Homo- and heterosynaptic long-term potentiation in the medial cortex of the turtle brain in vitro

Juvenile rheumatoid arthritis (JRA) is the most commonly diagnosed rheumatic disease in children and may represent not a single disease, but rather a syndrome of diverse aetiologies in which inflammation is an exceedingly complex process. Oxidative free radical production at inflammation sites contributes to tissue damage and could also play a significant role in the pathogenesis of JRA. The aim of this study was to evaluate the antioxidant status and lipid peroxidation parameters related to the clinical form of JRA. Plasma malondialdehyde and hydroperoxide concentrations in children with polyarticular and systemic JRA subtypes were significantly higher than in controls. Plasma vitamin E and beta-carotene levels of the JRA children were lower in the three forms compared with healthy children. Patients with JRA present an imbalance in the oxidant-antioxidant system that manifests clearly in the polyarticular and systemic forms through an increase in lipoperoxidation products and significant decrease in the lipid-soluble antioxidants vitamin E and beta-carotene.     

Metabotropic glutamate receptors are involved in long-term potentiation in isolated slices of rat medial frontal cortex

The prelimbic region of medial frontal cortex in the rat receives a direct input from the hippocampus and this functional connection is essential for aspects of spatial memory. Activity-dependent changes in the effectiveness of synaptic transmission in the medial frontal cortex, namely long-term potentiation (LTP) and long-term depression (LTD) can persist for tens of minutes or hours and may be the basis of learning and memory storage. Glutamatergic activation of ionotropic receptors is required to induce both LTP and LTD. We now present evidence of the involvement of metabotropic glutamate receptors in LTP in isolated slices of frontal cortex. Repetitive bursts of stimulation at theta frequencies (TBS) were applied to layer II, and monosynaptic EPSPs were monitored in layer V neurons of the prelimbic area. TBS was found to be more effective at inducing LTP than tetanic stimulation at 100 Hz and produced LTP that lasted >30 min in 8 out of 14 neurons. Tetanic stimulation at 100 Hz in the presence of the N-methyl--aspartate (NMDA)-antagonist 2-amino-5-phosphonopentanoate (AP5) was reported to be a reliable method of inducing LTD in prelimbic cortex (). However we found that this protocol did not facilitate the induction of LTD. The role of metabotropic glutamate receptors (mGluR) in LTP was assessed by using the selective, broad-spectrum antagonist (R, S)-alpha-methyl-4- carboxyphenylglycine (MCPG). This drug significantly reduced the incidence of LTP after TBS to only 1 of 14 neurons (P < 0.02, chi2 test). The pooled responses to TBS in MCPG showed significantly reduced potentiation [(P < 0.02, analysis of variance (ANOVA)]. The broad-spectrum mGluR agonist (1S, 3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) and the selective group I agonist S-3 hydroxyphenylglycine(S-3HPG) both produced membrane depolarization, an increase in number of spikes evoked by depolarizing current pulses, and a reduction in the afterhyperpolarization. Similar effects were produced by these agonists even when synaptic transmission was blocked by use of the gamma-aminobutyric acid-B (GABAB) receptor agonist, 200 microM baclofen, which suggests that group I mGluRs are present on layer V neurons. We conclude that mGluRs participate in the production of LTP in prelimbic cortex, and that this excitatory effect could be mediated by the postsynaptic group I mGluRs.     

