Biomedical subjects

Katsuhiko Mikoshiba

Publications and source records attributed to Katsuhiko Mikoshiba.

At least 19 recordsLinked to original sources

PubMed2007

The IP3 receptor/Ca2+ channel and its cellular function.

The IP3R [IP3 (inositol 1,4,5-trisphosphate) receptor] is responsible for Ca2+ release from the ER (endoplasmic reticulum). We have been working extensively on the P400 protein, which is deficient in Purkinje-neuron-degenerating mutant mice. We have discovered that P400 is an IP3R and we have determined the primary sequence. Purified IP3R, when incorporated into a lipid bilayer, works as a Ca2+ release channel and overexpression of IP3R shows enhanced IP3 binding and channel activity. Addition of an antibody blocks Ca2+ oscillations indicating that IP3R1 works as a Ca2+ oscillator. Studies on the role of IP3R during development show that IP3R is involved in fertilization and is essential for determination of dorso-ventral axis formation. We found that IP3R is involved in neuronal plasticity. A double homozygous mutant of IP3R2 (IP3R type 2) and IP3R3 (IP3R type 3) shows a deficit of saliva secretion and gastric juice secretion suggesting that IP3Rs are essential for exocrine secretion. IP3R has various unique properties: cryo-EM (electron microscopy) studies show that IP3R contains multiple cavities; IP3R allosterically and dynamically changes its form reversibly (square form-windmill form); IP3R is functional even though it is fragmented by proteases into several pieces; the ER forms a meshwork but also forms vesicular ER and moves along microtubules using a kinesin motor; X ray analysis of the crystal structure of the IP3 binding core consists of an N-terminal beta-trefoil domain and a C-terminal alpha-helical domain. We have discovered ERp44 as a redox sensor in the ER which binds to the luminal part of IP3R1 and regulates its activity. We have also found the role of IP3 is not only to release Ca2+ but also to release IRBIT which binds to the IP3 binding core of IP3R.

Animals↗

PubMed2007

Dvl regulates endo- and exocytotic processes through binding to synaptotagmin.

Dvl, an important component of the Wnt signalling pathway, is thought to be involved in synaptogenesis. In this study, we investigated whether Dvl regulates neurotransmitter release. Knockdown of Dvl in PC12 cells suppressed K(+)-induced dopamine release, and this phenotype was restored by expression of Dvl-1. We identified synaptotagmin (Syt) I, which is involved in neurotransmitter release, as a Dvl-binding protein. Dvl directly bound to the C2B domain of Syt I. Dvl colocalized with Syt I at the tip of neurites of differentiated PC12 cells and of neurons in the rat dorsal root ganglion. Dvl and Syt I was located in large dense-core vesicles, which contain dopamine. In addition, endocytosis of vesicles containing Syt I was suppressed in Dvl knockdown PC12 cells. Dvl inhibited the binding of Syt I to the complex consisting of syntaxin-1A and SNAP-25. Furthermore, micro2-adaptin of AP-2, which is known to play a role in endocytosis, formed a complex with Dvl and Syt I. Taken together, these results suggest that Dvl is involved in endo- and exocytotic processes through the binding to Syt I.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Collapsin response mediator protein 1 mediates reelin signaling in cortical neuronal migration.

Collapsin response mediator protein 1 (CRMP1) is one of the CRMP family members that mediates signal transduction of axon guidance molecules. Here, we show evidence that CRMP1 is involved in Reelin (Reln) signaling to regulate neuronal migration in the cerebral cortex. In crmp1-/- mice, radial migration of cortical neurons was retarded. This phenotype was not observed in the sema3A-/- and crmp1+/-;sema3A+/- cortices. However, CRMP1 was colocalized with disabled-1 (Dab1), an adaptor protein in Reln signaling. In the Reln(rl/rl) cortex, CRMP1 and Dab1 were expressed at a higher level, yet tyrosine phosphorylated at a lower level. Loss of crmp1 in a dab1 heterozygous background led to the disruption of hippocampal lamination, a Reeler-like phenotype. In addition to axon guidance, CRMP1 regulates neuronal migration by mediating Reln signaling.

Animals↗

PubMed2006

A case of limited cutaneous systemic sclerosis developing anti-mitochondria antibody positive primary biliary cirrhosis after acute myocardial infarction.

