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M Funahashi

Publications and source records attributed to M Funahashi.

At least 37 records · Page 2Linked to original sources

GABA receptor-mediated post-synaptic potentials in the retrohippocampal cortices: regional, laminar and cellular comparisons.

Inhibitory post-synaptic potentials (IPSPs) were studied in neurons of presubiculum, parasubiculum and medial entorhinal cortex in horizontal slices from rat brains. Isolated IPSPs were evoked by extracellular electrical stimuli in the presence of glutamate receptor antagonists. Cellular morphology was identified using Neurobiotin labeling. IPSPs were compared: (a) across morphological cell types, (b) across laminae within regions, and (c) across regions. IPSPs were visible in stellate and pyramidal cells from layers II, III, and V of all retrohippocampal areas during bath application of glutamate antagonists. Qualitative and quantitative differences in IPSPs were only found when comparing responses by superficial layer II, III cells to responses by deep layer V cells. Responses by stellate and pyramidal cells within the same or adjacent layers did not differ, nor did responses differ from region to region. All cell types exhibited an early hyperpolarizing response. The majority (85%) of superficial layer cells in all regions, regardless of cell shape, exhibited a second hyperpolarizing component. Fewer (50%) deep layer cells exhibited the late peak with similar long latencies. IPSPs were typically larger in superficial layer cells. IPSPs were comprised of GABAA and GABAB (gamma-aminobutyric acid) receptor-mediated components. With repetitive stimulation, the peak amplitude of the GABAA receptor-mediated component decreased with successive stimuli, but stabilized during the first five or fewer stimuli to a level that did not vary with stimulation frequency. The GABAB receptor-mediated component also stabilized, but the final amplitude appeared to decrease as the stimulation frequency increased. With high-frequency repetitive stimulation, both components of the IPSP showed summation. We conclude that the most meaningful distinction for IPSPs among retrohippocampal neurons is a laminar distinction, between superficial and deep layer neurons, and not one across cell shape or retrohippocampal subregion. These laminar differences can contribute to synchronous activity by deep layer neurons and restrict the activity of superficial layer neurons.

Animals↗

Presubicular and parasubicular cortical neurons of the rat: functional separation of deep and superficial neurons in vitro.

1. The presubiculum and parasubiculum are retrohippocampal structures bordered by the subiculum and medial entorhinal cortex. Deep layer (IV-VI) neurons from this region exhibit stable synaptically triggered burst behaviour which distinguishes them from superficial layer (I-III) cells. This functional separation was examined with intracellular and field potential recordings from horizontal slices of rat brain. Neurobiotin labelling and rapid Golgi techniques were used to obtain anatomical evidence of axonal trajectories. 2. Extracellular stimulation of the subiculum, deep medial entorhinal cortex or superficial pre- or parasubiculum caused, in deep layer cells only, a short latency burst discharge which could be followed by one or more after-discharges. Bursts appeared after repetitive stimulation and were stable for the life of the slice. Each event was supported by giant excitatory postsynaptic potentials (EPSPs). Events were similar whether they were evoked in horizontal slices or slices cut perpendicular to the horizontal plane. 3. Bath application of the NMDA receptor antagonist 3-[2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid (CPP; 5 microM) elevated the threshold for evoking the giant EPSP. Higher concentrations (10-15 microM) reduced the amplitude and duration of the giant EPSP. Bath application of the AMPA receptor antagonist beta-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 5 microM) eliminated the evoked EPSP. 4. In intact slices, superficial layer neurons of pre- and parasubiculum could exhibit EPSPs coincident with bursts recorded in the deep layers. However, in isolated subsections of horizontal slices or in 'vertical slices', both of which contained only pre- and/or parasubiculum, evoked or picrotoxin-induced bursts occurred only in deep layer cells. Superficial layer cells in these subsections showed no response to deep layer events. 5. Antidromic population spikes confirmed projections from superficial cell layers of pre- and parasubiculum down to their deep cell layers. Reciprocal antidromic responses were absent. 6. Axons of superficial layer stellate and pyramidal cells had horizontal collaterals and at least one ascending and one descending collateral. Branches of the descending collaterals were given off in layer V and some axons were found to reach the angular bundle. Axons of deep layer stellate and pyramidal cells also had horizontal collaterals and descending collaterals which could be traced to the angular bundle. One ascending axon collateral was found among the thirty-one deep layer cells examined morphologically. 7. We conclude that the deep layer cells of the presubiculum and parasubiculum are richly interconnected with excitatory synapses. These interconnections can generate giant excitatory synaptic potentials that support the bursting behaviour exhibited by these neurons. Any of the excitatory inputs to deep layer cells can trigger the population bursts and specific inputs from entorhinal cortex produce the after-discharges. Further, connections between superficial and deep layer cells appear to be almost exclusively in the direction of superficial to deep. The absence of significant ascending input can account for the functional separation of superficial and deep layer neurons of presubiculum and parasubiculum.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Regulation of hyaluronate metabolism by progesterone in cultured fibroblasts from the human uterine cervix.

