, Postdoctoral researcher, Psychological and Brain Sciences, Advisor: Ilia Karatsoreos
“Impact of traumatic brain injury on glial and neural function in the hippocampus”
Abstract: Traumatic brain injury (TBI) is an established risk factor for developing neurodegenerative disease. However, there is a lack of TBI models that relate injury forces to both macroscale tissue damage and brain function at the cellular level. Needle-induced cavitation (NIC) is a technique that induces highly localized injury to ex vivo brain tissue by applying fluid pressure. We have previously observed that NIC causes tissue damage along the hippocampus, a brain region critical for learning and memory formation. Injury to this region causes cognitive pathologies in humans and rodent models. However, the impact of NIC at the cellular level is unknown. NIC related injury activates specialized glial cells called astrocytes. We hypothesize that NIC induced astrocyte activation will lead to secretion of the signaling and remodeling proteins: tenascin-c (TN-C), thrombospondin (TSP), and connective tissue growth factor (CTGF) into the extracellular matrix (ECM). Although astrocyte secreted ECM proteins are known contributors to synapse formation, how NIC impacts synaptic function is unknown. We hypothesize that NIC will disrupt synaptic function in the hippocampus in the weeks following injury. Here we propose to combine a range of engineering and neuroscience techniques to test these hypotheses. Understanding how TBI impacts short- and long-term astrocyte responses and synaptic function is essential in determining the underlying mechanisms that relate acute brain injury with neurodegenerative disease. This collaboration lays the groundwork for advanced approaches in understanding how TBI impacts neural function, and the development of treatments that promote TBI repair and prevent neurodegenerative disease.
Devdhar Patel, PhD student, Information and Computer Sciences, Advisor: Hava Siegelmann
Francesca Walsh, PhD student, Psychological and Brain Sciences, Advisor: Youngbin Kwak
“TempoMod: Enhancing resiliency, efficiency, and learning capability with Neuron frequency modulation and temporal adaptivity”
Abstract: This project proposal aims to utilize the established research on sensorimotor control, dopamine neuromodulation during learning, and spinal reflexes to enhance artificial neural networks with temporal intelligence. Our project seeks to create a delay-aware artificial agent that can respond to changes in its environment with adaptive response times. Current artificial neural networks (ANNs) are not resilient to changing environments. Their learning policies are often rigid and highly specified to a single task and response time. Our methods will be a move towards ANNs with dynamic response capabilities, similar to how animals can learn and adapt in various natural environments with constantly changing information. Our project focuses on three ways of achieving temporal intelligence: quick distributed asynchronous control using reflexes, adaptive time-slicing using neuromodulation, and planning a sequence of actions for fast yet precise control. This project will utilize an agent-critic agent with reinforcement learning algorithms that will be built and tested in MuJuCo, a realistic physics environment. The ANN will be given tasks of various complexity so that we can track how the addition of biologically inspired mechanisms, such as reflexes and dopamine neuromodulation, improves learning, safety, and survivability. Our goal is to advance the understanding of intelligence, and this research is on the frontiers of Artificial Intelligence and Neuroscience. Supporting this project will support our future goals by funding a novel research project that will be a pillar of our graduate research portfolio and help us prepare for careers in academia as multidisciplinary researchers.
Sarah Dickinson, PhD student, Psychological and Brain Sciences, Advisor: Joseph Bergan
“In vivo characterization of social representations in the medial amygdala and their modulation by oxytocin”
Abstract: The medial amygdala (MeA) is a central node in a network of brain regions that process pheromones and produce social behaviors. A subset of aromatase expressing (arom+) neurons within the MeA facilitate sex specific social behaviors including sex recognition, mating behavior and aggression. Arom+ neurons integrate information from a wide array of subcortical neural circuits. The neuropeptide oxytocin is synthesized in the paraventricular nucleus of the hypothalamus (PVN) and released peripherally, for physiological regulation, and centrally, for social regulation. Oxytocin acts, in part, through arom+ neurons in the medial amygdala to influence social recognition and social memory; however, the functional, temporal and full behavioral dynamics of this modulation are unknown. The following proposal plans to pursue these questions by manipulating PVN oxytocin neurons while observing the moment-to-moment activity of MeA neurons devoted to producing social behavior. Briefly, I will measure activity from both arom+ and non-arom+ neurons within the MeA via a fiber photometry, genetic and viral approach, while controlling PVN oxytocin neuron activity. This approach will provide insight into the network dynamics of arom+ neurons within the MeA, between the PVN and MeA and social behavior production. It also employs existing methods to examine circuit dynamics and social behavior production with novel circuit precision. In concert, I will be engineering an innovative technical approach that will combine in vivo recording with novel access to target circuits. The experience of technical development, computational analysis and the subsequent communication of results will allow me to gain career relevant skills and exposure.
