Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Perforant Pathway”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 973 records · Page 54Linked to original sources
PubMed1994

Perforated-patch recording does not enhance effect of 3-isobutyl-1-methylxanthine on cardiac calcium current.

Conventional whole cell voltage-clamp recording results in washout of the cardiac Ca2+ current (ICa) response to the beta-adrenergic agonist isoproterenol (Iso), for reasons which are not clear. When dose-response curves for the phosphodiesterase (PDE) inhibitor 3-isobutyl-1-methylxanthine (IBMX) were compared using perforated-patch vs. conventional whole cell recording in guinea pig ventricular myocytes, the conventional whole cell IBMX responses were unexpectedly larger than the perforated-patch responses. Furthermore, during conventional whole cell recording the response to repeated application of Iso declined rapidly, whereas the IBMX response initially increased and then declined. When pipette [Ca2+] was increased to 10(-7) M, conventional whole cell responses to 300 microM IBMX and 10(-9) M Iso were identical to perforated-patch responses. Thus loss of the Iso response during conventional whole cell recording seems to not be solely due to a washout of some constituent of the adenosine 3',5'-cyclic monophosphate pathway. We suggest that unphysiological intracellular [Ca2+] enhances the relative PDE activity and that this contributes to the rapid decline of the Iso response and the initial enhancement of the IBMX response.

1-Methyl-3-isobutylxanthine↗
PubMed1996

Membrane delimited and intracellular soluble pathways in the somatostatin modulation of ACh release.

The signal transduction cascade between the activation of the somatostatin (SOM) receptor and modulation of transmitter release was study using Acetylcholine (Ach) release measurements and patch clamp recordings of Ca2+ current from acutely dissociated St 40 ciliary ganglion neurons. As in intact synapses, somal ACh release was blocked by 100 nM SOM or 100 microM dibutyril cGMP, and the SOM-mediated inhibition could be reversed by 10 microM 1-NAME (a selective inhibitor of nitric oxide synthase, NOS) or 100 microM Rp-8p-CPT-cGMPs (a selective inhibitor of a cGMP protein dependent kinase, PKG). In whole cell recordings, SOM inhibition of Ca2+ current rapidly relaxes to control levels but is sustained in perforated patch recordings which decreases cell dialysis. Inhibition of NOS or PKG in perforated patch recordings, however caused SOM effects to become transient again. We hypothesize that PKG alters the characteristics of the membrane-delimited G protein inhibition of Ca2+ current. Therefore SOM receptors trigger a membrane-delimited signal transduction cascade that is modulated by soluble messengers, converging on voltage activated Ca2+ channels. When both pathways are active together, SOM causes a sustained inhibition of neuronal Ca2+ current leading to a decrease in transmitter release.

Acetylcholine↗
PubMed1997

The effects of traumatic brain injury on inhibition in the hippocampus and dentate gyrus.

Changes in inhibitory neuronal functioning may contribute to morbidity following traumatic brain injury (TBI). Evoked responses to orthodromic paired-pulse stimulation were examined in the hippocampus and dentate gyrus at 2 and 15 days following lateral fluid percussion TBI in adult rats. The relative strength of inhibition was estimated by measuring evoked paired pulses in three afferent systems: the CA3 commissural input to the CA1 region of the hippocampus; the entorhinal cortical input to the ipsilateral CA1 area (temporoammonic system); and the entorhinal input to the ipsilateral dentate gyrus (perforant path). In addition to quantitative electrophysiological estimates of inhibitory efficacy, levels of gamma-aminobutyric acid (GABA) were qualitatively examined with immunohistochemical techniques. Effects of TBI on paired-pulse responses were pathway-specific, and dependent on time postinjury. At 2 days following TBI, inhibition of population spikes was significantly reduced in the CA3 commissural input to CA1, which contrasted with injury-induced increases in inhibition in the dentate gyrus seen at both 2 and 15 days postinjury. Low-level stimulation, subthreshold for population spikes, also revealed changes in paired-pulse facilitation of field extracellular postsynaptic potentials (fEPSPs), which depended on fiber pathway and time postinjury. Significant injury-induced electrophysiological changes were almost entirely confined to the hemisphere ipsilateral to injury. Intensity of GABA immunobinding exhibited a regional association with electrophysiological indices of inhibition, with the most pronounced increases in GABA levels and inhibition found in the dentate gyrus. TBI-induced effects showed a regional pattern within the hippocampus which corresponds closely to inhibitory changes reported to follow ischemia and kindling. This degree of similarity in outcome following dissimilar injuries may indicate common mechanisms in the nervous system response to injury.

