Lectures (Alphabetical order)


Speaker
Dr. James Bower (University of Texas, San Antonio)
( 脳・神経系スーパーコンピューティングワークショップ 2010)

Title
What does the cerebellum do, and how does it do it

Abstract
"In the back of our skulls, perched upon the brain stem under the overarching mantle of the great hemispheres of the cerebrum, is a baseball-sized, bean-shaped lump of gray and white brain tissue. This is the cerebellum, the 'lesser brain'." So began, somewhat inauspiciously, an article on the cerebellum published by Ray S. Snider in Scientific American in 1958. That introduction continued, "In contrast to the cerebrum, where men have sought and found the centers of so many vital mental activities, the cerebellum remains a region of subtle and tantalizing mystery, its function hidden from investigators." By the time the second Scientific American article on the cerebellum appeared 17 years later, the author, Rodolfo R. Llinas stated, "There is no longer any doubt that the cerebellum is a central control point for the organization of movement". Recently, however, the cerebellum's function has again become the subject of considerable debate. Human brain imaging studies have found that the human cerebellum is active during a wide range of activities that are not directly related to movement. At the same time psychophysical studies have revealed that damage to specific areas of the cerebellum can cause unanticipated impairments of non-motor functions. These results are now being interpreted to suggest that the cerebellum may play a significant role in an ever widening set of brain functions including: short-term memory, attention, impulse control, emotion, planning and scheduling mental activities, higher cognition and perhaps even conditions such as schizophrenia and autism. The cerebellum has once again become an area of "tantalizing mystery."

It is the premise of Dr. Bower's approach to understanding cerebellar function that, ultimately, the answer to the question "what does the cerebellum do” will be determined by understanding how and what its neurons compute, and how that computational influences neural processing in other regions of the brain. Here too the cerebellum is a bit embarrassing for neurobiologists as we have known the basic anatomical structure of the cerebellum for more than 100 years, but fundamental questions regarding the physiological relationships between its neurons are still being hotly debated. In this interactive dialog, Dr. Bower will start with a discussion of current beliefs with respect to the anatomical and physiological relationships between cerebellar neurons, and then show how his own model driven research has suggested that those beliefs must also be modified. We will then consider the implications of these changes for cerebellar function as a whole, and then consider new supportive evidence from human imaging and psychophysical results.

References
  Recommended Read:

  1. Marr,D. (1969) A theory of cerebellar cortex, J.Physiol.(Lond.), 202: 437-471

  2. Paulin, M (1993) The role of the cerebellum in motor control and perception. Brain Behav.Evol. 41: 39-50

  3. Apps, R., Hawkes, R. (2009) Cerebellar cortical organization: a one-map hypothesis. Nat Rev Neurosci 10: 670-81


Speaker
Dr. Geoffrey J Goodhill (University of Queensland)

Title
Growth cone guidance by molecular gradients

Abstract
Molecular gradients provide important guidance cues for developing axons. However, the computational mechanisms growth cones use to detect and respond to such gradients are largely unknown. I will discuss recent theoretical and experimental work addressing some of the fundamental physical constraints which limit the ability of growth cones to detect gradients. This work suggests that the guidance strategies employed by growth cones may be different for steep versus shallow gradients.

References
  Recommended Read:

  1. Mortimer D, Feldner J, Vaughan T, Vetter I, Pujic Z, Rosoff WJ, Burrage K, Dayan P, Richards LJ, Goodhill GJ (2009). A Bayesian model predicts the response of axons to molecular gradients. Proc. Natl. Acad. Sci. USA, 106, 10296-10301.

  2. Mortimer, D., Fothergill, T., Pujic, Z., Richards, L.J. & Goodhill, G.J. (2008). Growth Cone Chemotaxis. Trends in Neurosciences, 31, 90-98.

  Optional Read:

  1. Simpson, H, Mortimer, D. & Goodhill, G.J. (2009). Theoretical models of neural circuit development. Current Topics in Development Biology, 87, 1-51.

  2. Mortimer D, Pujic Z, Vaughan T, Thompson AW, Feldner J, Vetter I, and Goodhill GJ, (2010), Axon guidance by growth-rate modulation, PNAS, doi:pnas.0909254107


Speaker
Dr. Alex L. Kolodkin (The Johns Hopkins School of Medicine)

Title
Molecular Mechanisms Governing the Establishment of Neuronal Connectivity

Abstract
Complex neuronal connectivity patterns develop through the action of guidance cues and their neuronal receptors. Multiple cues, including semaphorin proteins, provide repulsive and attractive influences that sculpt developing neuronal trajectories. Studies in invertebrates and vertebrates reveal the receptors and intracellular signaling mechanisms semaphorins use to guide neurons and regulate their morphology. More recently, we have found that certain secreted semaphorin proteins and their receptors play key roles in coordinating distinct aspects of neural circuit connectivity during postnatal development. Our analyses of how signaling initiated by members of the large semaphorin guidance cue family provides a framework for understanding how diverse cues regulate distinct aspects of neural circuit assembly. In addition, our work on semaphorin function in neuronal and non-neuronal cell types suggests strategies for promoting neuronal regeneration.

