Alterations of sensory cell activity in the thalamic reticular nucleus by prefrontal cortex activation in anesthetized rats.

The thalamic reticular nucleus (TRN), receiving excitatory inputs from thalamic nuclei and cortical areas, regulates thalamic sensory processing through its inhibitory projections to thalamic nuclei. Higher cognitive function has been shown to affect this regulation from the prefrontal cortex (PFC). The present study examined how activation of the PFC modulates auditory or visual responses of single TRN cells in anesthetized rats, using juxta-cellular recording and labelling techniques. Electrical microstimulation of the medial PFC did not evoke cell activities in the TRN, but it altered sensory responses in the majority of auditory (40/43) and visual cells (19/20) with regard to response magnitude, latency and/or burst spiking. Alterations in response magnitude were bidirectional, either facilitation or attenuation, including induction of de novo cell activity and nullification of sensory response. Response modulation was observed in early (onset) and/or recurrent late responses. PFC stimulation, either before or after early response, affected late response. Alterations occurred in the two types of cells projecting to the first- and higher-order thalamic nuclei. Further, auditory cells projecting to the somatosensory thalamic nuclei were affected. Facilitation was induced at relatively high incidences as compared with that in the sub-threshold intra- or cross-modal sensory interplay in the TRN where attenuation is predominated in bidirectional modulation. Highly complex cooperative and/or competitive interactions between the top-down influence from the PFC and bottom-up sensory inputs are assumed to take place in the TRN to adjust attention and perception depending on the weights of external sensory signals and internal demands of higher cognitive function.

Molecular ratio of mature B-type natriuretic peptide in acute heart failure: an indicator for ventricular contractile recovery.

AIMS: The methodology to distinguish between the heart failure (HF) with recovered ejection fraction (HFrecEF) and those with continuously reduced ejection fraction (EF) (HFcrEF) on admission has not been established. We recently demonstrated that the ratio of plasma levels of pro-B-type natriuretic peptide (proBNP) to total BNP (proBNP plus mature BNP) is decreased on admission in patients with mild acute HF, but not in severe acute HF as a compensatory mechanism for activating cyclic GMP via increases of bioactive mature BNP. We aimed to test the hypothesis that the ratio of bioactive mature BNP to total BNP is associated with reverse remodelling capacity in patients with HF with reduced EF. METHODS AND RESULTS: Plasma proBNP and total BNP were measured in patients with acute decompensated HF by using specific and sensitive enzyme immunochemiluminescent assay. Estimated percent mature BNP (%emBNP) was calculated as ([total BNP - proBNP]/total BNP) × 100. We retrospectively identified the patients with reduced EF (≤40%, on admission) who had echocardiographic data after discharge (n = 93). We defined patients with increased EF by >10% during the follow-up term (median, 545 days) after the admission as HFrecEF group. We compared patient characteristics, %emBNP, and other biomarkers between HFrecEF and HFcrEF. Of the enrolled patients with HFrecEF (n = 32) and HFcrEF (n = 61), on admission, %emBNP was significantly higher in HFrecEF than in HFcrEF (44.1% vs. 36.9%; P < 0.05). There were no significant differences in left ventricular EF on admission between the two groups. The univariate analysis revealed that %emBNP on admission was associated with HFrecEF occurrence rate (P < 0.05), in contrast both total BNP and high-sensitive cardiac troponin-T levels were not associated with HFrecEF occurrence rate. CONCLUSIONS: The ratio of mature BNP to total BNP in plasma at the time of hospital admission may be predictive of left ventricular contractile recovery. Preservation of the capacity to convert proBNP to mature BNP, but not myocardial injury itself, is associated with future ventricular contractile recovery.

Sound Intensity-dependent Multiple Tonotopic Organizations and Complex Sub-threshold Alterations of Auditory Response Across Sound Frequencies in the Thalamic Reticular Nucleus.

