It then takes a few tens of milliseconds before FGM also emerges

It then takes a few tens of milliseconds before FGM also emerges in the center of the figure in V1 (Lamme et al., 1999). The effects of attention are observed

at buy Afatinib yet later time points; attention first increases FGM in V4 and it then also boosts center modulation in V1 (Ogawa and Komatsu, 2006 and Roelfsema et al., 2007). One must be cautious when inferring connectivity from latency differences alone. For example, the effect of feedback to V1 may under some conditions be faster than influences caused by horizontal connections (Bair et al., 2003). However, the difference between the mechanisms for edge- and center-FGM is supported by a number of additional observations. First, task-driven attention boosted the representation

of the figure center and had less effect on the edge representation (Figure 8E). This implies that edge-FGM is largely stimulus driven, whereas center-FGM depends more on feedback from higher areas. Second, a previous study (Lamme et al., 1998a) showed that lesions in higher Ixazomib research buy visual areas reduce center FGM in V1 but leave edge modulation intact (see also Hupé et al., 1998). Third, we could reproduce the timing and the spatial profile of the visual responses, the FGM and the attentional modulation in V1 and V4 with a model that detects boundaries with local inhibition and uses excitatory feedback for region filling. These results imply that the mechanisms proposed by us are sufficient to explain the data. The enhancement of neuronal activity at boundaries occurs quickly (Lamme et al., 1999 and Nothdurft et al., the 2000) and is not strongly modulated by attention. Previous studies demonstrated that texture elements surrounded by dissimilar elements are more salient

(Joseph and Optican, 1996). Image elements that pop out cause stronger neuronal activity in visual cortex during an early response phase (Burrows and Moore, 2009, Kastner et al., 1997, Knierim and van Essen, 1992, Lamme et al., 1999, Lee et al., 2002, Nothdurft et al., 1999 and Ogawa and Komatsu, 2006) and a similar increase in V1 activity occurs at the location of an edge where the orientation changes abruptly (Nothdurft et al., 2000). These saliency effects also occur when animals ignore the stimulus (Knierim and van Essen, 1992) (but see Burrows and Moore, 2009), and even if they are anesthetized (Kastner et al., 1997, Nothdurft et al., 1999 and Nothdurft et al., 2000). Accordingly, image elements can pop out in psychophysics (Theeuwes et al., 2006) if they are not relevant to the task, although these effects are transient and disappear after 250 ms (Donk and van Zoest, 2008 and Joseph and Optican, 1996). It is likely that edge-FGM is related to neuronal responses in V1, V2, and V4 that reflect the assignment of the edge to the figural side, because borders “belong” to figures and not to the background (Zhou et al., 2000).

In contrast, diazepam had no significant effects

on the f

In contrast, diazepam had no significant effects

on the frequency of mIPSCs (Ctrl: 11.8 ± 1.99 Hz; DZ: 12.8 ± 2.4 Hz; DZ+Flu: 11.9 ± 2.1 Hz, n = 8; p = 0.139; one-way RM ANOVA) (Figures 5A and 5C). We then examined whether the impaired CF synapse elimination in GAD67+/GFP mice Selleck Y27632 is rescued by chronic application of diazepam. Elvax containing 0.5 mM diazepam or vehicle was implanted to the cerebellum of GAD67+/GFP mice at P10. Then, CF innervation was examined at P22–P31. In 49% of PCs (22/45) from vehicle-treated mice, CF-EPSCs with two or three discrete steps were elicited (Figure 5D) as in untreated GAD67+/GFP mice (Figure 2A). By marked contrast, large CF-EPSCs with single steps were elicited in 77% of PCs (50/65) in diazepam-treated GAD67+/GFP mice (Figure 5D).

Summary data show significant difference in the frequency distribution of PCs between the two groups (p = 0.011) (Figure 5D). Basic properties of CF-EPSCs were similar (Table S2), indicating that kinetics of CF-EPSCs was not altered by diazepam. GSK2118436 manufacturer When the diazepam application was started at P17, many PCs remained innervated by multiple CFs at P22–P31 (Figure 5E) with no significant difference between the diazepam- and vehicle-treated groups (p = 0.164). Taken together, these results strongly suggest that GABAergic inhibitory tone from P10 to P16 within the cerebellum is an important factor that regulates Mephenoxalone developmental CF synapse elimination. Next, we investigated which type of GABAergic synapses in the cerebellum is crucial for CF synapse elimination. We first evaluated GABAergic transmission onto GCs. Spontaneous IPSCs (sIPSCs)

