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Chimpanzee mind: Primate origins of human cognition and behavior
Available online at www.sciencedirect.com
Neuroscience Research 65S (2009) S1–S2
Abstracts of the 32nd Annual Meeting of the Japan Neuroscience Society (Neuro 2009) PL1-A1 The rise and fall of REST: Creating the nervous system Gail Mandel Howard Hughes Medical Institute, Oregon Health and Science University, USA The orderly development of the nervous system relies on the control of repressor pathways. Inactivation of repressor pathways initiate neural induction, while new repressor pathways propel neuronal differentiation and establish the functional domains of neurons within the mature brain and spinal cord. Key players in these events are transcriptional repressors, but how their regulation controls different stages in neural development is poorly understood. Our studies focus on regulation of the repressor, REST, a master transcriptional regulator of thousands of genes, both coding and non coding, that define the neuronal phenotype. REST is present as early as the embryonic stem cell stage, where it serves as a chromatin safeguard of precocious expression of neuronal genes. In subsequent dividing neural progenitors, REST levels drop precipitously through a mechanism involved the proteasome degradation pathway, becoming undetectable at terminal neuronal differentiation commensurate with expression of neuronal genes. Recent in vivo studies, to be discussed, indicate that REST controls the timing of these developmental events, through the orchestration of specific chromatin modifications. doi:10.1016/j.neures.2009.09.006
PL2-A1 Schizophrenia as a progressive brain disorder: A challenge for neuroscience discovery Robert W. McCarley Harvard Department Psychiatry and Director, Neuroscience Laboratory, VA Boston Healthcare System, USA I will describe new findings in the mental disorder of schizophrenia, now clearly established as a brain disease, and affecting 1% of the world population. Its onset from 18–25 years cripples people in the most productive period of their lives with positive symptoms (thought disorder, delusions, hallucinations) and negative symptoms (poor social relationships and self care). Our new data show it is characterized by loss of brain gray matter (neuropil, not cells), some of which occurs before full symptom onset and some of which progresses in the 1–2 years after onset. This is most prominent in some neocortical regions and is associated with worsening of symptoms. Also concomitantly progressing are electrophysiological signs, such as mismatch negativity abnormality. One of the most intriguing abnormalities is a disturbance in gamma band oscillations, known to be dependent on pyramidal-GABA neuronal interaction and for which there are known relationships with neurotransmitter abnormalities. Hereditary factors are important but there are no genes with major effect. Unraveling the pathophysiology is a major issue, and I will discuss some current neuroscience efforts to understand the pathophysiology basis, including post-mortem work and in vitro modeling of abnormal circuitry. doi:10.1016/j.neures.2009.09.007
biology. We are facing a similar pursuit in determining the material basis of consciousness. How does the unmistakable smell of dogs after they have been in the rain or the awfulness of a throbbing tooth pain emerge from networks of neurons and their associated synaptic processes? I will summarize what is known about the neurobiology of consciousness, argue that attention is distinct from consciousness, outline the limits to our knowledge, and describe ongoing experiments using visual illusions to manipulate the relationship between physical stimuli and their associated conscious percepts using fMRI and single unit recordings in the human medial temporal lobe. I will conclude by discussing a promising information-theoretical approach to consciousness grounded in circuit complexity (Koch, 2004; Tononi and Koch, 2008). References Koch, C., 2004. The Quest for Consciousness: A Neurobiological Approach. Roberts & Publishers, Denver, Colorado, 2004 (www.questforconsciousness.com). Tononi, G., Koch, C., 2008. The neuronal correlates of consciousness—an update. New York Acad. Sci. 1124, 239–261. doi:10.1016/j.neures.2009.09.008
