シナプス可塑性 Synaptic Plasticity
P2-2-1 シナプスタギング・キャプチャーの段階的配送仮説 Stepwise delivery hypothesis for synaptic tagging and capture ○岡田大助1, 菅谷津貴子1 ○Daisuke Okada1, Tsukiko Sugaya1 北里大学医学部生化学1 Dept Biochem, Kitasato Univ, School of Medicine1 Late-phase of synaptic plasticity, implicated in long-term memory, depends on de novo protein synthesis in soma and dendrites. Newly synthesized plasticity-related proteins (PRPs) are believed to play pivotal roles in reconstruction of the postsynaptic protein complexes in late-plasticity. Thus, late-phase plasticity takes place in synapses where PRPs are delivered. To explain the input-specificity of late-plasticity, the synaptic tagging hypothesis was proposed, in which soma-derived PRPs prevailed in most dendrites and were specifically captured only in "tagged" synapses. We previously observed the spine entry of soma-derived Vesl-1S (Homer1a) protein, a postsynaptic PRP synthesized in soma, using an EGFP-fused protein (VE), and demonstrated that spine entry of VE conforms to the synaptic tagging hypothesis. However, in these experiments, spine entry was estimated from ensemble statistics, thus precise mechanisms underlying spine entry was not clear. In the present study, we directly observed VE entry into spines in rat hippocampal neurons by the use of fluorescence recovery after photobleaching (FRAP) techniques. VE fluorescence in single spines was specifically attenuated by laser beams, and time-dependent changes in fluorescence intensity in bleached and unbleached spines were measured. In normal ACSF, bleached spine consistently showed spontaneous FRAP, which was not inhibited by APV, CNQX, EGTA and TTX, but completely blocked by dichlorokynurenic acid (DCKA), an antagonist of D-serine site on GluN1 receptor. Inhibition by DCKA was reversed by addition of D-serine. On the other hand, spontaneous FRAP was not observed after incubation with an NO synthase blocker for 2 hrs. PKG activation enhanced spine fluorescence even in the presence of DCKA or after long-term NO blockade, suggesting two distinct mechanisms are working. We hypothesized that VE protein arrested in the PKG-dependent pool is transferred to entire spine head by a D-serine-dependent mechanism.	P2-2-2 デルタ2グルタミン酸受容体はAMPA受容体のセリンおよびチロシンのリン酸化を制御することによって小脳長期抑圧の誘導に寄与する GluD2 serves as a gatekeeper of cerebellar LTD by regulating balance between serine and tyrosine phosphorylation of AMPA receptors ○幸田和久1, 掛川渉1, 松田信爾1, 山本雅2, 平野久3, 柚崎通介1 ○Kazuhisa Kohda1, Wataru Kakegawa1, Shinji Matsuda1, Tadashi Yamamoto2, Hisashi Hirano3, Michisuke Yuzaki1 慶應義塾大学医学部生理学（I)教室1, 沖縄科学技術大学院大学 細胞シグナルユニット2, 横浜市立大学相関科学研究室3 Department of Physiology, School of Medicine, Keio University, Tokyo1, Cell Signal Unit, Okinawa Institute of Science and Technology Graduate University, Okinawa2, Division of Functional Proteomics, Yokohama City University, Yokohama3 Long-term depression (LTD), a form of synaptic plasticity underlying learning and memory process, has been discovered in various brain regions and is commonly caused by clathrin-dependent endocytosis of postsynaptic AMPA-type glutamate receptors (GluAs). Cerebellar LTD is unique in that it requires the presence of another class of glutamate receptors, the &delta2; glutamate receptor (GluD2), which is predominantly expressed at parallel fiber (PF)-Purkinje cell synapses. GluD2-null mice display impaired LTD and motor learning in addition to morphological abnormalities in PF-Purkinje cell synapses. Although it was recently demonstrated that interactions of GluD2 and Cbln1, secreted from PF terminals, played crucial roles in formation and maintenance of PF-Purkinje synapses, why and how cerebellar LTD is regulated by GluD2 still remains unclear. Here we demonstrated that the activity-dependent phosphorylation of serine 880 (S880) in the GluA2 subunit, which is an essential step for GluA endocytosis during LTD induction, was impaired in GluD2-null cerebellum. In contrast, the basal phosphorylation level of tyrosine 876 (Y876) in GluA2 was increased in GluD2-null cerebellum. An in vitro phosphorylation assay revealed that Y876 phosphorylation inhibited subsequent S880 phosphorylation. Virus-mediated transduction of the GluA2 mutants revealed that Y876 dephosphorylation was sufficient to restore S880 phosphorylation and LTD induction in GluD2-null Purkinje cells. Furthermore, the protein tyrosine phosphatase PTPMEG, which binds to the C-terminus of GluD2, directly dephosphorylated Y876. These data indicate that, interacting with PTPMEG, GluD2 gates LTD by regulating tyrosine dephosphorylation status of GluA2.
