Neuroscience 163 (2009) 965–976 MOLECULAR APPROACHES TO UNDERSTANDING NEURAL NETWORK PLASTICITY AND MEMORY: THE KAVLI PRIZE INAUGURAL SYMPOSIUM ON NEUROSCIENCE M. SANDER,a L. H. BERGERSENb AND cal markers, biological transport, biophysics, calcium signaling, J. STORM-MATHISENb* central nervous system, cerebellum, computer simulation, condition- aPage One Editorial Services, 685 Poplar Avenue, Boulder CO 80304, ing (classical), crustacea, crystallography (X-Ray), cytoskeletal pro- USA teins, dendritic spines, discrimination learning, electric stimulation, electrophysiology, excitatory amino acid antagonists, excitatory bDepartment of Anatomy, Institute of Basic Medical Sciences, and Centre postsynaptic potentials, fear, ganglia (invertebrate), gene expres- for Molecular Biology and Neuroscience, University of Oslo, PO Box 1105 sion, glutamates, glutamic acid, green fluorescent proteins, humans, Blindern, 0317 Oslo, Norway immunohistochemistry, kinetics, learning, leucine, ligands, maze learning, membrane potentials, membrane transport proteins, mice, Abstract—The Kavli Prizes were awarded for the first time in mice (knockout), mice (transgenic), microscopy (confocal), micros- Oslo, Norway on September 9, 2008 to seven of the world’s copy (immunoelectron), models (neurological), motor activity, motor most prominent scientists in astrophysics, nanoscience and neurons, nerve tissue proteins, neural conduction, neuronal plastic- neuroscience. The astrophysics prize was awarded jointly to ity, neurotransmitter agents, neurotransmitter transport proteins, Maarten Schmidt, of the California Institute of Technology, patch-clamp techniques, perforant pathway, protein conformation, USA, and Donald Lynden-Bell, of Cambridge University, UK; protein kinase C, protein structure (tertiary), protein subunits, psy- the nanoscience prize was awarded jointly to Louis E. Brus, chomotor performance, receptors (neurotransmitter), retention (psy- of Columbia University, USA, and Sumio Iijima, of Meijo Uni- chology), sodium, space perception, spatial behavior, symporters, versity, Japan; and the neuroscience prize was awarded synaptic potentials, tetanus toxin, transcription factors. jointly to Pasko Rakic, of the Yale University School of Med- icine, USA, Thomas Jessell, of Columbia University, USA, and Sten Grillner, of the Karolinska Institute, Sweden. The The field of neuroscience has experienced explosive Kavli Prize is a joint venture of the Kavli Foundation, the progress in the last decade, fueled by important and un- Norwegian Academy of Science and Letters, and the Norwe- expected discoveries in the areas of protein structure and gian Ministry of Education and Research. function, neural plasticity, neural networks, adult neuro- The Kavli Prize Inaugural Symposium on Neuroscience genesis, learning and memory (Table 1). Some of these was held at the University of Oslo on 8 September, 2008, organized by L.H. Bergersen, E. Moser M.-B. Moser, and J. recent discoveries went strongly against the grain of es- Storm-Mathisen. At this Symposium, seven leading neurosci- tablished dogma in the field of neurobiology. For example, entists described their groundbreaking work, which encom- early models of brain function proposed that adult brains passes some of the most important recent advances in the were relatively immutable, and that neural networks in the field of neuroscience, from molecule to synapse to network adult brain could be simply described as a static set of to behavior. The Symposium was a fitting tribute to Fred connections, akin to a wiring diagram in an electrical de- Kavli’s vision of neuroscience as an outstanding area of vice. In contrast, speakers at this Symposium repeatedly progress, and to the achievements of the winners of the first Kavli Prize in Neuroscience. The main points of the Sympo- emphasized the concept of neural plasticity, which is crit- sium presentations are summarized below. © 2009 IBRO. ical not only during normal brain development, but also for Published by Elsevier Ltd. All rights reserved. essential functions of the adult brain, including learning and memory. The hippocampus (Fig. 1A) is the focus of Key words: Grillner S, Jessell TM, Rakic P, Gouaux E, Shatz CJ, much research on learning and memory, because animals Marder E, Gage FH, Bliss TV, Seeburg PH, Tonegawa S, adult stem cells, amino acid transport systems (acidic), astrocytes, with experimentally-induced total or region-specific hip- dentate gyrus, embryonic stem cells, glutamate plasma mem- pocampal dysfunction demonstrate gross or selective loss brane transport proteins, hippocampus, histocompatibility anti- of capacity to process information and learn (Fig. 1B). gens class I, long-term potentiation, memory, nerve net, neural