, 2002 and Haase et al., 2002). The transcriptional targets of Pea3 that control CM pool position remain to be defined, but several lines of evidence have implicated the selleck chemical activity of classical cadherins. The profile of classical type II cadherins in CM motor neurons is altered in Pea3 mutant mice ( Livet et al., 2002). Moreover, molecular and genetic experiments in chick and mouse have shown that classical cadherin signaling is required for the clustering and positioning of motor pools ( Price et al., 2002 and Demireva et al., 2011). Thus, as

Romanes surmised, the exposure of motor neurons to limb-derived signals is a key step in the positioning of some motor pools. The ability to disrupt normal programs of motor pool clustering and positioning through manipulation

of cadherin signaling has also permitted a test of Romanes’s second conjecture—that motor neuron positioning contributes to the precision and fidelity of muscle target innervation. Here, however, scrambling motor neuron position through inactivation of cadherin signaling fails to undermine the predictive link between the transcriptional identity of a motor neuron and the selection of its muscle target (Demireva et al., 2011). Presumably, profiles of expression and activity of Eph kinases and other relevant motor axonal guidance systems are established in a manner independent of motor neuron cell body position (Bonanomi and Pfaff, 2010). These findings argue against the idea that the clustering VX-770 supplier and settling position of motor neurons helps to assign patterns of muscle target connectivity. The clustering of motor neurons into pools may, nevertheless, still have relevance for the development of the neuromuscular system. At embryonic stages, motor neurons within a pool are connected by

gap junction channels, and active junctional communication has been argued to promote coherence in the firing of motor neurons that innervate a particular muscle target (Chang during et al., 1999). Clustering motor neurons into pools should therefore increase the probability that motor neurons with a common muscle target connect through gap junctions. In support of this view, analysis of mutant mice in which gap-junctional communication has been prevented by targeted inactivation of the connexin channel subunit Cx40 reveals that the coherence of motor neuron firing is decreased (Personius et al., 2007). In addition, fewer neuromuscular synapses are maintained at postnatal stages in these mutants—an indication that the durability of neuromuscular connections is compromised. Thus, one reason for clustering motor neurons into pools may be to promote the stability of synaptic connections with target muscles.

Indeed, in the setting Selleckchem 3-deazaneplanocin A of peripheral nerve

injury, regeneration, particularly of large diameter axons, may be enhanced (Neumann et al., 2002). We demonstrated that MGE-transplanted cells make connections with a large number of spinal cord neurons. Importantly, even when the MGE cells were located ventral to lamina III, the entire mediolateral width of the superficial and dorsal horn was often encompassed by MGE-derived axonal arbors. The latter enveloped many transneuronally labeled WGA+ cells, including projection neurons of lamina I. Hence, MGE cells target and can influence a large variety of spinal cord neurons, including many that respond to noxious stimuli. We conclude that MGE-derived transplants do not serve merely as “cell-based chemical pumps,” which is characteristic of other cell-based approaches (e.g., intrathecal injection of adrenal chromaffin cell or other precursor cells). Rather, by integrating into functional circuits, MGE cells overcome a functional deficit that reverses a critical etiology (i.e., defects in endogenous inhibition) of the persistent pain (Eaton et al., 1999, Hao et al., 2005, Liu et al., 2004, Sagen et al., 1990, Winnie et al.,

1993 and Yu et al., 1998). Our results go considerably beyond previous efforts to overcome the loss of GABAergic inhibition. For example, both trigeminal injection of an adenoviral vector expressing the GABA synthesizing enzyme, GAD65, or peripheral injection of an HSV vector expressing GAD67 had antinociceptive effects Proteasome structure in models of facial aminophylline pain (Vit et al., 2009) and spinal nerve ligation (Hao et al., 2005), respectively. Intrathecal (Vaysse et al., 2011) and intraspinal (Mukhida et al., 2007) injection of human cell lines engineered in vitro to express GABA also attenuated nerve injury-induced mechanical allodynia in the rat. However, in none of these cases was there evidence for integration of the GABAergic cells into the host. Furthermore, embryonic human progenitor cells, whether immortalized or not, require

expansion in vitro. With increasing time in culture, i.e., after multiple passages, the properties of the cells can change, which reduces the likelihood of their differentiating into neurons (Jain et al., 2003). Furthermore, as many neural stem cells maintain their proliferative potential after transplantation (Mukhida et al., 2007), the potential for tumor development cannot be ignored. Finally, and of particular importance to long-term pain management, is that transplants reported to date have a relatively short survival, which reduces their clinical utility. In contrast, we show that MGE cells have the essential properties for a cell-based therapy: long survival rate, stability and safety, differentiation into functionally integrated mature interneurons, and presumptive rescue of GABAergic inhibitory control.

