Type I interferon induced by polyinosinic-polycytidylic acid does not contribute to the efficacy of a formalin-killed cell vaccine against Edwardsiella piscicida in the Japanese flounder (Paralichthys olivaceus).

Polyinosinic-polycytidylic acid (poly I:C) is a type of pathogen-associated molecular pattern that can strongly induce the expression of type I interferon (I-IFN). Our previous study has demonstrated that the combination of poly I:C with a recombinant protein antigen not only stimulated the expression of I-IFN but also conferred protection against Edwardsiella piscicida in the Japanese flounder (Paralichthys olivaceus). In this study, our aim was to develop a better immunogenic and protective fish vaccine, for which we intraperitoneally coinjected P. olivaceus with poly I:C and formalin-killed cells (FKCs) of E. piscicida and compared the efficiency of protection against E. piscicida infection with that of FKC vaccine alone. Results showed that the expression levels of I-IFN, IFN-γ, interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, and the interferon-stimulated genes (ISGs) ISG15 and Mx were significantly increased in the spleen of fish inoculated with poly I:C + FKC. The results of ELISA showed that the levels of specific serum antibodies in the FKC and FKC + poly I:C groups were gradually increased until 28 days postvaccination and were significantly higher than those in the PBS and poly I:C groups. At 3 weeks after vaccination in the challenge test, the respective cumulative mortality rates of fish in the PBS, FKC, poly I:C, and poly I:C + FKC groups were 46.7%, 20.0%, 33.3%, and 13.3% under low-concentration challenge and 93.3%, 46.7%, 78.6%, and 53.3% under high-concentration challenge. This study showed that poly I:C may not provide an effective adjuvant effect with FKC vaccine for intracellular bacterial infections.

Single-incision laparoscopic full-thickness anterior abdominal wall repair of a Morgagni hernia using a suture-assisting needle in a child: A case report.

Single-incision laparoscopic repair of a congenital Morgagni diaphragmatic hernia using a suture-assisting needle was performed in a 1-year-old boy. Three ports were inserted through a single umbilical incision to repair the 2.5 × 2.3-cm defect. The full-thickness muscle layer of the anterior abdominal wall and the posterior rim of the defect were penetrated with the suture-assisting needle holding a thread, which was then released. The needle tip was pulled back over the muscle layer, shifted laterally, and again passed through the muscle layer and the posterior rim. The thread was then captured by the needle and pulled out through the anterior abdominal wall. Five mattress sutures were placed in this way and tied subcutaneously. The postoperative course was uneventful, and the cosmetic outcome was favorable. A suture-assisting needle is useful for completing full-thickness anterior abdominal wall repair, which is important for preventing the recurrence of a congenital Morgagni diaphragmatic hernia.

[Orbital Compartment Syndrome Perhaps Secondary to Intra-Orbital Fluid Retention and Orbital/Palpebral Emphysema Following Frontotemporal Craniotomy for an Unruptured Cerebral Aneurysm:A Case Report].

A 58-year-old woman underwent left frontotemporal craniotomy for clipping of an unruptured cerebral aneurysm. A small defect was accidentally created in the orbital roof intraoperatively. The patient developed left eyelid edema and ocular pain after recovery from anesthesia. The following day, the eyelid edema worsened, and she had difficulty opening her eyes. On the 9th postoperative day, she noticed diminished visual acuity and diplopia in her left eye when she was able to spontaneously open her eyes. Ophthalmological evaluation revealed mild left visual loss, decreased light reflex, ophthalmoplegia, ptosis, and chemosis. Computed tomography(CT)/magnetic resonance imaging revealed left proptosis, optic nerve stretching, intra-orbital fluid retention, and orbital/palpebral emphysema. She was diagnosed with orbital compartment syndrome(OCS)and received conservative treatment;however, her visual acuity did not improve. OCS observed after cerebral aneurysm surgery is rare;to date, only 24 cases have been reported in the available literature. Although the mechanism of OCS after craniotomy is unclear, it may be attributed to ocular compression by a muscle flap or increased intra-orbital pressure secondary to venous congestion. In the present case, the left superior ophthalmic vein and cavernous sinus were not clearly visualized on CT angiography. Therefore, we concluded that the right superior ophthalmic vein and superficial facial veins underwent dilatation and served as collateral circulation of the left orbital venous system. We speculate that OCS occurred secondary to increased intra-orbital pressure, possibly caused by inflow of cerebrospinal fluid with air into the orbit through a small bone defect that was accidentally created during craniotomy in a setting of orbital venous congestion.