Harshada Sant, Postdoctoral researcher, Neuroscience and Behavior, Advisor: Paul Katz
“Using state-of-the-art technologies and machine learning algorithms to generate a high-resolution neural connectome of a molluscan ganglion”
Abstract: The goal of this project is to accelerate analysis of high-resolution volume electron microscope data by providing ground truth for machine learning algorithms to improve alignment of slices and autosegmentation of all neurons in the brain. This project is a collaboration between the Katz lab at UMass and the Lichtman lab at Harvard University to construct a full wiring diagram of an enigmatic brain structure, the rhinophore ganglion, in a previously unstudied species, Berghia stephanieae, an undertaking that would have impossible without advances in machine learning algorithms. Katz lab members will generate the ground truth by manually tracing wrinkles and neurons in hundreds of slices in VAST software. Computer scientists in the Lichtman lab will then use this as training and test data for a convolutional neural network that automatically generates a saturated wiring diagram that includes all cellular processes and all synapses. 3D reconstructions of neurons will be done using 3dsmax and Blender software. Expertise of the Katz lab in neuroscience and the Lichtman in connectomics with the help of machine learning experts and servers at Google will help accelerate the project. Combining the connectome data with transcriptome generated for Berghia will help identify diverse cell types in this system, something I aim to leverage in my own lab. This experience will help me develop a multidisciplinary research program to understand mechanisms that generate diversity of brains and behaviors by identifying cell types in adults and tracing development of individual neurons to determine the points of divergence.
Weixuan Chen, PhD student, Biomedical Engineering, Advisor: Siyuan Rao
“Electrical Modulation on Genetically Identifiable Neurons”
Abstract: Abnormal neural electrical signaling can result in various neurological diseases. Existing techniques allow for modulating neural electrical signals via electrical or magnetic fields; however, due to nature of electricity and negligible magnetoreception of biological tissues, these techniques lack the control of genetically identifiable neural populations and permit limited spatial precision. Here, we propose a transcranial magnetic stimulation (TMS)-assisted neural modulation technique that utilizes a genetic toolkit to provide tunable thresholds for neural depolarization and grant the selectivity of TMS on specific neural populations. We plan to on-demand express a series of protein with different conductivity on neural cell membranes. After validating the protein expression by immunostaining, we confirmed effect on membrane property regulation with one of our candidate proteins, pilA, in HEK 293 cells with patch clamp recording. We plan to further validate our hypothesis of modulating neural excitation/inhibition on mouse hippocampal and dorsal root ganglion neurons via protein expression on neural cell membranes. To prepare in vivo study, we plan to co-microinject AAV9 viral vector carrying candidate proteins and genetically encoded calcium indicator, GCaMP6s in mice brain. We will use patch clamp recording and calcium imaging of infected neurons in acute brain slices with or without magnetic field to validate the specific activation/inhibition of neurons via magnetic field ex vivo. The proposed technique, as the first phase of my PhD project, will provide new insight on cellular mechanism of neurological diseases related to abnormal neural electrical signaling and will be further developed into a useful tool for neuroscience community.
Jingyi Qiu, PhD student, Biomedical Engineering, Advisor: S. Thai Thayumanavan
“Modular nanoparticles for efficient and targeted neural system gene delivery”
Abstract: Non-viral delivery systems use dense cationic charges in their structures to bind and encapsulate nucleic acids. Although simple in its complementarity to negatively charged nucleic acids, the cationic charge of these carriers is simultaneously their key liability, entailing their high cytotoxicity. Viruses, on the other hand, do not use electrostatics for encapsulating nucleic acids. In fact, the “electrostatic pressure” from the lack of charge compensation in viruses is thought to be the key driving force for the efficient injection of their genetic material into the cytoplasm upon cell surface docking. However, viral delivery platforms have several liabilities for widespread use in vivo. My project aims to efficiently deliver gene editing tools to specific cells and across the BBB (blood-brain barrier) by engineering a novel class of nanocarriers. First, a novel polymer nanoparticle that encapsulates nucleic acids without charge compensation will be developed. Then the nanoparticle will be decorated with cell membranes that are known to cross the BBB and it can be homotypic to neuronal cells. The effect of such a coating in translocating the nanoparticles specific neurons and BBB crossing will be evaluated in vitro and in vivo. Finally, the efficiency of the Cas9/sgRNA combination will be evaluated to affect genome editing in neuronal cells in vivo. The proposed research projects will meet the urgent demands for safe and effective gene editing and provide a powerful neuron engineering toolset.
Anant Shinde, Postdoctoral researcher, Biomedical Engineering, Advisor: Gottfried Schlaug
“Building and Testing a novel MR-compatible non-invasive high-intensity brain-stimulator“
Abstract: Non-invasive brain-stimulation such as transcranial electrical stimulation (TES) can be used as a tool to causally examine and modulate the function of single brain regions as well as the intrinsic activity of entire brain networks. Dose of stimulation is a strong predictor of the magnitude of the biological and behavioral response. Concurrent TES-MRI using MR compatible devices offers a unique way of revealing the engagement of local brain regions and showing the modulation of brain activity using surrogate MR measures of change in brain activity. Higher dose stimulators (up to 5mA) have been shown to be safe for brain and skin and have good tolerability in human subjects. Data modeling and animal experiments have shown us that further dose increases have stronger biological effects without compromising safety. I have built a prototype of an MR-compatible high dose stimulator that needs to be further refined and tested in a well-established 3+3 dose escalation study to demonstrate safety, tolerability and brain-tissue efficacy in human studies. Such a high-dose MR compatible device would not only be novel and unique to UMass, but has the ability to change the field of non-invasive brain-stimulation since a safe high-dose stimulator has a higher likelihood of showing stronger effects in basic research and therapeutic studies.