SL1-A1 Strategies toward regenerating the damaged CNS using ES/iPS cells Hideyuki Okano Department of Physiology, Keio University School of Medicine, Japan For developing cell transplantation therapy to treat various intractable central nervous system (CNS) disorders, including spinal cord injury (SCI), we examined the transplantation of neural stem/progenitor cells (NS/PCs) derived from murine pluripotent stem cells, embryonic stem (ES) cells and induced pluripotent stem cells (iPS cells). In our newly-developed culture system, we could recapitulate the spatiotemporal regulation of CNS development in vitro by using a neurosphere-based culture system of mouse pluripotent stem cells including ES and iPS cells-derived neural stem/progenitor cells (NS/PCs). In this culture system, primary neurospheres (PNS) and passaged secondary neurospheres (SNS) exhibited neurogenic and gliogenic potentials, respectively. Here, we examined the distinct effects of the transplantation of neurogenic and gliogenic NS/PCs on the functional recovery of the mice model of SCI. When we transplanted ES and iPS cells-derived PNS and SNS 9 days after contusive injury at the Th10 level, they exhibited yet neurogenic and gliogenic differentiation tendency. Interestingly, transplantation of gliogenic SNS, but not neurogenic PNS, promoted axonal growth, remyelination, and angiogenesis, resulting in significant locomotor functional recovery after SCI. These findings gave important cues for the establishment of the regenerative medicine for damaged CNS using ES or iPS cells in the near future. I will also talk about our recent results using human ES and iPS-derived NS/PCs. doi:10.1016/j.neures.2009.09.010
PL2-A2 The neurobiology of consciousness: What do we know and how can we discover more? Christof Koch 1,2 1
Division of Biology, California Institute of Technology, USA; 2 Division of Engineering of Applied Science, California Institute of Technology, USA Half a century ago, many did not think it was possible to understand the secret of life. Then Watson and Crick discovered the structure of DNA, forever changing
0168-0102/$ – see front matter
SL2-A1 Chimpanzee mind: Primate origins of human cognition and behavior Tetsuro Matsuzawa Primate Research Institute, Kyoto University, Japan Fieldwork and laboratory work need to go hand in hand to provide us with a complete picture of the life and mind of the chimpanzee. Laboratory study is done with
S2
Abstracts
a community of 14 chimpanzees of 3 generations at KUPRI. The Ai project continues since 1978. My colleagues and I have covered various topics such as perception, cognition, memory and its development. Field study focuses on the community of 13 chimpanzees of 3 generations at Bossou, Guinea, West Africa. Bossou chimpanzees are well known to use a pair of stones as hammer and anvil to crack open nuts. Since 1986, I have explored developmental changes in the tool technology. The combination of laboratory and field studies has revealed a unique mode of social learning in chimpanzees, called “Education by master-apprenticeship”. The features are: (1) the strong mother-infant bond, (2) the lack of active teaching, (3) the infants’ intrinsic motivation to copy the mother’s behavior and (4) the high tolerance of the mothers. Through education by master-apprenticeship, chimpanzees can pass knowledge and skills from one generation to the next, thereby maintaining their community’s cultural repertoire. doi:10.1016/j.neures.2009.09.011
SL2-A2 ␥-Secretase: Stepwise processing of CTF Yasuo Ihara Department of Neuropathology, Faculty of Life and Medical Sciences, Doshisha University, Kizugawa, Japan Amyloid -protein (A), a pathogenic molecule associated with Alzheimer’s disease, is produced by ␥-secretase, which cleaves the -carboxyl terminal fragment (CTF) of -amyloid precursor protein in the middle of its transmembrane domain. How the cleavage proceeds within the membrane has long been enigmatic. We previously hypothesized that CTF is cleaved first at the membrane-cytoplasm boundary, producing two long As, A48 and A49, which are processed further by releasing three residues at each step to produce A42 and A40, respectively. To test this hypothesis, we used LC–MS/MS to quantify the specific tripeptides that are postulated to be released. Using CHAPSO-reconstituted ␥-secretase system, we confirmed that A49 is converted to A43/40 by successively releasing two or three tripeptides, and that A48 is converted to A42/38 by successively releasing two tripeptides or these plus an additional tetrapeptide. Most unexpectedly, LC–MS/MS quantification revealed a time lag, 3–4 min, in the generation of peptides. When extrapolated, each time line for each tripeptide, appears to intercept the same point on the x-axis. These results strongly suggest that Ab is generated through the stepwise processing of CTF by ␥-secretase. doi:10.1016/j.neures.2009.09.012