The thalamic reticular nucleus (TRN), a cluster of GABAergic cells, modulates sensory attention and perception through its inhibitory projections to thalamic nuclei. Cortical and thalamic topographic projections to the auditory TRN are thought to compose tonotopic organizations for modulation of thalamic auditory processing. The present study determined tonotopies in the TRN and examined interactions between probe and masker sounds to obtain insights into temporal processing associated with tonotopies. Experiments were performed on anesthetized rats, using juxta-cellular recording and labeling techniques. Following determination of tonotopies, effects of sub-threshold masker sound stimuli on onset and late responses evoked by a probe sound were examined. The main findings are as follows. Tonotopic organizations were recognized in cell location and axonal projection. Tonotopic gradients and their clarities were diverse, depending on sound intensity, response type and the tiers of the TRN. Robust alterations in response magnitude, latency and/or burst spiking took place following masker sounds in either a broad or narrow range of frequencies that were close or far away from the probe sound frequency. The majority of alterations were suppression recognizable up to 600 ms in the interval between masker and probe sounds, and directions of alteration differed depending on the interval. Finally, masker sound effects were associated with tonotopic organizations. These findings suggest that the auditory TRN is comprised of sound intensity-dependent multiple tonotopic organizations, which could configure temporal interactions of auditory information across sound frequencies and impose complex but spatiotemporally structured influences on thalamic auditory processing.

A case report of primary cardiac fibroma: an effective approach for diagnosis and therapy of a pathologically benign tumour with an unfavourable prognosis.

BACKGROUND: Primary cardiac fibroma is exceedingly rare. This condition involves a significant risk of life-threatening arrhythmias during follow-up and its prognosis is not as favourable as other benign tumours. We report a case of cardiac fibroma that was preoperatively diagnosed with echocardiography and magnetic resonance imaging. This fibroma was excised early as a preventative measure to avoid sudden death. CASE SUMMARY: A 46-year-old woman presented to our hospital with a 1-year history of chest tightness at rest. Echocardiography showed a large, isoechoic, well-circumscribed mass within the left ventricular myocardium with calcified tissue. Magnetic resonance imaging showed an intramural ventricular mass with iso signal intensity on T1-weighted imaging and low-signal intensity on T2-weighted imaging. There was no enhancement on first-pass perfusion imaging and homogeneous hyperenhancement on late gadolinium enhancement imaging. These features suggested a diagnosis of cardiac fibroma. Complete resection was performed to avoid sudden death and pathological analysis confirmed the tumour as cardiac fibroma. The patient was discharged 9 days after surgery and remains disease-free 5 months after surgery. DISCUSSION: Cardiac fibroma is a pathologically benign tumour with an unfavourable prognosis because of lethal arrhythmias, which can be controlled by its resection. Thus, it is important to preoperatively distinguish cardiac fibroma from other benign tumours, in order to prioritize surgical intervention for those with cardiac fibromas. Preoperative diagnosis with echocardiography and magnetic resonance imaging and early preventative surgery are the keys to improve prognosis of patients with cardiac fibromas.

Significance of medial preoptic area among the subcortical and cortical areas that are related to pain regulation in the rats with stress-induced hyperalgesia.

Psychophysical stresses frequently increase sensitivity and response to pain, which is termed stress-induced hyperalgesia (SIH). However, the mechanism remains unknown. The subcortical areas such as medial preoptic area (MPO), dorsomedial nucleus of the hypothalamus (DMH), basolateral (BLA) and central nuclei of the amygdala (CeA), and the cortical areas such as insular (IC) and anterior cingulate cortices (ACC) play an important role in pain control via the descending pain modulatory system. In the present study we examined the expression of phosphorylated -cAMP-response element binding protein (pCREB) and the acetylation of histone H3 in these subcortical and cortical areas after repeated restraint stress to reveal changes in the subcortical and cortical areas that affect the function of descending pain modulatory system in the rats with SIH. The repeated restraint stress for 3 weeks induced a decrease in mechanical threshold in the rat hindpaw, an increase in the expression of pCREB in the MPO and an increase in the acetylation of histone H3 in the MPO, BLA and IC. The MPO was the only area that showed an increase in both the expression of pCREB and the acetylation of histone H3 among these examined areas after the repeated restraint stress. Furthermore, the number of pCREB-IR or acetylated histone H3-IR cells in the MPO was negatively correlated with the mechanical threshold. Together, our data represent the importance of the MPO among the subcortical and cortical areas that control descending pain modulatory system under the condition of SIH.

Cross-modal modulation of cell activity by sound in first-order visual thalamic nucleus.

