Synapse (New York, N.y.)最新文献

{"title":"Genetic and pharmacological manipulations of the CB(1) receptor alter ethanol preference and dependence in ethanol preferring and nonpreferring mice.","authors":"K Yaragudri Vinod, Ratnakumar Yalamanchili, Panayotis K Thanos, Csaba Vadasz, Thomas B Cooper, Nora D Volkow, Basalingappa L Hungund","doi":"10.1002/syn.20533","DOIUrl":"10.1002/syn.20533","url":null,"abstract":"<p><p>Recent studies have indicated a role for the endocannabinoid system in ethanol-related behaviors. This study examined the effect of pharmacological activation, blockade, and genetic deletion of the CB(1) receptors on ethanol-drinking behavior in ethanol preferring C57BL/6J (B6) and ethanol nonpreferring DBA/2J (D2) mice. The deletion of CB(1) receptor significantly reduced the ethanol preference. Although the stimulation of the CB(1) receptor by CP-55,940 markedly increased the ethanol preference, this effect was found to be greater in B6 than in D2 mice. The antagonism of CB(1) receptor function by SR141716A led to a significant reduction in voluntary ethanol preference in B6 than D2 mice. A significant lower hypothermic and greater sedative response to acute ethanol administration was observed in both the strains of CB(1) -/- mice than wild-type mice. Interestingly, genetic deletion and pharmacological blockade of the CB(1) receptor produced a marked reduction in severity of handling-induced convulsion in both the strains. The radioligand binding studies revealed significantly higher levels of CB(1) receptor-stimulated G-protein activation in the striatum of B6 compared to D2 mice. Innate differences in the CB(1) receptor function might be one of the contributing factors for higher ethanol drinking behavior. The antagonists of the CB(1) receptor may have therapeutic potential in the treatment of ethanol dependence.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"574-81"},"PeriodicalIF":0.0,"publicationDate":"2008-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2667104/pdf/nihms-101281.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27466898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reuptake of L-DOPA-derived extracellular DA in the striatum of a rodent model of Parkinson's disease via norepinephrine transporter.","authors":"Akira Arai,&nbsp;Masahiko Tomiyama,&nbsp;Kazuya Kannari,&nbsp;Tamaki Kimura,&nbsp;Chieko Suzuki,&nbsp;Mitsunori Watanabe,&nbsp;Takeshi Kawarabayashi,&nbsp;Huo Shen,&nbsp;Mikio Shoji","doi":"10.1002/syn.20535","DOIUrl":"https://doi.org/10.1002/syn.20535","url":null,"abstract":"<p><p>To determine the role of norepinephrine transporter in reuptake of L-DOPA-derived extracellular DA in the DA-denervated Parkinsonian striatum, we examined extracellular DA levels in the striatum of 6-hydroxyDA-lesioned rats that received L-DOPA (50 mg/kg with 12.5 mg/kg of benserazide) and L-DOPA plus desipramine (25 mg/kg), a selective norepinephrine reuptake inhibitor, using in vivo microdialysis. The pretreatment with desipramine increased levels of extracellular DA derived from administrated L-DOPA in the DA-denervated striatum. This study provides evidence that L-DOPA-derived DA is taken up by the norepinephrine transporter, instead of the dopamine transporter, in the striatum with dopaminergic denervation. This result suggests that the norepinephrine transporter could be a promising target in the treatment for Parkinson's disease.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"632-5"},"PeriodicalIF":2.3,"publicationDate":"2008-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.20535","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27466899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microscopic computed tomography imaging of the cerebral circulation in mice: feasibility and pitfalls.","authors":"T Abruzzo,&nbsp;L Tumialan,&nbsp;C Chaalala,&nbsp;S Kim,&nbsp;R E Guldberg,&nbsp;A Lin,&nbsp;J Leach,&nbsp;J C Khoury,&nbsp;A E Morgan,&nbsp;C M Cawley","doi":"10.1002/syn.20511","DOIUrl":"https://doi.org/10.1002/syn.20511","url":null,"abstract":"<p><p>This study evaluates the utility and practical limitations of microcomputerized X-ray tomography (CT) as a research tool for examination of the cerebral circulation in mice. Six micro CT angiograms of the circle of Willis (COW) from six mice were obtained by scanning whole head and brain specimen perfused with a radio-opaque silicone contrast agent. Two-dimensional volume rendered images were postprocessed from three-dimensional image datasets using a partially automated high-throughput model that generated 10 surface projections for each specimen. The image processing model employed a straightforward global thresholding and computerized component labeling software algorithm. Postprocessed images were analyzed and results correlated with microdissection. Micro CT demonstration of COW vessels and their branch anatomy was assessed. 