An elderly case of paraneoplastic anti-NMDA receptor encephalitis associated with large cell neuroendocrine carcinoma of the lung.

BACKGROUND: Recent studies have suggested that N-methyl-D-aspartate (NMDA) receptors are involved in the cell proliferation in several tumors. However, there have been no reports demonstrating the expression of NR1 subunit of the NMDA receptor in large cell neuroendocrine carcinoma (LCNEC). CASE PRESENTATION: Here, we report the first elderly case of paraneoplastic anti-NMDA receptor encephalitis associated with LCNEC of the lung with NR1 expression. Of note, NR1 subunit expression in the tumor cells of the present case was confirmed by immunohistochemistry (IHC). Radiation therapy and immunotherapies, such as corticosteroids and intravenous immunoglobulin (IVIG), shrank the tumors and improved neurological symptoms in the present case. Additionally, we also confirmed the expression of NR1 in the tumor cells obtained from three other cases with LCNEC of the lung at our hospital by IHC. CONCLUSION: Our IHC results indicate that LCNEC generally expresses NR1 subunit and NMDA receptor may be involved in the tumor development and growth.

Differential effects of high-definition transcranial direct current stimulation on verbal working memory performance according to sensory modality.

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that modulates cortical excitability in a polarity-dependent manner. The diffuse nature of tDCS makes it difficult to investigate the optimal stimulation parameters for more effective and specific cognitive enhancement; to address this deficit, a more focalized stimulation technique, high-definition tDCS (HD-tDCS), has been developed. To date, only a few studies have examined the effects of HD-tDCS on cognitive functions; and none has investigated the effects of HD-tDCS on different sensory modalities of verbal working memory. Therefore, the present study compared the effects of prefrontal HD-tDCS on visual and auditory working memory tasks. Twenty healthy participants completed three sessions of each modality task, and additionally a sustained attention task. Anodal or sham HD-tDCS was administered to the dorsolateral prefrontal cortex (DLPFC) during the second session of the task in a parallel, single-blind design. Anodal stimulation to the DLPFC significantly enhanced the visual verbal working memory accuracy during and 20 min after the stimulation. In contrast, auditory verbal working memory performance was not modulated by anodal stimulation. Anodal stimulation to the DLPFC showed no effect on any other cognitive functions. The present study revealed the differential effects of HD-tDCS on two different modalities (visual vs. auditory) of working memory performance: important preliminary findings for the establishment of a more effective and specific use of tDCS.

Unexpected Photo-instability of 2,6-Sulfonamide-Substituted BODIPYs and Its Application to Caged GABA.

Investigation of the unexpected photo-instability of 2,6-sulfonamide-substituted derivatives of the boron dipyrromethene (BODIPY) fluorophore led to the discovery of a photoreaction accompanied by multiple bond scissions. We characterized the photoproducts and utilized the photoreaction to design a caged γ-aminobutyric acid (GABA) derivative that can release GABA upon irradiation in the visible range (>450 nm). This allowed us to stimulate neural cells in mouse brain slices.

Synaptic plasticity associated with a memory engram in the basolateral amygdala.

Synaptic plasticity is a cellular mechanism putatively underlying learning and memory. However, it is unclear whether learning induces synaptic modification globally or only in a subset of neurons in associated brain regions. In this study, we genetically identified neurons activated during contextual fear learning and separately recorded synaptic efficacy from recruited and nonrecruited neurons in the mouse basolateral amygdala (BLA). We found that the fear learning induces presynaptic potentiation, which was reflected by an increase in the miniature EPSC frequency and by a decrease in the paired-pulse ratio. Changes occurred only in the cortical synapses targeting the BLA neurons that were recruited into the fear memory trace. Furthermore, we found that fear learning reorganizes the neuronal ensemble responsive to the conditioning context in conjunction with the synaptic plasticity. In particular, the neuronal activity during learning was associated with the neuronal recruitment into the context-responsive ensemble. These findings suggest that synaptic plasticity in a subset of BLA neurons contributes to fear memory expression through ensemble reorganization.

Blockade of stimulus convergence in amygdala neurons disrupts taste associative learning.