Animals↗
PubMed1995

A cellular mechanism for nitric oxide-mediated cholinergic control of mammalian heart rate.

The biochemical signaling pathways involved in nitric oxide (NO)-mediated cholinergic inhibition of L-type Ca2+ current (ICa[L]) were investigated in isolated primary pacemaker cells from the rabbit sinoatrial node (SAN) using the nystatin-perforated whole-cell voltage clamp technique. Carbamylcholine (CCh; 1 microM), a stable analogue of acetylcholine, significantly inhibited ICa(L) after it had been augmented by isoproterenol (ISO; 1 microM). CCh also activated an outward K+ current, IK(ACh). Both of these effects of CCh were blocked completely by atropine. Preincubation of the SAN cells with L-nitro-arginine methyl ester (L-NAME; 0.2-1 mM), which inhibits NO synthase (NOS), abolished the CCh-induced attenuation of ICa(L) but had no effect on IK(ACh). Coincubation of cells with both L-NAME and the endogenous substrate of NOS, L-arginine (1 nM), restored the CCh-induced attenuation of ICa(L), indicating that L-NAME did not directly interfere with the muscarinic action of CCh on ICa(L). In the presence of ISO the CCh-induced inhibition of ICa(L) could be mimicked by the NO donor 3-morpholino-sydnonimine (SIN-1; 0.1 mM). SIN-1 had no effect on its own or after a maximal effect of CCh had developed, indicating that it does not inhibit ICa(L) directly. SIN-1 failed to activate IK(ACh), demonstrating that it did not activate muscarinic receptors. Both CCh and NO are known to activate guanylyl cyclase and elevate intracellular cGMP. External application of methylene blue (10 microM), which interferes with the ability of NO to activate guanylyl cyclase, blocked the CCh-induced attenuation of ICa(L). However, it also blocked the activation of IK(ACh), suggesting an additional effect on muscarinic receptors or G proteins. To address this, a separate series of experiments was performed using conventional whole-cell recordings with methylene blue in the pipette. Under these conditions, the CCh-induced attenuation of ICa(L) was blocked, but the activation of IK(ACh) was still observed. Methylene blue also blocked the SIN-1-induced decrease in ICa(L). 6-anilino-5,8-quinolinedione (LY83583; 30 microM), an agent known to decrease both basal and CCh-stimulated cGMP levels, prevented the inhibitory effects of both CCh and SIN-1 on ICa(L), but had no effect on the activation of IK(ACh) by CCh. In combination, these results show that CCh- and NO-induced inhibition of ICa(L) is mediated by cGMP.(ABSTRACT TRUNCATED AT 400 WORDS)

1-Methyl-3-isobutylxanthine↗
PubMed1999

The effect of 1,3-dinitrobenzene on the functioning of the auditory pathway in the rat.

