Physiology and Biophysics

Seminars

Apr
26
Thu
2018
Bertil Hille – Distinguished Science in Medicine @ Hogness Auditorium
Apr 26 @ 12:00 pm – 1:00 pm
Distinguished Science in Medicine Lecture Bertil Hille Thurs., April 26, 2018 NOON Hogness Auditorium.
May
3
Thu
2018
2018 Hille Lecture – Doris Tsao @ HSB T-747
May 3 @ 4:00 pm – 5:00 pm
Faces: a neural Rosetta stone Objects constitute the fundamental currency of the brain: they are things that we perceive, remember, and think about.  One of the most important objects for a primate is a face. Research on the macaque face patch system in recent years has given us a remarkable window into the detailed processes underlying object recognition. I will discuss recent findings from our lab elucidating the code for facial identity used by cells in face patches. I will then discuss how this code is used by downstream areas, as well as how the brain computes what constitutes an object in the first place. Doris Tsao Professor of Biology HHMI Investigator California Institute of Technology time: 4:00pm location: T-747, HSB host: Stan Froehner
May
10
Thu
2018
2018 Crill Lecture – J. Anthony Movshon @ HSB T-639
May 10 @ 2:00 pm – 3:00 pm
“Elements of visual form perception” J. Anthony Movshon, PhD

Professor, Department of Ophthalmology

Professor, Department of Neuroscience and Physiology

Thursday, May 10, 2018 2:00 p.m. T-639 HSB
May
17
Thu
2018
PBIO Seminar Series: Brent Doiron, Ph.D. @ HSB G-328
May 17 @ 9:30 am – 10:30 am

New Cortex.  Who dis(inhibition)?

  Brent Doiron, PhD Professor Department of Mathematics University of Pittsburgh host: Adrienne Fairhall seminar abstract: New Cortex.  Who dis(inhibition)?   It is now clear that the inhibitory circuitry within cortical networks is very complex, with multiple cell types interacting with one another and pyramidal neurons in complicated and cell specific ways.  The theoretical community has been slow to adapt to this new circuit reality, and much of our results are obtained from analysis of simpler recurrent excitatory-inhibitory circuits. Two often cited functional roles of inhibition is to: 1) stabilize the dynamics of recurrently coupled excitatory networks, and 2) enact gain control of excitatory neuron responses to a driving stimulus.  In classic excitatory-inhibitory networks mechanisms that place the network in a high gain state necessarily flirt with network instability.  We analyze how recurrent networks of pyramidal neurons (PN), parvalbumin-expressing (PV), somatostatin-expressing (SOM), and vasoactive intestinal polypeptide-expressing (VIP) interneurons compartmentalize stability and gain control through distinct inhibitory and disinhibitory pathways.  This permits a disassociation of stability and gain control in the circuit.  We further show how PC to SOM connections can be crucial in state dependent gain amplification with a simultaneous decrease of shared variability (noise correlations).  In sum, by expanding the complexity of inhibitory architecture cortical circuits can navigate distinct functional roles of inhibition through a “division of labor” with the inhibitory circuit.  This imparts a robustness to the functional operations of the circuit that is absent in the often fine-tuned reduced excitatory-inhibitory framework.
May
24
Thu
2018
PBIO Seminar Series: Ariel Rokem @ HSB G-328
May 24 @ 9:30 am – 10:30 am
seminar: T.B.A. Ariel Rokem, PhD Senior Data Scientist eScience Institute, University of Washington host: Fairhall
May
31
Thu
2018
PBIO Seminar Series: Nicholas Whitehead @ HSB G-328
May 31 @ 9:30 am – 10:30 am
Simvastatin: unexpected or logical therapy for muscular dystrophy? Nicholas P Whitehead, Ph.D. University of Washington host: Stanley C. Froehner
Jun
7
Thu
2018
PBIO Seminar Series: Amy Bastian @ HSB G-328
Jun 7 @ 9:30 am – 10:30 am

Learning and Relearning Movement

Human motor learning depends on a suite of brain mechanisms that are driven by different signals and operate on timescales ranging from minutes to years. Understanding these processes requires identifying how new movement patterns are normally acquired, retained, and generalized, as well as the effects of distinct brain lesions. The lecture focuses on normal and abnormal motor learning and how we can use this information to improve rehabilitation for individuals with neurological damage Amy Bastian, Ph.D. Professor of Neuroscience Johns Hopkins University Host: John Tuthill
Sep
25
Tue
2018
2018 Lamport Lecture – Richard Vallee @ HSB T-639
Sep 25 @ 4:00 pm – 5:00 pm
2018 Lamport Lecture