The effects of progesterone, dehydroepiandrosterone sulfate and 17beta-estradiol on the synthesis and degradation of hyaluronate were investigated using human uterine cervix fibroblasts. The cells were incubated with [3H]glucosamine in the presence of the hormones and then [3H]hyaluronate was isolated from the medium. The changes in the radioactivity of [3H]hyaluronate showed that progesterone suppressed hyaluronate synthesis by 22% of the control levels, while dehydroepiandrosterone sulfate and 17beta-estradiol enhanced it by 22% and 12% of the control levels, respectively. Furthermore, progesterone induced degradation of high-molecular-weight [14C]hyaluronate into low-molecular-weight hyaluronate (Mr approximately 40000). These results suggest that in cultured fibroblasts from the human uterine cervix progesterone converts hyaluronate metabolism from the synthesis phase to the degradation phase.

Cells, Cultured↗

Presubicular and parasubicular cortical neurons of the rat: electrophysiological and morphological properties.

Intracellular recordings and Neurobiotin-injection were used to examine the electrophysiology and morphology of presubicular and parasubicular cortical neurons in horizontal slices from rat brains. Evoked responses were obtained by stimulation of subicular and entorhinal cortices. Stellate cells were recorded in layers II and V of presubiculum and parasubiculum. Superficial layer cells had spiny dendrites that were found to reach layer I. Deep layer cells had sparsely spiny dendrites or dendrites without spines that did not reach past layer IV. Pyramidal cells were recorded in layers III and V of presubiculum and layers II and V of parasubiculum. Superficial layer cells had spiny dendrites that were found to reach layer I. Deep layer cells had sparsely spiny dendrites or dendrites without spines that could reach layer II. Electrophysiologically, stellate and pyramidal cells were similar to one another, regardless of cell layer, exhibiting repetitive single spiking in response to depolarizing current injection. No cells were found to burst in response to current injection. While there were subtle electrophysiological differences among the cell types, stellate cells were more similar to pyramidal cells from the same or adjacent layers than to other stellate cells from more distant layers. Similarly, pyramidal cells were electrophysiologically more similar to nearby stellate cells than to other distant pyramidal cells. Cells of all layers responded to subicular stimulation with a short latency (< 9 ms), excitatory postsynaptic potential. Superficial layer cells responded at short (< 9 ms), longer (10-20 ms) and very long latencies (> 20 ms) to stimulation of superficial layers of medial entorhinal cortex. Deep layer cells responded at short latencies (< 9 ms) to stimulation of deep layers of medial entorhinal cortex. Many cells responded to both subicular and entorhinal inputs. Both pyramidal and stellate cells in the deep layer of pre/parasubiculum could exhibit population bursting behavior in response to stimulation of subiculum or entorhinal cortex. The results define the cellular morphology and basic electrophysiology of presubicular and parasubicular neurons of the rat brain as a step toward understanding the physiology of the retrohippocampal cortices.

Action Potentials↗

Exaggerated C-fiber activation prevents peripheral nerve injury-induced hyperinducibility of c-Fos in partially deafferented spinal dorsal horn.