[Anomalous Origin of the Ophthalmic Artery from the Anterior Cerebral Artery Associated with the Paraclinoid Internal Carotid Artery Aneurysm].

The ophthalmic artery usually arises from the supraclinoid portion of the internal carotid artery. Here, we present an extremely rare case of abnormal origin of the ophthalmic artery from the anterior cerebral artery associated with the paraclinoid internal carotid artery aneurysm. As the embryology of the ophthalmic artery is complex, this case provides additional insight into the variation of the ophthalmic artery.

[Two Cases of Late-onset Brain Edema after Craniotomy for Unruptured Intracranial Aneurysms Suspected to be due to an Allergic Reaction to Arachnoid Plasty Material].

We report two rare cases of late-onset brain edema after craniotomy for clipping or coating of unruptured intracranial aneurysms, possibly due to an allergic reaction to topically applied fibrin glue or gelatin sponge used for arachnoid plasty to cover the opened sylvian cistern. Both patients were women in their 60s with an allergic predisposition and both followed a similar clinical course. A slight fever and headache persisted during the postoperative period. Five to six weeks after surgery without complications, MR images showed an extensive T2 prolongated region in the white matter around the operative field, indicative of vasogenic edema, with mass effect and meningeal enhancement around the sylvian fissure that had been covered with gelatin sponge and sprayed fibrin glue. Swelling of the cerebral cortex around the sylvian fissure subjected to arachnoid plasty was also observed. Blood tests showed the absence of an inflammatory reaction and cerebrospinal fluid examination showed lymphocytosis that was considered to be due to an aseptic meningeal reaction or meningitis. Clinical symptoms and imaging findings steadily improved with the administration of steroids and antiallergic agents. Delayed brain edema may occur around the arachnoid plasty area despite an uneventful chronic postoperative period, which could be due to an allergic reaction to locally administered fibrin glue or gelatin sponge. Thus, the application of arachnoid plasty using fibrin glue and gelatin sponge in patients with a predisposition to allergies needs to be carefully considered.

Development of a nanoparticle that releases nucleic acids in response to a mitochondrial environment.

The delivery of nucleic acids targeting mutant mtDNA represent a potential strategy for addressing a variety of mitochondria-related diseases. We previously developed a MITO-Porter, a nano carrier that is capable of delivering nanoparticles of nucleic acids to mitochondria of human cells. Here, we report on an investigation of a series of nanoparticles formed with various poly cationic peptides that can release nucleic acids in response to a mitochondrial environment. A significant relationship was found between the number of and the location of arginine and histidine residues in the peptide sequence and the release of nucleic acids in a mitochondrial environment.

[A Pediatric Case of Clinically Mild Encephalitis/Encephalopathy with a Reversible Splenial Lesion(MERS)with Recurrent TIA-like Symptoms over a Prolonged Period].

We report a rare case of pediatric clinically mild encephalitis/encephalopathy with a reversible splenial lesion(MERS)associated with transient ischemic attack(TIA)-like symptoms. A 13-year-old boy who presented with transient left hemiparesis and dysarthria was transferred to our hospital. He had experienced similar symptoms at the age of nine years and was diagnosed with MERS type 2 due to the typical clinical course and MR imaging findings. His elder brother showed a similar clinical history at the age of eight years. DW-MR images on admission revealed high signal intensity areas in the splenium of the corpus callosum and deep white matter. The territories were depicted as low intensity on apparent diffusion coefficient maps and slightly high intensity on T2-weighted images. Recurrence of MERS type 2 was considered because the symptoms of the patient disappeared within several hours and the abnormal signal intensities markedly decreased on the follow-up DWI performed eight days after initial MR imaging. The abnormal MR imaging findings completely disappeared after five weeks. After discharge, the patient experienced eight TIA-like episodes with a similar clinical course and MR imaging findings over a period of six years. MERS associated with TIA-like episodes is extremely rare, especially MERS associated with recurrent episodes in multiple phases over a long period, as seen in the present case. In addition, the findings in the last two MR imaging scans involving the internal capsule, thalamus, and midbrain were highly unusual and maybe considered to be indicative of an advanced form of MERS type 2, as reported in other familial cases.