References
  Recommended Read:

  1. Kolodkin, A. L., and Tessier-Lavigne, M. (2008). Growth Cones and Axon Pathfinding; in Fundamental Neuroscience, Third Edition; Squire et al., Editors; Elsevier Inc. Academic Press; 377-400.

  2. Tran, T.S., Kolodkin, A.L., Bharadwaj, R. (2007). Semaphorin regulation of cellular morphology. Ann. Rev. Cell and Dev. Biology, 29, 263-292.

  3. Tran, T.S., Rubio, M.E., Clem, R.L., Johnson, D.,Case, L.C., Tessier-Lavigne, M., Huganir, R.L., Ginty, D.D., and Kolodkin, A.L. (2009). Secreted Semaphorins Control Spine Distribution and Morphogenesis in the Postnatal CNS. Nature, 462, 1065-1069.

  4. Ayoob, J.C., Terman, J.R., and Kolodkin, A.L. (2006). Drosophila Plexin B is a Sema-2a receptor required for axon guidance. Development, 133, 2125-2135.

  Optional Read:

  1. Yazdani, U., Terman, J.R. (2006). The Semaphorins. Genome Biol., 7, 211.

  2. Kantor, D.B., Chivatakarn, O., Peer, K.L., Oster, S.F., Inatani, M., Hansen, M.J., Flanagan, J.G.,Yamaguchi, Y., Sretavan, D.W., Giger, R.J., and Kolodkin, A.L. (2004). Semaphorin 5A is a Bifunctional Axon Guidance Cue Regulated by Heparan and Chondroitin Sulfate Proteoglycans. Neuron, 44, 961-975.

  3. Gu, C, Yoshida, Y., Mann, F., Reimert, D.V., Livet, J., Merte, J., Henderson, C., Jessell, T.M., Kolodkin, A.L., Ginty, D.D. (2005). Sema3E and its receptor PlexinD1 control vascular patterning independent of neuropilins. Science, 307, 265-268.

  4. Terman, J.R., and Kolodkin, A.L. (2004). The AKAP Nervy directly couples Protein Kinase A to Plexin-mediated semaphorin repulsion. Science, 303, 1204-1207.


Speaker
Dr. Andreas Schaefer (Max-Planck Institute)

Title
Cellular mechanisms regulating behaviour:
Inhibition in the olfactory bulb and fast odor discrimination in mice

Abstract
Measurements of reaction times are a sensitive behavioural readout in both human and animal psychophysics. Here, I will discuss such psychophysical experiments for the sense of smell in mice, where one finds that odor discrimination is fast but speed critically depends on task difficulty. What are the cellular mechanisms involved in during this time-dependent process? In my talk I will focus on inhibitory mechanisms within the olfactory bulb, the first processing structure of the olfactory system. Generally, local inhibitory circuits are thought to shape neuronal information processing in various parts of the central nervous system, but it remains unclear how specific properties of inhibitory neuronal interactions translate into behavioral performance. In the olfactory bulb, inhibition of principal neurons may contribute to odor discrimination behavior by refining neuronal representations of odors. Employing a combination of classical transgenic techniques and virus-mediated gene ablation, we show that selective deletion of the fast, AMPA-type glutamate receptor subunit GluA2 in inhibitory neurons boosted synaptic Ca2+ influx, thus increasing inhibition of mitral cells. On a behavioral level, discrimination of similar odor mixtures was accelerated. In contrast, selective removal of NMDA receptors slowed discrimination of similar odors. These results demonstrate that inhibition of principal neurons controlled by interneuron glutamate receptors results in fast and accurate discrimination of similar odors. Thus, spatio-temporally defined molecular perturbations of olfactory bulb interneurons directly link stimulus-similarity, neuronal processing time and discrimination behavior to synaptic inhibition.

References
  Recommended Read:

  1. Abraham,N.M., Spors,H., Carleton,A., Margrie,T.W., Kuner,T., and Schaefer,A.T. (2004). Maintaining accuracy at the expense of speed: stimulus similarity defines odor discrimination time in mice. Neuron 44, 865-876.

  2. Isaacson,J.S. and Strowbridge,B.W. (1998). Olfactory reciprocal synapses: dendritic signaling in the CNS. Neuron 1998 Apr; 20, 749-761.

  3. Uchida,N. and Mainen,Z.F. (2003). Speed and accuracy of olfactory discrimination in the rat. Nat Neurosci 6, 1224-1229.

  4. Shimshek,D.R., Bus,T., Kim,J., Mihaljevic,A., Mack,V., Seeburg,P.H., Sprengel,R., and Schaefer,A.T. (2005). Enhanced odor discrimination and impaired olfactory memory by spatially controlled switch of AMPA receptors. PLoS Biol 3, e354.

  5. Urban,N.N. (2002). Lateral inhibition in the olfactory bulb and in olfaction. Physiol Behav 77, 607-612.

  Optional Read:

  1. Isaacson,J.S. (2001). Mechanisms governing dendritic gamma-aminobutyric acid (GABA) release in the rat olfactory bulb. Proc Natl Acad Sci U S A 98, 337-342.

