A combined experimental and computational approach to investigate emergent network dynamics based on large-scale neuronal recordings

Sviluppo di un approccio integrato computazionale-sperimentale per lo studio di reti neuronali mediante registrazioni elettrofisiologich

Probing circuits for spinal motor control

Spinal circuits can generate locomotor output in the absence of sensory or descending input, but the principles of locomotor circuit organization remain unclear. We sought insight into these principles by considering the elaboration of locomotor circuits across evolution. The identity of limb-innervating motor neurons was reverted to a state resembling that of motor neurons that direct undulatory swimming in primitive aquatic vertebrates, permitting assessment of the role of motor neuron identity in determining locomotor pattern. Two-photon imaging was coupled with spike inference to measure locomotor firing in hundreds of motor neurons in isolated mouse spinal cords. In wild type preparations we observed sequential recruitment of motor neurons innervating flexor muscles controlling progressively more distal joints. Strikingly, after reversion of motor neuron identity virtually all firing patterns became distinctly flexor-like. Our interneuron imaging experiments demonstrate a new approach for functionally mapping the types of inputs that motor neurons might receive during locomotor firing. These data revealed that En1-derived inhibitory spinal interneuron activity appears to be dominated by a flexor-like pattern across the ventrolateral extent of the lumbar spinal cord–even in the regions surrounding flexor and extensor motor pools. Together, these findings show that motor neuron identity directs locomotor circuit wiring, and indicate the evolutionary primacy of flexor pattern generation

PROGRAM and PROCEEDINGS THE NEBRASKA ACADEMY OF SCIENCES: 139th Anniversary Year, One Hundred-Twenty-Ninth Annual Meeting, April 12, 2019, NEBRASKA WESLEYAN UNIVERSITY, LINCOLN, NEBRASKA

PROGRAM AT-A-GLANCE FRIDAY, APRIL 12, 2019 7:30 a.m. REGISTRATION OPENS - Lobby of Lecture Wing, Olin Hall 8:00 Aeronautics and Space Science, Session A – Acklie 109 Aeronautics and Space Science, Session B – Acklie 111 Collegiate Academy; Biology, Session B - Olin B Biological and Medical Sciences, Session A - Olin 112 Biological and Medical Sciences, Session B - Smith Callen Conference Center Chemistry and Physics; Chemistry - Olin A 8:00 “Teaching and Learning the Dynamics of Cellular Respiration Using Interactive Computer Simulations” Workshop – Olin 110 9:30 “Life After College: Building Your Resume for the Future” Workshop – Acklie 218 8:25 Collegiate Academy; Chemistry and Physics, Session A – Acklie 007 8:36 Collegiate Academy; Biology, Session A - Olin 111 9:00 Chemistry and Physics; Physics – Acklie 320 9:10 Aeronautics and Space Science, Poster Session – Acklie 109 & 111 10:30 Aeronautics and Space Science, Poster Session – Acklie 109 & 111 11:00 MAIBEN MEMORIAL LECTURE: Dr David Swanson - OLIN B Scholarship and Friend of Science Award announcements 12:00 p.m. LUNCH – WESLEYAN CAFETERIA Round-Table Discussion – “Assessing the Academy: Current Issues and Avenues for Growth” led by Todd Young – Sunflower Room 12:50 Anthropology – Acklie 109 1:00 Applied Science and Technology - Olin 111 Biological and Medical Sciences, Session C - Olin 112 Biological and Medical Sciences, Session D - Smith Callen Conference Center Chemistry and Physics; Chemistry - Olin A Collegiate Academy; Biology, Session B - Olin B Earth Science – Acklie 007 Environmental Sciences – Acklie 111 Teaching of Science and Math – Acklie 218 1:20 Chemistry and Physics; Physics – Acklie 320 4:30 BUSINESS MEETING - OLIN B NEBRASKA ASSOCIATION OF TEACHERS OF SCIENCE (NATS) The 2019 Fall Conference of the Nebraska Association of Teachers of Science (NATS) will be held at the Younes Conference Center, Kearney, NE, September 19-21, 2019. President: Betsy Barent, Norris Public Schools, Firth, NE President-Elect: Anya Covarrubias, Grand Island Public Schools, Grand Island, NE AFFILIATED SOCIETIES OF THE NEBRASKA ACADEMY OF SCIENCES, INC. 1. American Association of Physics Teachers, Nebraska Section Web site: http://www.aapt.org/sections/officers.cfm?section=Nebraska 2. Friends of Loren Eiseley Web site: http://www.eiseley.org/ 3. Lincoln Gem & Mineral Club Web site: http://www.lincolngemmineralclub.org/ 4. Nebraska Chapter, National Council for Geographic Education 5. Nebraska Geological Society Web site: http://www.nebraskageologicalsociety.org Sponsors of a $50 award to the outstanding student paper presented at the Nebraska Academy of Sciences Annual Meeting, Earth Science /Nebraska Chapter, Nat\u27l Council Sections 6. Nebraska Graduate Women in Science 7. Nebraska Junior Academy of Sciences Web site: http://www.nebraskajunioracademyofsciences.org/ 8. Nebraska Ornithologists’ Union Web site: http://www.noubirds.org/ 9. Nebraska Psychological Association http://www.nebpsych.org/ 10. Nebraska-Southeast South Dakota Section Mathematical Association of America Web site: http://sections.maa.org/nesesd/ 11. Nebraska Space Grant Consortium Web site: http://www.ne.spacegrant.org