P2-2-3 Cbln1-GluD1シグナリングは海馬CA1錐体細胞で長期シナプス可塑性を調整する Cbln1-GluD1 signaling modulates long-term synaptic plasticity in hippocampal CA1 pyramidal cells ○岩室賢治1, 掛川渉1, 幸田和久1, 柚崎通介1 ○Kenji Iwamuro1, Wataru Kakegawa1, Kazuhisa Kohda1, Michisuke Yuzaki1 慶應義塾大学医学部生理学教室1 Dept Physiol, Univ of Keio, Tokyo1 Cbln1, which is released from cerebellar granule cells, plays a crucial role in synapse formation and synaptic plasticity by binding to its postsynaptic receptor GluRdelta2 (GluD2) located on Purkinje cell dendrites. Cbln1 is also expressed in the entorhinal cortex, which sends axons as the perforant path to the molecular layer of the dentate gyrus and CA1 stratum lacunosum moleculare in the hippocampus. While GluD2 is not expressed in the hippocampus, we recently found that its family member GluRdelta1 (GluD1) is expressed in the corresponding regions. Although Cbln1 binds to the GluD1 and shows similar synaptogenic activities to GluD2 in vitro, it has been unclear whether and how Cbln1-GluD1 signaling exerts its functions in the hippocampus in vivo. Here we showed that Cbln1 immunoreactivity was mostly localized in CA1 stratum lacunosum moleculare in the mouse hippocampus. Whole-cell patch-clamp recordings from CA1 pyramidal neurons in hippocampal slices prepared from postnatal-day 10-18 mice showed that the ratio of NMDA to AMPA receptor-dependent components of excitatory postsynaptic currents induced by stimulation of the perforant-path were significantly increased in GluD1-null mice compared to wild-type mice. Indeed, NMDA receptor-dependent component of postsynaptic currents were increased in GluD1-null CA1 neurons. Interestingly, although conventional tetanus stimulation of the perforant path induced long-term potentiation (LTP) in both GluD1-null and wild-type CA1 regions, the low-frequency stimulation inducing LTD in wild-type mice did not cause LTD in GluD1- null mice in an NMDA receptor-dependent manner. These results indicate that Cbln1-GluD1 signaling may regulate synaptic plasticity at perforant path-CA1 synapses in the hippocampus. Since CA1 neurons are thought to integrate information from CA3 place cells and entorhinal grid cells, elucidating Cbln1-GluD1 signaling will provide better understanding of the hippocampal memory formation.	P2-2-4 生後早期の感覚入力遮断はマウス前頭前野の抑制性ニューロン密度を変化させる Sensory deprivation in neonatal mice changes the density of GABAergic interneurons in the prefrontal cortex of the mouse ○上野浩司1, 末光俊介2, 松本洋輔3, 岡本基1 ○Hiroshi Ueno1, Shunsuke Suemitsu2, Yosuke Matsumoto3, Motoi Okamoto1 岡山大学大学院　保健学研究科1, 川崎医科大心療科2, 岡山大医歯薬精神3 Dept Med Tec, Grad Sch of Health Sci, Univ of Okayama, Okayama, Japan1, Dept Psychi, Med Sch of Kawasaki, Okayama, Japan2, Dept Pschi, Grad Sch of Med, Dent and Pharma, Univ of Okayama, Japan3 Loss of one sensory system improves function of other intact sensory systems. This is known as cross-modal plasticity. Recent studies using functional MRI suggest the role of the prefrontal cortex in cross-modal plasticity. The prefrontal cortex plays a critical role in attention by selecting relevant stimuli and inhibiting distracting stimuli both at thalamic relay nuclei and primary sensory cortices. On the other hand, it has been shown that changes in the density and laminar distribution of GABAergic interneurons contribute to cross-modal plasticity.Here, we examined the effects of somatosensory or/and visual deprivation on the density of parvalbumin (PV)-, calretinin (CR)-, or calbindin (CB)-containing interneurons in the prelimbic cortex (PrL). For somatosensory deprivation, all whiskers were trimmed from P0 to P28. For visual deprivation, mice were reared in complete darkness from P2 to P28. Somatosensory deprivation decreased PV, CR and glutamic acid decarboxylase 67 (GAD67) positive synapse terminals (puncta) around putative pyramidal neurons, but increased CB neurons in layer 5/6. In layer 2/3 somatosensory deprivation plus visual deprivation decreased PV and CR neurons and GAD67-positive puncta. Visual deprivation decreased CR neurons and GAD67-pisitive puncta, but not caused changes of PV and CB neurons. On the other hand, somatosensory deprivation decreased CR neurons and increased CB neurons, but not affected the density of PV neurons. The decrease of GAD67-positive synapse terminals around pyramidal neurons may enhance output from pyramidal neurons and the increase of CB neurons may enhance inhibition on distracting sensory inputs. Furthermore decrease of CR neurons in layer 2/3 is also expected to enhance inhibition on distracting sensory inputs by disinhibiting CB neurons in superficial layers. Thus our results suggest that changes of GABAergic interneurons and their synapse terminals in the PrL may contribute cross-modal plasticity.