Cytoplasmic Dynein and Kinesins in Brain Development and Autophagy

Microtubule Motor Proteins Are Involved in a Wide Range of cellular activities.  Recent work in our lab has involved the role of the motor proteins in neuronal migration and neurogenesis in the developing brain.  We have worked out mechanisms by which cytoplasmic dynein, its regulators Nde1 and Ndel1, and LIS1  and the kinesin Kif1a contribute to these functions as well as brain developmental disease. We have also found a new role for the dynein adaptor protein RILP as a master regulator of mTOR-dependent autophagy in neurons. Richard Vallee Professor of Pathology & Cell Biology Columbia University time: 4:00pm location: HSB, T-639 host: Stanley C. Froehner
Oct
4
Thu
2018
PBIO seminar series: Mohan Gupta @ G-328 H.S.B.
Oct 4 @ 9:30 am – 10:30 am
The role of microtubule-generated tension in accurate mitotic chromosome segregation Mohan ‘Moe’ Gupta, Ph.D. Assistant Professor Iowa State University Hosts: Linda Wordeman and Alex Paredez seminar abstract: To ensure genome stability in mitosis, the spindle assembly checkpoint (SAC) delays anaphase if sister chromosomes are not bound to microtubules from opposite spindle poles. Only in this configuration can dynamic microtubules produce tension across sister kinetochores. The interdependency between kinetochore-microtubule attachment and tension has proved challenging to elucidating the role(s) of tension at kinetochores. Thus, whether the SAC responds simply to kinetochore attachment status, or also to tension status remains obscure. Unlike higher eukaryotes, budding yeast kinetochores bind only one microtubule, simplifying the relationship between attachment and tension. To address the role of microtubule-generated tension in checkpoint signaling, we developed a Taxol-sensitive yeast model that allows tension to be reduced by microtubule stabilization in fully assembled spindles with attached kinetochores. Our results reveal that reducing tension on attached kinetochores delays anaphase onset. The tension-specific delay is transient relative to that imposed by kinetochores that are both unattached and tensionless. Furthermore, the mechanism requires only a subset of the core SAC proteins. Our results demonstrate that reduced tension generates a signal to delay anaphase that is temporally and mechanistically distinct from that characterized for unattached kinetochores.
Oct
11
Thu
2018
PBIO seminar series: [no speaker scheduled]
Oct 11 @ 9:30 am – 10:30 am
Oct
18
Thu
2018
PBIO seminar series: [no speaker scheduled]
Oct 18 @ 9:30 am – 10:30 am
Oct
25
Thu
2018
PBIO seminar series: [no speaker scheduled]
Oct 25 @ 9:30 am – 10:30 am
Nov
1
Thu
2018
PBIO seminar series: [no speaker scheduled] @ G-328 H.S.B.
Nov 1 @ 9:30 am – 10:30 am
Nov
8
Thu
2018
PBIO seminar series: Ellen Lumpkin @ G-328 H.S.B.
Nov 8 @ 9:30 am – 10:30 am
Exciting touch: Synaptic mechanisms in mamalian touch receptor
Ellen Lumpkin, Ph.D.
Associate Professor of Somatosensory Biology in Physiology & Cellular Biophysics and Dermatology
Columbia University
host: John Tuthill
seminar abstract A rich variety of mechanosensitive cells trigger distinct skin sensations such as pressure, flutter and pain.  A growing body of research indicates that epithelial cells play a key role in sensation by activating or modulating peripheral neurons in healthy skin.  Dr. Lumpkin’s research aims to unveil how epithelial Merkel cells work in concert with the nervous system to generate different qualities of touch sensation.  To tackle this question, her group uses neurophysiology, quantitative neuroanatomy, intersectional mouse genetics and optogenetics.  Recently, they demonstrated that Merkel cells have dual roles in mechanosensation: they transduce sustained pressure, and amplify information transfer during dynamic touch, which encodes shapes and textures.  The seminar will ocus on the molecular signaling mechanisms through which Merkel cells excite sensory neurons.
Nov
15
Thu
2018
PBIO seminar series: Daniel Denman @ G-328 H.S.B.
Nov 15 @ 9:30 am – 10:30 am
Correlated spike time variability, population coding, and synchrony in the early visual system.
Daniel Denman, PhD
Allen Institute
host: Adrienne Fairhall
 