1,3-Dinitrobenzene (DNB) has previously been shown to be neuropathic, causing gliovascular lesioning in the rat brainstem, with the nuclei of the auditory pathway being particularly affected. Lesion severity was shown to be dependent on functional activity, which could be markedly decreased within one pathway by monaurally reducing sensory input. The aim of this study was to characterise the changes in electrophysiological and vascular function associated with this asymmetric lesioning. Depth electrodes located in the inferior colliculi were used to measure wave II and IV of the auditory evoked response (AER) and collicular blood flow. These were measured up to eight days after DNB exposure in rats, in which preexisting reduction in sensory input in one ear was achieved by tympanic membrane rupture. Significant increases of between 14-27 dB were seen in the mean stimulus level required to generate a 50% isoamplitude response for wave IV in the intact (ie vulnerable) pathway over days 1-8 post DNB. No significant changes in this response for the other AER waves were seen over the same recording period. Significant increases in blood flow were seen in the inferior colliculi up to 24 hours after the final dose of DNB. Differences in increased flow between the colliculi were also highly significant, with peak increases of 200% and 80% seen in the intact and protected sides respectively. This difference shows that DNB enhanced blood flow appears to reflect the severity of the DNB induced functional deficit. In both cases, disturbance to normal glial function in maintaining K+ homeostasis, may underlie the neurophysiological deficit and the increase in blood flow seen at the level of the inferior colliculi. These asymmetric functional changes were also parallelled by the differential lesion severity between the protected and unprotected pathways. Hence, protection against DNB glial lesion severity by reduction in sensory input, and consequently metabolic demand, is paralleled by the early vascular response and functional neuronal deficit seen over the eight day post DNB recording period.

Acoustic Stimulation↗
PubMed2003

Gas-forming abdominal wall abscess: unusual manifestation of perforated retroperitoneal appendicitis extending through the superior lumbar triangle.

We present a case of an extensive gas-forming abdominal wall abscess secondary to ruptured retroperitoneal appendicitis in a diabetic patient. Computed tomography (CT) demonstrated a retroperitoneal abscess extending to the abdominal subcutaneous tissue through the superior lumbar triangle pathway, a known anatomical defect of the lumbar musculature. This case not only represents an unusual manifestation of acute appendicitis, but also alerts us to the importance of anatomical considerations in the imaging interpretation of disease extent. The applied anatomy of the lumbar triangle as a conduit of intra-abdominal and retroperitoneal processes into the abdominal wall is reviewed.

Abdominal Abscess↗
PubMed1988

Inhalation anaesthetics exhibit pathway-specific and differential actions on hippocampal synaptic responses in vitro.

The effects of halothane, isoflurane and enflurane were compared on three CNS excitatory synaptic pathways in vitro, to determine whether selective actions described in vivo result from differential effects on anatomically distinct cortical pathways and neurone populations. Halothane (0.25-1.25 vol%) depressed postsynaptic excitability of CA1 pyramidal neurones in response to activation of stratum radiatum synaptic inputs, and concentration-dependent excitatory (0.25-1.25 vol%) and depressant (1.5-2.0 vol%) actions were observed on dentate granule neurone excitability and perforant path evoked synaptic responses. In contrast, isoflurane increased CA1 neurone excitability (0.25-0.75 vol%) and produced postsynaptic depression of dentate neurones (0.5-4.0 vol%). Enflurane also increased CA1 excitability (0.5-4.0 vol%), but depressed synaptic responses at equivalent concentrations, and produced mixed excitatory (0.25-1.0 vol%) and depressant (1.0-4.0 vol%) effects on dentate synaptic responses. Differential actions were also observed for the three anaesthetics on stratum oriens excitatory inputs to CA1 neurones, and on antidromic responses. A good correlation (r = 0.992) exists between the membrane/buffer partition coefficients of these anaesthetics and their half-maximal concentrations for depression of synaptic responses; however, this correlation does not reflect the different, anaesthetic-specific actions observed. The results indicate that inhalation anaesthetics act at multiple and selective hydrophobic recognition sites which are heterogenously distributed on different synaptic pathways.

Action Potentials↗
PubMed1987

Facilitation of kindling by prior induction of long-term potentiation in the perforant path.