Combined Fundal and Segmental Adenomyomatosis of the Gallbladder in a Child: A Rare Case Report.

Adenomyomatosis of the gallbladder (AMG) is characterized by mucosal hyperplasia leading to invagination through the thickened muscle layer, which is relatively common in adults, but is rare in childhood. We report a 12-year-old boy with adenomyomatosis of the gallbladder combined segmental and fundal type. This combined type is rare in adults and is first reported here in childhood. Although initial imaging with computed tomography (CT) suggested the presence of a circular solid mass-like lesion because of its rare morphology, repeated ultrasonography (US) was useful for leading to a correct diagnosis.

[Reversible Cerebral Vasoconstriction Syndrome with Cortical Subarachnoid Hemorrhage due to Acute Cortical Infarction Beneath the Sulcus:A Case Report].

We report a rare case of reversible cerebral vasoconstriction syndrome(RCVS)with cortical subarachnoid hemorrhage(cSAH)associated with a fresh cortical infarction beneath the sulcus with thick cSAH. A 34-year-old woman presented with history of thunderclap headache. She was transferred to our hospital for further examination of a cSAH in the left frontal lobe. Results of the cerebrospinal fluid examination were unremarkable, but three-dimensional rotational angiography revealed multiple instances of narrowing of the cortical branches of the anterior and middle cerebral arteries, suggesting the diagnosis of RCVS. Diffusion weighted imaging(DWI)demonstrated a small cortical area with high-signal intensity around the sulcus , where a thick cSAH clot was observed. This cortical lesion appeared as low-signal intensity on the apparent diffusion coefficient maps, and the follow-up T2-weighted images(obtained 3 months after onset)demonstrated a residual lesion that was smaller than the initial DWI abnormality with high-signal intensity;thus indicating the presence of a coincident fresh cortical infarction. The position of the infarct next to the thickest portion of cSAH suggested that it was the bleeding source of the cSAH. Ten days after onset, the cerebral blood flow and volume in the cortex around the cSAH increased as compared to the same area on the contralateral side. These findings suggested that at least one of the bleeding mechanisms of the cSAH was related to the hemorrhagic infarction or subpial hemorrhage resulting from the "ischemia-reperfusion injury" due to the acute disturbance of the pial vessel microcirculation with subsequent rapid resolution of the blood flow during the early phases of RCVS. These dynamics could not be demonstrated with contemporary angiographic imaging.

[Unruptured Aneurysm Arising from the Proximal End of the Duplicate Origin of the Middle Cerebral Artery].

We report a rare case of an unruptured aneurysm arising from the junction between the internal carotid artery(ICA)and duplicate origin of the middle cerebral artery(MCA). A 49-year-old man who presented with vertigo was admitted to our hospital. Subsequent MR and CT angiograms revealed an incidental aneurysm arising from the proximal end of the duplicate origin of the left MCA. He underwent clipping via the distal transsylvian approach. The aneurysm projected to the posterior direction and several perforators from the two M1 segments were attached to the neck of the aneurysm, which made neck dissection very difficult. Approaching the space from the posterior/lateral direction to reach the M1 segment, the aneurysm neck was successfully dissected and clipped without sacrificing any perforators or stenosis of parent vessels. The postoperative course was uneventful, and the patient was discharged within 2 weeks. Duplicate origin of the MCA has been confused with a fenestration of the proximal M1 segment or terminal segment of the ICA. In this condition, two MCA branches arise separately from the terminal segment of the ICA and fuse early to form an arterial ring at the proximal M1 segment. An aneurysm originating from this anomaly has never been described. However, some aneurysms associated with this type of origin may have incorrectly been reported as those associated with proximal MCA or terminal ICA fenestrations. We summarize the cases that are similar to our case of duplicate origin of the MCA with an aneurysm, and discuss the precise diagnosis and significant intraoperative problems that were described in the literature.

[A Rare Case of a Ruptured De Novo Aneurysm Arising from the Twig-like Networks of an Anomalous Collateral Artery Associated with Hypoplasia of the M1 Segment of the Middle Cerebral Artery 4 Years after the Rupture of an A1 Aneurysm at the Origin of the Collateral Artery].