Seminar abstract: In response to repeated presentation of the same stimulus, many visual neurons produce a variable number of spikes. This variability in spike count can be independent, correlated, or anti-correlated between pairs of neurons, and the implications of such correlations on sensory encoding have been extensively explored. In addition, spikes can also occur at variable times within the response (i.e., jitter, or spike time variability). While the magnitude of correlated spike count variability in spike count has been well-studied, the magnitude and sign of correlations in jitter, and any potential implications for visual coding, are not known. In this talk I will present measurements, using high-density electrophysiology (Neuropixels), of correlated jitter within small populations of 20-200 simultaneously recorded neurons across lateral geniculate nucleus and primary visual cortex. I will further discuss proposed mechanisms of correlated jitter and implications for potential and observed synchrony in visual cortical population responses.
Nov
29
Thu
2018
PBIO seminar series: Luke Rice @ HSB G-328
Nov 29 @ 9:30 am – 10:30 am

Mechanism and regulation in microtubule dynamics

Luke Rice, Ph.D.
Associate Professor, Department of Biophysics, UT Southwestern Medical Center
host: Chip Asbury
Seminar abstract: Microtubules are dynamic polymers of αβ-tubulin that have essential roles in intracellular organization and chromosome segregation. The dynamic properties of MTs are central to their function, and they derive from the properties of individual tubulin subunits and their interactions within the MT lattice. Microtubule dynamics is a fascinating problem that tests our ability to integrate ‘one molecule at a time’ views of biochemistry and structure with lower-resolution measurements of collective behavior. My laboratory is focused on bridging this gap by discovering and quantifying the structural and molecular mechanisms that underlie microtubule dynamics and the action of regulatory factors. To provide a new way to study and perturb microtubule dynamics, my laboratory introduced methods for purifying recombinant αβ-tubulin on a scale that permits structural and biochemical studies.  Our work draws on structural, biochemical, and reconstitution studies as well as computational simulations. I will present recent work from my group that is uncovering the mechanisms of XMAP215-family polymerases and CLASP-family rescue factors. These are two cellular factors that regulate microtubule dynamics in different ways despite sharing a common domain organization. At the end of my talk I will presenting ongoing collaborative work in which we are applying interferometric scattering microscopy to observe the microtubule growth at the level of individual αβ-tubulins.
Dec
6
Thu
2018
PBIO seminar series: EJ Chichilnisky @ G-328 H.S.B.
Dec 6 @ 9:30 am – 10:30 am
Toward a high-fidelity artificial retina
EJ Chichilnisky
John R. Adler Professor, Professor of Neurosurgery and of Ophthalmology and, by courtesy, of Electrical Engineering
host: Greg Horwitz
seminar abstract: Retinal prostheses represent an exciting development in science, engineering, and medicine – an opportunity to create devices that exploit our knowledge of neural circuitry in order to replace or even enhance visual function. However, although existing retinal prostheses demonstrate proof of principle in treating incurable blindness, they produce limited visual function. Some of the reasons for this can be understood based on the exquisitely precise and specific circuitry that mediates visual signaling in the retina. These considerations suggest that future devices may need to operate at single-cell, single-spike resolution in order to mediate naturalistic visual function. I will show large-scale multi-electrode recording and stimulation data from the primate retina indicating that, in many cases, such resolution is possible. I will also discuss cases in which it fails, and propose that we can substantially improve ariticial vision in such conditions by incorporating our knowledge of the visual system in bi-directional devices that adapt to the host neural circuity. Finally, I will discuss the potential implications for other neural interfaces of the future.
Dec
13
Thu
2018
PBIO seminar series: Michael Long @ G-328 H.S.B.
Dec 13 @ 9:30 am – 10:30 am

