Members of The Center for Theoretical and Computational Neuroscience within the Department of Neurobiology and Anatomy use computational approaches to study a range of issues that span single-molecule interactions in dendritic spines to networks of interacting plastic neurons. The CTCN is part of The Gulf Coast Consortium in Theoretical and Computational Neuroscience (GCC-TCN), and includes faculty from six different Gulf Coast academic institutions: Rice University, Baylor College of Medicine (BCM), The University of Houston, the UT M.D. Anderson Cancer Center, the UT Medical Branch at Galveston, and the UT Medical School at Houston. The GCC-TCN has fostered collaboration between different labs in our department and departments in different universities. Thus, there is a rich environment for collaboration both within and among institutions.
A set of fundamental issues in neuroscience concerns the neural mechanisms underlying behavior and behavioral plasticity (e.g., learning). Dr. Baxter’s laboratory uses two approaches, one computational and the other experimental, to investigate the ways in which neural circuits are organized, what principles underlie their function, the consequences of sensory and modulatory influences and the outcome of learning-induced plasticity. Empirical studies utilize the marine mollusk Aplysia as a model system. Computational studies primarily utilize the SNNAP neurosimulator. Currently, two neural circuits are being examined: one mediates a defensive withdrawal reflex and the other mediates feeding. Both of these behaviors can be modified by learning and significant progress is being made toward identifying the network, cellular and molecular processes that underlie the behaviors and their modification by learning. These studies are contributing to our understanding of basic principles that underlie the function of the neural system.
The Beauchamp Laboratory studies multisensory integration and visual perception in the living human brain using a variety of techniques. The main technique is blood-oxygen level dependent functional magnetic resonance imaging (BOLD fMRI). Using BOLD fMRI, Dr. Beauchamp has shown that the human superior temporal sulcus (STS) is important for integrating visual, auditory and multisensory integration. He has also shown that the same region of STS responds to social stimuli such as emotional faces. Therefore, it may be an important brain target for treating disorders of language such as dyslexia or social cognition. Because BOLD fMRI offers only an indirect measure of neuronal activity, it is important to combine fMRI with other measures of brain function. Transcranial magnetic stimulation (TMS) allows for the creation of a temporary lesion in a brain area. By combining TMS with fMRI, it is possible to examine the necessity of a brain area for a cognitive function. For instance, Dr. Beauchamp has shown that the parietal lobe is important for integrating information from the visual and tactile modalities. When the subject receives a faint touch on their hand, they are much better able to detect it when they are able to see the touch. Interrupting parietal activity with TMS eliminates this behavioral advantage. In computational and modeling studies, the Beauchamp Lab is investigating neural codes that can account for the Bayes-optimal multisensory integration observed behaviorally: when modalities are combined, they are weighted by their reliability.
The Byrne laboratory studies the neuronal and molecular mechanisms underlying learning and memory using the marine mollusk Aplysia as a model system. He uses a variety of biochemical, biophysical, electrophysiological, molecular, morphological, and computer simulation techniques to analyze the properties of neural circuits and the individual neurons in those circuits. He studies simple forms of nonassociative and associative learning, reconstructing the behaviors and their modifications from the biochemical and biophysical properties of the neurons that produce them. These forms of learning involve changes in synaptic transmission at previously existing synaptic connections. Currently, he is investigating the roles of second messengers and gene expression in the induction and consolidation of long-term memory and synaptic facilitation. The current computational work is designed to extend existing models to include a more extensive signaling cascade that is believed to underlie long-term synaptic facilitation (LTF). The models will include processes beginning with serotonin (5-HT) treatment and ending with changes in synaptic weight. In addition, he collaborated with Douglas Baxter in modeling and simulating the neural circuitry underlying feeding and reflex behaviors. The models allow for an examination of the contribution of different sites of plasticity within the circuits to the changes in behavior. His laboratory, together with Dr. Baxter, developed the SNAAP software for simulating action potentials and neuronal networks.
The Dragoi laboratory is currently engaged in several lines of research to understand how individual neurons and networks in the visual cortex of behaving monkey construct real-time representations of incoming stimuli, how internal representations are updated as new information is acquired, and how neuronal coding relates to visually-guided behavior. To achieve these goals, the lab employs state-of-the-art electrophysiological and behavioral techniques that allow simultaneous recording of the activity of multiple neurons in the visual cortex of alert monkeys during specific behavioral tasks in combination with computational models of network function. The goal of this research is to understand the ways in which neural circuits produce emergent properties relevant for visual behavior. A key feature of this interdisciplinary approach is the combination of experimental and computational methods which allows him to uncover the fundamental principles employed by neuronal populations to optimize processing accuracy and energy consumption. The research in Dr. Dragoi’s lab will advance understanding of the neuronal mechanisms underlying visual perception, and, at the same time, help develop chronically-implantable human cortical prostheses to assist visually impaired people.