as having essential roles in a number of aspects of neuronal polarization. I here discuss how extracellular signals as well as intracellular signals regulate neuronal polarity. doi:10.1016/j.neures.2009.09.013
AL1-A1 Chemosensory receptor and behavior Kazushige Touhara Department of Integrated Biosciences, The University of Tokyo, Japan Animals are attracted by odorants derived from food or by pheromones released from the opposite sex. These ecologically and biologically important volatiles are recognized by chemosensory receptors (Touhara et al., 2009). In the silkmoth, the male-specific olfactory receptor BmOr1 in antenna is in charge of the response to bombykol, the sex pheromone released by female moths (Nakagawa et al., 2005; Sato et al., 2008). In the silkworm, the larval BmOr56 plays a role in sensing cis-jasmone, a potent chemoattractant for silkworms that is emitted by their food, mulberry leaves (Tanaka et al., 2009). In mice, the vomeronasal receptor V2Rp5 is the functional receptor for a male-specific peptide pheromone ESP1 that enhances female sexual behavior (Kimoto et al., 2005; Haga et al., submitted for publication). All of these chemosensory receptors are highly specific and narrowly-tuned to each chemosignal. The neural circuitry activated by the ‘specialist’ chemosensory receptor appears to govern a distinct behavioral output that is crucial for survival or mating in various animal species. References Haga et al., submitted for publication. Kimoto, et al., 2005. Nature. Nakagawa, et al., 2005. Science. Sato, et al., 2008. Nature. Tanaka, et al., 2009. Curr. Biol.. Touhara, et al., 2009. Ann. Rev. Phys.. doi:10.1016/j.neures.2009.09.014
AL1-A2 Connection and firing specificity of neocortical neurons Yasuo Kawaguchi National Institute for Physiological Sciences, Okazaki, Japan
SL3-A1 AL3-A1 Neuronal polarity: From extracellular signals to intracellular mechanisms Kozo Kaibuchi Nagoya University Graduate School of Medicine, Japan After neurons are born and differentiated, neurons break their previous symmetry, dramatically change their shape, and establish two structurally and functionally distinct compartments, axons and dendrites. The axons and dendrites differ from each other in the composition of their proteins and organelles. The axons contain synaptic vesicles from which they release neurotransmitters at axon terminals in response to electrical signals from the cell body. Dendrites, especially dendritic spines, contain receptors for these neurotransmitters. These two distinct cellular structures are fundamental for neuronal function, as they enable neurons to receive and transmit electrical signals. However, the molecular mechanisms underlying this neuronal polarization were unclear until a decade ago. Recent studies have implicated several signaling pathways including Rho family GTPases, Par proteins and specific kinases
Elucidation of neocortical organization principles is crucial for understanding the function of the cerebral cortex. We quantitatively identified GABAergic nonpyramidal cell subtypes on the basis of their physiological characteristics, differential molecular expression, and axonal and dendritic arborization. Excitatory pyramidal cell subtypes were classified based on their extracortical projections, physiology, and dendritic arborization. GABAergic cells exhibited subtype-specific preferences for forming synaptic connections onto specific target-cell surface domains. Similarly, pyramidal neurons exhibited selective connectivity, with several internal excitatory pathways segregated according to the extracortical targets of their efferent projection neurons. Fast-spiking GABAergic cells discharged during the slow wave according to local and global rhythms, and were further differentiated in based on their selective firing during different phases of the oscillations. Thus, the local synaptic organization and firing activity in the neocortex are specified according to global inter-regional circuits and their oscillatory interaction. doi:10.1016/j.neures.2009.09.015
