GABAergic mechanisms for shaping transient visual responses in the mouse superior colliculus.

An object that suddenly appears in the visual field should be quickly detected and responded to because it could be beneficial or harmful. The superficial layer of the superior colliculus (sSC) is a brain structure capable of such functions, as sSC neurons exhibit sharp transient spike discharges with short latency in response to the appearance of a visual stimulus. However, how transient activity is generated in the sSC is poorly understood. Here, we show that inhibitory inputs actively shape transient activity in the sSC. Juxtacellular recordings from anesthetized mice demonstrate that almost all types of sSC neurons, which were identified by post hoc histochemistry, show transient spike discharges, i.e., ON activity, immediately after visual stimulus onset. ON activity was followed by a pause before the visual stimulus was turned off. To determine whether the pause reflected the absence of excitatory drive or inhibitory conductance, we injected depolarizing currents juxtasomally, which enabled us to observe inhibition as decreased discharges. The pause was observed even under this condition, suggesting that inhibitory input caused the pause. We further found that local application of a mixture of GABAA and GABAB receptor antagonists additively diminished the pause. These results indicate that GABAergic inputs produce transient ON responses by attenuating excitatory activity through the cooperative activation of GABAA and GABAB receptors, allowing sSC neurons to act as a saliency detector.

Motor command for precision grip in the macaque monkey can be mediated by spinal interneurons.

In motor control, the general view is still that spinal interneurons mainly contribute to reflexes and automatic movements. The question raised here is whether spinal interneurons can mediate the cortical command for independent finger movements, like a precision grip between the thumb and index finger in the macaque monkey, or if this function depends exclusively on a direct corticomotoneuronal pathway. This study is a followup of a previous report (Sasaki et al. J Neurophysiol 92: 3142-3147, 2004) in which we trained macaque monkeys to pick a small piece of sweet potato from a cylinder by a precision grip between the index finger and thumb. We have now isolated one spinal interneuronal system, the C3-C4 propriospinal interneurons with projection to hand and arm motoneurons. In the previous study, the lateral corticospinal tract (CST) was interrupted in C4/C5 (input intact to the C3-C4 propriospinal interneurons), and in this study, the CST was interrupted in C2 (input abolished). The precision grip could be performed within the first 15 days after a CST lesion in C4/C5 but not in C2. We conclude that C3-C4 propriospinal interneurons also can carry the command for precision grip.

Quantitative inter-segmental and inter-laminar comparison of corticospinal projections from the forelimb area of the primary motor cortex of macaque monkeys.

Corticospinal projections from the forelimb area of the primary motor cortex to the C2-Th2 spinal cord segments were quantitatively analyzed using the high resolution anterograde tracer, biotinylated dextran amine (BDA), in rhesus monkeys (n=5). The majority of descending axons were located in the contralateral dorsolateral funiculus (DLF) (85-98%), but a minor portion was observed in the ipsilateral DLF (1-12%) and ventromedial funiculus (VMF) (1-7%). In the gray matter, axon collaterals and terminal buttons were found mainly in the contralateral laminae VI-VII and IX and ipsilateral lamina VIII. The majority of projections to the contralateral gray matter originated from the contralateral DLF, but a minority originated from the ipsilateral DLF. Axons from the ipsilateral DLF were not found to project collaterals on the ipsilateral side, but directly entered the contralateral side after crossing the midline. On the other hand, projections to the ipsilateral lamina VIII were from the ipsilateral VMF, and commissural axons were from the contralateral DLF. Terminal buttons in the motoneuron pool in the contralateral lamina IX were found mainly at the C7-Th1 spinal cord segments, whereas the projections to the contralateral laminae VI-VII, ipsilateral lamina VIII, and commissural axons were also found in more rostral segments, abundantly at the C4-C8 segments, 1-3 segments rostral to the motoneuronal projections. These results suggest that cortical control of contralateral forelimb motoneurons accompanies regulation of interneuronal systems in the contralateral laminae VI-VII and the ipsilateral lamina VIII located a few segments rostral to the motoneurons.

Color and surface temperature variation during bleaching in human devitalized primary teeth: an in vitro study.