P2-2-5 繰り返しLTD誘発後の長期持続性シナプス減弱での海馬錐体細胞樹状突起棘の動態 Dendritic spine dynamics in the long-lasting synaptic suppression after repetitive LTD induction ○長谷川翔1, 大江祐樹1, 冨永（吉野）恵子1, 小倉明彦1 ○Sho Hasegawa1, Yuki Oe1, Keiko Tominaga-Yoshino1, Akihiko Ogura1 大阪大学大学院　生命機能研究科　神経可塑性生理学研究室1 Lab. Synaptic Plasticity, Osaka Univ. Grad. Sch. Frontier Biosciences, Osaka, Japan.1 Behavioral memory is fixed through repeated task performance or exercise. However, the cellular mechanisms underlying this repetition-dependent memory consolidation are unrevealed. We previously showed in organotypic slice cultures of the rodent hippocampus that repeated inductions of LTP led to a slowly-developing long-lasting synaptic enhancement coupled with new synapse formation (RISE; Repetitive LTP-Induced Synaptic Enhancement), while that repeated inductions of LTD resulted in a long-lasting synaptic suppression accompanied by synapse elimination (LOSS; LTD-repetition-Operated Synaptic Suppression). We propose that RISE and LOSS may serve as model phenomena for analyzing the cellular mechanisms of the repetition-dependent memory consolidation.Previously we examined the process of synapse formation in RISE by time-intermittent confocal microscopy using a line of transgenic mouse (Thy1-YFP H-line) that expresses yellow fluorescent protein sparsely among the CA1 pyramidal neurons. In this study we pursued the process of synapse elimination in LOSS.Spines of the CA1 neurons' apical dendrites gradually decreased in number over 3 weeks after 3 exposures to DHPG, a metabotropic glutamate receptor agonist that induces LTD. The largest decrease occurred within the first 1 week. Chasing individual spines revealed that the spines were in a dynamic equilibrium between generation and retraction and that the repeated LTD induction increased the rate of retraction leaving the rate of generation unaffected. This spine dynamics is different from that in RISE, where both generation and retraction increased transiently (increased fluctuation) followed by an earlier cessation of retraction (biased random walk). Examination with shorter intervals revealed that the increased retraction of spines occurred within 24h after the third LTD induction. Such imbalance of spine generation and retraction did not occur after single LTD induction.	P2-2-6 聴覚皮質におけるニコチン誘導性長期増強のシナプス機構 Synaptic mechanisms underlying nicotine-induced long-term potentiation in auditory cortex ○山崎賢一1, 川井秀樹1 ○Kenichi Yamasaki1, Hideki D Kawai1 創価大院・工・生命情報1 Dept Bioinfo, Soka Univ, Tokyo1 Systemic nicotine exposure enhances tone-evoked responses in the upper layer of primary auditory cortex (A1) for at least 60 min, peaking at ~10 min, via nicotinic acetylcholine receptors containing α4 and β2 subunits (α4β2*-nAChRs) in early adolescent female mice (FVB, postnatal days 26-30). This enhancement is mediated by activation of extracellular signaling-regulated kinase (ERK), but downstream mechanisms underlying this nicotine-induced long-term potentiation (LTP) are not known. LTP at excitatory synapses could occur due to enhanced ion conductance or insertion of AMPARs, which results from phosphorylation of an AMPAR subunit, GluR1, at Ser831 or Ser845, respectively. Here we investigated whether nicotine-induced LTP phosphorylates these serine residues in A1 using Western blot techniques. Following systemic injection of saline or nicotine, we exposed animals to white-noise (WN) or no sound for 10 min. Synaptoneurosomes were then prepared from the upper layers of bilateral A1, and solubilized proteins were subjected to Western blot analysis for phosphorylated Ser831 and Ser845 of GluR1s. We found little change in the amount of GluR1 (normalized to GAPDH, loading control) in response to systemic nicotine, WN exposure, or a combined stimulation of nicotine and WN as compared to saline control. The amount of phosphorylated Ser831 changed little with any stimulation. Meanwhile, the amount of phosphorylated Ser845 increased in response to nicotine as well as nicotine and WN pairing. The extent of the increase was similar, suggesting that nicotinic activation, not WN, phosphorylates Ser845. Since PKA phosphorylates Ser845 to transport intracellular GluR1s to extrasynaptic zones and ERK activation leads to delivery of GluR1 to postsynaptic density, our data suggest that nicotine-induced LTP involves nicotinic activation of ERK and PKA, resulting in an increased number of synaptic AMPARs and enhanced excitatory transmission upon sound-evoked glutamate release in A1.