Role of platelet-activating factor in long-term potentiation of the rat medial vestibular nuclei

In rat brain stem slices, we investigated the role of platelet activating factor (PAF) in long-term potentiation (LTP) induced in the ventral part of the medial vestibular nuclei (MVN) by high-frequency stimulation (HFS) of the primary vestibular afferent. The synaptosomal PAF receptor antagonist, BN-52021 was administered before and after HFS. BN-52021 did not modify the vestibular potentials under basal conditions, but it reduced the magnitude of potentiation induced by HFS, which completely developed after the drug wash-out. The same effect was obtained by using CV-62091, a more potent PAF antagonist at microsomal binding sites, but with concentrations higher than those of BN-52021. By contrast both BN-52021 and CV-6209 had no effect on the potentiation once induced. This demonstrates that PAF is involved in the induction but not in the maintenance of vestibular long-term effect through activation of synaptosomal PAF receptors. In addition, we analyzed the effect of the PAF analogue, 1-O-hexadecyl-2-O- (methylcarbamyl)-sn-glycero-3-phosphocoline (MC-PAF) and the inactive PAF metabolite, 1-O-hexadecyl-sn-glycero-3-phosphocoline (Lyso-PAF) on vestibular responses. Our results show that MC-PAF, but not Lyso-PAF induced potentiation. This potentiation was prevented by D,L-2-amino 5-phosphonopentanoic acid, suggesting an involvement of N-methyl-D-aspartate receptors. Furthermore, under BN-52021 and CV-6209, the MC-PAF potentiation was reduced or abolished. The dose-effect curve of MC-PAF showed a shift to the right greater under BN-52021 than under CV-6209, confirming the main dependence of MC-PAF potentiation on the activation of synaptosomal PAF receptors. Our results suggest that PAF can be released in the MVN after the activation of postsynaptic mechanisms triggering LTP, and it may act as a retrograde messenger which activates the presynaptic mechanisms facilitating synaptic plasticity.     

Comparison of the electrophysiology and morphology of layers III and II neurons of the rat medial entorhinal cortex in vitro

The basic membrane characteristics of neurons in layers II and III of the medial entorhinal cortex (MEA) were recorded using the intracellular current clamp technique in in vitro slices of the rat brain. Two types of cells were distinguished according to the presence of a time-dependent inward rectification (SAG current) with hyperpolarizing current pulses. The cells in which this inward rectification was not observed (No-SAG cells) had a larger input resistance, a more negative resting membrane potential and a more depolarized firing threshold. They more often displayed a strongly adapting firing pattern, and their action potentials had a slower decay rate and lacked a depolarizing afterpotential, compared with the SAG cells. SAG cells typically had a prominent rebound depolarization at the end of a hyperpolarizing current and membrane potential oscillations (7 Hz) upon subthreshold depolarizations. Cs+ blocked the time-dependent inward rectification. The rebound depolarization persisted, even in the presence of tetrodotoxin. Biocytin labelling showed that layer III consisted mainly of pyramidal-shaped cells. Most layer III cells were of the No-SAG type. All cells in layer II, stellate and pyramidal cells, were classified as SAG cells. We conclude that the cells in MEA layers II and III display different electroresponsiveness, but that this appears to be more related to the layer where they are located than to a specific morphology. As layer III consisted mainly of cells of the No-SAG type, we suggest that layer III cells are less excitable than the SAG type layer II cells.     

Satiety-responsive neurons in the medial orbitofrontal cortex of the macaque.

Feeding-related gustatory, olfactory, and visual activation of the orbitofrontal cortex (OFC) decreases following satiety. Previous neurophysiological studies have concentrated on the caudolateral OFC (clOFC). We describe satiety-induced modulation of 23 gustatory, 5 water, and 15 control neurons in the medial OFC (mOFC), where gustatory neurons represent a much larger percentage of the population. For 15 of the 23 gustatory neurons (65%), every significant taste response evoked during pre-satiety testing decreased following satiety (X=70%). Responses evoked by the ineffective taste stimuli during pre-satiety testing were unchanged following satiety. The graded response decrements of the mOFC gustatory neurons stand in marked contrast to the clOFC responses, which are almost completely suppressed by satiety. Two other novel findings are reported here. First, all significant pre-satiety taste responses of four gustatory neurons increased following satiety (X=51%). Second, post-satiety emergent taste responses were observed in 7 of 15 neurons (47%) classified as non-responsive during pre-satiety testing. The presence of increased responsiveness and emergent gustatory neurons in the mOFC suggests that meal termination may require active processes as well as the passive loss of hedonic value. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Serotonin inhibits the induction of long-term potentiation in rat primary visual cortex