In this report, we present a 63-year-old woman who had limited cutaneous systemic sclerosis and subsequently developed typical primary biliary cirrhosis after an acute myocardial infarction. The patient initially developed Raynaud's phenomenon, and 4 years later visited the clinic in 1994 complaining of abdominal distress, xerostomia, and xerophthalmia. A diagnosis of limited cutaneous systemic sclerosis was based on Raynaud's phenomenon, sclerodactyly and anti-centromere antibodies. She was also found to have anti-inositol 1,4,5-trisphosphate receptor 3 (IP(3)R3) antibodies, but anti-mitochondrial antibodies were only weakly positive. Seven years later, she developed vertigo and nausea, and was hospitalized due to complaints of an oppressive sensation of the anterior chest. Electrocardiogram results showed a reduction of R waves and ST segment elevation in II, III, and aVf leads. Coronary angiography showed 99% obstruction of the left anterior descending artery and 50% of stenosis of the right coronary artery. Three years later, the patient was noted to have anti-mitochondrial antibodies. Retrospective analysis of the patient's sera showed that IP(3)R3 antibodies were decreasing. Since myocardium is particularly rich in mitochondria, it is thought that myocardial infarction may have been the triggering event that initiated antigen-presenting cells to selectively induce an anti-mitochondrial antibody response.

Autoantibodies↗

PubMed2006

2-Aminoethyl diphenylborinate analogues: selective inhibition for store-operated Ca2+ entry.

Capacitative calcium entry (CCE), the mechanism that replenishes the internal Ca2+ stores with Ca2+ from the extracellular milieu in response to depletion of the store, is mediated by Ca2+ channels in the plasma membrane generally referred to as store-operated channels (SOCs). However, the roles of SOCs in the more physiological context have been fully elucidated. 2-Aminoethyl diphenylborinate (2-APB) strongly inhibits SOCs, as well as inositol-1,4,5 trisphosphate (IP3) receptors. In the present study, we screened a library of 166 2-APB analogues for effects on CCE and IP3-induced Ca2+ release in order to discover specific SOC inhibitors, and found that some blocked both store-operated and receptor-operated Ca2+ influx more strongly and selectively than 2-APB. Indeed, these new compounds ceased the prolonged intracellular Ca2+ oscillations induced by a low concentration of ATP in CHO-K1 cells. These novel SOC inhibitors will be valuable pharmacological and biochemical tools for elucidating the physiological roles.

Animals↗

PubMed2006

Organelles containing inositol trisphosphate receptor type 2 in adrenal medullary cells.

To identify which organelles contained inositol trisphosphate (InsP(3)) receptor type 2 (InsP(3)R2) in adrenal medullary (AM) cells, immunocytochemical and biochemical studies were performed on AM cells of several species. InsP(3)R2-like immunoreactive materials produced by two different anti-InsP(3)R2 antibodies (Abs) (Chemicon and Sigma) were distributed in rat AM cells in agreement with BODIPY-FL-InsP(3) binding sites. For two other Abs (KM1083 and Santa Cruz), some of the anti-InsP(3)R2 immunoreactive materials were stained with an anti-dopamine-beta-hydroxylase Ab, but not by BODIPY-FL-InsP(3). BODIPY-FL-thapsigargin binding sites were consistent with a distribution of the endoplasmic reticulum (ER) identified by an anti-calnexin Ab, and a prior application of thapsigargin significantly eliminated BODIPY-FL-thapsigargin bindings, suggesting that BODIPY-FL-thapsigargin bindings were mediated by thapsigargin, but not the fluorescence molecule. The anti-InsP(3)R2 Ab that produced stainings consistent with BODIPY-FL-InsP(3) bindings recognized a protein with about 250 kDa. A fractional analysis of bovine adrenal medullae revealed that the 250 kDa InsP(3)R2 was detected in a crude membrane fraction, but not in a secretory granule fraction. The results suggest that the InsP(3)R2 was present in the ER, but not in secretory granules in AM cells.

Adrenal Medulla↗

PubMed2006

Up-regulated PAR-2-mediated salivary secretion in mice deficient in muscarinic acetylcholine receptor subtypes.