P2-2-7 Nogo受容体シグナルは成熟脳におけるAMPA受容体シナプス移行を制御する Nogo receptor signaling restricts experience-driven synaptic AMPA receptor trafficking in adult brain ○實木亨1, 竹本研1, 中島和希1, 高橋琢哉1 ○Susumu Jitsuki1, Kiwamu Takemoto1, Waki Nakajima1, Takuya Takahashi1 横浜市立大学大学院　医学研究科　生理学1 Dept Physiol, Yokohama City Univ, Yokohama1 While experience early in life actively refines neural circuits by virtue of a high capacity for plasticity, experience-dependent plasticity is limited in adult brain. Despite its fundamental importance, the molecular and cellular mechanism underlying the restriction of experience-driven neural plasticity in adult brain remains poorly understood. Removal of the myelin-inhibitor signaling protein, Nogo-66 receptor, restores neural plasticity in adult brain. Here, we find that natural whisker experience-driven synaptic glutamate AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)-type receptor insertion in the barrel cortex, which normally ceases in approximately 2 weeks after birth, lasts into adulthood for Nogo-66 receptor deficient mice. The mutant mice have sharpened whisker-dependent sensory map. Thus, Nogo receptor signaling restricts experience-driven synaptic plasticity and functional recovery after pathological trauma in adult brain by limiting synaptic AMPA receptor trafficking.	P2-2-8 ペリニューロナルネットはマウス海馬CA2領域のシナプス可塑性に関与する Perineuronal nets restrict synaptic plasticity in the CA2 region of the mouse hippocampus ○山田純1, 神野尚三1 ○Jun Yamada1, Shozo Jinno1 九州大院・医・形態機能形成1 Dept Dev Mol Anat, Kyushu Univ, Fukuoka1 The functional significance of the CA2 region in the hippocampus has long been a subject of controversy. Many scientists consider that the CA2 region is just a small transitional zone between the CA1 and CA3 regions without real identity, where the two classes of pyramidal neurons of the CA1 and CA3 regions mix up. However, several recent studies have indicated that the anatomical and physiological properties of the CA2 region are different from those of the CA1 and CA3 regions. For instance, long-term potentiation (LTP) cannot be induced in the CA2 region, although multiple forms of LTP have been seen in the CA1 and CA3 regions. The chondroitin sulphate proteoglycan-containing perineuronal nets (PNNs) are highly expressed in pyramidal neurons of the CA2 region but not in pyramidal neurons of the CA1 and CA3 regions. Because PNNs are involved in regulation of synaptic plasticity, here we examined whether impairment of LTP in CA2 neurons might be associated with their abundant expression of PNNs using slice preparation of the mouse hippocampus. High-frequency tetanic stimulation (100 Hz, 1 sec) of Schaffer collateral inputs induced only transient potentiation in CA2 neurons, and could not induce LTP. Application of chondroitinase ABC (chABC), which digests perineuronal nets, to hippocampal slice showed no effects on the basal synaptic transmission. However, we found that LTP could be induced in a preparation treated with chABC. We are currently investigating the detailed mechanisms regulating LTP in the CA2 region of the hippocampus.