Neuroscience Research 65S (2009) S1–S2
Abstracts of the 32nd Annual Meeting of the Japan Neuroscience Society (Neuro 2009) PL1-A1 The rise and fall of REST: Creating the nervous system Gail Mandel Howard Hughes Medical Institute, Oregon Health and Science University, USA The orderly development of the nervous system relies on the control of repressor pathways. Inactivation of repressor pathways initiate neural induction, while new repressor pathways propel neuronal differentiation and establish the functional domains of neurons within the mature brain and spinal cord. Key players in these events are transcriptional repressors, but how their regulation controls different stages in neural development is poorly understood. Our studies focus on regulation of the repressor, REST, a master transcriptional regulator of thousands of genes, both coding and non coding, that define the neuronal phenotype. REST is present as early as the embryonic stem cell stage, where it serves as a chromatin safeguard of precocious expression of neuronal genes. In subsequent dividing neural progenitors, REST levels drop precipitously through a mechanism involved the proteasome degradation pathway, becoming undetectable at terminal neuronal differentiation commensurate with expression of neuronal genes. Recent in vivo studies, to be discussed, indicate that REST controls the timing of these developmental events, through the orchestration of specific chromatin modifications. doi:10.1016/j.neures.2009.09.006
PL2-A1 Schizophrenia as a progressive brain disorder: A challenge for neuroscience discovery Robert W. McCarley Harvard Department Psychiatry and Director, Neuroscience Laboratory, VA Boston Healthcare System, USA I will describe new findings in the mental disorder of schizophrenia, now clearly established as a brain disease, and affecting 1% of the world population. Its onset from 18–25 years cripples people in the most productive period of their lives with positive symptoms (thought disorder, delusions, hallucinations) and negative symptoms (poor social relationships and self care). Our new data show it is characterized by loss of brain gray matter (neuropil, not cells), some of which occurs before full symptom onset and some of which progresses in the 1–2 years after onset. This is most prominent in some neocortical regions and is associated with worsening of symptoms. Also concomitantly progressing are electrophysiological signs, such as mismatch negativity abnormality. One of the most intriguing abnormalities is a disturbance in gamma band oscillations, known to be dependent on pyramidal-GABA neuronal interaction and for which there are known relationships with neurotransmitter abnormalities. Hereditary factors are important but there are no genes with major effect. Unraveling the pathophysiology is a major issue, and I will discuss some current neuroscience efforts to understand the pathophysiology basis, including post-mortem work and in vitro modeling of abnormal circuitry. doi:10.1016/j.neures.2009.09.007
biology. We are facing a similar pursuit in determining the material basis of consciousness. How does the unmistakable smell of dogs after they have been in the rain or the awfulness of a throbbing tooth pain emerge from networks of neurons and their associated synaptic processes? I will summarize what is known about the neurobiology of consciousness, argue that attention is distinct from consciousness, outline the limits to our knowledge, and describe ongoing experiments using visual illusions to manipulate the relationship between physical stimuli and their associated conscious percepts using fMRI and single unit recordings in the human medial temporal lobe. I will conclude by discussing a promising information-theoretical approach to consciousness grounded in circuit complexity (Koch, 2004; Tononi and Koch, 2008). References Koch, C., 2004. The Quest for Consciousness: A Neurobiological Approach. Roberts & Publishers, Denver, Colorado, 2004 (www.questforconsciousness.com). Tononi, G., Koch, C., 2008. The neuronal correlates of consciousness—an update. New York Acad. Sci. 1124, 239–261. doi:10.1016/j.neures.2009.09.008