Psr1p interacts with SUN/sad1p and EB1/mal3p to establish the bipolar spindle

Regular Abstracts - Sunday Poster Presentations: no. 382During mitosis, interpolar microtubules from two spindle pole bodies (SPBs) interdigitate to create an antiparallel microtubule array for accommodating numerous regulatory proteins. Among these proteins, the kinesin-5 cut7p/Eg5 is the key player responsible for sliding apart antiparallel microtubules and thus helps in establishing the bipolar spindle. At the onset of mitosis, two SPBs are adjacent to one another with most microtubules running nearly parallel toward the nuclear envelope, creating an unfavorable microtubule configuration for the kinesin-5 kinesins. Therefore, how the cell organizes the antiparallel microtubule array in the first place at mitotic onset remains enigmatic. Here, we show that a novel protein psrp1p localizes to the SPB and plays a key role in organizing the antiparallel microtubule array. The absence of psr1+ leads to a transient monopolar spindle and massive chromosome loss. Further functional characterization demonstrates that psr1p is recruited to the SPB through interaction with the conserved SUN protein sad1p and that psr1p physically interacts with the conserved microtubule plus tip protein mal3p/EB1. These results suggest a model that psr1p serves as a linking protein between sad1p/SUN and mal3p/EB1 to allow microtubule plus ends to be coupled to the SPBs for organization of an antiparallel microtubule array. Thus, we conclude that psr1p is involved in organizing the antiparallel microtubule array in the first place at mitosis onset by interaction with SUN/sad1p and EB1/mal3p, thereby establishing the bipolar spindle.postprin

29th Annual Computational Neuroscience Meeting: CNS*2020

Meeting abstracts This publication was funded by OCNS. The Supplement Editors declare that they have no competing interests. Virtual | 18-22 July 202

A Novel Synthetic Biology Method to Study the Cooperative Behavior of Kinesin Motors in Cells.

Collective motor dynamics drives important cellular processes ranging from muscle contraction to spindle organization to vesicle trafficking (Chapter 1). Although the biomechanical and biochemical properties of individual motors have been widely studied, how motors coordinate their motility when attached to the same cargo is largely unknown. In this dissertation, I present a synthetic biology technique (Chapter 2) to generate multi-motor assemblies whose biological properties can be examined in vitro and in living cells. To do this, we assembled a “toolbox” of protein components consisting of scaffolds and linkers. We characterized scaffold proteins of different lengths that allow for specific separation distances between the components. We then characterized four different linker systems that enable constitutive or regulated attachment of individual motors to scaffolds. We then showed, through FRET and subcellular localization experiments, that this toolbox could be used to generate defined assemblies in living cells. Next, I present a characterization of fluorescent tags for use in single-molecule experiments (Chapter 3), and show that certain tags lead to aberrant kinesin-1 run lengths due to oligomerization. This study will provide a valuable reference for the field in choosing proper fluorescent tags for single-molecule experiments. I then present a series of experiments where we use this system to investigate the behavior of two motors attached to a scaffold (Chapter 4). We find that two kinesin motors in complex act independently (do not help or hinder each other) and can alternate their activities. For complexes containing a slow kinesin-1 and fast kinesin-3 motor, the slow motor dominates motility in vitro but the fast motor can dominate on certain subpopulations of microtubules in cells. Both motors showed dynamic interactions with the complex, suggesting that motor-cargo linkages are sensitive to forces applied by the motors. We conclude that kinesin motors in complex act independently in a manner regulated by the microtubule track. Overall, the approach presented in this dissertation is applicable to other biological questions such as the generation of complex signaling networks as well as the assembly of artificial biological systems for engineering applications (Chapter 5).PHDBiophysicsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/110504/1/srnorris_1.pd