P2-2-9 ホスファチジルイノシトール3,4,5-3リン酸は、構造可塑性誘導時に、スパイン上のspinuleの形成を制御する PIP3 regulates spinule formation in dendritic spines during structural long-term potentiation ○上田善文1,2, 林康紀1,2,3 ○Yoshibumi Ueda1,2, Yasunori Hayashi1,2,3 RIKEN BSI memory mechanisms1, マサチューセッツ工科大学Picower研究所2, 埼玉大学、脳科学融合研究センター3 Memory mechanisms, BSI, RIKEN, Saitama1, RIKEN-MIT Neuroscience Research Center, The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, USA.2, Saitama University Brain Science Institute, Saitama University, Saitama, Japan3 Dendritic spines are small, highly motile structures on dendritic shafts that provide flexibility to neuronal networks. Spinules are small protrusions that project from spines. The number and the length of spinules increase in response to activity including theta burst stimulation and glutamate application. However, what function spinules exert and how their formation is regulated still remains unclear. Phosphatidylinositol-3,4,5-trisphosphate (PIP3) plays important roles in cell motility such as filopodia and lamellipodia by recruiting downstream proteins such as Akt and WAVE to the membrane, respectively. Here we reveal that PIP3 regulates spinule formation during structural long-term potentiation (sLTP) of single spines in CA1 pyramidal neurons of rat hippocampal slices. Since the local distribution of PIP3 is important to exert its functions, the subcellular distribution of PIP3 was investigated using a fluorescence lifetime (FLIM)-based PIP3 probe. PIP3 accumulates to a greater extent in spines than in dendritic shafts, which is regulated by the subcellular pattern of the activities of the proteins that produce and degrade PIP3. Subspine imaging revealed that when sLTP was induced in a single spine, PIP3 accumulates in the spinule whereas PIP3 concentration in the spine decreased according to the increase in spine size.	P2-2-10 シナプスの再固定化 Synaptic reconsolidation ○鈴木-大久保玲子1,2, 斎藤喜人1,2, 趙き1,2, 榎本洸1, 井ノ口馨1,2 ○Reiko Okubo-Suzuki1,2, Yoshito Saitoh1,2, Qi Zhao1,2, Hiroshi Enomoto1, Kaoru Inokuchi1,2 富山大学大学院 医学薬学研究部 生化学講座1 Department of Biochemistry, Faculty of Medicine, Graduate School of Medicine & Pharmaceutical Sciences, University of Toyama, Toyama1, CREST, JST2 When consolidated memory is retrieved, the memory becomes labile in which the memory enters the reconsolidation state and is stabilized again in a protein synthesis-dependent manner. Most studies thus far conducted on reconsolidation rely on the analyses of animal behavior. Therefore, neuronal and synaptic mechanisms underlying reconsolidation remain to be elucidated.In this study, we have employed in vivo LTP in the hippocampal dentate gyrus of freely moving rats to examine reconsolidation mechanisms, which allows us to observe changes in population spike amplitude at the similar time course with behavioral experiments. LTP was induced by high frequency stimulation (HFS) (Ms500, total of 500 pulses at 400 Hz). When anisomycin, a protein synthesis inhibitor, was injected into lateral ventricle immediately after the reactivation by low frequency stimulation (64 pulses at 8 Hz, theta frequency or 60 pulses at 0.1 Hz) 3 days after the LTP induction, we observed a rapid decay of population spike LTP compared with PBS group. LTP remained unmodified by protein synthesis inhibition without reactivation. Reactivation by HFS (500 pulses at 400 Hz or 90 pulses at 200 Hz) combined with anisomycin had no effect on LTP maintenance. These results indicate that low frequency stimulation has an ability to elicit reconsolidation-like processes in cellular and synaptic levels.
