Seminar Archives

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

Inbal Israely, Ph.D.

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 University

Abstract: 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

Jasmine Nirody,

Independent Research Fellow, All Souls College, University of Oxford

Independent Fellow, Center for Studies in Physics and Biology Rockefeller University

Abstract: 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 University

Abstract: 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.

1. R. Yuste, From the neuron doctrine to neural networks. Nat Rev Neurosci 16, 487-497 (2015).
2. 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).
3. 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).
4. L. Carrillo-Reid, W. Yang, Y. Bando, D. S. Peterka, R. Yuste, Imprinting and recalling cortical ensembles. Science 353, 691-694 (2016).
5. 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.

website: https://blogs.cuit.columbia.edu/rmy5/ Host: Adrienne Fairhall

Neurophysiology of dynamic decision making

Jeremiah Cohen, Ph.D.

Associate Professor, Department of Neuroscience, Johns Hopkins University

Abstract: Decisions take place in dynamic environments. The nervous system must continually learn the best actions to obtain rewards. In the theoretical framework of optimal control and reinforcement learning, behavioral policies are updated by feedback arising from errors in the predicted reward. These reward prediction errors have been mapped to dopamine neurons in the midbrain, but it is unclear how the decision variables that generate policies themselves are represented and modulated. We trained mice on a dynamic foraging task, in which they freely chose between two alternatives that delivered reward with changing probabilities. We found that corticostriatal neurons, in the medial prefrontal cortex (mPFC), maintained persistent changes in firing rates that represented relative and total action values over long timescales. These are consistent with control signals used to drive flexible behavior. We next recorded from serotonin neurons in the dorsal raphe, to test the hypothesis that their signals could be used to modulate dynamic learning. We found that serotonin neurons represented a quantity related to reward uncertainty over long timescales (tens of seconds), consistent with a modulatory signal used to adjust learning of ongoing decision variables. Our results provide a quantitative link between serotonin neuron activity and behavior.

Website: http://cohenlab.johnshopkins.edu/

host: Adrienne Fairhall

“Understanding the Role of Oral Neuromechanics in Alzheimer’s Disease and Age-related Dementia”

Fritzie Arce-Mcshane, Ph.D.

Assistant Professor Dept of Oral Health Sciences

University of Washington, School of Dentistry

website

host: Steve Perlmutter

Agonists to ions: getting deep into receptor activation

Speaker: Anthony Auerbach

Institution: University at Buffalo

Abstract: There is an intro on receptors suitable for students, then the topic is efficiency and suitable for pharmacologists, then it’s about linear free energy and suitable for bio chemists. In a nutshell I will talk about correlated energy changes inside binding and gating. I’ll tie it all up with a ‘zippet’ mechanism for receptor activation.

Host: William N. Zagotta (zagotta@uw.edu)

Cortical circuits for olfactory behavior

Cindy Poo, Ph.D.

Champalimaud Centre for the Unknown, Lisbon Portugal

Abstract: Olfaction is essential for the survival of living beings from unicellular organisms to mammals and is used for a wide range of natural behaviors. Rodents use odors in their environment to forage and navigate. To support these flexible behaviors, the brain seamlessly and dynamically integrates odor information with an internal model of the spatial environment. I am interested in how interconnected circuits in the brain for odor representation and spatial cognition interact to generate such behaviors. I will discuss my work examining synapses and circuits in primary olfactory (piriform) cortex (PCx) which make it an excellent site to investigate associative olfactory processes. I will also describe my work using neural ensemble recordings in freely moving rats performing an odor-cued spatial choice task, where I show that posterior piriform cortex neurons carry a robust spatial representation of the environment. Here, ensembles of piriform neurons concurrently represented odor identity as well as spatial locations of animals, forming an odor-place map. These results reveal a novel function for piriform cortex in spatial cognition, and importantly, provide a unique opportunity to understand the neural computations and organizing principles for computations critical for cognitive and behavioral flexibility. Host: Beth Buffalo

Mechanisms of mitochondrial calcium uptake — structure, function, and tissue-specific regulation.