We report a rare case of a de novo ruptured aneurysm arising from the twig-like networks(TLN)of an anomalous collateral artery associated with an aplastic or twig-like middle cerebral artery(Ap/T-MCA). A 65-year-old woman with a decreased level of consciousness, who had been diagnosed with a right Ap/T-MCA and was treated with coil embolization for a ruptured A1 aneurysm at the origin of the anomalous collateral artery 4 years ago, was transferred to our hospital. Head CT revealed an intracerebral hematoma extending from the right frontal lobe to the caudate nucleus with intraventricular hemorrhage. Subsequent 3D-rotational angiograms revealed a ruptured de novo aneurysm arising from the TLN and regrowth of the residual neck of the coiled aneurysm. The two aneurysms were successfully treated by surgical clipping combined with superficial temporal artery middle cerebral artery anastomosis in the subacute phase. To our knowledge, only 11 cases of this type of aneurysm have been reported, including our case, and this is the first report of a de novo aneurysm within the TLN so far. Although all previously reported aneurysms were small(<5-6mm), 10 of them(91%)ruptured. These data may indicate the vulnerability of this type of aneurysm to rupture despite their small size, probably due to hemodynamic stress and the fragile nature of their immature walls. To prevent recurrence of hemorrhage in these cases, revascularization may be necessary in addition to surgical clipping. Whether this concept is correct is an open question. Further studies are necessary to examine this issue.

[A Rare Case of Ruptured/Unruptured Miniature Aneurysms Originating from the Infundibular Dilatation of the Callosomarginal Artery, Branching from the Infracallosal(A2)Segment of the Azygos Anterior Cerebral Artery].

We report the first case of two de novo miniature aneurysms(ruptured/unruptured)emerging from the infundibular dilatation(ID)of the callosomarginal artery, which branches from the infracallosal(A2)segment of the azygos anterior cerebral artery(AACA), in a 36-year-old woman. The patient had previously been diagnosed with a miniature, unruptured aneurysm, occurring in the A2 segment of the AACA, detected by CT angiography(CTA)at another hospital two years ago, and had been followed up with MR angiography(MRA)every 6 months. Three months after the final check-up with MRA, which did not indicate a significant change in the aneurysm, the patient presented with subarachnoid hemorrhage. Subsequent CTA and digital subtraction angiograms revealed that the right callosomarginal artery, originating from the apex of the aneurysmal bulge, had a maximal diameter of 3mm, indicating an ID of the artery. Additionally, two miniature bleb-like aneurysms emerged from the ID, projecting in opposite directions:one projecting to the right-posterior/superior direction and the other to the left-anterior/inferior direction. Both aneurysms were successfully clipped via a right pterional approach with partial resection of the gyrus rectus, and the right-projecting aneurysm was confirmed to be ruptured during surgery. In the current report, we review previously reported cases of AACA with aneurysms, and discuss their clinical characteristics, and the possible mechanisms underlying the formation of the ID and de novo aneurysms in this extremely rare case.

[A Rare Case of Ruptured Internal Carotid-Posterior Communicating Artery Aneurysm Associated with Contralateral Delayed Oculomotor Nerve Palsy].

A 55-year-old man presented with difficulty breathing, chest pain, and disturbance of consciousness, and was transferred to our hospital. Initial whole body CT revealed a diffuse subarachnoid hemorrhage(SAH)with severe pulmonary edema that was considered neurogenic in origin. He received controlled ventilation under sedation and conservative care for the SAH. One day after the onset of the SAH, his left pupil suddenly became dilated to 6mm, with no reaction to light. Head CT showed no new bleeding. Subsequent CT angiogram revealed a right internal carotid-posterior communicating artery aneurysm(IC-PC AN)with a posterior-lateral projection; however, no vessel abnormality was observed in the left anterior or posterior circulations. The aneurysm was successfully treated with coil embolization. We reviewed reported cases of isolated oculomotor nerve palsy(ONP), without direct compression by ruptured aneurysms, and found that only 11 cases exist, including our case. Interestingly, six of them were associated with anterior communicating artery aneurysms. A mass effect, chemical stimulation, and a jet stream of blood were proposed as the mechanisms of this rare type of ONP, in addition to the specific neurovascular relationships between the oculomotor nerve and the posterior cerebral/posterior communicating/superior cerebellar arteries, with abnormal nerve contact or compression. Though rare, ruptured IC-PC ANs could cause contralateral ONP; other types of ruptured aneurysms may also lead to indirect effects on nervous structures without direct compression. This type of rare presentation of ruptured aneurysms should be considered, especially in cases of multiple aneurysms, such as IC-PC ANs.