P2-2-11 海馬CA1領域でのシナプス前短期可塑性におけるSNAP-25のリン酸化の役割 Roles of SNAP-25 phosphorylation in presynaptic short-term plasticity ○片山憲和1, 山森早織2, 深谷昌弘3, 渡辺雅彦4, 高橋正身2, 真鍋俊也1 ○Norikazu Katayama1, Saori Yamamori2, Masahiro Fukaya3, Masahiko Watanabe4, Masami Takahashi2, Toshiya Manabe1 東京大・医科研・神経ネットワーク1, 北里大・医・生化学2, 北里大・医・解剖3, 北海道大院・医・解剖発生4 Div. Neuronal Network, Inst. Med. Sci., Univ. of Tokyo, Tokyo, Japan1, Dept. Biochem., Kitasato Univ. Sch. of Med., Kanagawa, Japan2, Dept. Anatomy, Kitasato Univ. Sch. of Med., Kanagawa, Japan3, Dept. Anatomy, Hokkaido Univ. Grad. Sch. of Med., Sapporo, Japan4 Synaptosomal-associated protein of 25 kDa (SNAP-25) constitutes the SNARE complex essential for exocytosis of synaptic vesicles. SNAP-25 is phosphorylated at Ser187 by protein kinase C (PKC) known to enhance neurotransmitter release. Recent studies reveal that knock-in (KI) mice deficient in SNAP-25 phosphorylation by PKC exhibit anxiety-like behaviors and epilepsy and that SNAP-25 expression in KI mice is decreased to about 50% of that in WT mice. However, the physiological roles of the SNAP-25 phosphorylation remain unclear. Therefore, we examined basal synaptic transmission and short-term plasticity at hippocampal CA1 synapses in KI mice. We found that KI mice exhibited smaller amplitudes of AMPAR-EPSPs and enhanced paired-pulse facilitation, suggesting that the phosphorylation upregulated basal synaptic transmission by increasing the release probability. In addition, the magnitude of post-tetanic potentiation evoked by high-frequency stimuli was significantly larger and the recovery from transient synaptic depression caused by repetitive low-frequency stimuli was slower in KI mice. Electron microscopy revealed that KI mice exhibited the accumulation of synaptic vesicles in enlarged presynaptic terminals. These results suggest that the regulation of the size of functional vesicle pools and recycling efficiency of synaptic vesicles was also impaired. Moreover, these alterations in short-term plasticity became more remarkable with development in parallel with the increase of SNAP-25 phosphorylation. We also confirmed that these phenotypes were not caused by a decrease in SNAP-25 expression nor by an epileptic seizure. Taken together, PKC-dependent SNAP-25 phosphorylation plays a critical role in regulation of basal synaptic transmission and short-term plasticity via modification of the dynamics of synaptic vesicles in the presynaptic terminal.	P2-2-12 CAPS1 コンディショナル・ノックアウトマウスにおけるシナプス伝達 Synaptic transmission in hippocampus of CAPS1 conditional KO mice ○石井千晶1, 篠田陽1,2, 定方哲史3, 古市貞一1,2 ○Chiaki Ishii1, Yo Shinoda1,2, Tetsushi Sadakata3, Teiichi Furuichi1,2 東京理科大・理工・応用生物科学1, 科学技術振興機構/CREST2, 群馬大・先端科学研究指導者育成ユニット3 Dept. of Appl. Biol. Sci., Fac. of Sci. and Technol., Tokyo Univ. of Sci., Chiba, Japan1, JST/CREST, Saitama, Japan2, Adv. Sci. Res. Leaders Develop. Unit, Gumma Univ. Gumma, Japan3 Calcium dependent activator protein for secretion 1 (CAPS1) was discovered as a soluble protein which is necessary to restore Ca2+-dependent norepinephrine secretion in PC12 cells. Now, mammalian CAPS1 is known as a homolog protein of C. elegance UNC31 whose mutations cause a defect of the coordinated movement. CAPS1 has a Munc13 homologous domain (MHD) which has been shown to be essential for priming step of dense-core vesicle (DCV) exocytosis. However, whether CAPS1 is also involved in exocytosis of synaptic vesicles (SVs) is still controversial. In addition, since CAPS1 KO mice showed early-neonatal lethal phenotype, there are little information about biological significance of CAPS1 at the level of neural circuits and organism. To address these issues, we have recently generated CAPS1 conditional knockout (cKO) mice (Sadakata et al, submitted). In the present study, we investigated electrophysiological properties of hippocampal CA3-CA1 synapses in CAPS1 cKO mice. CAPS1 cKO showed smaller field EPSP amplitude but more potentiation in theta-burst induced LTP, compared with those of the control mice. The enhanced LTP of CAPS1 cKO was long-lasting, which is contrast to reduced late phase LTP of mice lacking another CAPS isoform CAPS2. Moreover, paired-pulse facilitation (PPF) was increased in CA3-CA1 synapses of CAPS1 cKO mice, suggesting that loss-of-function of CAPS1 may be concerned with presynaptic release probability. These findings give us a clue to evaluate whether CAPS1 involve directly or indirectly in the process of SV exocytosis.

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