Protease-activated receptor-2 (PAR-2) is expressed in the salivary glands and is expected to be a new target for the treatment of exocrine dysfunctions, such as dry mouth; however, the salivary secretory mechanism mediated by PAR-2 remains to be elucidated. Therefore, mechanism of the PAR-2-mediated salivary secretion was investigated in this study. We found that a PAR-2 agonist peptide, SLIGRL-OH, induced salivary flow in vivo and dose-dependent increase in [Ca(2+)](i) submandibular gland (SMG) acinar cells in wild-type (WT) mice and mice lacking M(3) or both M(1) and M(3) muscarinic acetylcholine receptors (mAChRs), whereas secretions in PAR-2 knockout (PAR-2KO) mice were completely abolished. The saliva composition secreted by SLIGRL-OH was similar to that secreted by mAChR stimulation. Ca(2+) imaging in WT acinar cells and beta-galactosidase staining in PAR-2KO mice, in which the beta-galactosidase gene (LacZ) was incorporated into the disrupted gene, revealed a nonubiquitous, sporadic distribution of PAR-2 in the SMG. Furthermore, compared with the secretion in WT mice, PAR-2-mediated salivary secretion and Ca(2+) response were enhanced in mice lacking M(3) or both M(1) and M(3) mAChRs, in which mAChR-stimulated secretion and Ca(2+) response in acinar cells were severely impaired. Although the mechanism underlying the enhanced PAR-2-mediated salivary secretion in M(3)-deficient mice is not clear, the result suggests the presence of some compensatory mechanism involving PAR-2 in the salivary glands deficient in cholinergic activation. These results indicate that PAR-2 present in the salivary glands mediates Ca(2+)-dependent fluid secretion, demonstrating potential usefulness of PAR-2 as a target for dry mouth treatment.

Animals↗

PubMed2006

Inositol 1,4,5-trisphosphate receptor type 1 in granule cells, not in Purkinje cells, regulates the dendritic morphology of Purkinje cells through brain-derived neurotrophic factor production.

Here, we show that cultured Purkinje cells from inositol 1,4,5-trisphosphate receptor type 1 knock-out (IP3R1KO) mice exhibited abnormal dendritic morphology. Interestingly, despite the huge amount of IP3R1 expression in Purkinje cells, IP3R1 in granule cells, not in the Purkinje cells, was responsible for the shape of Purkinje cell dendrites. We also found that BDNF application rescued the dendritic abnormality of IP3R1KO Purkinje cells, and that the increase in BDNF expression in response to activation of AMPA receptor (AMPAR) and metabotropic glutamate receptor (mGluR) was impaired in IP3R1KO cerebellar granule cells. In addition, we observed abnormalities in the dendritic morphology of Purkinje cells and in the ultrastructure of parallel fiber-Purkinje cell (PF-PC) synapses in IP3R1KO mice in vivo. We concluded that activation of AMPAR and mGluR increases BDNF expression through IP3R1-mediated signaling in cerebellar granule cells, which contributes to the dendritic outgrowth of Purkinje cells intercellularly, possibly by modifying PF-PC synaptic efficacy.

Animals↗

PubMed2006

Phosphorylation of the tubulin-binding protein, stathmin, by Cdk5 and MAP kinases in the brain.

Regulation of cytoskeletal dynamics is essential to neuronal plasticity during development and adulthood. Dysregulation of these mechanisms may contribute to neuropsychiatric and neurodegenerative diseases. The neuronal protein kinase, cyclin-dependent kinase 5 (Cdk5), is involved in multiple aspects of neuronal function, including regulation of cytoskeleton. A neuroproteomic search identified the tubulin-binding protein, stathmin, as a novel Cdk5 substrate. Stathmin was phosphorylated by Cdk5 in vitro at Ser25 and Ser38, previously identified as mitogen-activated protein kinase (MAPK) and p38 MAPKdelta sites. Cdk5 predominantly phosphorylated Ser38, while MAPK and p38 MAPKdelta predominantly phosphorylated Ser25. Stathmin was phosphorylated at both sites in mouse brain, with higher levels in cortex and striatum. Cdk5 knockout mice exhibited decreased phospho-Ser38 levels. During development, phospho-Ser25 and -Ser38 levels peaked at post-natal day 7, followed by reduction in total stathmin. Inhibition of protein phosphatases in striatal slices caused an increase in phospho-Ser25 and a decrease in total stathmin. Interestingly, the prefrontal cortex of schizophrenic patients had increased phospho-Ser25 levels. In contrast, total and phospho-Ser25 stoichiometries were decreased in the hippocampus of Alzheimer's patients. Thus, microtubule regulatory mechanisms involving the phosphorylation of stathmin may contribute to developmental synaptic pruning and structural plasticity, and may be involved in neuropsychiatric and neurodegenerative disorders.