This study's purpose was to make an in vitro assessment of 2 whitening techniques in primary teeth, regarding color and temperature surface variation, during dental bleaching using different catalytic sources. Twenty-one extracted human upper central deciduous incisors were used in this in vitro study. The teeth were darkened with human blood for a period of 21 days. After preparing the teeth, they were randomly distributed into 2 groups, according to bleaching source of activation: (1) a diode laser (DL) group; and (2) a halogen lamp (HL) group. The bleaching process was performed, according to the manufacturer's guidelines, using Whiteness HP (FGM, Joinville, Brazil). The color was assessed by spectrophotometer (CIELab) and the VITA scale (3M) before and immediately after tooth whitening. The temperature increase in the radicular surface during the bleaching was registered with a thermographic camera ThermaCAM SC 3000 (Flir Systems, Danderyd, Sweden) at the Nuclear and Energy Research Institute, IPEN-CNEN (São Paulo, Brazil). There was no significant difference between the groups in terms of color changes, but there was a statistically significant difference for temperature variation. The use of a diode laser and halogen lamp both promoted whitening in devitalized primary teeth in vitro. As a catalytic source of energy, the diode laser--with the applied parameters--promoted a smaller temperature increase compared to the halogen lamp during the bleaching procedure on nonvital primary teeth.

Whitening techniques using the diode laser and halogen lamp in human devitalized primary teeth.

The aim of this study was to make an in vivo assessment of 2 whitening techniques in deciduous teeth, with the variable being the source of energy activation. Ten upper central incisors darkened by trauma were selected and whitening agent used was a 35% hydrogen peroxide. The teeth were distributed into 2 groups: group 1-activation with an infrared diode laser (GaAlAs), and group 2-activation with a halogen lamp. Assessment of whitening was done by color analysis with the Vita 3D scale at 3 different times: before whitening, immediately after whitening, and 1 week after whitening. A Kruskal-Wallace test showed that there were no significant difference between the 2 groups when comparing group 1 and 2 and comparing 2 and 3 immediately and after 1 week of treatment. Laser activation of the whitening agent was not more effective than halogen light activation for root canal-treated deciduous teeth.

The C3-C4 propriospinal system in the cat and monkey: a spinal pre-motoneuronal centre for voluntary motor control.

This review deals with a spinal interneuronal system, denoted the C3-C4 propriospinal system, which is unique in the sense that it so far represents the only spinal interneuronal system for which it has been possible to demonstrate a command mediating role for voluntary movements. The C3-C4 propriospinal neurones govern target reaching and can update the descending cortical command when a fast correction is required of the movement trajectory and also integrate signals generated from the forelimb to control deceleration and termination of reaching.

Skilled digit movements in feline and primate--recovery after selective spinal cord lesions.

Recovery of voluntary movements after partial spinal cord injury depends, in part, on a take-over of function via unlesioned pathways. Using precise forelimb movements in the cat as model, spinal pathways contributing to motor restitution have been investigated in more detail. The food-taking movement by which the cat graSPS a morsel of food with the digits and brings it to the mouth is governed by interneurones in the forelimb segments (C6-Th1) and is normally controlled via the cortico- and rubrospinal tracts. Food-taking disappears after transection of these pathways in the dorsal part of the lateral funiculus (DLF) in C5/C6, but then recovers during a period of 2-3 weeks. Experiments with double lesions showed that the recovery depends on a take-over via ipsilateral ventral systems; a ventrally descending pathway, most probably cortico-reticulospinal, and a pathway via propriospinal neurones in the C3-C4 segments. It is postulated that the recovery involves a plastic reorganization of these systems. Dexterous finger movements in the macaque monkey are generally considered to depend on the monosynaptic cortico-motoneuronal (CM) connexion, which is lacking in the cat. Such movements are abolished after pyramidotomy at the level of the trapezoid body. However, experiments with transection of the corticospinal tract in the DLF and partly ventral part of the lateral funiculus in C5, showed a fast (1-28 days) recovery of precision grip and, to some extent, independent finger movements. Deficits in preshaping during the final approach to the morsel as well as lack of force were observed. A C5 DLF lesion spares corticofugal pathways to the brainstem and upper cervical segments. It is suggested that indirect corticomotoneuronal pathways may provide for recovery of dexterous finger movements and that the role of CM pathways for such movements should be broadened to include not only the monosynaptic connexion.

