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M L Errington

Publications and source records attributed to M L Errington.

At least 37 records · Page 2Linked to original sources
PubMed1996

Low-frequency trains of paired stimuli induce long-term depression in area CA1 but not in dentate gyrus of the intact rat.

We have examined the efficacy of a recently introduced protocol for inducing homosynaptic long-term depression (LTD) in area CA1 of the anesthetized rat (Thiels et al. [1994] J Neurophysiol 72:3009-3116.). In area CA1 of the awake animal, this protocol, consisting of 200 pairs of pulses delivered at 0.5 Hz, with an interpulse interval of 25 ms, consistently produced LTD, provided the initial pulse was sufficiently strong to produce significant paired-pulse depression of the evoked response. We extended these experiments to the dentate gyrus, using either paired pulses given to the perforant path in the awake adult rat, or, in the anesthetized adult, a two-pathway pairing procedure, in which the first pulse was delivered to the commissural input to the dentate gyrus and the second to the perforant path. In both cases, the first pulse led to substantial suppression of the response evoked by the second pulse. With neither protocol, however, was there any evidence for LTD or depotentiation. Paired-pulse stimulation of the perforant path of young rats (10-11 days) also failed to induce LTD or depotentiation of the population excitatory postsynaptic potential (EPSP). Thus, the dentate gyrus in the intact animal appears to be less susceptible to LTD and depotentiation than area CA1, a conclusion consistent with previous experiments in which we found that stimulation at 1-5 Hz produced LTD/depotentiation in area CA1 of young (but not adult) rats in vivo but was ineffective at any age in the dentate gyrus. Our results do not rule out the possibility that other, untested protocols may produce homosynaptic LTD and/or depotentiation in the dentate gyrus in vivo.

Anesthesia↗
PubMed1995

The rare association of right adrenal haemorrhage and renal vein thrombosis diagnosed with duplex ultrasound.

Neonatal adrenal haemorrhage with renal vein thrombosis, an almost exclusively left-sided phenomenon, may occasionally be bilateral in the presence of inferior vena cava thrombus but has only twice been reported as confined to the right side. These cases required a combination of ultrasound (USS), excretion urography, cystoscopy with retrograde pyelography, radioisotopes, and CT to diagnose this rare right-sided combination. We report a case of right adrenal haemorrhage causing right renal vein thrombosis accurately diagnosed using only duplex USS and radioisotopes. The potential complications of renal vein thrombosis and hypertension associated with adrenal haemorrhage requires accurate diagnosis and this paper emphasises the value of duplex USS.

Adrenal Gland Diseases↗
PubMed1995

Ascorbate and glutamate release in the rat hippocampus after perforant path stimulation: a "dialysis electrode" study.

Excitatory amino acids have been proposed to play a critical role in the development and maintenance of epileptic seizures and in the development of neuronal damage. Previous animal studies of glutamate during seizures, however, have often failed to measure any rise in glutamate. We have overcome many of the problems of these studies by using an animal model in which epileptic afterdischarges are induced by stimulation of the perforant path, and glutamate and ascorbate are measured using a newly developed microdialysis electrode that combines the advantages of microdialysis and in vivo electrochemistry. We have successfully shown (1) a rise in glutamate after an epileptic afterdischarge, (2) a concomitant initial fall and then a later rise in ascorbate, and (3) progressive dwindling of this effect when afterdischarges are repeated within minutes, despite similar electroencephalographic responses. The possible mechanisms of these effects are discussed and include ascorbate/glutamate heteroexchange, reversal of the glutamate uptake mechanism, and augmentation of glutamate uptake after a seizure.

Animals↗
PubMed1995

Stimulation at 1-5 Hz does not produce long-term depression or depotentiation in the hippocampus of the adult rat in vivo.

1. We examined the efficacy of low-frequency trains (1-5 Hz) in producing long-term depression (LTD) or depotentiation in the hippocampus of the awake adult rat and in anesthetized rats aged from 10 days to 3 mo. 2. In the dentate gyrus we found no evidence that low-frequency trains produce either depotentiation or LTD in the awake, adult animal or in the anesthetized animal at any age tested (10 days-adult). 3. In area CA1 of both awake and anesthetized adult rats, we also found no evidence that low-frequency trains induced either LTD or depotentiation. Only in area CA1 of very young rats (10-11 days) was clear evidence for LTD and depotentiation obtained; at this age experiments were only possible in anesthetized animals. By 16 days, the ability to display both LTD and depotentiation was lost. 4. These experiments suggest that repetitive low-frequency stimulation evokes a developmentally regulated form of activity-dependent depression that in the hippocampus is limited to specific pathways in the young animal. Our results leave open the question of whether alternative patterns of activity can induce LTD and/or depotentiation in the adult awake rat.