Pulmonary arterial hypertension associated with chronic active Epstein-Barr virus infection.

Chronic active Epstein-Barr virus (EBV) infection (CAEBV), characterized by persistent infectious mononucleosis-like symptoms, can lead to cardiovascular complications including coronary artery aneurysm or myocarditis. Here, we present the case of an 11-year-old boy with pulmonary arterial hypertension (PAH) and junctional ectopic tachycardia associated with CAEBV. The patient did not have any major symptoms attributed to CAEBV, such as fever, lymphadenopathy or splenomegaly when the PAH developed. Mild liver dysfunction was found at the first examination, and it persisted. Two years after the PAH symptoms appeared, CAEBV was evident, based on deteriorated liver function, hepatosplenomegaly, and coronary artery aneurysms. CAEBV should be considered as a cause of secondary PAH, particularly when liver dysfunction coexists.

New validated rapid screening methods for identifying Kudoa septempunctata in olive flounder (Paralichthys olivaceus).

Kudoa septempunctata is a newly identified causative agent of foodborne diseases associated with consuming raw olive flounder. Qualitative PCR and quantitative real-time PCR have been used as notification methods to identify K. septempunctata in Japan. However, these methods require expensive equipment and are time-consuming (2-3 h for screening). To address these problems, in this study, we developed new rapid and simple methods using real-time loop-mediated isothermal amplification (LAMP) and nucleic acid sequence based amplification-nucleic acid chromatography (NASBA-NAC). Using these methods, the total procedure required approximately 45 min and did not require any expensive equipment. With regard to validating these new methods in comparison with the notification methods used in Japan, we performed an inter-laboratory study of 5 laboratories using samples that included olive flounders infected with 4 different amounts of K. septempunctata. These results demonstrated that the sensitivity of NASBA-NAC was equivalent to that of qualitative PCR, and that the sensitivity of real-time LAMP was equivalent to that of quantitative real-time PCR, which indicated that these new methods were acceptable screening methods for identifying K. septempunctata.

Neurodevelopmental outcomes of children with periventricular leukomalacia.

OBJECTIVES: To examine the neurodevelopmental outcomes of children with periventricular leukomalacia (PVL). MATERIALS AND METHODS: Twenty-five children diagnosed with grade 1, 2 or 3 PVL on the basis of magnetic resonance imaging (MRI) findings between January 2002 and December 2011 were enrolled and followed from 15 months to 10 years of age. RESULTS: Of the 25 children, one was a term and 24 were preterm-births. Nine (36%) had spastic diplegia and 12 (48%) had quadriplegia. Ten of the 25 (40%) were able to walk independently at 36 months utilizing short leg braces, whereas 13 children (52%) were unable to walk independently. MRI findings revealed grade 1 PVL in nine (36%), grade 2 in 12 (48%), and grade 3 in four (16%) of the 25 children. Eleven of the 16 children (69%) with grade 2 or 3 PVL had Papile III or IV intraventricular hemorrhage (IVH), and many of these children had severe neurologic motor abnormalities, severe psychomotor delay, and seizures. Five of the nine children (56%) with grade 1 PVL had normal psychomotor development. There were statistically significant differences in the motor impairment and walking ability between the children with grade 1 and those with grade 2 PVL (p = 0.008 and 0.005, respectively). CONCLUSION: Most children with grade 2 or 3 PVL had severe neurodevelopmental delays, but attention should also be paid to the 56% of children with grade 1 PVL who presented with normal psychomotor development. Further studies of larger populations, including long-term follow-up, are necessary to evaluate the outcomes of children with PVL.

A novel connection between rods and ON cone bipolar cells revealed by ectopic metabotropic glutamate receptor 7 (mGluR7) in mGluR6-deficient mouse retinas.