Environmental stimuli modulate brain structure and func- pathways, neurogenesis, neurons, receptors (AMPA), receptors tion, such that an enriched environment and physical ac- (N-Methyl-D-Aspartate), synapses, aging, amino acid transport sys- tivity increase the rate at which new brain cells and new tems, amino acids, analysis of variance, animals, aspartic acid, avoidance learning, axons, behavior (animal), binding sites, biologi- synaptic connections form and persist in the adult brain. Many ongoing studies use rodent model systems, and ϩ ϩ *Corresponding author. Tel: 47 97193044; fax: 47-22851278. these systems allow neuroscientists to apply powerful mo- E-mail address: [email protected] (J. Storm-Mathisen). Abbreviations: AB, anterior burster neuron; GFP, green fluorescent lecular tools to analyze brain structure and function. So- protein; KO, knockout; LTP, long term potentiation; LP, lateral pyloric phisticated use of transgenic mouse strains and engi- neuron; MHC1, major histocompatibility complex class I; PD, pyloric neered viruses, as well as advances in imaging tech- dilator neuron; PIRB, paired immunoglobulin-like receptor B; PY, pyloric neuron; SPM, synaptic plasticity and memory; STG, stomato- niques, allow researchers to analyze the properties of gaster ganglion; ␤2M, ␤2-microglobulin. individual neural cells, to measure activity at individual 0306-4522/09 $ - see front matter © 2009 IBRO. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.neuroscience.2009.07.046 965 966 M. Sander et al. / Neuroscience 163 (2009) 965–976 Table 1. Symposium highlights output and behavior, indicating that multiple routes may lead to successful adaptation. As emphasized by Timothy Neurotransmitter transporters couple energetically-disfavorable Bliss at this Symposium, and recapitulated by the work of transport of one substrate to energetically-favorable co-transport Peter Seeburg and Susumu Tonegawa, a challenge of the of a second substrate or ion. Crystallography reveals how atoms in the protein interact with substrate and ions to effectuate future is to understand how groups of neural cells work transport. together as neural subnetworks, enabling critical brain Ocular dominance plasticity, which is subject to positive and functions such as memory and learning. A beginning to this negative regulatory control during development, is downregulated is the dissection of how different glutamate receptor types by an MHC1/PIR-B-dependent pathway. Thus proteins governing the immune system also contribute to the tuning of brain function. (Seeburg) and different hippocampal synapses subserve Neural circuit parameters in biological systems display a significant different memory functions. Thus the multisynaptic ento- amount of cell-to-cell and animal-to animal variation, without rhino-hippocampal circuit through the dentate gyrus and significant degradation in circuit performance. CA1 is required for one-trial learning of a new situation, as Adult neural stem cells, which reside in the subgranular zone of the hippocampal dentate gyrus and the subventricular zone of lateral opposed to slow multi-trial learning (Tonegawa). Could the ventricles, are pluripotent cells that are capable of self-renewal. adult neurogenesis in the dentate gyrus (Gage) be somehow Adult hippocampal neural stem cells give rise to neurons and involved in this clearly important function? In the realm of astrocytes in a context-dependent manner, and form functional neural networks, an exclusively reductionist approach may synapses that preferentially integrate with pre-existing circuits in the dentate gyrus. not be sufficient to reveal how a normal brain functions and The synaptic plasticity and memory hypothesis suggest that LTP is the causes of brain dysfunction, when it occurs. Undoubtedly, a physiological correlate of memory; this hypothesis is being future molecular analyses at the level of the single cell or tested by manipulating synaptic responses in memory-specific synapse, and at the network level, will continue to remodel neural subnetworks. Glutamatergic synapses play a key role in hippocampus-dependent our concept of human brain structure and function. learning. Specific AMPA and NMDA glutamate receptor subunits and subtypes in the hippocampus play differential roles in spatial SYMPOSIUM SEMINAR PRESENTATIONS working and spatial reference memory. The trisynaptic pathway in the hippocampus is required for rapid Eric Gouaux Portland, OR, USA one-time contextual learning, but is dispensable for slow multi-trial spatial tuning and other associative memory tasks in mice with a Structure and mechanism of neurotransmitter trans- functional monosynaptic pathway in the hippocampus. porters. Communication in the CNS of mammals is ef- fected by a gradient