Cross-modal auditory influence on cell activity in the primary visual cortex emerging at short latencies raises the possibility that the first-order visual thalamic nucleus, which is considered dedicated to unimodal visual processing, could contribute to cross-modal sensory processing, as has been indicated in the auditory and somatosensory systems. To test this hypothesis, the effects of sound stimulation on visual cell activity in the dorsal lateral geniculate nucleus were examined in anesthetized rats, using juxta-cellular recording and labeling techniques. Visual responses evoked by light (white LED) were modulated by sound (noise burst) given simultaneously or 50-400 ms after the light, even though sound stimuli alone did not evoke cell activity. Alterations of visual response were observed in 71% of cells (57/80) with regard to response magnitude, latency, and/or burst spiking. Suppression predominated in response magnitude modulation, but de novo responses were also induced by combined stimulation. Sound affected not only onset responses but also late responses. Late responses were modulated by sound given before or after onset responses. Further, visual responses evoked by the second light stimulation of a double flash with a 150-700 ms interval were also modulated by sound given together with the first light stimulation. In morphological analysis of labeled cells projection cells comparable to X-, Y-, and W-like cells and interneurons were all susceptible to auditory influence. These findings suggest that the first-order visual thalamic nucleus incorporates auditory influence into parallel and complex thalamic visual processing for cross-modal modulation of visual attention and perception.

Impact of body temperature at admission on inhospital outcomes in patients with takotsubo syndrome: insights from the Tokyo Cardiovascular Care Unit Network Registry.

BACKGROUND: Takotsubo syndrome occasionally occurs in patients with fever due to underlying diseases. However, the impact of body temperature on inhospital prognosis of patients with takotsubo syndrome remains unknown. METHODS: Using the patient cohort in the Tokyo Cardiovascular Care Unit Network Registry from 2013 to 2015, we identified 421 eligible patients whose data on body temperature at admission were available and classified them into three groups: high body temperature group (≥37.5°C; n=27), normal body temperature group (36.0-37.4°C; n=319), and low body temperature group (≤35.9°C; n=75). We compared the patient characteristics and inhospital outcomes among the three groups. RESULTS: On admission, the high body temperature group showed a higher proportion of men and preceding physical triggers, higher heart and respiratory rates, and higher C-reactive protein level than the other groups. Inhospital all-cause mortality was significantly higher in the high body temperature group than in the normal or low body temperature group (18.5% vs. 2.2% vs. 4.0%, respectively, P<0.001). Both cardiac mortality (11.1% vs. 1.3% vs. 1.3%, P=0.001) and non-cardiac mortality (7.4% vs. 0.9% vs. 2.7%, P=0.031) were also significantly higher in the high body temperature group. Multivariable logistic regression analysis showed that high body temperature (reference: normal body temperature) was significantly associated with higher inhospital mortality (adjusted odds ratio 4.22; 95% confidence interval 1.15-15.51; P=0.030). CONCLUSIONS: Our findings suggest that high body temperature at admission is a strong predictor of inhospital mortality in patients with takotsubo syndrome. Febrile takotsubo syndrome patients may need to be managed with recognition of life-threatening conditions from the time of diagnosis, no matter what the causes of fever are.

Apical Takotsubo syndrome versus anterior acute myocardial infarction: findings from the Tokyo Cardiovascular Care Unit network registry.

BACKGROUND:: Although the typical apical form of Takotsubo syndrome and anterior acute myocardial infarction have similar electrocardiographic and echocardiographic presentations, data on the clinical differences between the two disorders are limited. METHODS:: Using the Tokyo Cardiovascular Care Unit network registry, we identified patients hospitalised with apical Takotsubo syndrome ( n=540; 2010-2014) or anterior acute myocardial infarction ( n=2,806; 2013-2014) and created 522 age and sex-matched pairs (mean age 74.1 years; women 78.5%). We compared the clinical characteristics and inhospital outcomes between the two groups. RESULTS:: On admission, patients with apical Takotsubo syndrome showed a lower body mass index, less frequent chest pain/tightness, lower systolic blood pressure, higher heart rate, lower creatine kinase, higher C-reactive protein and brain natriuretic peptide, and less frequent ST-elevation than patients with anterior acute myocardial infarction. Patients with apical Takotsubo syndrome received catecholamine (12.8% vs. 24.5%, P<0.001) and intra-aortic balloon pumping (5.9% vs. 15.1%, P<0.001) less frequently. Despite similar all-cause mortality (5.4% vs. 7.9%, P=0.134), patients with apical Takotsubo syndrome showed lower cardiac mortality (2.1% vs. 6.7%, P<0.001; risk difference -4.6% (95% confidence interval -7.1% to -2.1%)) but higher non-cardiac mortality (3.3% vs. 1.1%, P=0.033; 2.1% (0.3%-3.9%)). In subgroup comparisons, patients with physically triggered Takotsubo syndrome had higher non-cardiac mortality (7.0%) than those with non-physically triggered Takotsubo syndrome (1.2%, P=0.001) or anterior acute myocardial infarction (1.1%, P<0.001). CONCLUSIONS:: This study found that cardiac and non-cardiac mortality risks differed significantly between apical Takotsubo syndrome and anterior acute myocardial infarction. Our findings underscore the importance of differentiating between the two disorders for appropriate management.