00 ± 0.11, n = 5). Increasing inhibitory output with diazepam for the last 5 days of chronic monocular deprivation enabled an ocular dominance shift in adult NARP−/− mice (15 mg/kg, i.p.; cMD + DZ 1.17 ± 0.10, n = 6; Figure 7). As expected, adult wild-type mice expressed a significant shift in contralateral bias MK-8776 datasheet in response to prolonged (7 days) and chronic (80 days) monocular deprivation (VEP amplitude contralateral eye/ipsilateral eye average ± SEM: adult WT no MD 2.04 ± 0.20,

n = 5; 7 days MD 1.14 ± 0.13, n = 5; cMD 0.99 ± 0.17, n = 3), which was unaffected by diazepam in adulthood (cMD + DZ 0.98 ± 0.09, n = 4). Thus, in the absence of NARP, the visual system is unable to respond to monocular deprivation, despite functional inhibitory output. Although NARP−/− mice do not express ocular dominance plasticity, other forms of experience-dependent synaptic plasticity, such as the plasticity of the VEP contralateral bias, remain intact

(Figure 5). To further explore the range of deficits in synaptic plasticity in NARP−/− mice, we examined the response to repetitive visual stimulation, previously shown to induce robust changes in VEP amplitudes in vivo (Sawtell et al., 2003, Frenkel et al., 2006, Ross et al., 2008, Cooke and Bear, 2010 and Beste et al., 2011). High-frequency visual stimulation (10 Hz reversals of 0.04 cycles/degree, 100% contrast, vertical gratings) induced a rapid enhancement of the VEP amplitude in P30 NARP−/− and wild-type mice (VEP amplitude 60 min poststimulation normalized to prestimulation: WT 1.48 ± 0.12, n = 5; NARP−/− 1.41 ± 0.06, n = 5; two-way ANOVA, selleck compound F1,1 = 0.316, p = 0.584; Figure 8A). The enhancement in VEP amplitude was dependent on the temporal frequency of the visual stimulation, as visual stimulation at an intermediate temporal frequency (5 Hz) did not affect VEP amplitudes in either genotype (VEP amplitude 60 min poststimulation normalized to prestimulation: WT 1.00 ± 0.03, n = 3; NARP−/− 0.97 ± 0.10, n = 3). The increase in VEP amplitude induced Urease by 10 Hz visual stimulation was specific for the orientation of the visual stimulus, as no VEP

enhancement was observed in response to a rotated grating (10 Hz: WT 0.96 ± 0.05, n = 5; NARP−/− 0.94 ± 0.06, n = 5; 5 Hz: WT 0.94 ± 0.03, n = 3; NARP−/− 0.97 ± 0.08, n = 3; two-way ANOVA, F1,1 = 0.002, p = 0.968; Figure 8B). In contrast, low-frequency visual stimulation (1 Hz reversals of 0.04 cycles/degree, 100% contrast vertical gratings) induced a slowly emerging increase in VEP amplitude in wild-type mice (VEP amplitude post-/prestimulation: 12 hr 0.98 ± 0.14; 15 hr 1.32 ± 0.12; 18 hr 1.45 ± 0.08; n = 5), that was inhibited by diazepam (12 hr 0.91 ± 0.01; 15 hr 0.91 ± 0.04; 18 hr 1.13 ± 0.01; n = 5, two-way ANOVA with repeated-measures, F1,8 = 18.288, p = 0.003; ∗p < 0.01 versus wild-type control; Figure 8C).