71% of COW vessels were completely demonstrated, 26% were partially demonstrated, and 3% were not demonstrated. All cases of nondemonstration and most cases of partial demonstration resulted from scan coverage or postprocessing clip error. Thresholding effect caused pseudostenosis of 8% of COW vessels and accounted for a minority of partial demonstration cases. No imaging artifacts were caused by contrast extravasation or ineffective contrast perfusion. Volume averaging caused minor angioarchitectural distortion of 58% of COW vessels. Ninety-five percent of COW > or =50 microm and 52% of COW vessels <50 microm were correctly identified by micro CT. Micro CT of the murine COW using a high-throughput image processing model is feasible. Angioarchitectural distortion due to volume averaging and thresholding effect can occur and pathological findings should be confirmed.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"557-65"},"PeriodicalIF":2.3,"publicationDate":"2008-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.20511","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27466897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antidepressant treatments regulate matrix metalloproteinases-2 and -9 (MMP-2/MMP-9) and tissue inhibitors of the metalloproteinases (TIMPS 1-4) in the adult rat hippocampus.","authors":"Madhurima Benekareddy,&nbsp;Purvi Mehrotra,&nbsp;Vaishali A Kulkarni,&nbsp;Parvathy Ramakrishnan,&nbsp;Brian G Dias,&nbsp;Vidita A Vaidya","doi":"10.1002/syn.20529","DOIUrl":"https://doi.org/10.1002/syn.20529","url":null,"abstract":"<p><p>Antidepressants induce structural remodeling in the adult hippocampus, including changes in dendritic arbors, axonal sprouting, neurogenesis, and endothelial cell proliferation. Such forms of structural plasticity take place in the context of the extracellular matrix environment and are known to be regulated by matrix metalloproteinases (MMPs), in particular MMP-2/9, and their endogenous regulators, the tissue inhibitors of the metalloproteinases (TIMPs 1-4). Given the hippocampal structural remodeling associated with antidepressant treatments, we hypothesized that antidepressants may regulate the expression and activity of MMP-2/9 and TIMPs 1-4. The influence of distinct classes of antidepressants, namely, electroconvulsive seizure, fluoxetine, tranylcypromine, and desipramine, on the gene expression of MMP-2, MMP-9, and TIMPs 1-4 in the hippocampus was determined using radioactive in situ hybridization. In addition, zymography studies addressed the regulation of the gelatinase activity of MMP-2/9 following acute and chronic antidepressant administration. We observed that acute and chronic ECS differentially regulate the transcript levels of MMP-2/9 and TIMPs 1-4 and also increase gelatinase activity in the hippocampus. Acute and chronic pharmacological antidepressants on the other hand differentially alter the expression of the TIMPs without any observed effect on hippocampal MMP-2/9 expression or activity. These findings raise the possibility that extracellular matrix modifying enzymes and their endogenous regulators may serve as targets for antidepressant treatments and suggests the possibility that they may contribute to antidepressant-mediated structural plasticity in the hippocampus.