Aging↗
PubMed1994

Increase in extracellular NCAM and amyloid precursor protein following induction of long-term potentiation in the dentate gyrus of anaesthetized rats.

The extracellular concentrations of the amyloid precursor protein (APP) and neural-cell adhesion molecule (NCAM) in the dentate gyrus of the anaesthetized rat were assayed before and after the induction of long-term potentiation (LTP) in vivo. Levels of high molecular weight neurofilament protein and activity of the lysosomal enzyme arylsulphatase were measured as internal controls and indicators of neuronal damage. Ninety minutes after the induction of LTP, the concentrations of NCAM and APP increased, in an NMDA-dependent manner, in the absence of changes in neurofilament and arylsulphatase levels. The delayed changes in the extracellular concentration of these molecules may reflect events leading to morphological modifications following LTP.

Amyloid beta-Protein Precursor↗
PubMed1994

Activation of metabotropic glutamate receptors is necessary for long-term potentiation in the dentate gyrus and for spatial learning.

We have examined the effects of the metabotropic glutamate receptor antagonist (RS)-a-methyl-4-carboxyphenylglycine (MCPG) on performance in the water maze, and on LTP in the dentate gyrus, MCPG (5 mM) reversibly blocked the induction of LTP in the perforant path-granule cell projection when perfused into the dentate gyrus of the anaesthetized rat. When injected bilaterally into the lateral ventricles, MCPG (20 mM) disrupted the performance of rats in a spatial learning version of the water maze task. In a terminal experiment, when tetanic stimulation was given to the perforant path, LTP, was found to be significantly reduced in MCPG-injected rats compared to control rats injected with vehicle. These experiments indicate that activation of MCPG-sensitive metabotropic glutamate receptors is necessary both for the full expression of LTP and spatial learning, and supply further evidence for the hypothesis that LTP provides synaptic mechanism for certain forms of learning.

Animals↗
PubMed1994

Spatial and temporal changes in signal transduction pathways during LTP.

Following LTP induction in freely moving rats, in situ hybridization revealed discrete changes in the expression of one isoform in each of four families of serine/threonine kinases constitutively expressed in the dentate gyrus of the hippocampus. Expression of the alpha isoform of CaMKII showed a transient increase over the soma and a more persistent increase over the dendritic field of dentate granule cells. Of the PKC isoforms, only gamma PKC was up-regulated substantially 2 hr after LTP induction, declining to control levels 48 hr later. An increase in the expression of mRNA for ERK2 and raf-B was seen at 24 hr only. These results show that, during the maintenance phase of LTP in the hippocampus, there are selective increases in the expression of serine/threonine kinases and that these increases have specific and characteristic temporal and spatial profiles.

Animals↗
PubMed1993

Transsynaptic expression of a presynaptic glutamate receptor during hippocampal long-term potentiation.

Repetitive activation of excitatory synapses in the hippocampus produces a persistent enhancement of synaptic efficiency known as long-term potentiation (LTP). In anesthetized and in freely moving rats, the induction of LTP in the perforant path led to a transient increase in the amount of messenger RNA (mRNA) coding for a presynaptic glutamate receptor (GR33) in dentate granule cells. The amount of GR33 mRNA was increased for at least 5 hours after the induction of LTP but was indistinguishable from control values 1 day after induction. The N-methyl-D-aspartate receptor antagonist 2-aminophosphonovalerate prevented the induction of both LTP and the increase in GR33 mRNA. The amount of GR33 protein was increased in the mossy fiber terminal zone of dentate granule cells 5 hours after the induction of LTP. These results suggest that the induction of LTP in synapses at one stage in a neural network may lead to modification in synaptic function at the next stage in the network.

2-Amino-5-phosphonovalerate↗
PubMed1993

The suppression of long-term potentiation in rat hippocampus by inhibitors of nitric oxide synthase is temperature and age dependent.