This could provide proteins for in situ repair of ribosomes, or even more interestingly could provide onsite “tuning” of translation (Lee et al., 2013). One of the most exciting clinically relevant findings

to emerge from recent work is the link between dysregulated synaptic protein synthesis and neurological disorders (Bear CX-5461 in vitro et al., 2008, Darnell and Klann, 2013 and Liu-Yesucevitz et al., 2011). Mouse models of neurodevelopmental disorders such as autism spectrum disorder (ASD) show significant improvement on treatment with reagents that target the protein-synthesis pathway (Bear et al., 2008, Darnell and Klann, 2013, Gkogkas et al., 2013 and Santini et al., 2013), opening up new possibilities in terms of potential therapeutics. Much of the focus has been on the postsynaptic side of the synapse, the predominant site of plasticity and learning. Recent evidence indicates that regulated protein synthesis in the presynaptic compartment is also important for synapse formation (Taylor et al., 2013) and axon arborization (Hörnberg and Holt, 2013, Hörnberg et al., 2013 and Kalous BGB324 solubility dmso et al., 2013), raising the question of whether defects in axonal protein synthesis contribute to the miswiring aspects of neurodevelopmental disorders. Dysregulated protein synthesis may also underlie a broad range of neurodegenerative disorders (Fallini et al., 2012 and Liu-Yesucevitz et al., 2011) consistent with axonal protein synthesis being required for axon maintenance (Hillefors

et al., 2007 and Yoon et al., 2012). Indeed, the first “effective” oral drug treatment that prevents neurodegeneration in a prion disease/Alzheimer’s mouse model targets a kinase (PERK) that shuts

down protein synthesis as part of the unfolded protein response (Moreno et al., 2013). Recent years have witnessed a transformation in our appreciation of RNA function in dendrites/axons on the one hand and of neuronal compartments as spatially distinct signaling/processing units on the other. Here we have highlighted the convergence of these two areas and have sought to define some of the many interesting questions and challenges that lie ahead. As technical approaches become increasingly tuclazepam sensitive for unbiased profiling there is the promise of improved “understanding” of the qualitative concepts that govern the various active RNA species and formation and function of compartments as well as quantitative details on the stoichiometries of all of the players positioned within the morphological framework of the neuron and its remarkable dendritic and axonal arbor. We thank Nicole Thomsen for editorial support. We thank Susu tom Dieck, Anais Bellon, and Bill Harris for comments and our labs for discussions. Research in C.H.’s laboratory is supported by The Wellcome Trust and the European Research Council and in E.R.’s lab by the Max Planck Society, The European Research Council, and the DFG (CRC 902, 1080, and the Cluster of Excellence for Macromolecular Complexes, Goethe University).

To generate the Obp49aD allele, the Obp49a1 flies www.selleckchem.com/products/ink128.html were crossed to flies containing the P[w+,Cre] transgene. The mosaic-eyed progeny were collected and crossed to balancer flies, and the white-eyed flies progeny of the latter cross were subjective to genomic PCR analysis using primers P1 and P3. To generate the UAS-Obp49a-t transgenic flies, we first amplified the Obp49a coding sequence lacking the translation stop codon from w1118

labellar complementary DNA (cDNA) using the High Fidelity PCR kit (Roche), and cloned the cDNA into the pUAST vector. Sequences encoding the 10 aa MYC linker (EQKLISEEDL) and the transmembrane domain from the platelet-derived growth factor receptor were amplified from the pDisplay vector (Invitrogen), and cloned in-frame 3′ to the coding region for Obp49a. We also subcloned the cDNA encoding Obp49a with a normal stop codon and without the sequences encoding MYC and the membrane-tethered tag (UAS-Obp49a)

into the pUAST vector. The transgenic flies were generated by BestGene. We extracted total RNA from the labella of adult male and female wild-type and poxn flies using the Trizol reagent (Invitrogen), and generated cDNAs from 0.5 μg RNA using the SuperScript III First Strand Synthesis

System http://www.selleckchem.com/products/pexidartinib-plx3397.html (Invitrogen). Quantitative PCR was performed using an ABI7500 real-time PCR machine (Applied Biosystems) and the ABI SYBR Green system. Transcript levels were normalized to rp49 as an internal control, and the ΔΔCT (CT = threshold cycle) method was used to calculate the relative why amount of mRNAs. We repeated the experiments at least four times. Rabbit polyclonal OBP49a antibodies were raised to a synthetic peptide (CKPPRGPPPSAEDM; amino acids 199–212). Twenty labella were dissected from wild-type, Obp49a1, and Obp49aD flies, and homogenized in 1× SDS sample buffer with pellet pestles (Kimble-Kontes). The extracts were subjected to electrophoresis by SDS-PAGE and transferred to PVDF membranes (Millipore). The membranes were probed with primary antibodies against OBP49a (1:1,000) and tubulin (1:3,000, 12G10 from Hybridoma Bank), and then with peroxidase-conjugated anti-mouse or rabbit IgG secondary antibodies (1:5,000; Sigma). Whole-mount fly labellar immunostaining was performed as described previously (Moon et al., 2009) using anti-OBP49a (1:400) and mouse anti-GFP (1:400; Molecular Probes) primary antibodies, and anti-mouse-Alexa488 (1:400; Molecular Probes) and anti-rabbit-Alexa568 (1:400; Molecular Probes) secondary antibodies.