Ming-Feng Tsai, Ph.D.

Department of Physiology and Biophysics, University of Colorado School of Medicine

Mitochondrial calcium uptake regulates key cellular processes, including ATP synthesis, cell death, and intracellular calcium signaling. It is important in virtually all aspects of human physiology, and its malfunction is implicated in detrimental diseases, such as heart failure, neurodegeneration, cancer metastasis, among others. In this talk, I will present our previous studies regarding the molecular mechanisms of a multi-subunit calcium channel called the mitochondrial calcium uniporter, which is the protein complex that mediates mitochondrial calcium uptake. I will also use the cardiac tissue as an example to share our ongoing efforts to understand how the uniporter is regulated in a tissue-specific manner to adapt to unique intracellular calcium signaling systems in different types of cells.   website:

Overcoming noise: how networks of neurons adapt to preserve behavior.

Walter G. Gonzalez, Ph.D.

Division of Biology and Biological Engineering, California Institute of Technology

How do neurons across multiple brain areas coordinate their activity to ensure accurate learning, stable memories, and efficient recall of behaviorally relevant information? More importantly, how do these neurons adapt their activity to overcome noise and ensure the persistence of a behavior? Answering these questions is fundamental to developing a framework describing brain function and the mechanisms underlying neurological disorders. Towards this goal, I have developed calcium imaging and electrophysiological recording approaches to monitor large-scale neuronal activity across multiple brain areas in freely moving mice and songbirds. In this talk, I will demonstrate how neuronal activity in the hippocampus of mice undergoes adaptive changes across days. Despite these apparent instabilities, neuronal representations of space at the network level remain stable across time and resilient to damage. In addition, I will present recordings of neuronal activity in singing zebra finches demonstrating how instabilities in neuronal activity lead to a decreased relay of information between brain areas and abnormal behavior. In some cases, this decrease in the transfer of information is corrected by reorganization of neuronal activity and production of special acoustic notes which lead to increased information transfer between brain areas. Overall, these results reveal the presence of adaptive mechanisms in distributed networks of neurons that facilitate the persistence of stable memories and robust performance of complex behaviors. host: Beth Buffalo

How kinesins shape the extracellular matrix

Allison Zajac, Ph.D.

The University of Chicago, Department of Molecular Genetics and Cell Biology

Abstract: The importance of the extracellular matrix (ECM) in providing chemical and mechanical cues during development is widely appreciated. However, we know little about how cells produce ECMs, which must be tailored in not only composition, but also structure, to support each tissue’s needs. In the Drosophila ovary, the ECM that lines the epithelium surrounding the developing egg, the basement membrane (BM), is assembled into a fibril-filled sheet whose anisotropic mechanical properties guide tissue morphogenesis. Working in this epithelium, I found the subcellular secretion site of BM proteins is critically important in shaping the networks they form. Ex vivo live imaging revealed that two kinesin motors transport BM secretory vesicles along an unusual microtubule array polarized in two axes to spatially target secretion and promote assembly of fibrils. Without kinesin transport, BM networks form in the wrong location, where they interfere with cell movements during development, compromise the mechanical properties of the BM, and ultimately block egg production. A major roadblock to our understanding of how cells assemble ECM structures is the need to bridge two spatiotemporal scales: (1) the cell-scale, rapid processes of protein sorting, transport, and secretion; and (2) the tissue-scale process of ECM structure assembly, which can take days or weeks. Future work in this simple Drosophila model epithelium that rapidly produces a series of intricately structured ECMs will allow us to combine the power of Drosophila genetics with live imaging that spans the cell- and tissue-scale to gain new insights into the production of ECMs.