Lack of monosynaptic corticomotoneuronal EPSPs in rats: disynaptic EPSPs mediated via reticulospinal neurons and polysynaptic EPSPs via segmental interneurons.

In the rat, some findings have been taken to suggest the existence of monosynaptic corticomotoneuronal (CM) connections. Because this connection is believed to be largely responsible for the ability to make independent digit movements in primates and man, it has been inferred that the monosynaptic CM connection in the rat is likewise important for skilled prehension. Comparison of intra- and extracellular recordings from forelimb motoneurons in anesthetized rats, revealed no monosynaptic CM excitatory postsynaptic potentials (EPSPs). The fastest descending excitation in forelimb motoneurons was disynaptically mediated via a corticoreticulospinal pathway and slowly conducted excitation via corticospinal fibers and segmental interneurons. The findings stress the importance of di- and trisynaptic excitatory corticofugal pathways to forelimb motoneurons in the control of skillful digit movements.

Functionally different AMPA-type glutamate receptors in morphologically identified neurons in rat superficial superior colliculus.

In the superficial superior colliculus, a center of sensory processing related to visual salience, glutamate is used as a major excitatory neurotransmitter. alpha-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type glutamate receptors include a Ca(2+)-impermeable, outwardly rectifying type (type I) and a Ca(2+)-permeable, inwardly rectifying type (type II). To study the contribution of these AMPA receptor subtypes to visual sensory processing in the superior colliculus, we investigated the expression of these two types of AMPA receptors in six morphologically identified subgroups of neurons in the superficial superior colliculus by whole-cell recording using slice preparations of young (17-23 days old) and adult (60-68 days old) rats. Both outwardly and inwardly rectifying current responses were observed to pressure applied 10 mM kainate, a non-desensitizing AMPA receptor agonist. These currents were completely abolished by the selective AMPA receptor antagonist 1-(4-aminophenyl)-3-methylcarbamyl-4-methyl-7,8-methylenedioxy-3,4-dihydro-5H-2,3-benzodiazepine (100 microM). The type II receptor antagonist spermine (1 mM) suppressed inwardly rectifying responses. The degree of inward rectification was correlated with the ratio of suppression by spermine, and inversely correlated with estimated Ca(2+) permeability, indicating that the degree of rectification reflects the relative amount of co-expressed type I and type II receptors. An inwardly rectifying and spermine-sensitive AMPA component of excitatory postsynaptic currents was observed, suggesting involvement of type II receptors in synaptic transmission. Morphological analysis revealed that a substantial population of horizontal cells in both young and adult rats (n=31/53 and 15/17, respectively) and all wide field multipolar cells in adult rats (n=6) showed inwardly rectifying AMPA receptor responses. From these results we suggest that type I and type II AMPA receptors are co-expressed with varying ratios in individual neurons in the rat superficial superior colliculus, and that type II receptors are abundantly expressed in most horizontal cells and wide field multipolar cells. Since these neurons are putatively GABAergic inhibitory neurons and have wide dendritic trees, type II receptors may contribute to the regulation of remote inhibitory interaction in the visual field map in the the superficial superior colliculus.

Facilitation of saccade initiation by brainstem cholinergic system.