Dorsal horn neurons chronically deafferented by peripheral nerve injuries acquire hypersensitivity to noxious input from outside the original receptive field. This study examines the effect of electrical nerve stimulation at the time of injury on such injury-induced hypersensitivity. The medial 3/8 of the dorsal horn laminae I/II around the junction of 4th and 5th lumbar segments (the tibial territory) was deafferented by transection of the ipsilateral tibial nerve in rats. At 2 days or 3 weeks postinjury, the hindpaw was injected with formalin to induce c-fos. At 2 days, neurons with induced c-Fos protein-like immunoreactivity (fos-neurons) were largely confined in the lateral 5/8 of laminae I/II (the peroneal and hip, thus P and H territory). At 3 weeks, fos-neurons significantly increased in the deafferented tibial territory. A similar increase was also noted in the P and H territory. Thus the dorsal horn neurons exhibited c-fos hyperinducibility, an indication of hypersensitivity. Electrical stimulation with a train of 150 shocks (10 V, 2 ms) of the proximal nerve stump immediately after transection prevented the c-fos hyperinducibility. The effect was greater with the stimulation frequency of 0.5 Hz than 0.1 Hz or 10 Hz. The stimulation had no effect on the c-fos inducibility at 2 days postinjury.

Animals↗

Effect of 4-methylumbelliferone on cell-free synthesis of hyaluronic acid.

Human skin fibroblasts were cultured in the presence of 0.5 mM 4-methylumbelliferone for 12 h, and cell-free synthesis of hyaluronic acid was performed using membrane-rich fraction from the cells. The preincubation of the cells with 4-methylumbelliferone reduced hyaluronic acid synthesis to 15% of that of non-preincubated cells, although its chain length was not changed. On the other hand, without preincubation of the cells with 4-methylumbelliferone, hyaluronic acid synthesis was not changed even when 4-methylumbelliferone was added directly to the reaction mixture. These results suggest that 4-methylumbelliferone represses the expression of hyaluronic acid synthase on the cell surface.

Cell Membrane↗

Are breaches in the glia limitans the primary cause of the micropolygyria in Fukuyama-type congenital muscular dystrophy (FCMD)? Pathological study of the cerebral cortex of an FCMD fetus.

A light and electron microscopic study of the brain of an 18-week fetus with a prenatal genetic diagnosis of Fukuyama-type congenital muscular dystrophy revealed a widespread mantle of abnormal neurogliomesenchymal tissue that covered a dysplastic cerebral cortex. In this area alone, the glia limitans that adjoined the abnormal mantle via one or two layers of basal lamina had frequent breaches, through which neuroglial elements extruded. In the most severely affected cortical region, which had only a rudimentary and fragmentary glia limitans, the majority of cortical neurons had migrated into the neurogliomesenchymal tissue. The massive overmigrated neurons still maintained a somewhat columnar arrangement, and the marked dysplasia abruptly shifted to a neurogliomesenchymal tissue-free normal cortical structure with an intact glia limitans, thus indicating essentially vertical overmigration of neurons without significant tangential migration of them. Together the above findings imply that breaches in the glia limitans may be the primary cause of the micropolygyria seen in this genetic disorder.

Cerebral Cortex↗

[Epidemiology of pertussis and studies on culture positive pertussis cases in Japan].

The number of pertussis patients has decreased steadily in the late 1960s and was extremely small in early 1970s. During 1973-74 the first national survey on pertussis cases confirmed by culture was conducted, when whole cell pertussis vaccine was used. The study revealed that 33.3% of culture positive cases had 2-4 doses of DT combined with whole cell pertussis vaccine. Acellular pertussis vaccine was introduced in 1981 and for the last several years the number of pertussis patients became low for the second time. During 1988-92 exactly the same study was conducted as the previous one. Among 2501 pertussis cases diagnosed clinically 403 were culture positive. Most of the patients were below 1 year of age. Most of the patients were below 1 year of age. Clinical symptoms of those infants were more serious than those of older children. Only 7 out of 403 (1.8%) had a history of 2-4 doses of DT combined with acellular pertussis vaccine. This proved that the acellular pertussis vaccine is by far more effective than the whole cell pertussis vaccine. Serotypes of 377 Bordetella pertussis were identified and 370/377 (98.1%) were serotype 1-3 group.

Adolescent↗

Glucose-responsive neurons in the brainstem.

