Peculiar properties of Kv2 ion channel gating
Jon Sack, Ph.D.
Associate Professor and Vice Chair, Department of Physiology and Membrane Biology, University of California, Davis.Abstract: Kv2 proteins form voltage-gated potassium ion channels that contribute to a wide variety of physiological responses throughout our bodies. In neurons, Kv2 proteins are abundant on and near the cell soma, where their unique voltage-gating regulates repetitive firing of action potentials. This seminar investigates mechanisms of modulators that shed light on the peculiar relation between voltage sensing and pore opening of Kv2 channels. website: https://basicscience.ucdmc.ucdavis.edu/Sack_and_Yarov-Yarovoy_Labs/ Host: Oscar Vivas
Activity driven spine structural dynamics in health and disease
Assistant Professor, Department of Pathology and Cell Biology in the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Department of Neuroscience, Columbia Translational Neuroscience Initiative, Columbia UniversityAbstract: Brain circuits can be structurally rearranged with experience, and synaptic connections can grow and be eliminated, even in adults. Dendritic spines are highly dynamic structures whose morphology and lifespan are modified as a response to synaptic efficacy changes between neurons. In order to understand how activity influences synaptic structure and function, we combine the precise stimulation of defined inputs using two-photon glutamate uncaging with whole cell electrophysiological recordings and imaging. We show that activity at specific inputs can lead to the production of new proteins, promoting bidirectional, long lasting plasticity of single spines, as well as cooperation and competition between multiple co-active synapses. Based on this, we predict that synaptic competition for newly made proteins constrains the number of inputs that can undergo structural changes during activity, a process that may become dysregulated in neurodevelopmental disorders with dysregulated proteostasis. We are determining with high precision whether abnormal synaptic competition contributes to altered micro-circuitry in Fragile X Syndrome, and consider whether this represents a core mechanism of dysfunction across Autism Spectrum Disorders (ASDs). Our goal is to gain an understanding of how diverse forms of activity drive spine interactions, and how these processes influence the refinement of local neural circuits both in health and disease.
host: Beth Buffalo
A tale of two motilities: mechanics and mechanosensing in adaptive locomotor systems
Independent Research Fellow, All Souls College, University of Oxford
Independent Fellow, Center for Studies in Physics and Biology Rockefeller UniversityAbstract: Natural environments are heterogeneous and can fluctuate with time. As such, biomechanical systems from proteins to whole organisms have developed strategies to sense and deal with considerable spatial and temporal variability. I will discuss two (quite different!) broadly successful locomotive modes: flagellated motility in bacteria and walking in panarthropods. (1) A bacterium’s life can be complicated: it must swim through fluids of varying viscosity as well as interact with surfaces and other bacteria. We characterize the mechanosensitive adaptation in bacterial flagella that facilitates these transitions by using magnetic tweezers to manipulate external torque on the bacterial flagellar motor. Our model for the dynamics of load-dependent assembly in the flagellar motor illustrates how this nanomachine allows bacteria to adapt to changes in their surroundings. (2) Panarthropods are a diverse clade containing insects, crustaceans, myriapods and tardigrades. We show that inter-limb coordination patterns in freely-behaving tardigrades replicate several key features of walking in insects across a range of speeds and substrates. In light of these functional similarities, we propose a simple universal locomotor circuit capable of robust multi-legged control across body sizes, skeletal structures, and habitats. website host: John Tuthill
Can you see a thought? Neuronal ensembles as emergent units of cortical function
Rafael Yuste, M.D, Ph.D.
Professor, Department of Biological Sciences, Director, NeuroTechnology Center, Columbia UniversityAbstract: Abstract: How neural activity is transformed into thought is arguably the central question of neuroscience. The design of neural circuits, with large numbers of neurons interconnected in vast networks, strongly suggest that they are specifically build to generate emergent functional properties (1). To explore this hypothesis, we have developed two-photon holographic methods to selective image and manipulate the activity of neuronal populations in 3D in vivo (2). Using them we find that groups of synchronous neurons (neuronal ensembles) dominate the evoked and spontaneous activity of mouse primary visual cortex (3). Ensembles can be optogenetically imprinted for several days and some of their neurons trigger the entire ensemble (4). By activating these pattern completion cells in ensembles involved in visual discrimination paradigms, we can bi-directionally alter behavioral choices (5). Our results are consistent with the possibility that neuronal ensembles are functional building blocks of cortical circuits and serve as elementary elements for perception, memories and thoughts.
- R. Yuste, From the neuron doctrine to neural networks. Nat Rev Neurosci 16, 487-497 (2015).
- L. Carrillo-Reid, W. Yang, J. E. Kang Miller, D. S. Peterka, R. Yuste, Imaging and Optically Manipulating Neuronal Ensembles. Annu Rev Biophys, 46: 271-293 (2017).
- J. E. Miller, I. Ayzenshtat, L. Carrillo-Reid, R. Yuste, Visual stimuli recruit intrinsically generated cortical ensembles. Proceedings of the National Academy of Sciences of the United States of America 111, E4053-4061 (2014).
- L. Carrillo-Reid, W. Yang, Y. Bando, D. S. Peterka, R. Yuste, Imprinting and recalling cortical ensembles. Science 353, 691-694 (2016).
- L. Carrillo-Reid, S. Han, W. Yang, A. Akrouh, R. Yuste, (2019). Controlling visually-guided behavior by holographic recalling of cortical ensembles. Cell 178, 447-457. DOI:https://doi.org/10.1016/j.cell.2019.05.045.