Previous studies have revealed that a form of synaptic potentiation resembling long-term potentiation (LTP) occurs at various sites as a result of stimulation that leads to kindling. The present study evaluates what role this synaptic potentiation plays in the development of kindling following periodic stimulation of the entorhinal cortex of the rat. LTP was repetitively induced in the pathway from the entorhinal cortex (EC) to the dentate gyrus (DG) by daily stimulation with high frequency trains that led to LTP, but did not evoke afterdischarge (AD). Subsequently, animals received stimulation designed to induce kindling (that led to AD), and this stimulation was delivered once per day until kindled seizures were induced. While repetitive induction of LTP was not sufficient to produce kindling, prior induction of LTP significantly increased the rate of subsequent kindling as evidenced by a decrease in the number of kindling stimulations required to induce the kindled state. As a group, animals that had received stimulation designed to induce LTP developed kindled seizures after an average of 10 AD's, whereas a control group that had received non-potentiating stimulation required 25 AD's. These results indicate that LTP at EC-DG synapses cannot represent the mechanism of kindling following EC stimulation. However, synaptic potentiation at this site can facilitate the development of epileptogenesis in response to subsequent activation of the perforant path.

Action Potentials↗
PubMed2001

Retinal pigment epithelial tear with vitreomacular attachment: a novel pathogenic feature.

BACKGROUND: The development of tears of the retinal pigment epithelium (RPE) has classically been described with or without choroidal neovascularization (CNV) or after laser treatment. Tangential shear forces within the RPE or CNV are usually considered to cause the dehiscence. METHODS: Three patients with CNV and spontaneous RPE tear and additional vitreomacular traction were examined by fluorescein angiography (FA), optical coherence tomography (OCT) and kinetic ultrasound. RESULTS: From the pre-tear to the tear stage a sudden decrease in vision was observed. Fluorescein angiographic images demonstrated RPE-tear formation with blocked filling in the area of the contracted RPE and a well-demarcated hyperfluorescence in the bed of the torn RPE. OCT-scans demonstrated vitreomacular traction at the foveal area in all three cases. Kinetic ultrasound revealed vitreous attachments at the optic disc and fovea. CONCLUSION: Magnitude, variation of mechanical forces, and the continuous shear stress of the aged vitreous gel transmitted across vitreoretinal attachments may cause a chronic stimulus to retina and RPE. Vitreomacular traction may contribute to the subsequent formation of RPE tears via mechanical or cell mediator pathways.

Aged↗
PubMed1993

Lateral olfactory tract input to dentate gyrus is depressed by prior noradrenergic activation using nucleus paragigantocellularis stimulation.

Nucleus paragigantocellularis stimulation potentiates the medial perforant path population spike in the dentate gyrus via beta-receptor activation. In this study, the same paragigantocellularis stimulation preceding lateral olfactory tract pulses depressed the lateral perforant path mediated synaptic potential in dentate gyrus. Depression of the lateral olfactory tract input was blocked by a beta-antagonist. These in vivo results confirm in vitro reports that norepinephrine induces potentiation of medial perforant path input and depression of lateral perforant path input to dentate gyrus.

Animals↗
PubMed1994

Fever and the control of gram-negative bacteria.

Although it seems obvious that fever has some important general adaptive value, it is still not clear by what means this function is manifested. One postulate is that febrile conditions result in the sequestration of soluble iron, effectively starving some pathogens of that essential nutrient. On the basis of our recent experiments, we propose a new mechanism for how fever serves to restrict a wide range of Gram-negative bacteria. The elevated temperature prevents the bacteria from synthesizing their protective LPS, thereby enabling serum complement to perforate and kill the invading pathogens even prior to the production of host antibodies.

Body Temperature↗
PubMed2006

Clinicopathologic correlation of stage 2 macular hole.

