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Trafficking, regulation, and function of NMDA-type glutamate receptors
S28
Abstracts
regional gray matter volume in most of the regions revealing larger in female sexdimorphism. Third study demonstrates the correlation between smaller-than normal volume of pIFG and worse function of social communication in the males with autism. These results suggest that sexually dimorphic factors may affect the neurodevelopment of these “social-brain” regions, leading to the pathophysiology of autism. doi:10.1016/j.neures.2009.09.1649
SY3-B1-1 The relationship between integrated information theory and the neuronal correlates of consciousness Christof Koch California Institute of Technology, USA Integrated Information Theory (IIT) (Balduzzi & Tononi 2008) posits that consciousness is the irreducible property of ‘complex’ networks of causally interacting components. IIT defines a fundamental quantity, integrated information (expressed in bits), which captures to what extent a system is more than a collection of parts. IIT provides a principled way of characterizing a quale, a particular conscious experience. Recently, brain scientists have initiated an empirical program searching for the neuronal correlates of consciousness (NCC), the minimal set of neuronal mechanisms jointly sufficient for any one conscious experience (Crick & Koch 1995). IIT emphasizes global properties of the brain while the NCC stresses local properties, such as particular neuro-anatomical connections or firing states. I will emphasize how these two different approaches are complementary rather than conflicting. I will discuss the relationship between activity in specific cortical regions and the quale as defined by IIT, and how the meaning of any one consciously perceived stimulus will be affected by the loss of specific neuronal populations. doi:10.1016/j.neures.2009.09.1650
SY3-B1-2 Consciousness and cognitive access Ned Block Dept Philosophy, New York University, USA Understanding the relation between consciousness and cognitive access to consciousness is a prerequisite for finding consciousness in the brain. If consciousness is distinct from cognitive access to it, then in our efforts to find the neural correlate of consciousness we may be finding only the neural correlate of the cognitive processes underlying reporting consciousness. This issue will be approached by way of a contrast between (1) the claim that conscious perception is “rich” we really do see the vast array of things we seem to see and (2) the claim that conscious perception is “sparse” we only see a few objects or locations despite the illusion of a rich conscious field. The claim of this paper is that only by resolving this issue can we get clear about the relation between consciousness and cognitive access to it. doi:10.1016/j.neures.2009.09.1651
SY3-B1-3 Volition and the functions of consciousness Hakwan Lau Columbia University, USA It is often assumed that conscious intentions are the causes of motor actions, and that awareness of sensory stimuli is essential to flexible control of behavior. I present data that seem to challenge these views. Using fMRI, we have shown that activity in the pre-supplementary motor area (pre-SMA) reflects motor intentions. Applying transcranial magnetic stimulation (TMS) can alter the reported onset of the experience of intention. Importantly, this was true even when TMS was applied at 200 ms after the action was completed, as if the experience of intention was not fully determined even up to that point. This is compatible with the theory that the experience of intention is just an illusion constructed after the action. In another study we tested if cognitive control can be biased by visual stimuli that are not consciously perceived. It was previously assumed that deciding and preparing for a certain task requires conscious control. However we showed that unconscious visual stimuli could bias this process, and “trick” the brain into using the wrong neural resources for task preparation and execution. Together, these results raise the question of why do cognitive processes need to be conscious at all. doi:10.1016/j.neures.2009.09.1652
SY3-B1-4 Awareness and decision in monkey with blindsight Masatoshi Yoshida 1,2 , Kana Takaura 1,2 , Tadashi Isa 1,2,3 1
Department Dev. Physiol., Nat’l Inst. Physiol. Sci., Okazaki, Japan; 2 Sch. 3 CREST, JST, Life Sci., Grad. University Adv. Stud., Hayama, Japan; Kawaguchi, Japan
We examined behavioral report of visual awareness in monkeys with unilateral V1 lesions and sought neural activity specific to blindsight. First, the monkeys were tested with a yes-no (YN) task, in which detection of the targets was required. The performance of the YN task indicates residual detection in the affected hemifield. Single-unit recording from the superior colliculus (SC) revealed that, in the ipsilesional SC, the neural response to the visual stimuli in the affected hemifield was larger when the monkeys successfully detect the targets than when the monkeys missed them. Finally, we examined decision process of these monkeys using a forced-choice (FC) task. We modeled the distribution of saccadic reaction times by a modified diffusion model and obtained evidence that the decision threshold in the affected hemifield was lower than that in the normal hemifield. Taken together, these results suggest that V1 lesion affect awareness and decision and that neural activity in the SC is a neural correlate of reduced awareness. doi:10.1016/j.neures.2009.09.1653