Increase of histone acetylation in the GABAergic neurons in the rostral ventromedial medulla associated with mechanical hypersensitivity after repeated restraint stress.

Psychophysical stresses frequently increase sensitivity and response to pain, which is termed stress-induced hyperalgesia (SIH). However, the mechanism remains unknown. The rostral ventromedial medulla (RVM) and locus coeruleus (LC) are core elements of the descending pain modulatory system, which modulate nociceptive transmission in the spinal dorsal horn. In the present study we examined the acetylation of histone H3 in the RVM and LC after repeated restraint stress for 3 weeks to clarify changes in the descending pain modulatory system in the rat with SIH. The repeated restraint stress induced mechanical hypersensitivity in the hindpaw and an increase in acetylation of histone H3 in the RVM but not the LC. The number of acetylated histone H3-IR cells in the RVM was significantly higher in the repeated restraint group (282.9 ± 43.1) than that in the control group (134.7 ± 15.6, p < 0.05). Furthermore, the repeated restraint stress increased acetylation of histone H3 in the RVM GABAergic neurons but not the RVM serotonergic neurons. The GAD67 protein level in the RVM was significantly higher in repeated restraint group (144.9 ± 17.0%) than that in the control group (100.0 ± 8.9%, p < 0.05). These findings suggest the possibility that the stress-induced neuroplasticity in the RVM GABAergic neurons is involved in the mechanical hypersensitivity due to the dysfunction of the descending pain modulatory system.

A Mass Filling the Right Atrium: Primary Cardiac Rhabdomyosarcoma.

A 43-year-old woman presented with worsening shortness of breath and lower-extremity edema. Echocardiography and computed tomography showed obstruction of blood flow due to a mass filling the right atrium. Emergency surgery was performed for circulatory failure. Primary cardiac rhabdomyosarcoma was diagnosed based on a histological examination. The patient died about two months after the diagnosis despite surgical excision and radiation therapy. The poor prognosis may have resulted from the grossly incomplete removal of the tumor and chemotherapy intolerance. We herein report a case of primary cardiac rhabdomyosarcoma filling the right atrium and offer possible reasons for the poor prognosis.

Robust Subthreshold Cross-modal Modulation of Auditory Response by Cutaneous Electrical Stimulation in First- and Higher-order Auditory Thalamic Nuclei.

Conventional extracellular recording has revealed cross-modal alterations of auditory cell activities by cutaneous electrical stimulation of the hindpaw in first- and higher-order auditory thalamic nuclei (Donishi et al., 2011). Juxta-cellular recording and labeling techniques were used in the present study to examine the cross-modal alterations in detail, focusing on possible nucleus and/or cell type-related distinctions in modulation. Recordings were obtained from 80 cells of anesthetized rats. Cutaneous electrical stimulation, which did not elicit unit discharges, i.e., subthreshold effects, modulated early (onset) and/or late auditory responses of first- (64%) and higher-order nucleus cells (77%) with regard to response magnitude, latency and/or burst spiking. Attenuation predominated in the modulation of response magnitude and burst spiking, and delay predominated in the modulation of response time. Striking alterations of burst spiking took place in higher-order nucleus cells, which had the potential to exhibit higher propensities for burst spiking as compared to first-order nucleus cells. A subpopulation of first-order nucleus cells showing modulation in early response magnitude in the caudal domain of the nucleus had larger cell bodies and higher propensities for burst spiking as compared to cells showing no modulation. These findings suggest that somatosensory influence is incorporated into parallel channels in auditory thalamic nuclei to impose distinct impacts on cortical and subcortical sensory processing. Further, cutaneous electrical stimulation given after early auditory responses modulated late responses. Somatosensory influence is likely to affect ongoing auditory processing at any time without being coincident with sound onset in a narrow temporal window.