PURPOSE: To provide histopathologic correlation of the appearance of a stage 2 macular hole. METHODS: A 79-year-old woman presented with a recent onset of mildly decreased vision in the right eye. With slit-lamp biomicroscopic examination and fundus photography, she was diagnosed as having a stage 2 macular hole. Her vision remained stable thereafter without intervention for 15 months. She died 6 months after her final follow-up examination. Postmortem histopathologic examination of the right eye was carried out by light microscopy of conventional and immunoperoxidase-stained sections. RESULTS: The clinical appearance of a stage 2 macular hole in this patient corresponded with findings of intraretinal splitting, which extended beyond an area of surface retinal defect. CONCLUSION: Surface retinal defects associated with intraretinal splitting are a pathway in the development of a macular hole.

Aged↗
PubMed2002

Arterial supply of the olfactory trigone and the anterior perforated substance in macrosmatic and microsmatic animals.

An investigation was conducted into the differences between macrosmatic and microsmatic animals of arterial supply in the area of the olfactory trigone and the anterior perforated substance. A brain of domestic cat was taken as an example of a macrosmatic animal and a brain of baboon as an example of a microsmatic animal. The cerebral blood vessels of the cadavers of 30 cats and 11 baboons were filled with latex and, after fixation in acid alcohol by means of microscopic operation, the cortical and deep branches of the anterior and middle cerebral arteries were dissected. We discovered that there were differences between these two groups of animals in the places of arising of deep branches and in their course. In the cat the deep branches running through the area of the olfactory trigone arose from the beginning part of the middle cerebral artery in numbers 5-10 and entered the brain in the olfactory tubercle. In the baboon the deep branches arose from two sources: the middle cerebral artery and the anterior cerebral artery. The branches of the middle cerebral artery went through the anterior perforated substance, forming two groups of branches: lateral and medial.

Animals↗
PubMed1999

Is learning blocked by saturation of synaptic weights in the hippocampus?

Long-term potentiation (LTP) has become a leading candidate mechanism for memory formation. The proposed link between LTP and memory rests primarily on a single type of behavioural evidence: disruption of learning by interventions that block critical steps in the induction of LTP. As such blockade may disrupt non-mnemonic functions also, the LTP-learning question should be approached with multiple strategies. One alternative approach is to determine whether hippocampus-dependent learning is blocked by saturation of hippocampal LTP before training. Early investigations found that spatial learning was impaired after cumulative LTP in dentate perforant-path synapses. Several groups failed to replicate these findings, but it is now clear that hippocampus-dependent spatial learning is disrupted only if LTP is saturated throughout the terminal field of the tetanized pathway. Moreover, to prevent compensatory modifications in the hippocampal network, a massed tetanization and training protocol may be required. The blockade of learning by repetition of the very same stimulus that induces LTP suggests that LTP-like modifications are necessary for memory encoding in the hippocampus.

Animals↗
PubMedDate not supplied

Calcium action potentials in retinal bipolar neurons.

Patch-clamp and calcium-indicator measurements were used to examine the electrical excitability of large-terminal bipolar neurons from goldfish retina. Large, transient increases in intracellular calcium occurred spontaneously in the synaptic terminal but not in the soma of bipolar neurons. Calcium transients were blocked by hyperpolarization, by external application of calcium-channel blockers, and by the neurotransmitters GABA and glutamate. These observations suggest that calcium action potentials are responsible for the spontaneous increases in intraterminal calcium, which was directly confirmed by electrical recordings of calcium-dependent action potentials in both whole-cell and perforated-patch recordings. We suggest that regenerative depolarization produced by the opening of calcium channels in the synaptic terminal of on-type bipolar neurons represents an amplification mechanism in the high-sensitivity ON pathway in the dark-adapted fish retina.

Action Potentials↗
PubMed1991

A comparison of excimer laser, thermal probe, and mechanical devices for recanalizing occluded human arteries.