were recorded in control and GAD67+/GFP GCs at P10–P13. Neither the amplitude (control: 50 ± 4.3 pA, n = 20; GAD67+/GFP: 40 ± 3.7 pA, n = 12; p = 0.138) nor the frequency (control: 2.2 ± 0.4 Hz, n = 20; GAD67+/GFP: 1.5 ± 0.2 Hz, n = 12; p = 0.179) of sIPSC was different between control and GAD67+/GFP GCs, indicating that GABAergic transmission onto GCs is not altered in GAD67+/GFP mice during the GAD67-sensitive period of CF synapse elimination. To narrow down the candidate GABAergic synapses responsible for CF synapse elimination, we generated conditional GAD67 knockout mice by intercrossing GAD67 floxed mice (Obata et al., 2008) with a D2CreN line (GluD2+/Cre) whose Cre gene was driven under the control of the GluD2 promotor (Hashimoto et al., 2011 and Yamasaki et al., 2011). Although GluD2 was previously thought to be a PC specific molecule, a recent study has demonstrated a low level of GluD2 expression in molecular layer interneurons (Yamasaki et al., 2011). Accordingly, in the D2CreN mice, Cre gene is expressed in not only PCs but also SCs and BCs, but is undetectable in other cell types (Yamasaki et al., 2011). Thus, in our conditional GAD67 KO mice, GAD67 was deleted from PCs, SCs and BCs (Figure S5), which we termed PC/SC/BC-GAD67 (−/−) mice.

The time course of this drop and recovery was cell type specific,

The time course of this drop and recovery was cell type specific, was correlated with changes in mEPSC amplitude, and was manifested across sleep-wake states. These data establish that homeostatic mechanisms within the intact CNS act to stabilize selleck kinase inhibitor neuronal firing rates in the face of sensory perturbations. Because we followed ensemble average firing rates, we do not know for certain that the average firing rates of individual neurons are restored to their predeprivation values. It is suggestive that the distribution of average firing

rates for baseline and MD6 is indistinguishable (Figure 2E), consistent with the interpretation that homeostatic regulation of firing in vivo is a cell-autonomous process that restores individual neurons back to an individual set point. However, we cannot exclude the alternative possibility that it is the

ensemble average that is regulated, while firing rates of individual neurons change over time and come to occupy a different point in the distribution. This would necessitate some kind of competitive network-level mechanism that enhances average firing of some neurons at the Idelalisib concentration expense of others to maintain the ensemble average (Hirase et al., 2001). While no such circuit-level mechanism has been identified within neocortex, there is strong evidence that neocortical neurons express cell-autonomous forms of homeostatic plasticity that could serve to regulate average firing (Desai et al., 2002, Maffei and Turrigiano, 2008 and Lambo and Turrigiano, 2013). Thus, the most likely scenario is that firing rate homeostasis

is implemented in a cell-autonomous manner and that there is a broad distribution of firing rate set points across neocortical neurons. Interestingly, heterogeneity in the homeostatic set point has been shown to improve performance in a network model of working memory (Renart et al., 2003), suggesting that this heterogeneity could be of biological significance. Acute lid suture abolishes stimulus-driven activity but has little effect on spontaneous thalamic firing rates (Linden et al., 2009), which may in part explain why there is no immediate drop in RSU firing on MD1. A MYO10 second important factor is the drop in firing of pFS cells at MD1, which may temporarily boost RSU activity by reducing inhibition from FS cells. Over time the desynchronized pre- and postsynaptic firing induced by lid suture is predicted to induce LTD (Linden et al., 2009), and the drop in RSU firing on MD2 correlates well with the induction of LTD within V1. Two days of MD during the critical period (P21–P33) induces depression of thalamocortical and intracortical excitatory synapses (Heynen et al., 2003, Khibnik et al., 2010, Maffei and Turrigiano, 2008 and Wang et al.