SL1-A1 Strategies toward regenerating the damaged CNS using ES/iPS cells Hideyuki Okano Department of Physiology, Keio University School of Medicine, Japan For developing cell transplantation therapy to treat various intractable central nervous system (CNS) disorders, including spinal cord injury (SCI), we examined the transplantation of neural stem/progenitor cells (NS/PCs) derived from murine pluripotent stem cells, embryonic stem (ES) cells and induced pluripotent stem cells (iPS cells). In our newly-developed culture system, we could recapitulate the spatiotemporal regulation of CNS development in vitro by using a neurosphere-based culture system of mouse pluripotent stem cells including ES and iPS cells-derived neural stem/progenitor cells (NS/PCs). In this culture system, primary neurospheres (PNS) and passaged secondary neurospheres (SNS) exhibited neurogenic and gliogenic potentials, respectively. Here, we examined the distinct effects of the transplantation of neurogenic and gliogenic NS/PCs on the functional recovery of the mice model of SCI. When we transplanted ES and iPS cells-derived PNS and SNS 9 days after contusive injury at the Th10 level, they exhibited yet neurogenic and gliogenic differentiation tendency. Interestingly, transplantation of gliogenic SNS, but not neurogenic PNS, promoted axonal growth, remyelination, and angiogenesis, resulting in significant locomotor functional recovery after SCI. These findings gave important cues for the establishment of the regenerative medicine for damaged CNS using ES or iPS cells in the near future. I will also talk about our recent results using human ES and iPS-derived NS/PCs. doi:10.1016/j.neures.2009.09.010
PL2-A2 The neurobiology of consciousness: What do we know and how can we discover more? Christof Koch 1,2 1
Division of Biology, California Institute of Technology, USA; 2 Division of Engineering of Applied Science, California Institute of Technology, USA Half a century ago, many did not think it was possible to understand the secret of life. Then Watson and Crick discovered the structure of DNA, forever changing
0168-0102/$ – see front matter
SL2-A1 Chimpanzee mind: Primate origins of human cognition and behavior Tetsuro Matsuzawa Primate Research Institute, Kyoto University, Japan Fieldwork and laboratory work need to go hand in hand to provide us with a complete picture of the life and mind of the chimpanzee. Laboratory study is done with
S2
Abstracts
a community of 14 chimpanzees of 3 generations at KUPRI. The Ai project continues since 1978. My colleagues and I have covered various topics such as perception, cognition, memory and its development. Field study focuses on the community of 13 chimpanzees of 3 generations at Bossou, Guinea, West Africa. Bossou chimpanzees are well known to use a pair of stones as hammer and anvil to crack open nuts. Since 1986, I have explored developmental changes in the tool technology. The combination of laboratory and field studies has revealed a unique mode of social learning in chimpanzees, called “Education by master-apprenticeship”. The features are: (1) the strong mother-infant bond, (2) the lack of active teaching, (3) the infants’ intrinsic motivation to copy the mother’s behavior and (4) the high tolerance of the mothers. Through education by master-apprenticeship, chimpanzees can pass knowledge and skills from one generation to the next, thereby maintaining their community’s cultural repertoire. doi:10.1016/j.neures.2009.09.011
SL2-A2 ␥-Secretase: Stepwise processing of CTF Yasuo Ihara Department of Neuropathology, Faculty of Life and Medical Sciences, Doshisha University, Kizugawa, Japan Amyloid -protein (A), a pathogenic molecule associated with Alzheimer’s disease, is produced by ␥-secretase, which cleaves the -carboxyl terminal fragment (CTF) of -amyloid precursor protein in the middle of its transmembrane domain. How the cleavage proceeds within the membrane has long been enigmatic. We previously hypothesized that CTF is cleaved first at the membrane-cytoplasm boundary, producing two long As, A48 and A49, which are processed further by releasing three residues at each step to produce A42 and A40, respectively. To test this hypothesis, we used LC–MS/MS to quantify the specific tripeptides that are postulated to be released. Using CHAPSO-reconstituted ␥-secretase system, we confirmed that A49 is converted to A43/40 by successively releasing two or three tripeptides, and that A48 is converted to A42/38 by successively releasing two tripeptides or these plus an additional tetrapeptide. Most unexpectedly, LC–MS/MS quantification revealed a time lag, 3–4 min, in the generation of peptides. When extrapolated, each time line for each tripeptide, appears to intercept the same point on the x-axis. These results strongly suggest that Ab is generated through the stepwise processing of CTF by ␥-secretase. doi:10.1016/j.neures.2009.09.012