1. The effect of serotonin (5-hydroxytryptamine; 5-HT) on the induction of long-term potentiation (LTP) in rat visual cortex was investigated by using slice preparations in vitro. 2. Bath application of 5-HT (0.1-10 microM) did not affect the baseline synaptic potentials evoked by single-pulse test stimulation, but inhibited the induction of LTP in a concentration-dependent manner. 3. The effect of 5-HT was blocked by the 5-HT1 receptor antagonist pindolol or the 5-HT2,7 receptor antagonist ritanserin, but not by the 5-HT3,4 receptor antagonist MDL72222. 4. These results suggest that 5-HT plays a role in suppressing the induction of LTP in the rat visual cortex.     

Involvement of the rat medial prefrontal cortex in novelty detection.

The prefrontal cortex in humans has been implicated in processes that underlie novelty detection and attention. This study examined the contribution of the rat medial prefrontal cortex to novelty detection using the targeting, or orienting, response (OR) as a behavioral index. Lesions to the medial prefrontal cortex (specifically the prelimbic and infralimbic cortices) influenced neither the OR to a novel visual stimulus from a localized light source (V1), nor the change in this OR over the course of a series of exposures to V1. However, after exposure to V1, the OR to a 2nd visual stimulus from the same source, V2, was more pronounced in control rats than in lesioned rats. These results suggest that the medial prefrontal cortex in the rat contributes to the process of novelty detection. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Brain-derived neurotrophic factor enhances long-term potentiation in rat visual cortex

Brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), members of the nerve growth factor (NGF) gene family, have been suggested to play a role in experience-dependent modification of neural networks in the developing nervous system. In this study we addressed the question of whether these neurotrophins are involved in long-term potentiation (LTP) in developing visual cortex. We recorded layer II/III field potentials and whole-cell currents evoked by test stimulation of layer IV at 0.1 Hz in visual cortical slices prepared from young rats (postnatal day 15-25) and observed effects of BDNF, NT-3, and NGF on these responses. Then we analyzed the effects of these neurotrophins on LTP induced by tetanic (Theta-burst type) stimulation of layer IV. We found that BDNF at 200 ng/ml potentiated field potentials and EPSCs in most cases and that this potentiation lasted after cessation of the BDNF application. At the concentration of 20 ng/ml, BDNF did not show such an effect, but it enhanced the magnitude of expressed LTP. On the other hand, NT-3 and NGF had none of these effects. Immunohistochemical staining of slices with antibody against BDNF showed that exogenous BDNF penetrated into the whole slice within approximately 5 min of its application. The actions of BDNF were blocked by preincubation of slices with TrkB-IgG fusion protein, a BDNF scavenger, or coapplication of K252a, an inhibitor for receptor tyrosine kinases. TrkB-IgG or K252a itself completely blocked LTP, suggesting that endogenous BDNF or another TrkB ligand plays a role in LTP in the developing visual cortex.     

Function of the dorsal and medial cortex of turtles in learning.

The effects of damage to the dorsal and medial cortex of turtles were investigated in two experiments. In the first, damage to the dorsal cortex disrupted acquisition and reversal of a go–no-go discrimination but had no effect on retention of the discrimination if it had been learned preoperatively. Medial cortex damage had no effect. In the second experiment, dorsal cortex damage impaired acquisition, but not extinction or reacquisition, of a discrete-trial keypress. Again, medical cortex damage had no effect. The results suggest that the dorsal cortex is involved in learning in turtles. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