host: Beth Buffalo

The neural basis of heat seeking in a human-infective parasitic nematode

Astra Bryant

Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles

Soil-transmitted parasitic nematodes infect over a billion people and cause devastating morbidity, primarily in the world’s most socioeconomically disadvantaged communities. The skin-penetrating Strongyloides stercoralis is estimated to infect at least 610 million people globally, nearly three times as many people as malaria. Previous studies have shown that both mosquitoes and parasitic worms actively seek out human hosts using body heat. However, while much is known about the mechanisms that enable mosquitoes and other insect vectors to target humans, virtually nothing was known about how parasitic worms locate hosts.   I investigated the molecular and cellular mechanisms underlying temperature-driven host seeking in parasitic nematodes using S. stercoralis. Using CRISPR-Cas9 mutagenesis, I found that heat seeking by S. stercoralis infective larvae (iL3s) is dependent on a cGMP signaling pathway that is conserved across free-living and parasitic nematodes. I identified the primary thermosensory neurons in S. stercoralis and characterized their responses to thermal stimuli by applying single-cell genetic targeting, cell-type specific neural silencing, and genetically-encoded fluorescent biosensors for the first time in any endoparasitic animal. These neurons display unique thermal response properties that support the ability of parasitic worms to engage in long-distance host targeting using body heat. I investigated the molecular substrates that contribute these unique response properties: I identified the thermoreceptor proteins confer parasite-specific sensitivity to body heat, and revealed evidence that additional molecular elements of the cGMP signaling cascade are regulated by temperature in a parasite-specific manner. Together, these results are the first direct evidence that the sensory neurons of parasitic worms exhibit unique molecular adaptations that allows them to target humans, a finding with important implications for efforts to develop new therapeutic strategies for nematode control.   Host: Beth Buffalo

Mechanisms of autonomic dysfunction

Oscar Vivas, Ph.D.

University of Washington

Abstract: Every organ in the body is innervated by the autonomic nervous system. Through this innervation, autonomic neurons control organ function to maintain an equilibrium in response to internal and external cues. As we age, this autonomic function is altered, and so it is organ control. The main goal of my research is to identify the mechanisms behind age-associated autonomic dysfunction. My lab is especially interested in studying how aging affects the electrical activity and function of autonomic motor neurons. In the last decade, I have studied these autonomic motor neurons to answer relevant questions related to the modulation of neuronal excitability, the regulation of ion channels, and how these two aspects are linked to lipid metabolism in the context of pathological conditions. In the first part of my seminar, I will present some of my previous work on the molecular mechanisms underlying the neurodegenerative disorder called Niemann-Pick Type C Disease. I will show how we demonstrated that an accumulation of cholesterol in the lysosomes leads to changes in neuronal excitability. In the second part, I will present some of the work from my lab on the effects of aging on the function of autonomic motor neurons. We have found that aging leads to alterations in several ionic currents, resulting in neuronal hyperexcitability. During my chalk talk, I will go deeper into how we plan to investigate the mechanisms behind this autonomic hyperexcitability at the cellular and tissue levels. I am looking forward to discussing my research program with the broad scientific audience of the PBio department.   Host: Beth Buffalo  

Flexibility of visual input to the Drosophila compass network

Yvette Fisher

UC Berkeley

We can maintain some sense of direction in the dark by keeping track of our own movements, but when visual landmarks are available, our sense of direction is more accurate and stable. Moreover, we can learn new landmarks in new environments. What mechanisms reconcile self-movement information with ever-changing landmarks to generate a coherent sense of direction? In the Drosophila brain, compass neurons form an attractor network whose activity tracks the angular position of the fly using both self-movement and visual inputs. Using whole-cell recordings and calcium imaging from Drosophila compass neurons, we show that each compass neuron is inhibited by visual cues in specific horizontal positions, with different visual maps in different individuals. Inhibition arises from GABAergic axons that form an all-to-all matrix of synaptic connections onto compass neurons. We show that visual input to the compass network can reorganize over minutes when visuo-motor correlations change in virtual reality. This reorganization causes persistent changes in the reference frame of the compass network and can depress or potentiate visually-evoked inhibition in a manner that depends on visual-heading correlations. Plasticity of sensory inputs, when combined with network attractor dynamics, should allow the brain’s spatial maps to incorporate sensory cues in new environments.
https://www.fisherlab.science/
host: John Tuthill