To provide consistent compass information, E-vector information from the relevant part of the sky (90° axis, 20°–90° elevation) has to

match AZD2281 the neuronal ΔΦmax values (absolute Φmax values normalized to the azimuth tuning). Importantly, polarized light information in this sky region changes with increasing solar elevation, as a result of the decreasing angular distance between the observed points and the sun ( Figure 1B; Figure S4). Because the DRA is exposed to a mixture of different E-vector angles at all times, we calculated the average perceived E-vector ( Figure 8C). Thereby, the contribution of individual E-vectors was weighted, based on the associated degree of polarization at the observed sky-point ( Figure S4). As the solar elevation changes predictably over the day, we calculated the mean perceived E-vector as a function of daytime for the date and location the migratory monarchs were captured (the last configuration of skylight cues they have experienced) ( Figure 8D). Indeed, the mean ΔΦmax value (29°) predicted with this function for the average recording time (ZT 5.4) closely matches the mean of the experimental data for monarchs (35°; p = 0.217) ( Figure 8A). Furthermore, the model predicts increasing ΔΦmax values at earlier and later times during the day. In fact, retrospective Selleck Talazoparib analysis of variation

in recording times around ZT 5 was consistent with time-dependent changes for E-vector tuning ( Figure S5). Overall, our data suggest that time-dependent adjustment of E-vector tunings provides a consistent representation of solar azimuth in the monarch sun compass over the course of the day. In the current studies, we have begun to unravel the anatomical and physiological properties of the essential sun compass system in migratory monarch butterflies. The results provide

a new synthesis of the navigational capabilities of migrating monarchs, which includes describing the structural similarity and functional equivalence between the locust and monarch sun compass network, defining how migrating monarchs integrate skylight cues for directional information, and proposing two distinct clock-compass interactions necessary for migration. We have shown that the central brain of the monarch butterfly contains all the brain regions associated with sun compass from navigation in other species (Homberg, 2004 and Sakura et al., 2008). These include the AOTu, the lateral triangle, the LAL, and all compartments of the CC. These homologies, particularly between the monarch butterfly and the desert locust, could be extended to the level of single neuronal cell types and subtypes (Table 1; Figure 3). Furthermore, the comparison of the distribution of pre- and postsynaptic endings within single cell types suggests highly similar patterns of connectivity, especially in specialized elements of the CC-polarization-vision network (TB1 and CL1 neurons; Heinze and Homberg, 2007 and Heinze and Homberg, 2009).

, 2010). However, the same dhc-1 mutation only buy Bleomycin subtly suppresses the DD phenotype of the cyy-1 cdk-5 double mutants, suggesting that additional downstream pathways are required in the remodeling process (data not shown). Second, the functions of CDK-5 appear to be different in these two cell types. Loss of cdk-5 results in marked increase in the number of both retrograde and anterograde-trafficking events in the DA9 axons, arguing that CDK-5 does not likely promote anterograde trafficking ( Ou et al., 2010). On the hand, CDK-5 facilitates UNC-104-mediated anterograde traffic during the DD remodeling process. Considering the numerous target substrates of

CDK-5,

it is conceivable that CDK-5 also facilitates anterograde trafficking, but this effect is masked by its effect in suppressing retrograde transport. Third, the cyy-1-activated PCTAIRE kinase, PCT-1, plays a more important role in DA9 than in DDs because loss of pct-1 alone causes a full penetrant phenotype in DA9 ( Ou et al., 2010), but not in DDs (data not shown). Further understanding of the molecular downstream players in the CYY-1 and CDK-5 pathway will elucidate the similarity and differences in these two cells. Strains and genetics, molecular biology, heat-shock experiment, and confocal imaging are described in the Supplemental Experimental Procedures. To precisely GPCR Compound Library molecular weight synchronize the worms at a stage, gravid adult worms were collected and allowed to lay eggs for 1 hr at 25°C. Eggs were placed at 25°C to develop for appropriate duration, mainly 11, 16, 18, 19.5, 22, and 26 hr for each experimental purpose. Then, the phenotype of DD synaptic remodeling was examined. We did not notice any obvious egg-laying