We have previously observed that recombinant tau fibrils will ind

We have previously observed that recombinant tau fibrils will induce aggregation of full-length intracellular tau in cultured cells and that aggregated forms of tau transfer between cells (Frost et al., 2009). Further, we found that intracellular tau fibrils are released free into the media, where they propagate aggregation by direct interaction

with native tau in recipient cells. An anti-tau antibody (HJ9.3) blocks this process by preventing Selleck Temsirolimus tau aggregate uptake into recipient cells (Kfoury et al., 2012). In addition to similar experiments with recombinant tau (Guo and Lee, 2011), others have shown that paired helical filaments from AD brain induce cytoplasmic tau aggregation (Santa-Maria et al., 2012). Injection of brain extract from human P301S

tau transgenic mice into the brains of mice expressing wild-type human tau induces assembly of wild-type human tau into filaments and spreading of pathology (Clavaguera et al., 2009). Similar effects occurred after injection of recombinant full-length or truncated tau fibrils, which caused rapid induction of NFT-like inclusions that propagated from injected sites to connected brain regions in a time-dependent manner (Iba et al., 2013). Selective tau expression in the entorhinal cortex caused late pathology in the axonal terminal zones in cells in the dentate gyrus and hippocampus, consistent with transsynaptic movement of aggregates (de Calignon et al.,

2012 and Liu et al., 2012). A growing body Talazoparib in vitro of work thus supports the idea that tau aggregates transfer between cells and might be targeted with therapeutic antibodies. In mouse models that mimic aspects of AD and Parkinson’s disease, passive immunization using antibodies against Aβ and alpha synuclein can reduce Aβ and alpha-synuclein deposition in brain (Bard et al., 2000, DeMattos et al., 2001 and Masliah et al., 2011) and improve behavioral deficits (Dodart et al., 2002, Kotilinek et al., 2002 and Masliah et al., 2011). Active immunization in tauopathy mouse models using tau phospho peptides reduced tau pathology (Bi et al., 2011 and Boimel et al., 2010) and in some studies improved behavioral deficits because (Asuni et al., 2007, Boutajangout et al., 2010 and Troquier et al., 2012). In two passive vaccination studies, there was reduced tau pathology and improved motor function when the antibody was given prior to the onset of pathology (Boutajangout et al., 2011 and Chai et al., 2011). While several of the tau immunization studies appear to show some beneficial effects, the maximal expected efficacy of anti-tau antibodies administered after the onset of pathology, the optimal tau species to target, and the mechanism of the therapeutic effect have remained unknown. Our prior work in cell culture has suggested that aggregate flux in and out of cells might be central to progressive pathology (Kfoury et al., 2012).

Thus, OMI measures the relative

Thus, OMI measures the relative PD-0332991 order change in firing rate during odor application compared to baseline conditions and ranges from −1 (complete suppression of activity) to +1 (strongly driven responses). Indeed, this analysis showed that photostimulation had a suppressive action on odor responses regardless of whether the firing rate of individual odor-cell pairs was increased (p < 0.001, n = 22) or decreased (p < 0.05, n = 18) by the odor alone (Wilcoxon signed-rank test; Figure 8F). We also asked whether there was any relationship between the effects of cortical activation on spontaneous and odor-evoked responses within individual cells. To address this, we calculated a light modulation

index (LMI) ((RLED – RControl)/(RLED + RControl), where RLED = average firing rate with photostimulation,

Afatinib RControl = average rate without photostimulation) to compare the relative effects of cortical activation on both spontaneous and odor-evoked firing for each odor-cell pair (LMI ranges from −1 for complete suppression of firing by photostimulation, to +1 indicating strong enhancement of the response). This analysis revealed little correlation (r = 0.5, Spearman’s correlation coefficient) between the effects of photostimulation on spontaneous activity and responses to odors within individual cells (Figure 8G). However, across the population of M/T cells, the effect of cortical activation on odor-modulated activity was significantly greater than that on spontaneous activity (p < 0.05, Wilcoxon signed-rank

test). Thus, the effect of cortical feedback on M/T cell activity is context-dependent such that cortical activity preferentially suppresses M/T cell responses during sensory stimulation. In additional recordings, we considered whether the cortical modulation of M/T cell activity was related to features of the sensory stimulus. We investigated whether the cortical suppression of M/T cell responses depended on odor identity by examining M/T single units tested with three different odors at matched concentrations SB-3CT (50 ppm; Figure S2). Across this cell population (n = 35 single units, nine mice), cortical activation significantly suppressed odor-evoked M/T cell activity (p < 0.001, Wilcoxon signed-rank test). However, the proportion of M/T cells in which odor responses were selectively modulated (suppression of responses to only one or two of the tested odors versus suppression of responses to all three odors) was not significant (Figure S2). Thus, under our conditions, the effects of cortical feedback on M/T cell responses were not highly specific to particular odors. We next asked whether the actions of cortical feedback on odor-evoked M/T cell responses depended on odor intensity by examining responses of cells (n = 30 single units, 12 mice) to the same odor at three different concentrations.