It is well known that the intermediate layer (SGI) of the mammalian superior colliculus (SC) receives cholinergic inputs originating from the pedunculopontine tegmental nucleus (PPTN). The action of the cholinergic input on the SGI neurons was investigated using whole-cell patch-clamp recording technique in slice preparations obtained from rats. Application of acetylcholine (ACh) induced fast inward currents mediated by nicotinic ACh receptors in the SGI neurons. Depolarization induced by nicotine enhanced the N-methyl-D-aspartate receptor-mediated excitatory postsynaptic potential component and lowered the threshold of bursting response in the SGI neurons to stimulation of the superficial layer. Thus, the cholinergic input to the SGI facilitates the signal transmission through the direct visuomotor pathway in the SC. The behavioral correlate of this observation was explored by microinjection of nicotine into the SC of awake monkeys during visually guided saccade task; injection of nicotine increased frequency of express saccades, the saccades with extremely short reaction times (<120 ms). Analysis of single unit activity of the PPTN neurons revealed that a population of the PPTN neurons increased firing preceding saccades in a particular direction and also during the GAP period between the offset of fixation point and onset of the saccade target. Thus, PPTN neurons may be involved in execution and preparation of saccades. All these results explain the mechanisms of how the brainstem cholinergic system facilitates initiation of saccades presumably depending on attention or vigilance level of the animal.

The direct visuo-motor pathway in mammalian superior colliculus; novel perspective on the interlaminar connection.

The mammalian superior colliculus (SC) is a center controlling the orienting behaviors such as saccadic eye movements. The superficial layers receive visual inputs and the deeper layers send descending motor command to the brainstem and spinal cord. Existence of the interlaminar connection from the superficial to the deeper layers has been an issue of debate during the last two decades. Recent studies have proved the existence of the interlaminar connection by introducing the in vitro slice preparations. When the collicular circuit is disinhibited from gamma-amino butyric acid A (GABA(A)) receptor-mediated inhibition, the signal transmission through the interlaminar connection is enormously facilitated and neurons in the deeper layers exhibit bursting response to stimulation of the superficial layer with non-linear amplification mechanism that depends on the activation of NMDA-type glutamate receptors. In addition, the cholinergic input to the intermediate layer lowers the threshold for the bursting response and facilitates the transmission through the interlaminar connection via activation of nicotinic receptors. The signal transmission through the interlaminar connection may lead to execution of extremely short latency saccades called express saccades.

Fundic adenomyomatosis bulged with the subserosal excessive fat of the gallbladder mimicking polypoid carcinoma: a case report with unusual imaging and morphological features.

This report describes a 41-year-old female who presented with adenomyomatosis of the gallbladder mimicking polypoid carcinoma, on the diagnostic imaging findings and revealing unusual histologic features for such a localized adenomyomatosis. The mass was located on the gallbladder liver-side wall at the fundus and papillary hyperechoic growth showed no clear ultrasonographic features of adenomyomatosis. The patient underwent a laparoscopic cholecystectomy with a tentative diagnosis of superficial polypoid carcinoma. Histologically, the tumor bulged due to subserosal excessive fat tissue.

Predictive factors for long-term survival in patients with intrahepatic cholangiocarcinoma.

BACKGROUND: In order to elucidate the predictive factors for long-term survival in patients with intrahepatic cholangiocarcinoma (ICC), we evaluated 7 patients who survived for more than 5 years (5-year survivors). METHODS: We examined the clinicopathologic and biologic factors of the 5-year survivors, and these findings were then compared with those in 20 patients who died within 5 years after surgery (control group). RESULTS: In the 5-year survivors, the gross appearance of the tumors included a mass-forming (MF) type in 5 cases, an intraductal growth (IG) type in 1, and another type (microcarcinoma with hepatolithiasis) in 1. No case demonstrated a periductal infiltrating (PI) type. Except for 1 case with an IG type tumor, no lymph node metastasis was seen in any patients. All of the 5-year survivors were classified from stage I to III, and all also underwent a curative resection. The clinicopathologic factors demonstrating significant differences between the 5-year survivors and the control group included the gross type of the tumor, lymph node involvement, the surgical margin, curability, and pTNM stage. CONCLUSION: The predictive factors for long-term survival in patients with ICC are thus suggested to include not only tumor staging and curability, but also lymph node metastasis and the gross type of the tumors.

Natural progression of untreated hepatolithiasis that shows no clinical signs at its initial presentation.