GABAergic presubicular projections to the medial entorhinal cortex of the rat

We characterized presubicular neurons giving rise to bilateral projections to the medial entorhinal cortex (MEA) of the rat. Retrograde labeling of presubiculo-entorhinal projections with horseradish peroxidase and subsequent GABA immunocytochemistry revealed that 20-30% of the ipsilaterally projecting neurons are GABAergic. No GABAergic projections to the contralateral MEA were observed. GABAergic projection neurons were observed only in the dorsal part of the presubiculum, which, when taking into account the topography of presubicular projections to MEA, indicates that only the dorsal part of MEA receives GABAergic input. The GABAergic projection neurons constitute approximately 30-40% of all GABAergic neurons present in the superficial layers of the dorsal presubiculum. Using double-label fluorescent retrograde tracing, we found that the ipsilateral and contralateral presubiculo-entorhinal projections originate from different populations of neurons. Anterograde labeling of presubiculo-entorhinal projections and electron microscopical analysis of labeled terminals substantiated the presence of a restricted GABAergic presubiculo-entorhinal projection. A small fraction of afferents to only ipsilateral dorsal MEA formed symmetrical synapses with dendritic shafts. No symmetrical synapses on spines were noted. Most afferents to the dorsal part of ipsilateral MEA, as well as all afferents to the remaining ipsilateral and contralateral MEA, formed asymmetrical synapses with both spines and dendritic shafts in an almost equal ratio. Thus, we conclude that the majority of the presubiculo-entorhinal projections exert an excitatory effect on both principal neurons and interneurons. The projections from the dorsal part of the presubiculum comprise a small inhibitory component that originates from GABAergic neurons and targets entorhinal interneurons.     

Long-term potentiation of the neuronal activity in the motor cortex induced by simultaneous stimulation of the thalamus and somatosensory cortex in cats

Long-lasting potentiation of the cat motor cortex units induced by tetanic stimulation of the VL + SCx led to an increase of the motor cortex unit discharge rate. The findings suggest that co-activation of cortico-cortical and thalamo-cortical afferents modifies neuronal activity of the motor cortex at the specific site which receives convergent sensory input from the thalamus and the somatosensory cortex.     

Electrical stimulation of the medial prefrontal cortex increases dopamine release in the striatum

Exogenous and endogenous glutamate has been shown to evoke dopamine (DA) release in the striatum using both in vitro and in vivo techniques. We hypothesized that stimulation of the prefrontal cortex (PFC) would phasically enhance striatal DA release via the glutamatergic corticostriatal pathway. To test this hypothesis, in vivo brain microdialysis was employed to measure extracellular concentrations of DA in the striatum during electrical stimulation of the PFC. Five rats were implanted with bilateral electrodes located in the medial PFC and dialysis probes in the dorsal striatum. Two days later the PFC of these awake, freely moving rats was stimulated first at 50 microA and then at 100 microA for 20 minutes at 2-hour intervals. Both currents significantly increased DA release. Extracellular DA rose rapidly during stimulation, peaked immediately afterward, and then slowly returned to baseline values. Dopamine reached 118% of baseline values with 50 microA stimulation and 138% with 100 microA stimulation. Histologic analysis using the fluorescent retrograde dye Fluoro Gold confirmed that cells projecting to the vicinity of the striatal dialysis probe originated in the vicinity of the PFC electrodes. These results provide direct evidence for phasic, excitatory modulation of striatal DA release by the PFC.     