, 2007; see Chédotal, 2011 for a review) Interestingly, DCC has

, 2007; see Chédotal, 2011 for a review). Interestingly, DCC has been shown to associate with the protein synthesis machinery and to regulate protein translation in axons ( Brittis et al., 2002; Tcherkezian et al., 2010). Therefore, a dysregulation of axonal protein synthesis following a failure of axon midline crossing could lead to expression changes of presynaptic proteins, and/or trophic factors relevant for the maturation of synapse function. It was shown recently that the absence of RIM1 and RIM2 proteins at the calyx of Held results in a marked reduction of presynaptic

Ca2+ currents, and a smaller fast-releasable vesicle pool ( Han et al., 2011). The variable Ca2+ current density and smaller vesicle pools observed here in Robo3 cKO mice are reminiscent of the RIM1/2

KO phenotype. Everolimus chemical structure It is possible that the decreased presynaptic function of calyx synapses of Robo3 cKO mice is the consequence of reduced levels of RIM protein, or of other proteins involved in the functional organization of active zones ( Schoch and Gundelfinger, BVD-523 research buy 2006). It is noteworthy that while functional maturation of Ca2+ channel-release coupling is well documented at the calyx synapse ( Chuhma et al., 2001; Fedchyshyn and Wang, 2005; Taschenberger and von Gersdorff, 2000), the underlying changes in presynaptic protein expression and/or post-translational changes of presynaptic proteins are largely unknown (but see Yang et al., 2010). We observed that the functional maturation of

most calyces of Held was defective in Robo3 cKO mice, while the initial formation of the typical calyx structure, despite a moderate synapse elimination deficit, was largely unchanged. Therefore, it seems that a program of morphological Mephenoxalone growth of calyces was not strongly affected in Robo3 cKO mice. It has been shown that unilateral inner ear removal and the ensuing degeneration of the cochlear nucleus and denervation of the contralateral MNTB, leads to sprouting of GBC axons which can form ipsilateral calyces of quite typical morphology (Hsieh et al., 2007; Kitzes et al., 1995). In this denervation paradigm, a program of morphological calyx formation also seems to take place readily. Of note, denervation-induced ipsilateral calyces arise from axons that have already successfully crossed the midline. Therefore, ipsilateral calyces formed after denervation might show normal functional maturation, a possibility that should be tested in future work. The trophic factors and signaling molecules that drive the morphological development of the highly specialized calyx-type synapses, which are found on several levels of the lower auditory system (Grothe et al., 2010), are just beginning to be investigated (Nakamura and Cramer, 2011).

This interaction effect showed to be not significant (IRR = 0 70,

This interaction effect showed to be not significant (IRR = 0.70, 95% CI = 0.35–1.38, p = 0.301). This study is the first to show the importance of passive (imitation)

peer influence VX770 over and above the impact of active (pressure) peer influence on young adult smoking in an experimental design. In our study, peer smoking increased significantly young adults’ likelihood to smoke more cigarettes while peer pressure did not. In the literature, peer smoking is suggested to tap into the passive peer influence, and the underlying mechanism in experimental studies and survey studies on smoking is often contributed to imitation. Students confronted with smoking peers are more likely to smoke regardless of being offered a cigarette or not: seeing is doing. Several theoretical models may explain the underlying mechanisms leading to imitation of behavior of others. One of these theories that have frequently been examined in previous studies is social conformity (see also a meta-analysis of Bond and Smith, 1996). Solomon Asch’s

work showed that in a group setting participants conform to the norm of the group, i.e., they tended to conform to the behavior of the other group members (Asch, 1951). Thus, social conformity may explain our findings and imply that young adults imitating peer smoking have been intentional. However, in our study we tested peer dyads and not peer groups. There is evidence that conformity of people is more likely to occur in groups than in dyads, and thus this explanation may have played a minor role in our present study. Another SB203580 molecular weight possible explanation is that imitating the other in human interaction may reflect a basic instinct in human beings that might even be biological in origin, as has been shown by studies on the importance of imitation for social interaction and social