HOLDING – co-host with Bloedel SHACS series

One receptor, two surprises: unexpected mGluR-mediated neuromodulation in sound localization circuits

Yong Lu, PhD

Professor of Anatomy and Neurobiology

College of Medicine

Northeast Ohio Medical University (NEOMED)

Abstract: Neuromodulation affects brain function and development. We investigated neuromodulation mediated by group I metabotropic glutamate receptors (mGluR I) in the brainstem sound localization circuits. Activation of mGluR I exerts differential modulation of synaptic transmission depending on the transmitter type and its release mode. Furthermore, the modulation generates temporally patterned spontaneous synaptic responses, implying a potential central mechanism underlying the spontaneous activity necessary for the development of the sound localization circuits. website: https://www.neomed.edu/directory-profile/lu-yong-138787/

Identifying mechanisms of cognitive computations from spikes

Tatiana Engel, Ph.D.

Assistant Professor

Cold Spring Harbor Laboratory

  website: https://www.cshl.edu/research/faculty-staff/tatiana-engel/

Population activity in the cerebellar cortex that mediates behavior and learning

Court Hull

Associate Professor, Department of Neurobiology, Duke University

host: Greg Horwitz

Abstract: The cerebellum is a key brain region involved in associative learning, and in particular for generating predictive sensorimotor associations.  To mediate such learning, convergent input from two main pathways is thought to be required; the climbing fiber and granule cell pathways.  Using multiphoton imaging in awake behaving mice, we have investigated how each of these pathways encodes the sensory and motor information necessary for learning.  These studies have revealed surprising results that extend current views of cerebellar learning.  Specifically, we have found that cerebellar climbing fibers can exhibit reward-related responses that are consistent with many of the predictions of reinforcement learning, in contrast with the long-held view that the cerebellum operates exclusively according to supervised learning principles.  In addition, we have found that granule cells generate sparse population codes that rely on local synaptic inhibition to enable pattern separation and learned sensorimotor discriminations.  I will discuss the implications of these results in the context of cerebellar associative learning.

Awake perception is associated with dedicated neuronal assemblies in cerebral cortex

Alain Destexhe

Saclay Paris and European Institute for Theoretical Neuroscience

Host: Adrienne Fairhall

Spiking codes for skilled motor control

Sam Sober, PhD

Director of the Simons-Emory International Consortium on Motor Control

Emory University

Abstract: Neurons coordinate patterns of muscle activity to produce an astonishing variety of behaviors. However, the biological and computational bases of sensorimotor control remain mysterious, in part due to a lack of experimental hardware and computational frameworks for examining motor signals. To address these challenges, my group combines physiological, computational, and engineering approaches to understand motor control across species and behaviors. My talk will provide an overview of three projects. First, physiological and computational studies of vocal production in songbirds reveal that neurons in the motor system employ millisecond-resolution spike timing codes to regulate vocal behavior, highlighting the need to examine spiking codes across cortical, basal ganglia, and spinal motor circuits. Second, to examine spiking codes across motor circuits, we have developed electrode arrays for examining spiking patterns in muscle tissue during natural behaviors. These “Myomatrix” arrays reveal the spatiotemporal structure of muscle activity at motor-unit resolution across effectors (forelimb, trunk, orofacial, respiratory, and vocal muscles) and species – including humans – during unconstrained behavior. Third, in-progress studies examining muscle spike trains in mice (locomotion) and monkeys (reaching movements) reveal how complex patterns of motor unit activity shape skilled forelimb control. https://scholarblogs.emory.edu/soberlab/  

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