AREA POSTREMA: The influence on feeding behavior caused by ablation of the area postrema (AP) in rodents indicates the participation of this structure in the control of ingestion. Two types of glucose responsive neurons were identified in the AP: one is characterized by increasing the discharge rate in response to glucose (glucoreceptor type) and the other by decreasing the discharge rates in response to glucose (glucose sensitive type). These glucose responsive neurons may participate in glycemic homeostasis. NUCLEUS OF SOLITARY TRACT: The glucose responsive neurons exist within the caudal portion of nucleus of the solitary tract (NTS), a relay station in visceral afferents. Two types similar to the AP were also recognized. It is confirmed that hepatic glucose sensitive afferents terminate on some of the glucose sensitive neurons. This convergence may serve as a fail-safe mechanism. In addition, the NTS involving complex neural networks of excitatory and inhibitory interneurons may be concerned with integration of glycemic information. DORSAL MOTOR NUCLEUS OF VAGUS: Some neurons within the dorsal motor nucleus of the vagus (DMV) were identified as the glucose responsive ones. Both types were also recognized. It is confirmed by antidromic activation that these glucose responsive DMV neurons send their axons toward the gastric or coeliac branch that innervates either the stomach, intestine or pancreas. Some of the DMV neurons may subserve an enteroceptor function by themselves. They may also play a role in the brainstem neural control of glycemic homeostasis as the fail-safe mechanism.

Animals↗

Tissue fibronectin is an endogenous ligand for galectin-1.

A 14K beta-galactoside-binding lectin (galectin-1) is present in many animal tissues. In a search for endogenous ligands, we surveyed galectin-1-binding proteins in human placenta. Extract of human placenta with 2 M urea was applied to a Sepharose 4B column conjugated with galectin-1 purified from frog (Rana catesbeiana) eggs. Two major proteins eluted with 100 mM lactose from the column-bound fraction showed apparent molecular masses of 220 and 180 kDa on SDS-PAGE under reducing conditions. Western blotting analysis using monoclonal antibodies indicated that these proteins were fibronectin and laminin, respectively. Most placental and amniotic fibronectins bound strongly to the column, whereas almost all plasma fibronectin passed through the column. The galectin-1, fibronectin and laminin were immunohistochemically shown to be co-localized in the extracellular matrix of placental tissue. In a cell attachment assay, rhabdosarcoma cells adhered to a plate coated with placental fibronectin, even in the presence of GRGDS peptide, if galectin-1 were also present. This adhesive effect of galectin-1 was inhibited by lactose. These results indicate that tissue fibronectin, as well as laminin, serve as endogenous ligands for galectin-1, suggesting that galectin-1 may play a role in assembly of the extracellular matrix, or in the control of cell adhesion based on lectin-extracellular matrix interaction.

Animals↗

Glucose-responsive neurons exist within the area postrema of the rat: in vitro study on the isolated slice preparation.

Responses to glucose of spontaneously active neurons were investigated by extracellular recording in the rat area postrema slice preparations (in vitro). Among 67 spontaneously active neurons, 16 neurons displayed a marked increase or decrease in discharge rate in response to increases or decreases of the glucose concentration in perfusate. These results confirm the existence of glucose-responsive neurons within the area postrema suggested in prior in vivo experiments. Response to CCK or dopamine was also examined on the isolated area postrema slices. The neuron that showed a marked increase in discharge rate responding to glucose elicited a marked increase of discharge rate in response to 2.1 microM CCK, suggesting that glucose and CCK affect the same neurons. Some neurons showed a marked increase or decrease in the discharge rate in response to 20 microM dopamine, but these neurons showed neither response to CCK nor to glucose. It is likely that different neuronal networks in the area postrema contribute to control of ingestion and to initiation of nausea.

Animals↗

Comparing the cell population on different intraocular lens materials in one eye.

We developed a method to evaluate cell adherence to different intraocular lens (IOL) materials in one eye in which we coated one half of the anterior surface of a poly(methyl methacrylate) (PMMA) IOL with poly(dimethyl siloxane), a silicone material. The lenses were implanted in the anterior chamber of rabbit eyes without lens extraction. Postoperative cellular reaction on the IOL surfaces was studied by specular microscopy. The IOLs were fixed in situ, removed from the eyes, and stained with hematoxylin-eosin so we could evaluate the cell population on the silicone and PMMA surface. Fewer cells were scattered on the silicone surface than on the PMMA surface. This method excludes surgical effects and allows a comparison of various IOL materials in the same eye.

Animals↗

[A case of cardiac arrest encephalopathy in athetotic cerebral palsy].