Animals↗

PubMed2006

Homer 1 mediates store- and inositol 1,4,5-trisphosphate receptor-dependent translocation and retrieval of TRPC3 to the plasma membrane.

Store-operated Ca(2+) channels (SOCs) mediate receptor-stimulated Ca(2+) influx. Accumulating evidence indicates that members of the transient receptor potential (TRP) channel family are components of SOCs in mammalian cells. Agonist stimulation activates SOCs and TRP channels directly and by inducing translocation of channels in intracellular vesicles to the plasma membrane (PM). The mechanism of TRP channel translocation in response to store depletion and agonist stimulation is not known. Here we use TRPC3 as a model to show that IP(3) and the scaffold Homer 1 (H1) regulate the rate of translocation and retrieval of TRPC3 from the PM. In resting cells, TRPC3 exists in TRPC3-H1b/c-IP(3)Rs complexes that are located in part at the PM and in part in intracellular vesicles. Binding of IP(3) to the IP(3)Rs dissociates the interaction between IP(3)Rs and H1 but not between H1 and TRPC3 to form IP(3)Rs-TRPC3-H1b/c. TIRFM and biotinylation assays show robust receptor- and store-dependent translocation of the TRPC3 to the PM and their retrieval upon termination of cell stimulation. The translocation requires depletion of stored Ca(2+) and is prevented by inhibition of the IP(3)Rs. In HEK293, dissociating the H1b/c-IP(3)R complex with H1a results in TRPC3 translocation to the PM, where it is spontaneously active. The TRPC3-H1b/c-IP(3)Rs complex is reconstituted by infusing H1c into these cells. Reconstitution is inhibited by IP(3). Deletion of H1 in mice markedly reduces the rates of translocation and retrieval of TRPC3. Conversely, infusion of H1c into H1(-/-) cells eliminates spontaneous channel activity and increases the rate of channel activation by agonist stimulation. The effects of H1c are inhibited by IP(3). These findings together with our earlier studies demonstrating gating of TRPC3 by IP(3)Rs were used to develop a model in which assembly of the TRPC3-H1b/c-IP(3)Rs complexes by H1b/c mediates both the translocation of TRPC3-containing vesicles to the PM and gating of TRPC3 by IP(3)Rs.

Animals↗

PubMed2006

IRBIT suppresses IP3 receptor activity by competing with IP3 for the common binding site on the IP3 receptor.

The inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) are IP3-gated intracellular Ca2+ channels. We previously identified an IP3R binding protein, IRBIT, which binds to the IP3 binding domain of IP3R and is dissociated from IP3R in the presence of IP3. In the present study, we showed that IRBIT suppresses the activation of IP3R by competing with IP3 by [3H]IP3 binding assays, in vitro Ca2+ release assays, and Ca2+ imaging of intact cells. Multiserine phosphorylation of IRBIT was essential for the binding, and 10 of the 12 key amino acids in IP3R for IP3 recognition participated in binding to IRBIT. We propose a unique mode of IP3R regulation in which IP3 sensitivity is regulated by IRBIT acting as an endogenous "pseudoligand" whose inhibitory activity can be modulated by its phosphorylation status.

Adenosylhomocysteinase↗

PubMed2006

IRBIT, an inositol 1,4,5-trisphosphate receptor-binding protein, specifically binds to and activates pancreas-type Na+/HCO3- cotransporter 1 (pNBC1).

Inositol 1,4,5-trisphosphate (IP(3)) receptors (IP(3)Rs) are IP(3)-gated Ca(2+) channels that are located on intracellular Ca(2+) stores. We previously identified an IP(3)R binding protein, termed IP(3)R binding protein released with IP(3) (IRBIT). Because IRBIT is released from IP(3)R by physiological concentrations of IP(3), we hypothesized that IRBIT is a signaling molecule that is released from IP(3)R and regulates downstream target molecules in response to the production of IP(3). Therefore, in this study, we attempted to identify the target molecules of IRBIT, and we succeeded in identifying Na(+)/HCO(3)(-) cotransporter 1 (NBC1) as an IRBIT binding protein. Of the two major splicing variants of NBC1, pancreas-type NBC1 (pNBC1) and kidney-type NBC1 (kNBC1), IRBIT was found to bind specifically to pNBC1 and not to bind to kNBC1. IRBIT binds to the N-terminal pNBC1-specific domain, and its binding depends on the phosphorylation of multiple serine residues of IRBIT. Also, an electrophysiological analysis in Xenopus oocytes revealed that pNBC1 requires coexpression of IRBIT to manifest substantial activity comparable with that of kNBC1, which displays substantial activity independently of IRBIT. These results strongly suggest that pNBC1 is the target molecule of IRBIT and that IRBIT has an important role in pH regulation through pNBC1. Also, our findings raise the possibility that the regulation through IRBIT enables NBC1 variants to have different physiological roles.