development of animals (Hurley and Chater, 2005). An alternative theory to explain our findings is the cue-reactivity paradigm. According to this paradigm, smokers react to smoking-related mafosfamide cues/stimuli (e.g., handling a lit cigarette, ashtrays, lighters, or smelling another person’s cigarette) in their environment by an increase in craving to smoke (see also meta-analyses of Carter and Tiffany, 1999 and Conklin et al., 2008). The smoking-related cues of ashtrays, lighters and package of cigarettes were present in all four conditions, although handling a lit cigarette and smelling another person’s cigarette were only present in the condition were the confederate smoked. Thus, these latter two smoking-related cues may have elicited craving in the daily smoking young adults and triggered them to smoke. However, in our previous experimental study (Harakeh and Vollebergh, in press) we excluded in our research design the alternative hypothesis concerning smelling another person’s cigarette smoke. These findings showed that when the participant interacted with a smoking peer through the internet and webcam (i.e.

, 1998) The consistently very shallow slopes indicate that beta

, 1998). The consistently very shallow slopes indicate that beta oscillations emerge with only small time delays throughout the cortical-BG network. Overall, our results are consistent click here with ∼20 Hz beta having a selective, distinct role in coordinating information processing within the BG of normal behaving animals. To explore beta timing in more detail, we examined trial-by-trial LFP traces during GO trials (Figure 3A). Epochs of high

beta power appeared to occur stochastically, with some task events either increasing (Cue) or diminishing (Side In) the probability of entering this beta state. Around detected movement onset (Nose Out) the pattern of beta power change was unexpectedly complex, showing a marked dependence on reaction time. For the most rapid responses, the beta ERS began around the time of movement

onset and peaked shortly afterwards (Figures 3A and 3B). On trials with slower responses, the beta ERS began well before movements and was mostly completed by movement onset. To quantify this phenomenon we compared beta power for fast- selleckchem versus slow-RT trials during the 300 ms epochs immediately preceding and following movement onset ( Figure 3B, top). In both epochs all subjects had a significant difference in beta power (paired t tests before Nose out: for 3 rats p < 10−4, for the other p = 0.024; after Nose out: p < 10−3 for all rats). In addition, we calculated

correlation coefficients between beta power and reaction time at each moment during task performance ( Figure 3B, bottom). A strong positive correlation was found about 750 ms after the Cue event, driven by the ERD that is maximal around movement completion (see Kühn et al., 2004 and Williams et al., 2005 for related observations in humans). In addition, a smaller but reliable correlation occurred ∼30–100 ms before movement initiation. This suggests that the presence of the high-beta state during a critical period delays movement onset, consistent with evidence in humans associating increased beta power Cell press with slower movements ( Levy et al., 2002, Brown et al., 2001, Chen et al., 2007 and Pogosyan et al., 2009). The Go/NoGo task variant (Figure 3C) is similar to the Immediate-Go task, except that there are three possible instruction cues: Go left, Go right, or hold in place (NoGo). As before, simply holding before the instruction cue was not associated with elevated beta. However, both Go and NoGo cues were similarly followed after several hundred milliseconds by a beta ERS (Figures 3D and 3E). This observation suggests that planning not to move is also associated with enhanced beta and confirms that the main beta ERS that we analyze here is not rigidly linked to either movement initiation or suppression. At the same time, we observed two interesting differences between GO and NOGO trials.

To date, treatment options for metastatic uveal melanoma are limi

To date, treatment options for metastatic uveal melanoma are limited, and compelling evidence that any systemic therapy, including chemotherapy, improves overall survival is lacking.6 Disease stabilization is described in several patients receiving ipilimumab, which recently has shown survival benefit in metastatic cutaneous melanoma patients.22 However, data are based on a limited number of patients.23 and 24 Therefore, effective therapies resulting in meaningful clinical benefit are required urgently, and immunotherapy may be a promising treatment method. Immune-based ATM Kinase Inhibitor ic50 therapies

aim to induce antitumor immunity. Despite uveal melanoma developing in the immune-privileged environment of the eye, immune cells have been found within uveal melanoma, including dendritic cells and T cells.25, 26 and 27 Dendritic cells are antigen-presenting cells with the MLN8237 unique capacity to activate naïve antigen-specific T cells, and hence are suitable for inducing immunologic

antitumor responses (Figure 1). Dendritic cell-based immunotherapy has shown promising results in cutaneous melanoma patients.28 Although uveal and cutaneous melanoma are different biologically, cutaneous melanoma and uveal melanoma share many antigenic features, including tumor antigens, providing a rationale for the application of dendritic cell-based therapies in uveal melanoma. The tumor antigens used in our dendritic cell vaccination studies for metastatic melanoma patients, gp100 and tyrosinase, are both expressed in most human uveal melanoma tumor cells,29 and 30 and thus constitute an appropriate target for immunotherapy in uveal melanoma. Our research group has performed several prospective dendritic cell vaccination studies in patients with melanoma, of which most consisted of patients with cutaneous melanoma. We here present data on the subset of metastatic uveal melanoma patients who were enrolled in these studies. The studies were approved by the Dutch Centrale Commissie Mensgebonden Onderzoek