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"590-600"},"PeriodicalIF":2.3,"publicationDate":"2008-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.20529","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27466895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"7-nitroindazole, nitric oxide synthase inhibitor, attenuates physical dependence on butorphanol in rat.","authors":"Yu-Hua Tian,&nbsp;Kwang-Wook Lee,&nbsp;In-Jee You,&nbsp;Seok-Yong Lee,&nbsp;Choon-Gon Jang","doi":"10.1002/syn.20530","DOIUrl":"https://doi.org/10.1002/syn.20530","url":null,"abstract":"<p><p>Butorphanol is a synthetic opioid agonist/antagonist analgesic agent that mainly exerts its effects through kappa-opioid receptors. It has been demonstrated that kappa-opioid receptors preferentially mediate the development of physical dependence upon butorphanol and the associated withdrawal syndrome. However, it is not fully understood whether or not nNOS-containing neurons in the various brain regions play an important role in butorphanol withdrawal. Therefore, this study was conducted to determine whether the selective nNOS inhibitor, 7-NI, modifies the development of butorphanol withdrawal and changes of nNOS expressions in different brain regions in physically butorphanol-dependent rats. The first part of the study focused on withdrawal behaviors in male Sprague-Dawley rats. Physical dependence was induced by a 72-h i.c.v. infusion with butorphanol (26 nmol/mixrol/h) and withdrawal was subsequently precipitated by i.c.v. challenge with naloxone (48 nmol/5 microl/rat) 2 h after termination of the butorphanol infusion. The butorphanol/7-NI coadministration group showed a significant decrease in several signs of withdrawal such as teeth chattering, as compared with the butorphanol-treated group. In the second part of the study, immunohistochemical analysis was performed to determine the expression of nNOS in the various brain regions. In the butorphanol/7-NI coadministration group, the number of cells labeled for nNOS was significantly lower in the various brain regions (including the caudate putamen, nucleus accumbens, and hippocampus) than in the butorphanol group. Therefore, 7-NI decreased in butorphanol-induced physical dependence and nNOS expression. Taken together, these findings suggest that the nNOS system is involved in the development of butorphanol-induced physical dependence, and 7-NI has potential clinical application as a candidate for the treatment of opioid withdrawal syndrome.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"582-9"},"PeriodicalIF":2.3,"publicationDate":"2008-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.20530","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27468945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serotoninergic dorsal raphe neurons possess functional postsynaptic nicotinic acetylcholine receptors.","authors":"Luis Galindo-Charles,&nbsp;Salvador Hernandez-Lopez,&nbsp;Elvira Galarraga,&nbsp;Dagoberto Tapia,&nbsp;José Bargas,&nbsp;Julieta Garduño,&nbsp;Carmen Frías-Dominguez,&nbsp;René Drucker-Colin,&nbsp;Stefan Mihailescu","doi":"10.1002/syn.20526","DOIUrl":"https://doi.org/10.1002/syn.20526","url":null,"abstract":"<p><p>Very few neurons in the telencephalon have been shown to express functional postsynaptic nicotinic acetylcholine receptors (nAChRs), among them, the noradrenergic and dopaminergic neurons. However, there is no evidence for postsynaptic nAChRs on serotonergic neurons. In this study, we asked if functional nAChRs are present in serotonergic (5-HT) and nonserotonergic (non-5-HT) neurons of the dorsal raphe nucleus (DRN). In rat midbrain slices, field stimulation at the tegmental pedunculopontine (PPT) nucleus evoked postsynaptic currents (eEPSCs) with different components in DRN neurons. After blocking the glutamatergic and GABAergic components, the remaining eEPSCs were blocked by mecamylamine and reduced by either the selective alpha7 nAChR antagonist methyllycaconitine (MLA) or the selective alpha4beta2 nAChR antagonist dihydro-beta-eritroidine (DHbetaE). Simultaneous addition of MLA and DHbetaE blocked all eEPSCs. Integrity of the PPT-DRN pathway was assessed by both anterograde biocytin tracing and antidromic stimulation from the DRN. Inward currents evoked by the direct application of acetylcholine (ACh), in the presence of atropine and tetrodotoxin, consisted of two kinetically different currents: one was blocked by MLA and the other by DHbetaE; in both 5-HT and non-5-HT DR neurons. Analysis of spontaneous (sEPSCs) and evoked (eEPSCs) synaptic events led to the conclusion that nAChRs were located at the postsynaptic membrane. The possible implications of these newly described nAChRs in various physiological processes and behavioral events, such as the wake-sleep cycle, are discussed.