Uncovering circuit principles that enable robust behavioral sequences


Michael Long, PhD
Associate Professor, Neuroscience and Physiology
NYU, School of Medicine
host: Adrienne Fairhall
Abstract: For us to interact with the outside world, our brains must plan and dictate our actions and behaviors. In many cases, we learn to reproducibly execute a well-defined series of muscle movements to perform impressive feats, such as hitting a golf ball or playing the violin. How does the brain step through a reliable sequence of premotor commands for behavior? To address this issue, we study the cellular and circuit mechanisms that enable the production of the zebra finch song, a highly stable behavior executed with a high degree of precision. We use techniques ranging from 2-photon imaging, electron microscopy and in vivo recordings to test models of sequence generation at the circuit level. From this work, we can begin to understand the large-scale circuit motifs that underlie sequence generation across a variety of brain regions.
Dec
20
Thu
2018
PBIO seminar series: [no speaker scheduled]
Dec 20 @ 9:30 am – 10:30 am
Jan
3
Thu
2019
PBIO seminar series: [no speaker scheduled]
Jan 3 @ 9:30 am – 10:30 am
Jan
10
Thu
2019
PBIO seminar series: [no speaker scheduled]
Jan 10 @ 9:30 am – 10:30 am
Jan
17
Thu
2019
PBIO seminar series: [no speaker scheduled]
Jan 17 @ 9:30 am – 10:30 am
Jan
24
Thu
2019
PBIO seminar series: [no speaker scheduled]
Jan 24 @ 9:30 am – 10:30 am
Jan
31
Thu
2019
PBIO seminar series: [no speaker scheduled]
Jan 31 @ 9:30 am – 10:30 am
Feb
7
Thu
2019
PBIO seminar series: [no speaker scheduled]
Feb 7 @ 9:30 am – 10:30 am
Feb
14
Thu
2019
PBIO seminar series: [no speaker scheduled]
Feb 14 @ 9:30 am – 10:30 am
Feb
21
Thu
2019
PBIO seminar series: Carlos Portera-Cailliau @ G-328 H.S.B.
Feb 21 @ 9:30 am – 10:30 am
Circuit Dysfunction Underlying Atypical Sensory Processing in Fragile X Syndrome Carlos Portera-Cailliau, M.D., Ph.D. Depts. of Neurology and Neurobiology David Geffen School of Medicine at UCLA Host: Andres Barria Abstract: To uncover the circuit-level alterations that underlie atypical sensory processing associated with autism, we have adopted a symptom-to-circuit approach in the Fmr1-/- mouse model of Fragile X syndrome (FXS).  For example, using a go/no-go behavior task and in vivo 2-photon calcium imaging, we find that impaired visual discrimination in Fmr1-/- mice correlates with marked deficits in orientation tuning of principal neurons, and a decrease in the activity of parvalbumin (PV) interneurons in primary visual cortex.  Restoring visually evoked activity in PV cells in Fmr1-/-mice with a chemogenetic (DREADD) strategy was sufficient to rescue their behavioral performance.  Strikingly, human subjects with FXS exhibit similar impairments in visual discrimination as Fmr1-/- mice.  These results suggest that manipulating inhibition may help sensory processing in FXS.
Feb
28
Thu
2019
PBIO seminar series: [no speaker scheduled]
Feb 28 @ 9:30 am – 10:30 am
Mar
7
Thu
2019
PBIO seminar series: [no speaker scheduled]
Mar 7 @ 9:30 am – 10:30 am
Mar
14
Thu
2019
PBIO seminar series: Robert Fettiplace @ G-328 H.S.B.
Mar 14 @ 9:30 am – 10:30 am

THE CONTRIBUTIONS OF TMC1 TO TRANSDUCTION IN COCHLEAR HAIR CELLS

Robert Fettiplace, PhD Steenbock Professor of Neural and Behavioral Sciences

Department of Neuroscience University of Wisconsin-Madison

host: Peter Detwiler

Functional mechanoelectrical transduction (MET) channels of cochlear hair cells require the presence of transmembrane channel-like protein isoforms TMC1 or TMC2. We show that TMCs distinctively influence channel properties. TMC1-dependent channels have larger single-channel conductance, faster adaptation and, in outer hair cells (OHCs), support a tonotopic apex-to-base gradient in channel conductance. The MET channel has a high permeability to calcium which is reduced in two different Tmc1 mutations associated with autosomal dominant deafness. Each MET channel complex exhibits multiple conductance states in ~50 pS increments, basal MET channels having more large-conductance levels. Using mice expressing fluorescently tagged TMCs, we show a three-fold increase in number of TMC1 molecules per stereocilium tip from cochlear apex to base, mirroring the channel conductance gradient in OHCs. The results suggest there are varying numbers of channels per MET complex, each requiring multiple TMC1 molecules, and together operating in a coordinated manner.