SY3-B2-1 Trafficking, regulation, and function of NMDA-type glutamate receptors Andres Barria University of Washington, USA Calcium-permeable NMDA-type glutamate receptors (NMDA-Rs) play critical roles during induction of synaptic plasticity, brain development, and pathology. We study the molecular events that control type and number of NMDA-Rs at synapses and the role of different NMDA-R subunits in defining synaptic properties.Synapses in many brain regions undergo a switch in the subunit composition of NMDA-Rs from predominantly containing NR2B to predominantly containing NR2A. This switch requires synaptic activity or sensory experience, alters receptor function, and it is thought to affect learning and memory. The NR2B subunit is expressed prenatally, its incorporation into synapses is activity-independent, and can move laterally between synaptic and extrasynaptic pools. In contrast, NR2A is expressed later in development, is incorporated into synapses in an activity-dependent manner, accumulates intracellularly when activity is blocked, and shows less surface motility. I will discuss the latest advances on our understanding of the process of synaptic incorporation of NMDA-Rs and the role played by different NR2 subunits in regulating trafficking and function. doi:10.1016/j.neures.2009.09.1654
SY3-B2-2 New mechanisms regulating the number of AMPA receptors at synapses Michisuke Yuzaki, Shinji Matsuda School of Medicine, Keio University, Japan It has become increasingly clear that memory is stored at least partly as changes in the number of postsynaptic AMPA receptors. In the cerebellum, long-term depression (LTD) of synaptic transmission at parallel fiber-Purkinje cell synapses serve as the basis of certain forms of motor learning. During LTD, postsynaptic AMPA receptors are thought to be phosphorylated by protein kinase C, detached from an anchoring protein GRIP, endocytosed in a clathrin-dependent manner, and bound to another anchoring protein PICK1. However, it remains unclear how the endocytic process per se is regulated during LTD. For example, how is an adaptor protein complex AP-2 recruited to the postsynaptic site? Is phosphatidylinositol 4,5-bisphosphate regulated in the postsynaptic membrane during LTD? How about small GTPases, such as Arf and Rab, which generally define the identity of vesicles during membrane traffic? We tried to address these questions by investigating mutant mice that showed abrogated LTD. In this talk, I would like to introduce our recent data and discuss these issues. doi:10.1016/j.neures.2009.09.1655
SY3-B2-3 Experience dependent synaptic delivery of AMPA receptors Takuya Takahashi Dept Physiol, Yokohama City Univ, Yokohama, Japan The molecular and cellular mechanisms underlying experience-dependent plasticity of brain function are poorly understood. Recent in vitro studies have identified the regulated trafficking of AMPA receptors (-Rs) into synapses as a major molecular component of neural plasticity. Here we ask if experience-driven plasticity in the developing rat barrel cortex is accompanied by and/or requires AMPA-R delivery to synapses. By combining in vivo gene delivery with in vitro recordings, we show that experience drives recombinant GluR1, an AMPA-R subunit, into synapses formed between layer 4 and layer 2/3 neurons.These studies show that synaptic delivery of AMPA-Rs contributes to plasticity driven by natural stimuli in the mammalian
Abstracts
regional gray matter volume in most of the regions revealing larger in female sexdimorphism. Third study demonstrates the correlation between smaller-than normal volume of pIFG and worse function of social communication in the males with autism. These results suggest that sexually dimorphic factors may affect the neurodevelopment of these “social-brain” regions, leading to the pathophysiology of autism. doi:10.1016/j.neures.2009.09.1649
SY3-B1-1 The relationship between integrated information theory and the neuronal correlates of consciousness Christof Koch California Institute of Technology, USA Integrated Information Theory (IIT) (Balduzzi & Tononi 2008) posits that consciousness is the irreducible property of ‘complex’ networks of causally interacting components. IIT defines a fundamental quantity, integrated information (expressed in bits), which captures to what extent a system is more than a collection of parts. IIT provides a principled way of characterizing a quale, a particular conscious experience. Recently, brain scientists have initiated an empirical program searching for the neuronal correlates of consciousness (NCC), the minimal set of neuronal mechanisms jointly sufficient for any one conscious experience (Crick & Koch 1995). IIT emphasizes global properties of the brain while the NCC stresses local properties, such as particular neuro-anatomical connections or firing states. I will emphasize how these two different approaches are complementary rather than conflicting. I will discuss the relationship between activity in specific cortical regions and the quale as defined by IIT, and how the meaning of any one consciously perceived stimulus will be affected by the loss of specific neuronal populations. doi:10.1016/j.neures.2009.09.1650
SY3-B1-2 Consciousness and cognitive access Ned Block Dept Philosophy, New York University, USA Understanding the relation between consciousness and cognitive access to consciousness is a prerequisite for finding consciousness in the brain. If consciousness is distinct from cognitive access to it, then in our efforts to find the neural correlate of consciousness we may be finding only the neural correlate of the cognitive processes underlying reporting consciousness. This issue will be approached by way of a contrast between (1) the claim that conscious perception is “rich” we really do see the vast array of things we seem to see and (2) the claim that conscious perception is “sparse” we only see a few objects or locations despite the illusion of a rich conscious field. The claim of this paper is that only by resolving this issue can we get clear about the relation between consciousness and cognitive access to it. doi:10.1016/j.neures.2009.09.1651