abnormalities for the mutant and transgenic strains we Edoxaban have used for our analysis. L1 worms around 16–18 hr after egg laying (i.e., before starting synaptic remodeling) were sampled under a coverslip in Levamisole (1 mM; Sigma). Worms expressing Dendra2::RAB-3 were identified by the expression of coinjection marker Podr-1::dsred. Dendra2::RAB-3 puncta in the DD2 ventral process were locally photoconverted using a 405 nm laser at 30 mW power for 20 s through 63× objective (NA 1.4). Eight to 10 hr after UV irradiation, photoconverted red fluorescent signals were examined and quantified. To measure the average fluorescence intensity, the V+D of DD neurons without the cell bodies were carefully traced, and the background intensity was subtracted from the intensity in the traced regions using ImageJ. The ratio of [D/(V+D)] GFP::RAB-3 was calculated by the following formula: average intensity of dorsal GFP::RAB-3/(average intensity of ventral GFP::RAB-3 + average intensity of dorsal GFP::RAB-3).

It also enabled us to make direct comparisons between our results from area 5d and earlier data from PRR and PMd (Pesaran et al., 2006, 2010). The data were aligned at movement onset (0 ms) and

the delay period was defined as −500 to −100 ms. For each neuron, mean firing rates during the delay period were converted into twelve firing rate response matrices, four for each of the three possible combinations of variables (TH, TG, HG; see Figure S1 available online). For example, a single 4-by-4 target-hand (TH) matrix represents the firing rates for all 16 different arrangements of target location and starting hand position, but with gaze position constant at, say, −20 degrees in all trials. The other three TH matrices have the same target and hand structure, but TSA HDAC in vivo are composed of trials in which gaze was located at −10, 0, or 10 degrees, respectively. Each element within a matrix therefore Adriamycin purchase represents the mean firing rate for a single trial type. The TG matrices, in which H was held constant, and the HG matrices, in which T was held constant, were formed similarly. The main analysis was conducted on the subset of matrices in which the third variable was held constant at the response field peak (e.g.,

gaze at −10 degrees for a TH matrix). This results in a set of three matrices per neuron, one for each variable pair (see Figure 3B and Figure S1). Figures 2A and 2B (left panels) illustrate how a matrix would appear for an idealized cell with a purely gain field relationship between a given pair of variables (T and H in this example). The peak of the

tuning curve for T remains located at the same extrinsic position (−10 degrees) for all values of H, with the effect of H being to scale the magnitude of the response. In other words, changes in H and T produce multiplicatively separable changes in the response of the cell. Etomidate Figure 2C shows the quite distinct “diagonal” pattern for an idealized cell that codes the extrinsic reach vector T-H: the peak of the tuning curve for T shifts as H is varied. The influence of the two variables cannot be separated from each other in this hand-centered reference frame for target position. Such a vector relationship need not involve full shifts (Figure 2D). Furthermore, cells may simultaneously represent both a vector and a postural gain field (Figure 2E). A population of cells of this type could contain a distributed code for the location of the target in head/body-centered space (Andersen et al., 1990; Zipser and Andersen, 1988). We used singular value decomposition (SVD) to determine whether each variable-pair matrix was separable or inseparable, and hence whether the defining relationship between a pair of variables for a cell was better described as a gain field or as a vector (Peña and Konishi, 2001; Pesaran et al.

One way to expand our research to more natural situations could be by changing the cost function to mimic an ecological survival game with perishable

outcomes. Such a paradigm would allow one to determine if subjects indeed follow a variance minimizing strategy and incorporate Paclitaxel cell line information about reward correlations. The recent financial crisis has amply demonstrated that even experts have difficulties regulating correlated risks in the financial domain and investors often deviate from rationality when making financial decisions (Daniel et al., 2002 and Kuhnen and Knutson, 2005). In contrast, we show here that individuals are adept at detecting and responding to correlations and appropriately selecting actions to minimize risk in an intricate learning task. Indeed, this exquisite sensitivity taps into an adaptive and evolutionary conserved ability of implicit neurobiological systems to learn environmental reward structure through trial-by-trial sampling; intrinsic behavior that might even supersede that of financial experts deciding about explicitly described statistics. Sixteen healthy subjects