(Central Committee on Research Involving Human Subjects), and written informed consent to Modulators participate in research was obtained from all patients. The trials were registered at (identifiers also NCT00940004, NCT01690377, NCT01530698, and NCT00243529). We analyzed a cohort of 14 patients with metastatic uveal melanoma who were enrolled in our prospective dendritic cell vaccination studies between October 2002 and May 2011. Patients were required to have at least 1 measurable target lesion. Additional inclusion criteria were melanoma expressing the melanoma-associated antigens gp100 (compulsory) and tyrosinase (noncompulsory), HLA-A*02:01 phenotype (protocols I, III, IV, V, and VI), known HLA-DRB*01:04 status (protocol IV), and World Health Organization performance status 0 or 1. Patients with serious concomitant disease or a history of second malignancy were excluded.

gingivalis (103 CFU) into the gums of ICR mice everyday for 3 day

gingivalis (103 CFU) into the gums of ICR mice everyday for 3 days induced greater gum swelling than Libraries injection of individual bacterium (data not shown), suggesting that bacterial co-aggregation exacerbates gum inflammation. To examine if FomA contributes to the exacerbation of gum inflammation, F. nucleatum (4 × 108 CFU) was neutralized with either anti-FomA or anti-GFP serum [2.5% (v/v)] prior to mixing with P. gingivalis (103 CFU). To induce gum inflammation, this bacterial mixture was injected into the gums of the lower incisors of naïve ICR mice everyday for 3 days. learn more Three days after injection, the severity of gum swelling was recorded for 4

days. Injection of P. gingivalis with anti-GFP serum-neutralized F. nucleatum induced a swollen gum with the volume ranging E7080 in vivo from 2.95 to 7.36 mm3. The greatest degree of swelling (7.36 ± 0.12 mm3) was observed on the day 3 after recording ( Fig. 4A and B). The gum swelling was significantly suppressed when the gum was injected with P. gingivalis along with anti-FomA serum-neutralized F. nucleatum. These results reveal the essential role of FomA in bacterial co-aggregation-induced gum inflammation and further supported FomA as a potential therapeutic

target for treatment of bacterial co-aggregation-associated diseases. To evaluate if FomA can be a valuable target for the development of vaccines against periodontal infection, mice were immunized with UV-inactivated-E. coli BL21(DE3) FomA or GFP for 9 weeks. To induce inflammation, the gums of lower incisors in the immunized mice were challenged with live F. nucleatum (4 × 108 CFU) alone, P. gingivalis (103 CFU) alone, and F. nucleatum plus P. gingivalis (4 × 108/103 CFU) everyday for 3 days. The severity of bacteria-induced gum swellings was measured daily for 4

days after 3-day challenge. Vaccination with E. coli BL21(DE3) FomA or GFP did not make a significant difference in of the amount of gum swelling induced by the injection of F. nucleatum alone or P. gingivalis alone ( Fig. 5A). However, compared to the mice immunized with E. coli BL21(DE3) GFP, the amount of others gum swelling induced by co-injection of F. nucleatum and P. gingivalis was considerably attenuated in the mice immunized with E. coli BL21(DE3) FomA. Histological examination by H&E staining illustrated the gum inflammation with thickened gum epithelium and gramulomatsis. In addition, there was greater inflammation caused by bacterial co-injection in the GFP-immunized mice than in the FomA-immunized mice ( Fig. 5B). Previous studies have shown that the induction of pro-inflammatory cytokines plays a crucial role in the pathogenesis of periodontal infection [30]. To determine whether immunization with FomA alters the level of bacterial co-injection-induced pro-inflammatory cytokines, MIP-2 cytokine in swollen gums was quantified by ELISA. On day 2 following a 3-day challenge with both F. nucleatum and P. gingivalis, a significant elevation in the level of MIP-2 (15,528.88 ± 68.