Since the discovery of direct chemical synapses between rod photoreceptor and OFF cone bipolar cells in mouse retinas, whether the ON cone bipolar cell also receive direct chemical input from rod has been a pending question. In finding that metabotropic glutamate receptor 7 (mGluR7) was uniquely expressed in dendrites of ON cone bipolar cells in the mGluR6-deficient mouse retina, we used this ectopic mGluR7 immunoreactivity as a specific marker for the ON cone bipolar to search for its rod connection. Here, we show that a certain type of ON cone bipolar cell forms ribbon-associated synapses not only with cones, but also rods. This finding was verified in the wild-type mouse retina by three-dimensional reconstruction of bipolar cells from serial electron micrographs. These ON cone bipolars were further identified as corresponding to type 7 of mouse bipolar cell described by Ghosh et al. (2004) and also to the green fluorescent protein (GFP)-labeled type 7 bipolars in the alpha-gustducin-GFP transgenic mouse. Our findings suggest that, in mice, rod signals bifurcate into a third ON and OFF pathway in addition to the two known routes to cone bipolar cells: (1) via rod chemical synapse --> rod bipolar --> AII amacrine --> ON and OFF cone bipolar cells; (2) via rod-cone gap junction --> cone chemical synapse --> ON and OFF cone bipolar cells; and (3) via rod chemical synapse --> ON and OFF cone bipolar cells. This third novel pathway is thought to transmit fast and moderately light-sensitive rod signals, functioning to smooth out the intensity changes at the scotopic-mesopic interface.

Spinal curvature of cultured Japanese mackerel Scomber japonicus associated with a brain myxosporean, Myxobolus acanthogobii.

Skeletal deformities were found in the cultured Japanese mackerel Scomber japonicus. External and radiographical observations showed the deformed fish to exhibit a dorso-ventral spinal curvature (kyphosis) without fracture or dislocation of the vertebrae. Numerous myxosporean cysts, ca. 0.3 to 1.0 mm in diameter, formed in the 4th ventricle, the cavity of the optic tectum, the surface of the olfactory lobe and bulb, the optic lobe and the inferior lobe of the brain. Spore morphology and molecular analysis of the small subunit ribosomal RNA gene sequence identified the myxosporean parasite as Myxobolus acanthogobii, a parasite which also causes scoliosis in yellowtail Seriola quinqeradiata. Histopathological observation showed that the myxosporean cysts were encapsulated within the host's collagenous layer although some had disintegrated to disperse mature spores into the cranial cavity. Occasionally, lymphocytic infiltration and local granulomatous inflammation were found to be associated with spore dispersion.

Rhabdomyoma of the base of the tongue.

The histopathological and imaging findings of a rhabdomyoma of the base of the tongue were studied. An immunohistochemical examination of the tumour cells showed positive immunostaining for myoglobin, desmin, and striated muscle actin, but negative immunostaining for smooth muscle actin. Electron microscopy showed many glycogen granules and mitochondria in the tumour cells. The T2-weighted and contrast-enhanced magnetic resonance images (MRI) clearly delineated morphological features of this tumour, but T1-weighted MRI and computed tomography (CT) images showed no important features. These findings are typical for an adult extracardiac rhabdomyoma located in the head and neck region, and they will be useful for diagnosis of this tumour.

Subtype-specific coupling with ADP-ribosyl cyclase of metabotropic glutamate receptors in retina, cervical superior ganglion and NG108-15 cells.

Cyclic ADP-ribose (cADP-ribose) is a putative second messenger or modulator. However, the role of cADP-ribose in the downstream signals of the metabotropic glutamate receptors (mGluRs) is unclear. Here, we show that glutamate stimulates ADP-ribosyl cyclase activity in rat or mouse crude membranes of retina via group III mGluRs or in superior cervical ganglion via group I mGluRs. The retina of mGluR6-deficient mice showed no increase in the ADP-ribosyl cyclase level in response to glutamate. GTP enhanced the initial rate of basal and glutamate-stimulated cyclase activity. GTP-gamma-S also stimulated basal activity. To determine whether the coupling mode of mGluRs to ADP-ribosyl cyclase is a feature common to individual cloned mGluRs, we expressed each mGluR subtype in NG108-15 neuroblastoma x glioma hybrid cells. The glutamate-induced stimulation of the cyclase occurs preferentially in NG108-15 cells over-expressing mGluRs1, 3, 5, and 6. Cells expressing mGluR2 or mGluRs4 and 7 exhibit inhibition or no coupling, respectively. Glutamate-induced activation or inhibition of the cyclase activity was eliminated after pre-treatment with cholera or pertussis toxin, respectively. Thus, the subtype-specific coupling of mGluRs to ADP-ribosyl cyclase via G proteins suggests that some glutamate-evoked neuronal functions are mediated by cADP-ribose.