Attenuation of pCREB and Egr1 expression in the insular and anterior cingulate cortices associated with enhancement of CFA-evoked mechanical hypersensitivity after repeated forced swim stress.

The perception and response to pain are severely impacted by exposure to stressors. In some animal models, stress increases pain sensitivity, which is termed stress-induced hyperalgesia (SIH). The insular cortex (IC) and anterior cingulate cortex (ACC), which are typically activated by noxious stimuli, affect pain perception through the descending pain modulatory system. In the present study, we examined the expression of phospho-cAMP response element-binding protein (pCREB) and early growth response 1 (Egr1) in the IC and ACC at 3h (the acute phase of peripheral tissue inflammation) after complete Freund's adjuvant (CFA) injection in naïve rats and rats preconditioned with forced swim stress (FS) to clarify the effect of FS, a stressor, on cortical cell activities in the rats showing SIH induced by FS. The CFA injection into the hindpaw induced mechanical hypersensitivity and increased the expression of the pCREB and Egr1 in the IC and ACC at 3h after the injection. FS (day 1, 10min; days 2-3, 20min) prior to the CFA injection enhanced the CFA-induced mechanical hypersensitivity and attenuated the increase in the expression of pCREB and Egr1 in the IC and ACC. These findings suggested that FS modulates the CFA injection-induced neuroplasticity in the IC and ACC to enhance the mechanical hypersensitivity. These findings are thought to signify stressor-induced dysfunction of the descending pain modulatory system.

Robust interactions between the effects of auditory and cutaneous electrical stimulations on cell activities in the thalamic reticular nucleus.

The thalamic reticular nucleus (TRN), a cluster of GABAergic cells, is thought to regulate bottom-up and top-down streams of sensory processing in the loop circuitry between the thalamus and cortex. Provided that sensory inputs of different modalities interact in the TRN, the TRN could contribute to fast and flexible cross-modal modulation of attention and perception that incessantly takes place in our everyday life. Indeed, diverse subthreshold interactions of auditory and visual inputs have been revealed in TRN cells (Kimura, 2014). To determine whether such sensory interaction could extend across modalities as a universal neural mechanism, the present study examined TRN cell activities elicited by auditory and cutaneous electrical stimulations in anesthetized rats. Juxta-cellular recording and labeling techniques were used. Recordings were obtained from 129 cells. Auditory or somatosensory responses were modulated by subthreshold electrical stimulation or sound (noise burst) in the majority of recordings (77 of 85 auditory and 13 of 15 somatosensory cells). Additionally, 22 bimodal cells and seven cells that responded only to combined stimulation were recognized. Suppression was predominant in modulation that was observed in both early and repeatedly evoked late responses. Combined stimulation also induced de novo cell activities. Further, response latency and burst spiking were modulated. Axonal projections of cells showing modulation terminated in first- or higher-order thalamic nuclei. Nine auditory cells projected to somatosensory thalamic nuclei. These results suggest that the TRN could regulate sensory processing in the loop circuitry between the thalamus and cortex through the sensory interaction pervasive across modalities.

Repeated forced swim stress affects the expression of pCREB and ΔFosB and the acetylation of histone H3 in the rostral ventromedial medulla and locus coeruleus.