45Ca exchange in rat cortex slices in conditions of long-term potentiation

OBJECTIVE: An attempt was made to find out how many operations were performed in Europe in 1995 for congenital heart disease. METHODS: Representatives from the 20 most active European countries which could supply reliable information were contacted. They were asked to contact all surgeons performing significant numbers of operations for congenital heart disease in their country. The numbers of operations on children under and over 1 year operated on with and without cardiopulmonary bypass were collected. No attempt was made to collect more detailed information such as operative mortality as it was felt that many surgeons would be reluctant to give their results and the data would be incomplete. RESULTS: A total of 27,976 operations were recorded, of which 20,318 were performed with cardiopulmonary bypass and 7658 without. The total population of the 20 European countries was 448 million and the mean number of operations performed with cardiopulmonary bypass per million was 45.4. However, the rate varied from 9.1 to 70.1. The percentage of operations on cardiopulmonary bypass performed in the first year of life varied from 9.4% to 44.4%. CONCLUSIONS: The total of nearly 28,000 operations in 1995 is probably an underestimate, but it has been difficult to collect this data at all. Obviously many smaller countries have not been included, and some older patients undergoing operations such as atrial septal defect closure in adult units have been missed. The number of open heart operations per million vary in different countries and this presumably represents differing referral patterns. If their numbers are low in some countries, these results may be helpful in persuading their governments that more resources are needed for congenital heart surgery. It is also interesting to see the variation in the number of operations performed in the first year of life. Those countries with a lower rate may have a backlog of older patients who were previously palliated, or their surgeons may still prefer initial palliation and later correction in some conditions rather than early correction. It is hoped that with better prospective data collection, an assessment can be repeated in 2000.     

Cognitive enhancers and hippocampal long-term potentiation in vitro

We review our works on the pharmacological modulation of long-term potentiation (LTP) at guinea pig hippocampal mossy fiber-CA3 synapses in vitro. The magnitude of tetanus-induced LTP at the mossy fiber synapse was augmented by perfusion of slices with several cognitive enhancers, such as bifemelane (1 microM). The mossy fiber LTP was enhanced by somatostatin (0.32 microM) and inhibited in somatostatin-depleted slices from cysteamine-treated guinea pigs. An involvement of the 5-HT3 receptor also showed that granisetron (0.1 microM) enhanced the mossy fiber LTP. The above-mentioned enhancements by perfused agents were commonly reversed, at least in part, by muscarinic antagonists. However, the magnitude of mossy fiber LTP was bidirectionally modulated by muscarinic stimulations of slices with physostigmine or carbachol at different concentrations. The enhancing effects of high-concentration carbachol was antagonized by pirenzepine, and in contrast, the inhibition by low-concentration carbachol was antagonized in the presence of AF-DX116. When guinea pigs were preinjected with the cholinotoxin AF64A, the magnitude of LTP was decreased in the slices prepared from AF64A-treated animals. These results suggest that endogenous acetylcholine dominantly plays facilitatory roles through muscarinic M1 receptors in the induction of mossy fiber LTP. The pharmacological characterization of mossy fiber LTP may be of help to the evaluation of cognitive enhancers at a neuronal circuit level.     

Cholinergic agonist carbachol enables associative long-term potentiation in piriform cortex slices

Pyramidal cells in piriform (olfactory) cortex receive afferent input from the olfactory bulb as well as intrinsic association input from piriform cortex and other cortical areas. These two functionally distinct inputs terminate on adjacent apical dendritic segments of the pyramidal cells located in layer Ia and layer Ib of piriform cortex. Studies with bath-applied cholinergic agonists have shown suppression of the fast component of the inhibitory postsynaptic potentials (IPSPs) evoked by stimulation of the association fibers. It was previously demonstrated that an associative form of LTP can be induced by coactivation of the two fiber systems after blockade of the fast, gamma-aminobutyric acid-A-mediated IPSP. In this report, we demonstrate that an associative form of long-term potentiation can be induced by coactivation of afferent and intrinsic fibers in the presence of the cholinergic agonist carbachol.     

Glutamate receptors in the rat medial prefrontal cortex regulate set-shifting ability.

The authors examined set-shifting abilities in rats injected with antagonists of N-methyl-D-aspartate (NMDA) receptors (MK801) or alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors (LY293558) into the medial prefrontal cortex (mPFC). Set-shifting was assessed with a maze-based task requiring a switch between brightness and texture discrimination strategies. Intra-mPFC injection of MK801 prior to training on the 2nd discrimination impaired discrimination strategy acquisition. The MK801-induced deficit was due to increased perseverative responding. AMPA receptor blockade also impaired acquisition of the 2nd discrimination, these impairments were due to more general cognitive deficits. Results suggest that, within the mPFC, both AMPA and NMDA receptors are necessary for set-shifting, and that NNMA receptor hypofunction impairs the capacity to modify existing knowledge or to inhibit responses that are no longer appropriate. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The role of the medial prefrontal cortex in the play fighting of rats.