as having essential roles in a number of aspects of neuronal polarization. I here discuss how extracellular signals as well as intracellular signals regulate neuronal polarity. doi:10.1016/j.neures.2009.09.013
AL1-A1 Chemosensory receptor and behavior Kazushige Touhara Department of Integrated Biosciences, The University of Tokyo, Japan Animals are attracted by odorants derived from food or by pheromones released from the opposite sex. These ecologically and biologically important volatiles are recognized by chemosensory receptors (Touhara et al., 2009). In the silkmoth, the male-specific olfactory receptor BmOr1 in antenna is in charge of the response to bombykol, the sex pheromone released by female moths (Nakagawa et al., 2005; Sato et al., 2008). In the silkworm, the larval BmOr56 plays a role in sensing cis-jasmone, a potent chemoattractant for silkworms that is emitted by their food, mulberry leaves (Tanaka et al., 2009). In mice, the vomeronasal receptor V2Rp5 is the functional receptor for a male-specific peptide pheromone ESP1 that enhances female sexual behavior (Kimoto et al., 2005; Haga et al., submitted for publication). All of these chemosensory receptors are highly specific and narrowly-tuned to each chemosignal. The neural circuitry activated by the ‘specialist’ chemosensory receptor appears to govern a distinct behavioral output that is crucial for survival or mating in various animal species. References Haga et al., submitted for publication. Kimoto, et al., 2005. Nature. Nakagawa, et al., 2005. Science. Sato, et al., 2008. Nature. Tanaka, et al., 2009. Curr. Biol.. Touhara, et al., 2009. Ann. Rev. Phys.. doi:10.1016/j.neures.2009.09.014
AL1-A2 Connection and firing specificity of neocortical neurons Yasuo Kawaguchi National Institute for Physiological Sciences, Okazaki, Japan
SL3-A1 AL3-A1 Neuronal polarity: From extracellular signals to intracellular mechanisms Kozo Kaibuchi Nagoya University Graduate School of Medicine, Japan After neurons are born and differentiated, neurons break their previous symmetry, dramatically change their shape, and establish two structurally and functionally distinct compartments, axons and dendrites. The axons and dendrites differ from each other in the composition of their proteins and organelles. The axons contain synaptic vesicles from which they release neurotransmitters at axon terminals in response to electrical signals from the cell body. Dendrites, especially dendritic spines, contain receptors for these neurotransmitters. These two distinct cellular structures are fundamental for neuronal function, as they enable neurons to receive and transmit electrical signals. However, the molecular mechanisms underlying this neuronal polarization were unclear until a decade ago. Recent studies have implicated several signaling pathways including Rho family GTPases, Par proteins and specific kinases
Elucidation of neocortical organization principles is crucial for understanding the function of the cerebral cortex. We quantitatively identified GABAergic nonpyramidal cell subtypes on the basis of their physiological characteristics, differential molecular expression, and axonal and dendritic arborization. Excitatory pyramidal cell subtypes were classified based on their extracortical projections, physiology, and dendritic arborization. GABAergic cells exhibited subtype-specific preferences for forming synaptic connections onto specific target-cell surface domains. Similarly, pyramidal neurons exhibited selective connectivity, with several internal excitatory pathways segregated according to the extracortical targets of their efferent projection neurons. Fast-spiking GABAergic cells discharged during the slow wave according to local and global rhythms, and were further differentiated in based on their selective firing during different phases of the oscillations. Thus, the local synaptic organization and firing activity in the neocortex are specified according to global inter-regional circuits and their oscillatory interaction. doi:10.1016/j.neures.2009.09.015