The rostral ventromedial medulla (RVM) and locus coeruleus (LC) play crucial roles in descending pain modulation system. In the present study we examined the expression of phospho-cAMP response element-binding protein (pCREB) and ΔFosB and the acetylation of histone H3 in the RVM and LC after forced swim stress (FS) and complete Freund's adjuvant (CFA) injection to clarify changes in descending pain modulatory system in a rat model of stress-induced hyperalgesia. FS (day 1, 10min; days 2-3, 20min) induced a significant increase in the expression of pCREB and ΔFosB and the acetylation of histone H3 in the RVM, whereas the FS induced a significant increase only in the acetylation of histone H3 in the LC. CFA injection into the hindpaw did not induce a significant change in those expression and acetylation. Quantitative image analysis demonstrated that the numbers of pCREB-, acetylated histone H3- and ΔFosB-IR cells in the RVM were significantly higher in the FS group than those in the naive group. The CFA injection after the FS did not affect the FS-induced increases in the expression of pCREB and ΔFosB and the acetylation of histone H3 in the RVM even though nullified the increase in the acetylation of histone H3 in the LC. These findings suggest different neuroplasticities between the RVM and LC after the FS, which may be involved in activity change of descending pain modulatory system after the CFA injection.

Anatomically structured burst spiking of thalamic reticular nucleus cells: implications for distinct modulations of sensory processing in lemniscal and non-lemniscal thalamocortical loop circuitries.

The thalamic reticular nucleus (TRN) occupies a highly strategic position to modulate sensory processing in the thalamocortical loop circuitries. It has been shown that TRN visual cells projecting to first- and higher-order thalamic nuclei have distinct levels of burst spiking, suggesting the possibility that the TRN exerts differential influences on information processing in first- and higher-order thalamic nuclei that compose the lemniscal and non-lemniscal sensory systems, respectively. To determine whether this possibility could extend across sensory modalities, the present study examined activities of TRN auditory cells projecting to the ventral and dorsal divisions (first- and higher-order auditory thalamic nuclei) of the medial geniculate nucleus (TRN-MGV and TRN-MGD cells) in anesthetized rats, using juxta-cellular recording and labeling techniques. Burst spiking of TRN-MGV cells consisted of larger numbers of spikes with shorter inter-spike intervals as compared with that of TRN-MGD cells in auditory response evoked by noise burst stimuli. Similar distinctions, although not statistically significant, were observed in spontaneous activity. Furthermore, the features of burst spiking varied in association with the topographies of cell body and terminal field locations. These features of burst spiking are similar to those observed in the two types of TRN visual cells. First- and higher-order thalamic nuclei are known to have distinct levels of burst spiking across sensory modalities. Taken together, it is suggested that the distinctions in burst spiking in the TRN, in conjunction with those in thalamic nuclei, could constitute distinct circuitries for lemniscal and non-lemniscal sensory processing in the thalamocortical loop.

Diverse subthreshold cross-modal sensory interactions in the thalamic reticular nucleus: implications for new pathways of cross-modal attentional gating function.

Our attention to a sensory cue of a given modality interferes with attention to a sensory cue of another modality. However, an object emitting various sensory cues attracts attention more effectively. The thalamic reticular nucleus (TRN) could play a pivotal role in such cross-modal modulation of attention given that cross-modal sensory interaction takes place in the TRN, because the TRN occupies a highly strategic position to function in the control of gain and/or gating of sensory processing in the thalamocortical loop. In the present study cross-modal interactions between visual and auditory inputs were examined in single TRN cells of anesthetised rats using juxta-cellular recording and labeling techniques. Visual or auditory responses were modulated by subthreshold sound or light stimuli, respectively, in the majority of recordings (46 of 54 visual and 60 of 73 auditory cells). However, few bimodal sensory cells were found. Cells showing modulation of the sensory response were distributed in the whole visual and auditory sectors of the TRN. Modulated cells sent axonal projections to first-order or higher-order thalamic nuclei. Suppression predominated in modulation that took place not only in primary responses but also in late responses repeatedly evoked after sensory stimulation. Combined sensory stimulation also evoked de-novo responses, and modulated response latency and burst spiking. These results indicate that the TRN incorporates sensory inputs of different modalities into single cell activity to function in sensory processing in the lemniscal and non-lemniscal systems. This raises the possibility that the TRN constitutes neural pathways involved in cross-modal attentional gating.

Evolutionarily conserved glycan signal to degrade aberrant brassinosteroid receptors in Arabidopsis.