Although decorticated rats are able to engage in play, their play is abnormal in three ways. First, decorticates do not display the normal, age-related shifts in defensive strategies during development. Second, decorticates do not modify their defensive tactics in response to the social identity of their partners. Third, decorticates display a global shift in defensive tactics from more complex to less complex strategies. It has been shown that lesions of the motor cortex (MC) selectively produce the abnormal developmental effects on play, and that lesions of the orbitofrontal cortex (OFC) selectively produce the deficits in behavioral discrimination between social partners. In the current set of experiments, we demonstrate that lesions of the medial prefrontal cortex (mPFC) produce the shift from more complex to less complex defensive tactics, while leaving intact the age-related and partner-related modulation of defensive strategies. Thus, we have evidence for a triple dissociation of function between the MC, the OFC, and the mPFC with respect to social play behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Astroglial changes in the cerebral cortex of AIDS brains: a morphometric and immunohistochemical investigation

Sutureless phacoemulsification with implantation of a 7-mm PMMA intraocular lens was performed through a modified scleral tunnel in 100 consecutive patients. This was done to minimize postoperative astigmatism while retaining the advantages of implanting intraocular lenses with large optics. Visual and keratometric results and complications are reported after completion of a follow-up period of 6 months for the first 30 patients. Average uncorrected visual acuity improved from 0.13 preoperatively to 0.30 as early as 1 week postoperatively. Average best-corrected visual acuity improved from 0.23 before surgery to 0.51 as early as 1 week after surgery. No significant changes in visual acuity were recorded thereafter. The absolute value of keratometric astigmatism was not increased significantly at any postoperative examination time. The induced cylinder (Jaffe and Clayman) shifted from -1.27 D x 166 degrees at 1 week to 1.18 D x 91 degrees at 1 month postoperatively without further relevant changes thereafter. Endothelial cell loss did not differ from that reported by other authors after conventional cataract surgery. Corneal thickness was not increased significantly at any postoperative examination time. Implantation of intraocular lenses with large optics through a scleral tunnel allows quick visual rehabilitation as well as early stability of refraction.     

45Ca metabolism in slices of rat cerebral cortex during long-term potentiation

Ca45 kinetics was studied in 5, 15 and 30 min after potentiation. In the induction phase (1-5 min), the potentiation decreased the fraction of intracellular bound Ca. The 15-25 min potentiation the intra- and extracellular Ca levels was equal to the control ones. In 30 min, a considerable redistribution of Ca in the cells occurred.     

Morphological characteristics of layer II projection neurons in the rat medial entorhinal cortex

Idiopathic left ventricular tachycardia (ILVT) differs from idiopathic right ventricular outflow tract (RVOT) tachycardia with respect to mechanism and pharmacologic sensitivity. ILVT can be categorized into three subgroups. The most prevalent form, verapamil-sensitive intrafascicular tachycardia, originates in the region of left posterior fascicle of the left bundle. This tachycardia is adenosine insensitive, demonstrates entrainment, and is thought to be due to reentry. The tachycardia is most often ablated in the region of the posteroinferior interventricular septum. A second type of ILVT is a form analogous to adenosine-sensitive RVOT tachycardia. This tachycardia appears to originate from deep within the interventricular septum and exits from the left side of the septum. This form of VT also responds to verapamil and is thought to be due to cAMP-mediated triggered activity. A third form of ILVT is propranolol sensitive. It is neither or initiated or terminated by programmed stimulation, does not terminate with verapamil, and is transiently suppressed by adenosine, responses consistent with an automatic mechanism. Recognition of the heterogeneity of ILVT and its unique characteristics should facilitate appropriate diagnosis and therapy in this group of patients.