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"601-15"},"PeriodicalIF":2.3,"publicationDate":"2008-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.20526","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27468947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential synaptic changes in the striatum of subjects with undifferentiated versus paranoid schizophrenia.","authors":"Rosalinda C Roberts,&nbsp;Joy K Roche,&nbsp;Robert R Conley","doi":"10.1002/syn.20534","DOIUrl":"https://doi.org/10.1002/syn.20534","url":null,"abstract":"<p><p>Subjects with schizophrenia (SZ) have an increased density of synapses characteristic of corticostriatal or thalamostriatal glutamatergic inputs in the caudate matrix and putamen patches. SZ is a heterogeneous disease in many aspects including symptoms. The purpose of the present study was to determine if the synaptic organization in two different DSM-i.v. subgroups of SZ was differentially affected. Postmortem striatal tissue was obtained from the Maryland Brain Collection from normal controls (NC), chronic paranoid SZs (SZP), and chronic undifferentiated SZs (SZU). Tissue was prepared for calbindin immunocytochemistry to identify patch matrix compartments, prepared for electron microscopy and analyzed using stereological methods. The synaptic density of asymmetric synapses, characteristic of glutamatergic inputs, was elevated equivalently in striatal patches in the SZP and SZU versus NC. The SZU also had an increased density of asymmetric synapses in the striatal matrix compared to NC. Moreover, symmetric axospinous synapses, characteristic of intrinsic inhibitory inputs and dopaminergic afferents, showed a dichotomy in synaptic density between the SZU and SZP in the striatal and caudate matrix. These data show discreet differences in synaptic organization between SZU and SZP and/or NCs. The results suggest that abnormal corticostriatal and/or corticothalamic inputs to striatal patches may be related to limbic dysfunction, which is perturbed in both subtypes of SZ. The selective increase in axospinous synapses in the matrix of the SZU subgroup compared to the SZP may be related to more severe cognitive problems in that subset of SZ compared to SZP.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"616-27"},"PeriodicalIF":2.3,"publicationDate":"2008-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.20534","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27466896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynorphin and prodynorphin mRNA changes in the striatum during nicotine withdrawal.","authors":"Raffaella Isola,&nbsp;Hailing Zhang,&nbsp;Gopi A Tejwani,&nbsp;Norton H Neff,&nbsp;Maria Hadjiconstantinou","doi":"10.1002/syn.20515","DOIUrl":"https://doi.org/10.1002/syn.20515","url":null,"abstract":"<p><p>Nicotine withdrawal causes somatic and negative affective symptoms that contribute to relapse and continued tobacco smoking. So far, the neuronal substrates involved are not fully understood, and an opioid role has been suggested. In this regard, the opioid dynorphin (Dyn) is of interest as it produces aversive states and has been speculated to play a role in the nicotine behavioral syndrome. These studies explore whether Dyn metabolism is altered during withdrawal following chronic administration of nicotine. Mice were administered nicotine, 2 mg/kg, s.c., four times daily for 14 days, and Dyn and prodynorphin (PD) mRNA estimated in selective brain regions at various times (30 min to 96 h) following drug discontinuation. The content of Dyn, estimated by RIA, was decreased in the striatum for a protracted time, from 30 min to over 72 h. In contrast, the mRNA for PD, evaluated by Northern blot, was elevated, appearing by 8 h and lasting over 96 h. Dyn was decreased in both ventral and dorsal striatum, and PD mRNA was differentially increased in the two striatal compartments as demonstrated by in situ hybridization. PD message was predominantly augmented in the nucleus accumbens, rostral pole, core, and shell, and the medial aspects of caudate/putamen. We interpret these data to indicate increased activity of striatal, particularly accumbal, dynorphinergic neurons during nicotine withdrawal resulting in enhanced peptide release and compensatory synthesis. Heightened dynorphinergic tone might be responsible, in part, for the emergence of the negative affective states observed during nicotine withdrawal.