Asparagine-linked glycans (N-glycans) are crucial signals for protein folding, quality control, and endoplasmic reticulum (ER)-associated degradation (ERAD) in yeast and mammals. Although similar ERAD processes were reported in plants, little is known about their biochemical mechanisms, especially their relationships with N-glycans. Here, we show that a missense mutation in the Arabidopsis EMS-mutagenized bri1 suppressor 3 (EBS3) gene suppresses a dwarf mutant, bri1-9, the phenotypes of which are caused by ER retention and ERAD of a brassinosteroid receptor, BRASSINOSTEROID-INSENSITIVE 1 (BR1). EBS3 encodes the Arabidopsis ortholog of the yeast asparagine-linked glycosylation 9 (ALG9), which catalyzes the ER luminal addition of two terminal α1,2 mannose (Man) residues in assembling the three-branched N-glycan precursor [glucose(Glc)](3)(Man)(9)[N-acetylglucosamine(GlcNAc)](2). Consistent with recent discoveries revealing the importance of the Glc(3)Man(9)GlcNAc(2) C-branch in generating an ERAD signal, the ebs3-1 mutation prevents the Glc(3)Man(9)GlcNAc(2) assembly and inhibits the ERAD of bri1-9. By contrast, overexpression of EBS4 in ebs3-1 bri1-9, which encodes the Arabidopsis ortholog of the yeast ALG12 catalyzing the ER luminal α1,6 Man addition, adds an α1,6 Man to the truncated N-glycan precursor accumulated in ebs3-1 bri1-9, promotes the bri1-9 ERAD, and neutralizes the ebs3-1 suppressor phenotype. Furthermore, a transfer (T)-DNA insertional alg3-T2 mutation, which causes accumulation of an even smaller N-glycan precursor carrying a different exposed α1,6 Man, promotes the ERAD of bri1-9 and enhances its dwarfism. Taken together, our results strongly suggest that the glycan signal to mark an ERAD client in Arabidopsis is likely conserved to be an α1,6 Man-exposed N-glycan.

Auditory thalamic reticular nucleus of the rat: anatomical nodes for modulation of auditory and cross-modal sensory processing in the loop connectivity between the cortex and thalamus.

The auditory sector of the thalamic reticular nucleus (TRN) plays a pivotal role in gain and/or gate control of auditory input relayed from the thalamus to cortex. The TRN is also likely involved in cross-modal sensory processing for attentional gating function. In the present study, we anatomically examined how cortical and thalamic afferents intersect in the auditory TRN with regard to these two functional pathways. Iontophoretic injections of biocytin into subregions of the auditory TRN, which were made with the guidance of electrophysiological recording of auditory response, resulted in retrograde labeling of cortical and thalamic cells, indicating the sources of afferents to the TRN. Cortical afferents from area Te1 (temporal cortex, area 1), which contains the primary and anterior auditory fields, topographically intersected thalamic afferents from the ventral division of the medial geniculate nucleus at the subregions of the auditory TRN, suggesting tonotopically organized convergence of afferents, although they innervated a given small part of the TRN from large parts. In the caudodorsal and rostroventral parts of the auditory TRN, cortical afferents from nonprimary visual and somatosensory areas intersected thalamic afferents from auditory, visual, and somatosensory nuclei. Furthermore, afferents from the caudal insular cortex and the parvicellular part of the ventral posterior thalamic nucleus, which are associated with visceral processing, converged to the rostroventral end of the auditory TRN. The results suggest that the auditory TRN consists of anatomical nodes that mediate tonotopic and/or cross-modal modulation of auditory and other sensory processing in the loop connectivity between the cortex and thalamus.

Activation of mitogen-activated protein kinase in descending pain modulatory system.

The descending pain modulatory system is thought to undergo plastic changes following peripheral tissue injury and exerts bidirectional (facilitatory and inhibitory) influence on spinal nociceptive transmission. The mitogen-activated protein kinases (MAPKs) superfamily consists of four main members: the extracellular signal-regulated protein kinase1/2 (ERK1/2), the c-Jun N-terminal kinases (JNKs), the p38 MAPKs, and the ERK5. MAPKs not only regulate cell proliferation and survival but also play important roles in synaptic plasticity and memory formation. Recently, many studies have demonstrated that noxious stimuli activate MAPKs in several brain regions that are components of descending pain modulatory system. They are involved in pain perception and pain-related emotional responses. In addition, psychophysical stress also activates MAPKs in these brain structures. Greater appreciation of the convergence of mechanisms between noxious stimuli- and psychological stress-induced neuroplasticity is likely to lead to the identification of novel targets for a variety of pain syndromes.