Humans and non-human animals learn associations of temporally contingent stimuli to better cope with the changing environment. In animal models of classical conditioning, a neutral conditioned stimulus (CS) predicts an aversive unconditioned stimulus (US). Several lines of indirect evidence indicate that this learning may rely on stimulus convergence in a subset of neurons, but this hypothesis has not been directly tested. In the current study, we tested this hypothesis using a pharmacogenetic approach, the cAMP response element-binding protein (CREB)/Allatostatin Receptor system, to target a subset of amygdala neurons receiving convergent stimuli in mice during conditioned taste aversion. Virally infected basolateral amygdala neurons with higher CREB levels were predominantly active during CS presentation. Blocking stimulus convergence in infected neurons by silencing them during US disrupted taste associative memory. Moreover, silencing infected neurons only during CS also disrupted associative memory formation. These results provide support for the notion that convergent inputs of CS and US in a subpopulation of neurons are critical for associative memory formation.

Differential calcium dependence in basal and forskolin-potentiated spontaneous transmitter release in basolateral amygdala neurons.

Action potential-independent transmitter release, or spontaneous release, is postulated to produce multiple postsynaptic effects (e.g., maintenance of dendritic spines and suppression of local dendritic protein synthesis). Potentiation of spontaneous release may contribute to the precise modulation of synaptic function. However, the expression mechanism underlying potentiated spontaneous release remains unclear. In this study, we investigated the involvement of extracellular and intracellular calcium in basal and potentiated spontaneous release. Miniature excitatory postsynaptic currents (mEPSCs) of the basolateral amygdala neurons in acute brain slices were recorded. Forskolin, an adenylate cyclase activator, increased mEPSC frequency, and the increase lasted at least 25 min after washout. Removal of the extracellular calcium decreased mEPSC frequency in both naïve and forskolin-treated slices. On the other hand, chelation of intracellular calcium by BAPTA-AM decreased mEPSC frequency in naïve, but not in forskolin-treated slices. A blockade of the calcium-sensing receptor (CaSR) resulted in an increase in mEPSC frequency in forskolin-treated, but not in naïve slices. These findings indicate that forskolin-induced potentiation is accompanied by changes in the mechanisms underlying Ca(2+)-dependent spontaneous release.

Effect of climatic conditions on epidemic patterns of influenza in Okinawa, Japan, during the pandemic of 2009: surveillance of rapid antigen test results.

Climatic conditions may have affected the incidence of influenza during the pandemic of 2009 as well as at other times. This study evaluated the effects of climatic conditions on influenza incidence in Okinawa, a subtropical region in Japan, during the 2009 pandemic using surveillance data from rapid antigen test (RAT) results. Weekly RAT results performed in four acute care hospitals in the Naha region of the Okinawa Islands from January 2007 to July 2011 were anonymously collected for surveillance of regional influenza prevalence. Intense epidemic peaks were noted in August 2009 and December 2009-January 2010 during the influenza pandemic of 2009. RAT positivity rates were lower during the pandemic period than during the pre- and post-pandemic periods. Lower ambient temperature was associated with higher influenza incidence during pre- and post-pandemic periods but not during the pandemic of 2009. Lower relative humidity was associated with higher influenza incidence during the pandemic as well as during the other two periods. The association of climatic conditions and influenza incidence was less prominent during the pandemic of 2009 than during pre- and post-pandemic periods.

Epidemiology of influenza from 2007 to 2008 in naha area, okinawa prefecture: surveillance of rapid antigen test results.

The incidence of influenza in the Naha city area in the southernmost part of Japan was surveyed in 2007 and 2008. Patients who had influenza-like symptoms and visited one of four general hospitals in Naha City, Okinawa, Japan were included in this study. The nasal or throat swab samples were applied to the rapid test for detecting influenza A and B virus antigens. The positive rate of influenza A and/or B virus antigen was 26.2% (8,480/32,380). Most cases (82.9%) were influenza A. In 2007, influenza A cases were detected during the entire year, and an epidemic peak was also noted in July, while no outbreak occurred in the summer of 2008. The surveillance of the rapid influenza virus antigen test seemed to provide reliable epidemiological data. This finding warrants further study in this region, including study of the influences of climate and socio-behavior patterns of the residents in the region on influenza epidemics.