シナプス・神経回路の活動調節機構 Balancing synapses and circuit activity
O1-7-2-1 視覚剥奪ラットの体性感覚野における側方抑制の強化 Visual deprivation enhances lateral inhibition in the rat barrel cortex ○中島和希1, 實木亨1, 高橋琢哉1 ○Waki Nakajima1, Susumu Jitsuki1, Takuya Takahashi1 横浜市立大学大学院　医学研究科　生理学1 Department of physiology, Yokohama City University, Yokohama1 Loss of one type of sensory input can cause improved functionality of other sensory systems. This form of plasticity, cross-modal plasticity, is well established (Bavelier and Neville, 2002; Goel et al., 2006). We have previously shown that visual deprivation (VD) induces trafficking of the AMPA-type glutamate receptors into layer 4 to layer 2/3 synapses (Jitsuki et al., 2011). VD leads to sharpening of the functional whisker-barrel map at layer 2/3. However, the mechanism maintaining sharpened functional whisker barrel map is still unclear.In this study, we found that VD increases evoked miniature inhibitory postsynaptic current (evoked mIPSC) and IPSC/excitatory postsynaptic current (EPSC) ratio in the layer 2/3 to 2/3 synapses (lateral pathway), but not in the layer 4 to 2/3 (vertical pathway). Moreover, VD sharpened functional whisker-barrel map in layer 2/3 of the barrel cortex. These results indicate that VD enhances lateral inhibition and that maintains sharpened neural circuits in the barrel cortex.	O1-7-2-2 線条体ドパミンシナプスはGABAシナプスと共通のポストシナプス分子を発現する So-called "dopamine synapses" are heterologous contacts that tether midbrain dopaminergic afferents to striatal neurons via GABAergic postsynaptic machineries ○内ヶ島基政1, 渡辺雅彦1 ○Motokazu Uchigashima1, Masahiko Watanabe1 北海道大学大学院 医学研究科 解剖発生学1 Dept. of Anat., Grad. Sch. of Med., Hokkaido Univ., Sapporo, Japan1 Dopaminergic (DA) afferents frequently form symmetrical contacts with striatal neurons, being often referred to as dopamine synapses. Although striatal neurons richly express dopamine receptors D1R and D2R, molecular organization for DA transmission remains unclear at dopamine synapses. To address this issue, we applied immunofluorescence and immunoelectron microscopy to the mouse dorsolateral striatum. Symmetrical contacts were found between DA afferents and somatodendritic elements of striatal neurons, especially, medium spiny neurons. D1R and D2R were widely dispersed on the extrasynaptic membrane of somatodendritic elements of medium spiny neurons and some nerve terminals, showing no particular clustering at, or accumulation toward, DA contacts. Instead, we found selective localization at contact sites of GABAergic postsynaptic molecules, including GABAA receptor α1 subunit, scaffolding protein gephyrin, and synaptic adhesion molecule neuroligin-2. The labeling density of these GABAergic molecules was similar between DA contacts and conventional GABAergic synapses. In the presynaptic side, DA contacts expressed plasmalemmal dopamine transporter DAT and active zone protein CAST, but lacked detectable immunoreactivities for GABA and its synthetic enzyme GAD. Thus, DA contacts are provided with DA molecules in the presynaptic side, and GABAergic molecules in the postsynaptic side. These findings suggest that DA afferents utilize GABAergic postsynaptic machineries to tether them to particular striatal neurons, and that DA transmission in the striatum adopts the mode of volume transmission principally. We propose that such a heterologous tethering will be a novel strategy to generate and increase the target specificity of neuromodulation.
O1-7-2-3 Inhibitory Spike-Timing Dependent Plasticity supports efficient spike transmission ○Florence Kleberg1, Gilson Matthieu1, Tomoki Fukai1 RIKEN BSI, Tomoki Fukai Lab for Neural Circuit Theory1 In cortical circuits, excitatory and inhibitory inputs onto a neuron are believed to be globally balanced. Balancing within signaling pathways, the hypothetical 'detailed balance', allows for gating specific signals from these pathways (Vogels and Abbott, 2009).We use a simple model with Spike-Timing Dependent Plasticity (STDP), simultaneously in both excitatory and inhibitory synapses onto a single postsynaptic neuron (eSTDP and iSTDP, respectively).We show that eSTDP and iSTDP combined can achieve both global and detailed balance. In both cases, inhibitory inputs increase the overall single-to-noise ratio of the postsynaptic response. Additionally, in the detailed balanced regime, inhibition sharpens the temporal response of the postsynaptic neuron, depending on the delay with which inhibition arrives and the correlation structure of the inputs. We examine the properties of an iSTDP learning rule which optimizes this latter configuration.	O1-7-2-4 Activity-Dependent Regulation of Feed-Forward Inhibition in the Dentate Gyrus ○Cheng-Chang Lien1, Yu-Chao Liu1, Irene H Cheng1 National Yang-Ming University1 The dentate gyrus (DG) serves as a gateway to control information transfer from the cortex to the hippocampus. Cortical afferent inputs provide direct excitation with subsequent feed-forward inhibition (FFI) onto granule cells (GCs) of the DG. GABAergic (γ-aminobutyric acid-releasing) inhibitory interneurons, which comprise two distinct classes of interneurons: fast-spiking (FS) and non-fast spiking (non-FS) cells, mediate FFI onto GCs. Detailed morphological analysis revealed that FS cells are soma-targeting interneurons, whereas non-FS cells are dendrite-targeting interneurons. These two types of interneurons are preferentially recruited by the specific activity patterns of their inputs and exert distinct spatial inhibition onto GCs. However, it is unclear how FS and non-FS interneurons transform their activities to inhibitory output. Here, we show that FFI is dominated by reliable somatic FFI during sparse afferent inputs, whereas pronounced dendritic FFI is rapidly switched on during high-level bursting activities. This fast state-dependent GABA release is reversible and sensitive to presynaptic activities and is mediated by 4-aminopyridine-sensitive K+ channels. Such dynamic regulation of dendritic FFI may act as an activity-dependent filter to prevent overt excitation to the DG and set the balance of excitation and inhibition onto the GCs.

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