SY3-B1-3 Volition and the functions of consciousness Hakwan Lau Columbia University, USA It is often assumed that conscious intentions are the causes of motor actions, and that awareness of sensory stimuli is essential to flexible control of behavior. I present data that seem to challenge these views. Using fMRI, we have shown that activity in the pre-supplementary motor area (pre-SMA) reflects motor intentions. Applying transcranial magnetic stimulation (TMS) can alter the reported onset of the experience of intention. Importantly, this was true even when TMS was applied at 200 ms after the action was completed, as if the experience of intention was not fully determined even up to that point. This is compatible with the theory that the experience of intention is just an illusion constructed after the action. In another study we tested if cognitive control can be biased by visual stimuli that are not consciously perceived. It was previously assumed that deciding and preparing for a certain task requires conscious control. However we showed that unconscious visual stimuli could bias this process, and “trick” the brain into using the wrong neural resources for task preparation and execution. Together, these results raise the question of why do cognitive processes need to be conscious at all. doi:10.1016/j.neures.2009.09.1652
SY3-B1-4 Awareness and decision in monkey with blindsight Masatoshi Yoshida 1,2 , Kana Takaura 1,2 , Tadashi Isa 1,2,3 1
Department Dev. Physiol., Nat’l Inst. Physiol. Sci., Okazaki, Japan; 2 Sch. 3 CREST, JST, Life Sci., Grad. University Adv. Stud., Hayama, Japan; Kawaguchi, Japan
We examined behavioral report of visual awareness in monkeys with unilateral V1 lesions and sought neural activity specific to blindsight. First, the monkeys were tested with a yes-no (YN) task, in which detection of the targets was required. The performance of the YN task indicates residual detection in the affected hemifield. Single-unit recording from the superior colliculus (SC) revealed that, in the ipsilesional SC, the neural response to the visual stimuli in the affected hemifield was larger when the monkeys successfully detect the targets than when the monkeys missed them. Finally, we examined decision process of these monkeys using a forced-choice (FC) task. We modeled the distribution of saccadic reaction times by a modified diffusion model and obtained evidence that the decision threshold in the affected hemifield was lower than that in the normal hemifield. Taken together, these results suggest that V1 lesion affect awareness and decision and that neural activity in the SC is a neural correlate of reduced awareness. doi:10.1016/j.neures.2009.09.1653
SY3-B2-1 Trafficking, regulation, and function of NMDA-type glutamate receptors Andres Barria University of Washington, USA Calcium-permeable NMDA-type glutamate receptors (NMDA-Rs) play critical roles during induction of synaptic plasticity, brain development, and pathology. We study the molecular events that control type and number of NMDA-Rs at synapses and the role of different NMDA-R subunits in defining synaptic properties.Synapses in many brain regions undergo a switch in the subunit composition of NMDA-Rs from predominantly containing NR2B to predominantly containing NR2A. This switch requires synaptic activity or sensory experience, alters receptor function, and it is thought to affect learning and memory. The NR2B subunit is expressed prenatally, its incorporation into synapses is activity-independent, and can move laterally between synaptic and extrasynaptic pools. In contrast, NR2A is expressed later in development, is incorporated into synapses in an activity-dependent manner, accumulates intracellularly when activity is blocked, and shows less surface motility. I will discuss the latest advances on our understanding of the process of synaptic incorporation of NMDA-Rs and the role played by different NR2 subunits in regulating trafficking and function. doi:10.1016/j.neures.2009.09.1654
SY3-B2-2 New mechanisms regulating the number of AMPA receptors at synapses Michisuke Yuzaki, Shinji Matsuda School of Medicine, Keio University, Japan It has become increasingly clear that memory is stored at least partly as changes in the number of postsynaptic AMPA receptors. In the cerebellum, long-term depression (LTD) of synaptic transmission at parallel fiber-Purkinje cell synapses serve as the basis of certain forms of motor learning. During LTD, postsynaptic AMPA receptors are thought to be phosphorylated by protein kinase C, detached from an anchoring protein GRIP, endocytosed in a clathrin-dependent manner, and bound to another anchoring protein PICK1. However, it remains unclear how the endocytic process per se is regulated during LTD. For example, how is an adaptor protein complex AP-2 recruited to the postsynaptic site? Is phosphatidylinositol 4,5-bisphosphate regulated in the postsynaptic membrane during LTD? How about small GTPases, such as Arf and Rab, which generally define the identity of vesicles during membrane traffic? We tried to address these questions by investigating mutant mice that showed abrogated LTD. In this talk, I would like to introduce our recent data and discuss these issues. doi:10.1016/j.neures.2009.09.1655
SY3-B2-3 Experience dependent synaptic delivery of AMPA receptors Takuya Takahashi Dept Physiol, Yokohama City Univ, Yokohama, Japan The molecular and cellular mechanisms underlying experience-dependent plasticity of brain function are poorly understood. Recent in vitro studies have identified the regulated trafficking of AMPA receptors (-Rs) into synapses as a major molecular component of neural plasticity. Here we ask if experience-driven plasticity in the developing rat barrel cortex is accompanied by and/or requires AMPA-R delivery to synapses. By combining in vivo gene delivery with in vitro recordings, we show that experience drives recombinant GluR1, an AMPA-R subunit, into synapses formed between layer 4 and layer 2/3 neurons.These studies show that synaptic delivery of AMPA-Rs contributes to plasticity driven by natural stimuli in the mammalian