(7 female; 18–35 years old) with no history of neurological or psychiatric illness participated in the study. Two additional pilot subjects from the lab were excluded from the final analysis, as they were already familiar with the hypotheses in the experiment. The study was approved by the Institute of Neurology (University College London) Research Ethics Committee. IWR-1 To investigate whether and how subjects learn the reward structure in the environment we designed a portfolio-mixing task in which knowledge of the correlation between two resource outcomes could improve Rolziracetam performance. Subjects’ task was to keep the combined output of two power

stations as stable as possible (i.e., minimize the variance of an energy portfolio) by mixing the fluctuating outcomes of these two individual resources. They accomplished this by adjusting weights that determined how the resources were linearly combined. A normative best performance is achievable in this task by finding a solution that directly depends on knowledge of the covariance structure of these resources, a task design that approximates a simple portfolio problem in finance (Markowitz, 1952). We presented the task to subjects as a resource management game that invoked a scenario whereby a power company generates fluctuating amounts of electricity from two renewable energy sources, a solar plant and a wind park. The resource outputs rsun and rwind were drawn as random numbers in every trial from distributions with a common mean M and variances σ2sun and σ2wind.

3C) was smaller than those in serum from poly(I:C)-immunized mice ( Fig. 3A), implying that general humoral components in saliva reduced KSHV infection to 293 cells. Consequently, these data suggest that the body fluids from KSHV-immunized mice are able to reduce the efficacy of in vitro KSHV infection to 293 cells. Some of the KSHV-encoded Libraries proteins were identified as immunogens in human so far [4] and [34]. Among them, six KSHV-encoded proteins, K8, K8.1, ORF26,

ORF59, ORF65, and ORF73 (LANA-1) were synthesized in E. coli as GST-fusion proteins to ascertain immunogens in KSHV-immunized mice [4]. Western blot revealed that GST-K8.1 and ORF59 proteins reacted more strongly with the serum from KSHV-intraperitoneally immunized mice than did other proteins ( Fig. 4A). The serum also produced faint bands in the lanes of K8, ORF26, and ORF65 proteins, but not of ORF73C and ORF73N. Immunofluorescence Selleck Alectinib assays using the serum and anti-KSHV-encoded protein antibodies demonstrated that the stain of the serum overlapped with those of K8.1 and ORF 59 frequently, of ORF26 and ORF65 partially, but not of K8 and ORF73. These data suggest that the serum of KSHV-immunized mice recognized AG 14699 mainly K8.1 and ORF59 protein, partially ORF26 and ORF65, but not K8 and ORF73. To know whether the KSHV-encoded proteins induce humoral

immunity in mice, these proteins with poly(I:C) were immunized intranasally and intraperitoneally to mice. IFA using KSHV-infected cells MTMR9 revealed that intranasal and intraperitoneal immunization with the protein induced serum IgG and IgA to KSHV in the mice (Fig. 5A and B). Intranasal immunizations with the proteins also induced IgA to KSHV in the NW and saliva, as effectively as immunization with KSHV particles and ORF73 protein (Fig. 5C and D). The neutralization assay revealed that the serum from mice intraperitoneally

immunized with GST-K8.1 reduced the numbers of KSHV-infected 293 cells in this assay (P < 0.05), whereas the serum from mice intraperitoneally immunized with ORF59 and ORF73 proteins did not reduce them significantly (P = 0.55, Fig. 6A). Neutralization activity of body fluid of K8.1-immunized mice was also shown in the NW of mice intranasally immunized with K8.1 protein (P < 0.01, Fig. 6B). These data suggest the neutralization activity of the antibodies to K8.1 in vitro. In the present study, we demonstrated that KSHV immunization resulted in cellular and humoral immune response in mice. Spleen cells from KSHV-immunized mice produced IFN-γ, and the serum, NW and saliva of KSHV-immunized mice neutralized KSHV infection to 293 cells in vitro. The serum of KSHV-immunized mice recognized KSHV-encoded K8.1 and ORF59 proteins. The serum and NW from K8.1-immunized mice neutralized KSHV infection to 293 cells in vitro as effectively as the serum from KSHV-immunized mice. These results suggest a possibility of mucosal vaccine using inactivated KSHV particles or recombinant K8.