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"448-55"},"PeriodicalIF":2.3,"publicationDate":"2008-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.20515","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27339550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vivo electrophysiology of dopamine-denervated striatum: focus on the nitric oxide/cGMP signaling pathway.","authors":"Salvatore Galati,&nbsp;Vincenza D'angelo,&nbsp;Eugenio Scarnati,&nbsp;Paolo Stanzione,&nbsp;Alessandro Martorana,&nbsp;Teresa Procopio,&nbsp;Giuseppe Sancesario,&nbsp;Alessandro Stefani","doi":"10.1002/syn.20510","DOIUrl":"https://doi.org/10.1002/syn.20510","url":null,"abstract":"<p><p>Within the striatum, the gaseous neurotransmitter nitric oxide (NO) is produced by a subclass of interneurons containing the neuronal NO synthase (nNOS). NO promotes the second messenger cGMP through the activation of the soluble guanyl cyclase (sGC) and plays a crucial role in the integration of glutamate (GLU) and DA transmission. The aim of this study was to characterize the impact of 6-hydroxyDA (6-OHDA) lesion of the rat nigrostriatal pathway on NO/cGMP system. In vivo extracellular single units recordings were performed under urethane anesthesia to avoid any potentially misleading contributions of cortically-driven changes on endogenous NO. Hence, no electrical extrastriatal stimulation was performed and great attention was paid to the effects of 3-morpholinosydnonimine (SIN-1, a NO donor), N(G)-nitro-L-arginine methyl ester (L-NAME, a nonselective NOS inhibitor) and Zaprinast (a PDE inhibitor) delivered by iontophoresis upon the main striatal phenotypes. The latter were operationally distinguished in silent medium spiny-like neurons (MSN), with negligible spontaneous activity but displaying glutamate-induced firing discharge at rest and spontaneously active neurons (SAN), representing to a large extent nonprojecting interneurons. SANs were excited by SIN-1 and Zaprinast while MSNs showed a clear inhibition during local iontophoretic application of SIN-1 and Zaprinast. In 6-OHDA animals, SIN-1-induced excitation in SANs was significantly increased (on the contrary, the inhibitory effect of L-NAME was less effective). Interestingly, in DA-denervated animals, a subclass of MSNs (40%) displayed a peculiar excitatory response to SIN-1. These findings support the notion of an inhibitory modulatory role exerted by endogenous NO on control striatal projection cells. In addition, these findings suggest a functional cross-talk between NO, spontaneously active interneurons, and projection neurons that becomes critical in the parkinsonian state.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"409-20"},"PeriodicalIF":2.3,"publicationDate":"2008-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.20510","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27339548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered synaptic synchrony in motor nerve terminals lacking P/Q-calcium channels.","authors":"Rafael S Depetris,&nbsp;Silvana I Nudler,&nbsp;Osvaldo D Uchitel,&nbsp;Francisco J Urbano","doi":"10.1002/syn.20516","DOIUrl":"https://doi.org/10.1002/syn.20516","url":null,"abstract":"<p><p>The variance in synaptic delays among endplate potentials events (referred here as jitter) was measured to study the contribution of voltage dependent calcium channels to transmission synchronicity in neuromuscular synapses from wild type and alpha-1A knockout mice (i.e., lacking P/Q type calcium channels). Knockout synapses presented higher jitter values than wild type ones under a wide range of extracellular calcium concentration ([Ca2+]o) values. Accordingly, wild type synapses showed less synchronic neurotransmitter release when P/Q type calcium channels were partially blocked as well as under lower [Ca2+]o. In the knockout synapses, N-type calcium channels mediated neurotransmitter release in a more temporally precise way than the R-type ones. Our results suggest that the type of calcium channels mediating transmitter release influenced the degree of synaptic synchrony. Thus, these results provide insight on the mechanisms underlying several pathologies associated with P/Q type calcium channels.</p>","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"466-71"},"PeriodicalIF":2.3,"publicationDate":"2008-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.20516","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27339551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}