  2. Margrie,T.W. and Schaefer,A.T. (2003). Theta oscillation coupled spike latencies yield computational vigour in a mammalian sensory system. J Physiol 546, 363-374.

  3. Rinberg,D., Koulakov,A., and Gelperin,A. (2006). Speed-accuracy tradeoff in olfaction. Neuron 51, 351-358.

  4. Schaefer,A.T. and Margrie,T.W. (2007). Spatiotemporal representations in the olfactory system. Trends Neurosci 30, 92-100.

  5. Schoppa,N.E. and Urban,N.N. (2003). Dendritic processing within olfactory bulb circuits. Trends Neurosci 26, 501-506.

  6. Yokoi,M., Mori,K., and Nakanishi,S. (1995). Refinement of odor molecule tuning by dendrodendritic synaptic inhibition in the olfactory bulb. Proc Natl Acad Sci U S A 92, 3371-3375.


Speaker
Dr. 重本 隆一 (生理学研究所)
( 脳・神経系スーパーコンピューティングワークショップ 2010)

Title
Glutamate receptors: Their localization, function, and roles in physiological learning processes

Abstract
Glutamate receptors serve as key molecules for synaptic plasticity such as long-term potentiation and depression, which are believed to underlie various types of physiological learning processes. Although many lines of evidence obtained with in vitro studies and knock out mice support essential roles of NMDA- and AMPA-type glutamate receptor subunits in synaptic plasticity and learning, we have rather sparse evidence demonstrating what kind of alteration occurs in vivo in localization and function of glutamate receptors and synapses during physiological learning. I will introduce a newly developed quantitative freeze-fracture replica immunolabeling and dynamic changes of synapses and synaptic receptors detected with this and conventional electron microscopic methods after physiological spatial and motor learning, and discuss about roles of glutamate receptors in physiological learning processes.

References
  Recommended Read:

  1. Sheng M, Hoogenraad CC, The postsynaptic architecture of excitatory synapses: a more quantitative view. Annu Rev Biochem, 76; 823-47, 2007.

  2. Kessels HW, Malinow R, Synaptic AMPA receptor plasticity and behavior, Neuron. 2009 Feb 12;61(3):340-50.

  3. Masugi-Tokita M, Shigemoto R,. High-resolution quantitative visualization of receptors at central synapses. Current Opinion in Neurobiology, 17:387-93, 2007.

  Optional Read:

  1. Kawakami R, Shinohara Y, Kato Y, Sugiyama H, Shigemoto R, Ito I. Asymmetrical allocation of NMDA receptor ε2 subunits in hippocampal circuitry. Science, 300, 990-994, 2003.

  2. Shinohara Y, Hirase H, Watanabe M, Itakura M, Takahashi M, Shigemoto R, Left-right asymmetry of the hippocampal synapses with differential subunit allocation of glutamate receptors, Proc. Natl. Aca. Sci. USA, 105:19498-503, 2008.


Speaker
Dr. Nelson Spruston (Northwestern University)

Title
Mechanisms of dendritic integration and plasticity

Abstract
This lecture will consider how the structure of pyramidal neurons and the expression of voltage-gated channels in dendrites influence the integration of synaptic responses as well as the induction of synaptic plasticity. Topics to be covered include basic synaptic integration, voltage attenuation in dendrites, expression of voltage-gated channels in dendrites, action potential backpropagation from the axon into the dendrites, initiation and propagation of dendritic spikes, and the contribution of backpropagating action potentials and dendritically initiated spikes to the induction of long-term potentiation.

References
  Recommended Read:

  1. Hille, B. Chapter 1 of "Ion Channels of Excitable Membranes,” 3rd edition. Sinauer Associates, Sunderland, Massachusetts, USA.

  2. Spruston N. Pyramidal neurons: dendritic structure and synaptic integration. Nature Reviews Neuroscience, 9:206-221, 2008.

  3. Häusser M, Spruston N, Stuart G. Diversity and dynamics of dendritic signaling. Science, 290:739-744, 2000.

  4. Kampa BM, Letzkus JJ, Stuart GJ. Dendritic mechanisms controlling spike-timing-dependent synaptic plasticity. Trends Neurosci. 30:456-463, 2007.

  Optional Read:

  1. Spruston N, Häusser M, Stuart G. Dendritic integration. In: Dendrites, 2nd edition, Stuart G, Spruston N, Häusser M, eds. Oxford University Press, 2nd edition, pp. 351-399, 2008.

  2. Stuart G, Spruston N, Sakmann B, Häusser M. Action potential initiation and backpropagation in neurons of the mammalian central nervous system. Trends in Neurosciences, 20:125-131, 1997.

  3. Lisman J, Spruston N. Postsynaptic depolarization requirements for LTP and LTD: a critique of spike timing dependent plasticity. Nature Neuroscience, 8:839-841, 2005.

  4. Sjöström PJ, Rancz EA, Roth A, Häusser M. Dendritic excitability and synaptic plasticity. Physiol Rev. 88:769-840, 2008.