Adenosylhomocysteinase↗

PubMed2006

Cytosolic inositol 1,4,5-trisphosphate dynamics during intracellular calcium oscillations in living cells.

We developed genetically encoded fluorescent inositol 1,4,5-trisphosphate (IP3) sensors that do not severely interfere with intracellular Ca2+ dynamics and used them to monitor the spatiotemporal dynamics of both cytosolic IP3 and Ca2+ in single HeLa cells after stimulation of exogenously expressed metabotropic glutamate receptor 5a or endogenous histamine receptors. IP3 started to increase at a relatively constant rate before the pacemaker Ca2+ rise, and the subsequent abrupt Ca2+ rise was not accompanied by any acceleration in the rate of increase in IP3. Cytosolic [IP3] did not return to its basal level during the intervals between Ca2+ spikes, and IP3 gradually accumulated in the cytosol with a little or no fluctuations during cytosolic Ca2+ oscillations. These results indicate that the Ca2+ -induced regenerative IP3 production is not a driving force of the upstroke of Ca2+ spikes and that the apparent IP3 sensitivity for Ca2+ spike generation progressively decreases during Ca2+ oscillations.

Calcium↗

PubMed2006

Distinct role of the N-terminal tail of the Na,K-ATPase catalytic subunit as a signal transducer.

Mounting evidence suggests that the ion pump, Na,K-ATPase, can, in the presence of ouabain, act as a signal transducer. A prominent binding motif linking the Na,K-ATPase to intracellular signaling effectors has, however, not yet been identified. Here we report that the N-terminal tail of the Na,K-ATPase catalytic alpha-subunit (alphaNT-t) binds directly to the N terminus of the inositol 1,4,5-trisphosphate receptor. Three amino acid residues, LKK, conserved in most species and most alpha-isoforms, are essential for the binding to occur. In wild-type cells, low concentrations of ouabain trigger low frequency calcium oscillations that activate NF-kappaB and protect from apoptosis. All of these effects are suppressed in cells overexpressing a peptide corresponding to alphaNT-t but not in cells overexpressing a peptide corresponding to alphaNT-t deltaLKK. Thus we have identified a well conserved Na,K-ATPase motif that binds to the inositol 1,4,5-trisphosphate receptor and can trigger an anti-apoptotic calcium signal.

Animals↗

PubMed2006

A wide-range phylogenetic analysis of Zic proteins: implications for correlations between protein structure conservation and body plan complexity.

We compared Zic homologues from a wide range of animals. Striking conservation was found in the zinc finger domains, in which an exon-intron boundary has been kept in all bilateralians but not cnidarians, suggesting that all of the bilateralian Zic genes are derived from a single gene in a bilateralian ancestor. There were additional conserved amino acid sequences, ZOC and ZF-NC. Combined analysis of the zinc finger, ZOC, and ZF-NC revealed the presence of two classes of Zic, based on the degree of protein structure conservation. The "conserved" class includes Zic proteins from the Arthropoda, Mollusca, Annelida, Echinodermata, and Chordata (vertebrates and cephalochordates), whereas the "diverged" class contains those from the Platyhelminthes, Cnidaria, Nematoda, and Chordata (urochordates). The result indicates that the ancestral bilateralian Zic protein had already acquired an entire set of conserved domains, but that this was lost and diverged in the platyhelminthes, nematodes, and urochordates.

Amino Acid Sequence↗

PubMed2006

Modulation of Reelin signaling by Cyclin-dependent kinase 5.