The long-term goal of the Heidelberger laboratory is to understand the mechanisms by which visual information is transferred across the vertebrate retina. The laboratory quantitatively studies synaptic vesicle dynamics and neurotransmitter release at the level of individual central nerve terminals using state-of-the art biophysical techniques that are combined with computational and molecular approaches. The laboratory is currently interested in activity-dependent forms of modulation that alter synaptic signaling in retinal ribbon synapses. Specific goals are to characterize the roles of select synaptic proteins on presynaptic physiology and to understand the interplay between Ca2+ and other second messengers on the Ca2+-sensitivity of neurotransmitter release and vesicle recruitment. Computational models of synaptic vesicle dynamics and neurotransmitter release that derive from the physiological data will be used to perform in silico experiments that predict the pattern and extent of neurotransmitter release and to generate hypotheses about vesicle dynamics that can be experimentally tested. The models will also be used to extract quantitative information from the physiological data, providing insights into the underlying mechanisms. The results of these studies will reveal important new information about a fundamental feature of the nervous system (i.e., synaptic communication) and will position the laboratory to understand the role of select synaptic proteins implicated in disorders of vision. The synaptic signals originating from ribbon synapses are modulated as they transit the retina to both reliably relay and extract information about the visual scene.
The research in the Sereno laboratory covers a broad array of methodologies to address higher cognitive function in humans and nonhuman primates with the long-term goals of understanding attention and memory. The laboratory is highly interdisciplinary and includes research techniques utilizing eye-tracking technology, nonhuman primate electrophysiology, behavioral testing, and computational modeling. The laboratory has four basic lines of experimental and theoretical investigation: 1) neurophysiological investigations of shape and spatial processing, 2) neurophysiological investigations of attention and working memory, 3) investigations of eye movements in human clinical populations and 4) theoretical and computational models. This research will allow design of better methods for diagnosis of higher cognitive dysfunctions, to improve evaluation of treatment effects on cognitive function, prediction and development of individualized treatments, and development of biomarkers of cognitive dysfunction in human disorders. The research will provide both an overarching framework to guide the experimental studies and a quantitative method of testing these neurally based hypotheses.
Dr. Shouval’s research focuses on identifying the rules by which changes in synaptic strength form the basis of learning, memory and development in the cortex. Dr. Shouval’s research has several components. One is designed to examine the molecular basis of synaptic plasticity. To achieve this goal, Dr. Shouval performs complex simulations of signal transduction pathways involved in synaptic plasticity, as well as analysis of the molecular dynamics of molecules such as calcium that are essential for synaptic plasticity. As part of this project, Dr. Shouval is concentrating on the stability of long-term synaptic plasticity. He develops biophysical models that may account for the long-term maintenance of synaptic plasticity, despite the rapid turnover of synaptic receptors, which encode synaptic efficacy. A second research area is the development of simplified cellular models of synaptic plasticity. To achieve this goal, Dr. Shouval derives simplified models of synaptic plasticity, either by approximating the more complex molecular models, or from first principles. He is also examining the contribution of synaptic plasticity to receptive field development and examining whether the simplified plasticity models can account for the development of receptive fields as well. Finally, Dr. Shouval is examining the impact of synaptic plasticity on the cortical encoding of time. In this project simplified plasticity models are used, and the effect of reward is taken into account as well.
Increase in intracellular Ca2+ regulates a wide variety of neuronal responses and leads to increases and decreases in synaptic efficacy. Dr. Waxham’s laboratory is interested in quantifying this spectrum of changes in both normal and pathologic situations. Events following increased intracellular Ca2+ are the activation of calmodulin and subsequently activation of Ca2+-dependent enzymes such as Ca2+/calmodulin-dependent protein kinase (CaMKII). Due to the theoretical potential that CaMKII has to act as a "memory" molecule, Dr. Waxham’s laboratory has detailed the mechanism of its regulation by Ca2+/calmodulin and autophosphorylation. Dr. Waxham has discovered a class of molecules that alter the Ca2+-binding characteristics of calmodulin. These small neuronal IQ motif containing proteins, previously shown to play roles in LTP and LTD, can either sensitize or desensitize the capacity of calmodulin to bind Ca2+. Thus, the Ca2+-sensitivity of calmodulin is finely tuned so that it can respond to Ca2+ signals of varying amplitude and frequency. Dr. Waxham’s laboratory is also investigating the important issue of intracellular diffusion of signaling molecules using fluorescence based imaging and spectroscopy. These cutting edge approaches are providing a first glimpse of the movement of these molecules in different neuronal compartments in real time.
Dr. Waxham’s computational approach is designed to accommodate this wealth of detailed biochemical and intracellular diffusion data into a model of signaling at synapses that are driven by changes in the Ca2+ second messenger pathway. To do this, Dr. Yoshi Kubota, a member of his laboratory, has created a new simulation environment called the cellular dynamics simulator (CDS) that is the most accurate algorithmic scheme developed to date capable of accommodating diffusion and chemical reactions within the crowded environment thought to exist inside neurons. Applications of this new simulation environment to evaluate the spatial and temporal nature of Ca2+ dynamics and how the Ca2+ signal is decoded by downstream signaling molecules is underway. Dr. Waxham’s long-term goal is to build a comprehensive understanding of signaling at synaptic connections that underlie synaptic plasticity using multi-scale modeling.