シンポジウム（Symposium）

Symposium Compartmentalized dendritic integration: from molecular mechanisms to behavior シンポジウム樹状突起におけるシナプス入力の局所統合

7月28日（日）8:48～9:15　第4会場（朱鷺メッセ　3F　301） 4S04m-1 Differential pre and postsynaptic contributions in setting the synaptic strengths across a dendritic tree in hippocampal neurons Yukiko Goda（合田裕紀子）¹，Mathieu Letellier（Letellier Mathieu）² ¹理化学研究所　脳神経科学研究センター ²Institut Interdisciplinaire de Neurosciences, UMR5297, Bordeaux, FRANCE The efficacy of synaptic transmission, called synaptic strength and its use-dependent changes are crucial for how the brain perceives the environment, learns and stores memories. The highly diverse synaptic strengths found in a given connection at a particular moment in time in the hippocampal circuit may therefore reflect varied information coding and on-going learning associated with hippocampal-dependent tasks. However, at the level of individual synapses, the cellular and molecular basis by which synaptic strengths are set and controlled in relationship to other synapses sharing the connection, which then shape the behavior of the circuit, remain to be clarified. Here we have taken a reductionist approach followed by confirmation in a more physiological model, and combined patch-clamp recordings with live-cell imaging in cultured hippocampal neurons and organotypic slices to gain insights into the basic cellular rules that drive the activity-dependent spatial distribution of pre and postsynaptic strengths across incoming axons onto a target dendrite. Under basal conditions, both pre and postsynaptic strengths cluster on single dendritic branches according to the identity of the presynaptic neurons, consistent with the ability of single dendritic branches to transmit input-specific information. Moreover, stimulating a single presynaptic neuron induces input-specific and dendritic clustering of presynaptic strengths, which accompanies a multiplicative global downscaling of postsynaptic strengths. Our findings highlight a potential homeostatic mechanism by which the rapid and global downscaling of postsynaptic strengths compensates for input-specific presynaptic plasticity.		7月28日（日）9:15～9:35　第4会場（朱鷺メッセ　3F　301） 4S04m-2 発達期における樹状突起コンパートメント特異的スパイン密度制御 Takeshi Imai（今井猛）九大医 Dendrites receive most of their excitatory synaptic inputs from dendritic spines. It has been generally believed that the dendritic spine density in the mammalian cortex increases during childhood, and then declines during adolescence to form mature circuits. Its dysregulation is known as a cause of various neuropsychiatric diseases. However, their distribution on a whole-neuron scale has not been fully established, due to technical limitations. Here we describe a comprehensive map of dendritic spines in layer 5 cortical pyramidal neurons in mice using SeeDB2 and volumetric super-resolution imaging. We found that the spine density is highly biased along their apical dendrites (~10-fold), forming a spine density "hotspot". In contrast, the spine density was less biased in layer 2/3 neurons and basal dendrites of layer 5 neurons. We also found that the spine density continues to increase at the hotspot during adolescence. Other parts of the dendrites underwent a moderate reduction in spine density during that stage, most likely as a result of cortical volume expansion (~1.5 fold). Spine accumulation to the hotspot during adolescence was specifically impaired in NMDAR knockout, suggesting a specialized molecular mechanism for spine accumulation during this stage. Thus, the spine density is differentially controlled among dendritic compartments rather than simply reduced, and the spine accumulation to the hotspot is a hallmark of cortical circuit maturation during adolescence.