GOALS: To elucidate the natural progression of hepatolithiasis that showed no signs at the time of initial presentation. STUDY: Over a 17-year period, we observed 122 of 311 patients with hepatolithiasis who reported no symptoms and, thus, who received no treatment at initial presentation. The follow-up period was for up to 15 years (mean, 10.08 years). RESULTS: Fourteen of 112 patients (11.5%) developed some symptoms attributed to hepatolithiasis. The interval until the onset of symptoms ranged from 9 months to 7.33 years (mean, 3.42 years ). The developing symptoms included abdominal pain, hepatic abscess, cholangitis, and cholangiocarcinoma. Nine of the 14 patients (64.3%) developed stone migration to the extrahepatic bile duct at the onset of clinical symptoms. The incidence of lobar liver atrophy on computed tomography in the patients with symptomatic hepatolithiasis (13 of 14 patients; 92.9%) was significantly higher than that in the patients with asymptomatic hepatolithiasis (14 of 108 patients; 13.0%). The prognosis of the patients with symptomatic hepatolithiasis were as follows: 2 died of cholangiocarcinoma, 1 died of hepatic failure, and 11 survived. Fifteen of asymptomatic patients died, but none of these deaths were attributed to hepatolithiasis. CONCLUSIONS: Close observation is an alternative management at initial presentation for patients with asymptomatic hepatolithiasis without extrahepatic stones or lobar liver atrophy.

Long-term results of hepaticojejunostomy for hepatolithiasis.

The results of a hepaticojejunostomy as a biliary-enteric bypass for benign disease are usually excellent. On the other hand, hepatolithiasis features a high rate of residual and recurrent stones with cholangitis after surgery. This study aims to evaluate the long-term results of a hepaticojejunostomy for hepatolithiasis regarding both the degree of the occurrence of postoperative cholangitis and the outcome. The clinical records of 159 patients with hepatolithiasis who underwent surgical treatment over a 23-year period were also retrospectively reviewed. Ninety-four of 159 patients underwent a hepatecetomy and 65 patients were subjected to liver-preserving surgery by means of intra- and postoperative endoscopic lithotripsy. In addition 72 patients underwent a hepaticojejunostomy. The rate of residual or recurrent stones was 31.4 per cent after complete stone removal. Twenty-two (30.6%) of the 72 patients developed some kind of cholangitis. This rate was significantly higher than that (three of 87 patients) of the non-biliary-enteric anastomosis group regarding the occurrence of biliary complications. We conclude that the use of a hepaticojejunostomy for patients with possible residual stones or intrahepatic bile duct lesions remains controversial.

Clinical relevance of the concentrations of both pyrimidine nucleoside phosphorylase (PyNPase) and dihydropyrimidine dehydrogenase (DPD) in colorectal cancer.

BACKGROUND: Pyrimidine nucleoside phosphorylase (PyNPase) converts 5'-deoxy-5-fluorouridine (5'-DFUR) to 5'-fluorouracil (5-FU), which exerts an anti-cancer effect before being catabolized by dihydropyrimidine dehydrogenase (DPD). We examined the possible correlation of the tissue concentrations of both PyNPase and DPD with the clinicopathological features of colorectal cancer. METHODS: In 36 cases of colorectal cancer, the concentrations of both PyNPase and DPD in fresh-frozen samples from either tumor or normal tissue were quantified using ELISA. RESULTS: The concentration of PyNPase was found to be significantly higher in the tumor than in the normal tissue (p = 0.001), whereas DPD showed no difference. The tumor/normal tissue ratio of PyNPase was higher in advanced stage cases, and also in the presence of liver metastasis, lymph node metastasis and vessel invasion (each p < 0.05). On the other hand, the tumor/normal tissue ratio of DPD was also higher in advanced stage cases and also in the presence of vessel invasion (each p < 0.05), thus indicating a poor response to 5-FU. The PyNPase/DPD ratio, which is known to be correlated with the tissue concentration of 5'-DFUR, was higher in the tumor than in the normal tissue (p = 0.001). CONCLUSIONS: The tumor/normal tissue ratios of both PyNPase and DPD might be useful candidates for predicting the prognosis of colorectal cancer. The PyNPase/DPD ratio was higher in the tumor tissue than in the normal tissue; however, further investigations are needed to clarify the effectiveness of fluoropyrimidine therapy.

Subunit composition of AMPA receptors expressed by single hippocampal neurons.

