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Frontal lobe mechanisms for rules and control
Neuroscience Research 58S (2007) S1–S244
Abstracts of the 30th Annual Meeting of the Japan Neuroscience Society (Neuro 2007)
PL1 Glycine neurotransmission: From molecules to mice and disease Heinrich Betz 1 Neurochemistry, Max-Planck-Institute for Brain Research, Frankfurt, Germany Glycine is a major inhibitory neurotransmitter in the mammalian CNS. Upon Ca2+ -triggered release from glycinergic nerve terminals, glycine causes postsynaptic inhibition by binding to strychnine-sensitive glycine receptors (GlyRs) which exist in different (␣1–␣4) isoforms. Synaptic localization of GlyRs requires the scaffolding protein gephyrin which also is found at GABAergic synapses. Glycinergic neurotransmission is terminated by the reuptake of glycine into glycinergic nerve terminals and neighbouring glial cells via the Na+ /Cl− -dependent glycine transporters, GlyT1 and GlyT2. We have used gene targeting to dissect the physiological functions of distinct GlyR subtypes and GlyT isoforms. Accordingly, ␣1 GlyRs are mainly involved in motor control, whereas ␣3 GlyRs are crucial for pain sensitization. Inactivation of the gephyrin gene causes lethality due to a loss of postsynaptic GlyR (and GABAA receptor) clustering. Similarly, ablation of the GlyT1 and GlyT2 genes is postnatally lethal. Our results underline the vital roles of glycinergic neurotransmission and mutant mice deficient in distinct GlyR and establish GlyT isoforms as animal models of hereditary human disorders caused by mutations in GlyR, gephyrin and GlyT genes.
PL2 Signaling networks that control synapse development and cognitive function Michael E. Greenberg Neurobiology Program Children’s Hospital and Harvard Medical School, Boston, USA Experience plays a crucial role in the development of the nervous system by promoting the maturation, and elimination of synapses. We have found that synaptic stimulation by promoting calcium influx into neurons regulates a complex gene program that controls aspects of synapse development. We have identified a signaling network that conveys the calcium signal from the site of entry to the nucleus where transcription is activated. Of the activity-regulated genes, brain derived neurotrophic factor (BDNF) is one of the best characterized. Studies of BDNF gene regulation indicate the presence of a repressor complex bound to the BDNF promoter prior to stimulation that becomes replaced by an activator complex in stimulated cells. Mutations in MeCP2 a component of the BDNF repressor complex lead to Rett Syndrome an X linked human disorder marked by severe cognitive and motor impairment. Mutations in additional components of the activity-dependent signaling network also lead to cognitive impairment in humans indicating a critical role for this gene program in controlling normal cognitive function.
0168-0102/$ – see front matter doi:10.1016/j.neures.2007.06.001
PL3 Frontal lobe mechanisms for rules and control Earl K. Miller The Picower Institute for Learning and Memory, RIKEN-MIT Neuroscience Research Center, and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, USA What controls your thoughts? How do you focus attention? How do you know how to act while dining in a restaurant? This is cognitive control, the ability to organize thought and action around goals. Results from our laboratory have shown that neurons in the prefrontal cortex and related brain areas have properties commensurate with a role in “executive” brain function. They are involved in directing attention, in recalling stored memories, predicting reward value, and they integrate the diverse information needed for a given goal. Perhaps most importantly, they transmit acquired knowledge. Their activity reflects learned task contingencies, concepts and rules. In short, they seem to underlie our internal representations of the “rules of the game”. This may provide the foundation for the complex behavior of primates, in whom this structure is most elaborate.
Abstracts of the 30th Annual Meeting of the Japan Neuroscience Society (Neuro 2007)
PL1 Glycine neurotransmission: From molecules to mice and disease Heinrich Betz 1 Neurochemistry, Max-Planck-Institute for Brain Research, Frankfurt, Germany Glycine is a major inhibitory neurotransmitter in the mammalian CNS. Upon Ca2+ -triggered release from glycinergic nerve terminals, glycine causes postsynaptic inhibition by binding to strychnine-sensitive glycine receptors (GlyRs) which exist in different (␣1–␣4) isoforms. Synaptic localization of GlyRs requires the scaffolding protein gephyrin which also is found at GABAergic synapses. Glycinergic neurotransmission is terminated by the reuptake of glycine into glycinergic nerve terminals and neighbouring glial cells via the Na+ /Cl− -dependent glycine transporters, GlyT1 and GlyT2. We have used gene targeting to dissect the physiological functions of distinct GlyR subtypes and GlyT isoforms. Accordingly, ␣1 GlyRs are mainly involved in motor control, whereas ␣3 GlyRs are crucial for pain sensitization. Inactivation of the gephyrin gene causes lethality due to a loss of postsynaptic GlyR (and GABAA receptor) clustering. Similarly, ablation of the GlyT1 and GlyT2 genes is postnatally lethal. Our results underline the vital roles of glycinergic neurotransmission and mutant mice deficient in distinct GlyR and establish GlyT isoforms as animal models of hereditary human disorders caused by mutations in GlyR, gephyrin and GlyT genes.
PL2 Signaling networks that control synapse development and cognitive function Michael E. Greenberg Neurobiology Program Children’s Hospital and Harvard Medical School, Boston, USA Experience plays a crucial role in the development of the nervous system by promoting the maturation, and elimination of synapses. We have found that synaptic stimulation by promoting calcium influx into neurons regulates a complex gene program that controls aspects of synapse development. We have identified a signaling network that conveys the calcium signal from the site of entry to the nucleus where transcription is activated. Of the activity-regulated genes, brain derived neurotrophic factor (BDNF) is one of the best characterized. Studies of BDNF gene regulation indicate the presence of a repressor complex bound to the BDNF promoter prior to stimulation that becomes replaced by an activator complex in stimulated cells. Mutations in MeCP2 a component of the BDNF repressor complex lead to Rett Syndrome an X linked human disorder marked by severe cognitive and motor impairment. Mutations in additional components of the activity-dependent signaling network also lead to cognitive impairment in humans indicating a critical role for this gene program in controlling normal cognitive function.
0168-0102/$ – see front matter doi:10.1016/j.neures.2007.06.001
PL3 Frontal lobe mechanisms for rules and control Earl K. Miller The Picower Institute for Learning and Memory, RIKEN-MIT Neuroscience Research Center, and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, USA What controls your thoughts? How do you focus attention? How do you know how to act while dining in a restaurant? This is cognitive control, the ability to organize thought and action around goals. Results from our laboratory have shown that neurons in the prefrontal cortex and related brain areas have properties commensurate with a role in “executive” brain function. They are involved in directing attention, in recalling stored memories, predicting reward value, and they integrate the diverse information needed for a given goal. Perhaps most importantly, they transmit acquired knowledge. Their activity reflects learned task contingencies, concepts and rules. In short, they seem to underlie our internal representations of the “rules of the game”. This may provide the foundation for the complex behavior of primates, in whom this structure is most elaborate.