The Reelin signaling and Cyclin-dependent kinase 5 (Cdk5) both regulate neuronal positioning in the developing brain. Using double-transgenic mice, we have previously shown that these two signaling pathways lie in parallel fashion and have a genetic interaction. Disabled-1 (Dab1), an adapter protein, mediates Reelin signaling and becomes tyrosine-phosphorylated on the binding of Reelin to its receptors. Several isoforms of Dab1 are expressed in embryonic mouse brain, and p80 [Dab1(555)] is the major protein translated. In the present study, we investigated whether Cdk5-mediated phosphorylation of Dab1 modulates Reelin signaling. Cdk5 phosphorylates p80 Dab1 at multiple sites in its carboxyl-terminal region, and tyrosine phosphorylation of p80 Dab1 by Fyn tyrosine kinase is attenuated by this Cdk5-mediated phosphorylation in vitro. Tyrosine phosphorylation of p80 Dab1 induced by exogenous Reelin is enhanced in Cdk5-deficient neurons, corroborating the inhibitory effect of Cdk5-mediated Ser/Thr phosphorylation on tyrosine phosphorylation of p80 Dab1. Another isoform, p45 Dab1 [Dab1(271)], however, is phosphorylated by Cdk5 at one serine residue within a unique carboxyl-terminal region, and its serine phosphorylation enhances tyrosine phosphorylation by Fyn and results in progressive degradation of p45 Dab1. These results indicate that Cdk5 modulates Reelin signaling through the Ser/Thr phosphorylation of Dab1 differently in an isoform-specific manner.

Animals↗

PubMed2006

4.1N binding regions of inositol 1,4,5-trisphosphate receptor type 1.

Zhang et al. and Maximov et al. [S. Zhang, A. Mizutani, C. Hisatsune, T. Higo, H. Bannai, T. Nakayama, M. Hattori, and K. Mikoshiba, Protein 4.1N is required for translocation of inositol 1,4,5-trisphosphate receptor type 1 to the basolateral membrane domain in polarized Madin-Darby canine kidney cells, J. Biol. Chem. 278 (2003) 4048-4056; A. Maximov, T. S. Tang, and I. Bezprozvanny, Association of the type 1 inositol (1,4,5)-trisphosphate receptor with 4.1N protein in neurons, Mol. Cell. Neurosci. 22 (2003) 271-283.] reported that 4.1N is a binding partner of inositol 1,4,5-trisphosphate receptor type 1 (IP(3)R1), however the binding site of IP(3)R1 differed: the former determined the C-terminal 14 amino acids of the cytoplasmic tail (CTT14aa) as the binding site, while the latter assigned another segment, cytoplasmic tail middle 1 (CTM1). To solve this discrepancy, we performed immunoprecipitation and found that both the segments had binding activity to 4.1N. Both segments also interfered the 4.1N-regulated IP(3)R1 diffusion in neuronal dendrites. However, IP(3)R1 lacking the CTT14aa (IP(3)R1-DeltaCTT14aa) does not bind to 4.1N [S. Zhang, A. Mizutani, C. Hisatsune, T. Higo, H. Bannai, T. Nakayama, M. Hattori, and K. Mikoshiba, Protein 4.1N is required for translocation of inositol 1,4,5-trisphosphate receptor type 1 to the basolateral membrane domain in polarized Madin-Darby canine kidney cells, J. Biol. Chem. 278 (2003) 4048-4056.] and its diffusion constant is larger than that of IP(3)R1 full-length in neuronal dendrites [K. Fukatsu, H. Bannai, S. Zhang, H. Nakamura, T. Inoue, and K. Mikoshiba, Lateral diffusion of inositol 1,4,5-trisphosphate receptor type 1 is regulated by actin filaments and 4.1N in neuronal dendrites, J. Biol. Chem. 279 (2004) 48976-48982.]. We conclude that both the CTT14aa and CTM1 sequences can bind to 4.1N in peptide fragment forms. However, we propose that the responsible binding site for 4.1N binding in full-length tetramer form of IP(3)R1 is CTT14aa.

Animals↗

PubMed2006

Short-term potentiation at the parallel fiber-Purkinje cell synapse.

Changes in synaptic efficacy at the parallel fiber (PF)-Purkinje cell (PC) synapse are postulated to be a cellular basis for motor learning. Although long-term efficacy changes lasting more than an hour at this synapse, i.e., long-term potentiation and depression, have been extensively studied, relatively short lasting synaptic efficacy changes, namely short-term potentiation (STP) lasting for tens of minutes, have not been discussed to date. Here we report that this synapse shows an apparent STP reliably by a periodic burst pattern of homosynaptic stimulation. This STP is presynaptically expressed, since it accompanies with a reduced paired-pulse facilitation and is resistant to postsynaptic Ca(2+) reduction by BAPTA injection or in P/Q-type Ca channel knockout cerebella. This novel type of synaptic plasticity at the PF-PC synapse would be a clue for understanding the presynaptic mechanisms of plasticity at this synapse.

Animals↗