A 25-year-old woman with cerebral palsy of spastic quadriplegia and athetosis showed typical cardiac arrest encephalopathy on neuropathology. The etiology of cerebral palsy was perinatal origin including prematurity, asphyxia and hyperbilirubinemia. Ventricular premature beats had developed since about 20 years of age. Muscle tone also increased with aging and symptoms of vago-vagal reflex were occasionally observed after eating. At 25 years, cardiac arrest occurred and cardiopulmonary resucitation was done immediately. She remained unconscious with absent corneal reflex and irregular respiration. EEG or auditory brain stem response showed flat activity. She died of respiratory failure 53 days after the episode of cardiac arrest. Neuropathology showed bilaterally symmetrical necrosis in the superior colliculi, gracilis nuclei, cuneate nuclei and spinotrigeminal nuclei accompanied with severe necrosis in the cerebrum and cerebellum. These findings in this adult case of total asphyxia were compatible with those observed in total plus partial asphyxia in the neonates. This discrepancy may be due to difference in cerebral maturity. Children or young adults with athetotic type cerebral palsy have a high risk of sudden death. Sudden cardiac arrest seems to play an important role in sudden death of these patients.

Adult↗

Encainide-induced diabetes: analysis of islet cell function.

OBJECTIVE: The purpose of this study was to gain insight into the mechanisms responsible for encainide-induced diabetes. Specifically, we sought to determine if absolute insulinopenia was present or whether encainide-induced diabetes was metabolically more like type II than type I diabetes. RESEARCH DESIGN AND METHODS: Islet function was assessed in a 65 year old white male with encainide-induced diabetes. After 6 months of encainide treatment and 2 months duration of diabetes, C-peptide, glucagon, and glucose levels were measured at baseline and at 30 minute intervals for 120 minutes following an oral mixed meal. These measurements allowed assessment of islet beta and alpha cell function in comparison to control data from our laboratory. RESULTS: In this patient with encainide-induced diabetes, basal and peak C-peptide concentrations were similar to controls although peak C-peptide occurred substantially later than in controls. At peak glucose, the patient's C-peptide/glucose ratio was low indicating relative (but not absolute) insulinopenia. At baseline, glucagon was relatively depressed. Following Sustacal, there was an increase in glucagon of 100% over baseline compared to a mean glucagon rise in controls of only 8%. There was no serological evidence for autoimmune diabetes as islet cell autoantibodies were absent. CONCLUSIONS: Similar to other forms of diabetes, encainide-induced diabetes is a bihormonal disorder. The metabolic pattern was more like type II than type I diabetes with C-peptide secretion in the normal range, yet persistent hyperglycemia that suggests relative insulinopenia and concurrent insulin resistance.

Aged↗

Potentiating effect of morphine upon d-methamphetamine-induced hyperthermia in mice. Effects of naloxone and haloperidol.

We have examined changes in rectal temperature of mice after subcutaneous administrations of d-methamphetamine alone or methamphetamine plus morphine. Methamphetamine 5 mg/kg produced slight hyperthermia, while simultaneous administration of morphine (25-100 mg/kg), which alone produces hypothermia, potentiated markedly the increase in body temperature by methamphetamine. Methamphetamine showed a hyperthermic effect in a dose-dependent manner in the presence of morphine. The hyperthermia due to methamphetamine plus morphine was avoided by pretreatment with 10 mg/kg naloxone. When animals were pretreated with 2.5 mg/kg haloperidol, hyperthermia due to methamphetamine alone was completely abolished, while that due to methamphetamine plus morphine was still observed. These results showed that dopamine may be implicated in methamphetamine hyperthermia and a haloperidol-nonsensitive mechanism may be involved in the methamphetamine-morphine hyperthermia.

Animals↗

Gastric lesions in rats fed salted food materials commonly eaten by Japanese.

A high intake of salted food is thought to be related to the high incidence of stomach cancer in Japan. In the present study, female F344 rats were divided into four groups. They were fed a nutritionally deficient purified diet (Group 1) and standard purified diet (Group 3) for 113 weeks and the same diets supplemented with salted cuttlefish guts, broiled, salted, dried sardines, pickled radish, and soy sauce (Groups 2 and 4). The incidence of papillomas and ulcers of the forestomach was highest in Group 4, which was given the standard diet supplemented with the salty food materials (p less than 0.05). These results suggest the importance of salted food as a suspicious causal factor in human stomach cancer in Japan.

Animals↗