7月28日（日）9:35～9:55　第4会場（朱鷺メッセ　3F　301） 4S04m-3 樹状突起への時空間特異的グルタミン酸入力が視覚運動の方向と速度を計算する Keisuke Yonehara（米原圭祐）¹，Akihiro Matsumoto（松本彰弘）¹，Kevin Briggman（Briggman Kevin）² ¹DANDRITE, Dept Biomed, Aarhus University, Aarhus, Denmark ²Center of Advanced European Studies And Research (caesar), Bonn, Germany The detection of visual stimuli moving in dynamically changing velocities is a fundamental function of visual system. The retina is the first stage in the mammalian nervous system in which visual motion is computed. Retinal direction-selective (DS) ganglion cells preferentially show spiking responses to visual stimulus moving in a particular direction (preferred direction), and show less spiking to the opposite, null direction. How motion speed and direction are computed together at the cellular levels remains largely unknown. Here we suggest a circuit mechanism by which excitatory inputs to DS cells in the mouse retina become sensitive to the speed and direction of image motion. Electrophysiological and two-photon glutamate imaging experiments provide evidence that the dendrites of ON DS cells receive spatially offset and asymmetrically filtered glutamatergic inputs along their motion preference axis from bipolar cells with distinct release dynamics. Our computational model shows that, with such spatiotemporal input structure, the amplitude of summated inputs become sensitive for motion speed and direction by preferred direction enhancement mechanism. Our results highlight the role of excitatory mechanism in retinal motion computation with which feature selectivity emerges from non-selective inputs.		7月28日（日）9:55～10:15　第4会場（朱鷺メッセ　3F　301） 4S04m-4 Subclass-specific dendritic activation of cortical pyramidal neurons gates tactile perception in mice Naoya Takahashi（高橋直矢），Matthew Larkum（Larkum Matthew） Institute for Biology, Humboldt University of Berlin, Berlin, Germany The role of perception is to detect relevant sensory stimuli in a given behavioral context to guide adaptive behaviors. There is as yet no consensus concerning the neural basis of perception and how it operates at the cellular and circuit level. Recently, we showed that the threshold for perceptual detection of whisker deflection is correlated with active calcium currents in the apical dendrites of an unidentified subset of layer 5 (L5) pyramidal neurons in the primary somatosensory cortex (S1) in mice (Takahashi et al., 2016). In the current study we genetically targeted L5 neuron subclasses in S1 based on their projection type, and found that the activation of apical dendrites was highly selective in neurons that project to subcerebral regions when the mice detected whisker deflections, but not in intratelencephalic-projecting neurons (Takahashi et al., unpublished). The apical calcium currents were strongly modulated by behavioral context. Subclass-specific manipulation of dendritic activity proved the causal relationship between apical calcium currents in subcerebral-projecting neurons and the perceptual threshold of the animal. Our results suggest that an active dendritic mechanism plays a key role in facilitating the transmission of sensory information to subcerebral regions in a context-dependent manner, instructing subcerebral processes to guide behaviors.

7月28日（日）10:15～10:42　第4会場（朱鷺メッセ　3F　301） 4S04m-5 Learning and sleep-dependent branch-specific dendritic spine plasticity in the cortex Wenbiao Gan（Gan Wenbiao）¹，Zhiwei Xu（Xu Zhiwei）¹，Yanmei Zhou（Zhou Yanmei）^1,3，Cora Lai（Lai Cora）²，Guang Yang（Yang Guang）³ ¹New York University School of Medicine ²School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong ³Department of Anesthesiology, Columbia University Medical School Experience-dependent synaptic plasticity is critical for information encoding and storage. How learning-induced synaptic plasticity is distributed and maintained within complex neuronal networks remains unclear. Dendritic spines are the postsynaptic sites of most excitatory synapses in the mammalian brain. Using in vivo two-photon microscopy, we examined the effects of motor and fear learning experiences on dendritic spine remodeling in the mouse cortex. We found that new spines are formed on different sets of dendritic branches of layer 5 pyramidal neurons in the motor cortex in response to different motor learning tasks. This branch-specific spine formation facilitates the maintenance of new spines when multiple tasks are learned. In addition, we found that fear conditioning by an auditory cue paired with footshock induces dendritic spine elimination on a subset of dendritic branches of layer 5 pyramidal neurons in the motor cortex. Subsequent fear extinction induces dendritic spine formation in a cue- and branch-specific manner. Interestingly, during rapid eye movement (REM) sleep, there is a substantial increase in the number of dendritic calcium spikes on apical dendrites of layer 5 pyramidal neurons. Blockade of dendritic calcium spikes during REM sleep reduces branch-specific spine plasticity induced by motor learning and fear conditioning. Together, these findings suggest that learning and subsequent REM sleep induce dendritic branch-specific synaptic remodeling, resulting in experience-specific information storage.