To evaluate the mechanism of excimer laser recanalization and compare the results with those of laser-assisted thermal probe recanalization and mechanical recanalization, a total of 42 human atherosclerotic totally occluded arterial segments (2-15 cm long) were recanalized by excimer laser with a 400-800 micron quartz fiber pulsed at 20 Hz with 50 mJ/mm2 of energy (n = 21), an Argon heated thermal probe at 10-12 watts (n = 11), a guidewire directed through a 6 Fr multipurpose catheter, or an angioplasty balloon catheter (n = 10). On histologic examination, the excimer laster created a single round lumen or multiple lumens ("Swiss-cheese" like appearance) with no evidence of thermal injury at the perimeter of the lumen. The incidence of perforation in vitro was less with an excimer laser catherter (8/21 or 38%) than with the thermal prove (10/11 or 91%) (p less than 0.01). However, serial histologic cross-sectional examination showed that the pathway of the devices were essentially the same in all recanalization procedures. The pathway of the device was located outside the atheroma but proximal to the internal elastic membrane in 13 arteries with the excimer laser (62%), in 10 arteries with the thermal probe (91%), and 8 arteries with mechanical devices (80%). These results indicate that although the eximer laser could recanalize human atherosclerotic arteries without thermal injury, the fiber frequently deflected around firm atherosclerotic plaque and advanced in a dissection plane between the plaque and media. A similar course was noted for the thermal probe or during mechanical recanalization with a guidewire and catheter. To insure the safety of an excimer fiber or a thermal probe to reopen complete occlusions, better guidance systems must be developed.

Arteries↗
PubMed2000

Opioid modulation of recurrent excitation in the hippocampal dentate gyrus.

kappa opioid receptor activation inhibits granule cell-mediated excitatory neurotransmission in the hippocampal formation via a decrease in glutamate release from both perforant path and mossy fiber terminals. We now report a third, anatomically and pharmacologically distinct site of such kappa opioid inhibition within the hippocampus. Granule cell population responses to selective stimulation of an excitatory hilar pathway were decreased by the kappa(1) opioid receptor agonist U69,593, an effect blocked by the kappa(1) antagonist norbinaltorphimine. U69,593 also inhibited hilar path induced long-term potentiation (LTP) of granule cell responses. LTP in this pathway was also blocked by the NMDA receptor antagonist d-2-amino-5-phosphonovalerate, unlike granule cell mossy fiber LTP in CA3. The kappa opioid peptide dynorphin is present in hilar mossy fiber collaterals. Ultrastructural analysis of these collaterals demonstrated dynorphin-containing vesicles in asymmetric synapses formed between axon terminals and granule cell dendrites, suggesting direct granule cell-granule cell connections. Evoked release of endogenous dynorphin within the hilus was effective in reducing hilar excitation of granule cells, although this release, in contrast to the release of dynorphin in the dentate molecular layer, was not dependent on L-type calcium channels. No hilar path excitation was observed in the absence of bicuculline, suggesting a strong GABA(A)-mediated inhibition of this pathway. However, hilar path activity could be seen after LTP, with or without bicuculline. Thus, kappa opioids can inhibit granule cell recurrent excitation, likely via effects on excitatory mossy fiber collaterals. Such collaterals are thought to be important in mediating temporal lobe epilepsy.

2-Amino-5-phosphonovalerate↗
PubMed1984

Pneumomediastinum: a diagnostic problem.

Pneumomediastinum has numerous etiologies and its pathways of spread are multiple and well defined. Knowledge of these anatomic pathways and possible etiologies is important in order to avoid extensive and unnecessary evaluations. For example, if there is a known reason for pneumomediastinum, and pneumoperitoneum is present without associated abdominal findings, further evaluation for perforated viscus is unnecessary. In a patient who is an asthmatic or a diabetic, the presence of pneumomediastinum should not lead to work-up with contrast studies unless there are specific clinical reasons to do so. In critically ill infants and adults, pulmonary interstitial emphysema is an important warning sign for impending pneumothorax or pneumomediastinum and the patient's physicians should be alerted. There are occasional difficulties in differentiating pneumomediastinum from pneumopericardium and from a medial pneumothorax. Analysis of anatomic details and decubitus views are helpful in this regard.

Adult↗