Using a patch-clamp, reverse transcription-polymerase chain reaction (RT-PCR) method, we determined AMPA receptor subunits expressed in neurons in rat hippocampal slices at the single-cell level. In a population of non-pyramidal neurons (type II neurons) expressing AMPA receptors with strong inward rectification and Ca2+ permeability, no GluR2 was detected, and GluR1 and GluR4 were the most frequently detected subunits. Analysis of the splicing variants revealed that only the flop form of GluR4 was expressed, but both flip and flop forms of GluR1 were expressed in these neurons. In contrast, GluR2 was the most frequently detected subunit both in CA1 pyramidal cells and type I non-pyramidal cells possessing AMPA receptors with outwardly rectifying current-voltage relationships and little Ca2+ permeability.

Voltage-gated transient outward currents in neurons with different firing patterns in rat superior colliculus.

1. We investigated the electrophysiological properties of transient outward currents (TOCs) in neurons with different firing patterns, regular-spiking, fast-spiking and late-spiking neurons, in the intermediate layer (SGI) of the superior colliculus using the whole-cell patch clamp technique in slice preparations obtained from young rats (post-natal days 17-22). 2. Analysis of inactivation kinetics and normalized amplitude revealed that TOCs in regular-and fast-spiking neurons had fast inactivation kinetics (decay time constants (mean +/- s.e.m.) of 13.8 +/- 1.5 and 11.4 +/- 1.2 ms, respectively) and low current densities (36.6 +/- 3.3 and 32.1 +/- 4. 9 pA pF-1, respectively). TOCs in late-spiking neurons, on the other hand, displayed a wide range of both inactivation kinetics (36.7 +/- 2.4 ms, with a range from 11.3 to 147.8 ms) and current density (54. 0 +/- 2.9 pA pF-1, with a range from 9.8 to 131.2 pA pF-1). 3. In regular-, fast- and late-spiking neurons having TOCs with slow time constants (> 50 ms, class II late-spiking neurons), the TOCs were sensitive to 4-aminopyridine (4-AP), with IC50 values of 2.9, 2.4 and 1.2 mM, respectively. In late-spiking neurons having TOCs with fast decay time constants (< 30 ms, class I late-spiking neurons), the TOCs were composed of at least two 4-AP-sensitive components (IC50 values of 0.2 microM and 3.6 mM). 4. Class I late-spiking neurons displayed non-inactivating outward currents which were highly sensitive to 4-AP. They changed their firing patterns to the regular-spiking mode, not only in response to low concentrations of 4-AP (< 50 microM), but also in response to dendrotoxin (200 nM), suggesting that non-inactivating outward currents contribute to the late-spiking property. However, the components of TOCs which were highly sensitive to 4-AP were also sensitive to dendrotoxin. These results suggest that both or either of the two currents contribute to the late-spiking property of class I late-spiking neurons. 5. Although class II late-spiking neurons also displayed non-inactivating outward currents, the late-spiking property was not abolished by low concentrations of 4-AP and dendrotoxin. They changed to a regular firing pattern in response to a high concentration of 4-AP (5 mM), suggesting that TOCs contribute to late-spiking property of class II late-spiking neurons. 6. The results suggest that TOCs with different properties contribute to the different firing patterns of SGI neurons.

Combined endoscopic and surgical treatment for multiple polyps of the small intestine in Peutz-Jeghers syndrome: a case report.

Combined endoscopic and surgical treatment in a 14-year-old girl with Peutz-Jeghers syndrome is reported herein. The patient was diagnosed with Peutz-Jeghers syndrome because of mucocutaneous pigmentation and hamartomas of the small intestine at 10 years of age, when she underwent an emergency laparotomy for an intussusception of the small intestine. Since this diagnosis, she has undergone follow-up, and barium radiologic and endoscopic studies have shown multiple polyps of various sizes from the stomach throughout the small intestine and to the colon. This time, with the use of combined endoscopic and surgical treatment for polyps of the small intestine, 26 polyps were removed endoscopically by performing only one enterotomy. This combined technique may allow for a longer interval between laparotomies, therefore reducing the complications associated with multiple laparotomies and resections.