Acetylcholine critically influences hippocampal-dependent learning. Cholinergic fibers innervate hippocampal neuron axons, dendrites, and somata. The effects of acetylcholine on axonal information processing, though, remain unknown. By stimulating cholinergic fibers and making electrophysiological recordings from hippocampal dentate gyrus granule cells, we show that synaptically released acetylcholine preferentially lowered the action potential threshold, enhancing intrinsic excitability and synaptic potential-spike coupling. These effects persisted for at least 30 min after the stimulation paradigm and were due to muscarinic receptor activation. This caused sustained elevation of axonal intracellular Ca2+ via T-type Ca2+ channels, as indicated by two-photon imaging. The enhanced Ca2+ levels inhibited an axonal KV7/M current, decreasing the spike threshold. In support, immunohistochemistry revealed muscarinic M1 receptor, CaV3.2, and KV7.2/7.3 subunit localization in granule cell axons. Since alterations in axonal signaling affect neuronal firing patterns and neurotransmitter release, this is an unreported cellular mechanism by which acetylcholine might, at least partly, enhance cognitive processing.
The super-heater (SH) tubes in an incinerator have been locally corroded by nonuniform partially accelerated gas flow. It effects maintenance and cost performance. In order to level the gas velocity at the super-heater entrance, putting a baffle in a boiler may be effective. The leveling effect of a baffle was studied by using a three-dimension model and employing PTV (Particle Tracking Velocimetry) analysis. After some trial and error, a baffle configuration was found to give the reduction of maximum velocity and standard deviation of the gas flow.
We investigated the effect of dopamine on the in vivo expression of brain‐derived neurotrophic factor (BDNF) in the striatum of mouse. BDNF mRNA expression in the striation, which was Quantified with the reverse transcriptase polymerase chain reaction, was up‐repulated from 2 h after oral administration of levodopa, a precursor of dopamine. The increase was sustained for 16 h. Co‐administrstion of haloperidol partially inhibited dopamine‐induced BDNF enhancement. These data suggest that dopaminergic stimulation directly promotes the expression of BDNF in the striatum in vivo.
Cbln1, secreted from cerebellar granule cells, and the orphan glutamate receptor delta2 (GluD2), expressed by Purkinje cells, are essential for synapse integrity between these neurons in adult mice. Nevertheless, no endogenous binding partners for these molecules have been identified. We found that Cbln1 binds directly to the N-terminal domain of GluD2. GluD2 expression by postsynaptic cells, combined with exogenously applied Cbln1, was necessary and sufficient to induce new synapses in vitro and in the adult cerebellum in vivo. Further, beads coated with recombinant Cbln1 directly induced presynaptic differentiation and indirectly caused clustering of postsynaptic molecules via GluD2. These results indicate that the Cbln1-GluD2 complex is a unique synapse organizer that acts bidirectionally on both pre- and postsynaptic components.
The anterolateral tract (ALT), which originates from neurons in lamina I and the deep dorsal horn, represents a major ascending output through which nociceptive information is transmitted to brain areas involved in pain perception. Although there is detailed quantitative information concerning the ALT in the rat, much less is known about this system in the mouse, which is increasingly being used for studies of spinal pain mechanisms because of the availability of genetically modified lines. The aim of this study was therefore to determine the extent to which information about the ALT in the rat can be extrapolated to the mouse. Our results suggest that as in the rat, most lamina I ALT projection neurons in the lumbar enlargement can be retrogradely labelled from the lateral parabrachial area, that the majority of these cells (∼ 90%) express the neurokinin 1 receptor (NK1r), and that these are larger than other NK1r-expressing neurons in this lamina. This means that many lamina I spinoparabrachial cells can be identified in NK1r-immunostained sections from animals that have not received retrograde tracer injections. However, we also observed certain species differences, in particular we found that many spinoparabrachial cells in laminae III and IV lack the NK1r, meaning that they cannot be identified based solely on the expression of this receptor. We also provide evidence that the majority of spinoparabrachial cells are glutamatergic and that some express substance P. These findings will be important for studies designed to unravel the complex neuronal circuitry that underlies spinal pain processing.
VGLUTs, which are essential for loading glutamate into synaptic vesicles, are present in various neuronal systems. However, to our knowledge the expression of VGLUTs in neurons innervating the bladder has not yet been analyzed. We studied VGLUT1, VGLUT2 and VGLUT3 in mouse bladder neurons.We analyzed the expression of VGLUT1, VGLUT2 and calcitonin gene-related peptide by immunohistochemistry in the retrograde labeled primary afferent and autonomic neurons of BALB/c mice after injecting fast blue in the bladder wall. To study VGLUT3 we traced the bladder of transgenic mice, in which VGLUT3 is identified by enhanced green fluorescent protein detection.Most bladder dorsal root ganglion neurons expressed VGLUT2. A smaller percentage of neurons also expressed VGLUT1 or VGLUT3. Co-expression with calcitonin gene-related peptide was only observed for VGLUT2. Occasional VGLUT2 immunoreactive neurons were seen in the major pelvic ganglia. Abundant VGLUT2 immunoreactive nerves were detected in the bladder dome and trigone, and the urethra. VGLUT1 immunoreactive nerves were discretely present.We present what are to our knowledge novel data on VGLUT expression in sensory and autonomic neurons innervating the mouse bladder. The frequent association of VGLUT2 and calcitonin gene-related peptide in sensory neurons suggests interactions between glutamatergic and peptidergic neurotransmissions, potentially influencing commonly perceived sensations in the bladder, such as discomfort and pain.
A man patient in his 70s underwent left nephrectomy and laparoscopic partial gastrectomy for the treatment of a left renal cell carcinoma and gastrointestinal stromal tumor(GIST)arising from the stomach. Histopathologically, both the renal cell carcinoma and GIST were kit-positive, CD34-positive, and S-100 protein-negative, and the Ki-67 index was about 40% as determined by the hot spot method, so that it was diagnosed as an intermediate-group GIST. After surgery, the patient was followed without adjuvant therapy, as he did not wish to receive postoperative chemotherapy. A computed tomography(CT)conducted 3 years after the surgery revealed tumorous shadows in the abdominal wall, inferior periesophageal region, and dorsal aspect of the pancreas. Positron emission tomography(PET)-CT showed fluorodeoxyglucose(FDG) accumulation in these lesions. Therefore, based on a suspicion of recurrent renal cell carcinoma or GIST, we carried out abdominal wall tumor resection for both exploratory and diagnostic purposes, which yielded histopathological diagnosis of GIST, with features similar to those observed at the time of the initial operation. Because the number of tumors remained unchanged during the subsequent follow-up period, the tumorous lesions in the periesophageal region and on the dorsal aspect of the pancreas were resected laparoscopically. Each of the resected tumors showed histological features consistent with GIST. The patient was started on oral imatinib therapy after this operation. To date(5 years after the surgery for the recurrent tumors and 8 years after the initial operation), the patient has remained free of recurrence. The pattern of tumor recurrence noted in the present case(ie, metastasis/dissemination to the skeletal muscles)is relatively rare, and few reports have been published concerning long-term survivors through multidisciplinary treatment (surgical treatment and others). We report this case with a review of the literature.