At room temperature (23 degrees C-25 degrees C), the induction of long-term potentiation (LTP) in area CA1 of slices from young male Sprague-Dawley rats was depressed by preincubation with the nitric oxide synthase inhibitors NG-nitro-L-arginine (L-NA, 100 microM) and NG-nitro-L-arginine methyl ester (L-NAME, 100 microM). The D isomers were ineffective under the same conditions. Hemoglobin (20 microM) reduced but did not completely block LTP. Neither L-NA (at concentrations up to 1 mM) nor hemoglobin (20 microM) had any significant effect on LTP in slices from adult rats at room temperature, or in young rats at 29 degrees C-30 degrees C. These results suggest that nitric oxide is unlikely to play a role in the induction of LTP under physiological conditions.

Aging↗
PubMed1992

Effect of hypertonic sodium chloride (7.5%) on uncontrolled hemorrhage in rats and its interaction with different anesthetic procedures.

Small volumes (4-6 ml/kg) of hypertonic NaCl (7.5%, HS) have been shown to correct the hemodynamic alterations caused by severe blood loss, but it has been claimed that its use is detrimental to rats undergoing uncontrolled arterial bleeding. The interaction between uncontrolled hemorrhage and HS was reexamined in experiments performed on male Wistar rats anesthetized with neurolidol-ketamine (NK), pentobarbital (P), chloralose (C), or urethane (U), (n = 20 in each group), half of them treated with HS (4 ml/kg IV) 15 min after start of bleeding. Uncontrolled hemorrhage was induced by cutting the tail at 12% (T12%) or 50% (T50%) from its tip. NK induced large blood loss (T50%, 32.6 ml/kg; T12%, 16.2 ml/kg) and hypotension (T50%, 70 mmHg drop, T12%; 25 mmHg). Mortality was 3/10 (T50%) and 2/10 (T12%). HS produced a significant transient recovery of mean arterial pressure (MAP) and increased blood loss to 38.9 and 21.8 ml/kg for T50% and T12% respectively, but mortality was not significantly different (T50%, 5/10; T12%, 3/10). The other three anesthetics with a T50% cut produced mild blood loss and slight hypotension, unaffected by HS. Only three of 60 rats died under these anesthetics (two HS, one untreated). In a supplementary P-anesthetized group (P-MIMIC), blood was forcibly removed from a large artery to mimic the loss observed in the NK-T50% group. Hypotension and death rates in P-MIMIC (four HS, one control) were comparable to those observed in NK-T50%. It is concluded that the effects of NK are probably due to its powerful vasodilator effect, apparently sufficient to impede the normal vasoconstrictor response to shock.

Anesthesia↗
PubMed1990

Increased efflux of a haemoglobin-like protein and an 80 kDa protease into push-pull perfusates following the induction of long-term potentiation in the dentate gyrus.

In a previous communication, we reported an increase in protein efflux into perfusates obtained from push-pull cannulation of the dentate gyrus, following induction of long-term potentiation (LTP) in the perforant path. LTP was accompanied by a delayed but general increase in protein efflux. Protein B5 (MW 14 kDa), because of its relatively high concentration in the perfusates and absence from serum, has been chosen for further characterization. Spectrophotometric analysis, in situ proteolysis, two-dimensional electrophoresis and immunoblotting, revealed that protein B5 is indistinguishable from haemoglobin. A persistent increase in an 80 kDa protease, detected by SDS-PAGE zymography, was also seen after the induction of LTP. We consider the possibility that the increased haemoglobin content of perfusates after the induction of LTP may reflect an LTP-associated increase in the release (or activation) of proteases into extracellular space, leading to proteolytic breakdown of blood clots in the vicinity of the cannula. Evidence in favour of this hypothesis is provided.

Animals↗
PubMed1990

Differential expression of immediate early genes in the hippocampus and spinal cord.

We have demonstrated that immediate early genes can be differentially activated within the central nervous system. We examined the effects of tetanic stimulation in the hippocampus and of noxious sensory stimulation of the spinal cord on the expression of eight immediate early genes. Induction of long-term potentiation (LTP) in the dentate gyrus resulted in an increase in mRNA and protein for NGFI-A (also termed Zif/268, Egr-1, or Krox 24), and less consistently for jun-B mRNA. No increase was seen for c-fos, NGFI-B, c-jun, jun-D, SRF, or PC4 mRNAs. Blockade of the NMDA receptor prevented the induction of both LTP and NGFI-A mRNA in the dentate gyrus. However, commissural stimulation, which prevented the induction of LTP, resulted in bilateral activation of all the genes examined, including NGFI-A. No change was seen in animals trained in a water maze. These results suggest that no simple relationship exists between LTP, spatial learning, and immediate early gene induction. Stimulation of sensory fibers resulted in an increase in mRNA for NGFI-A, c-fos, SRF, NGFI-B, and c-jun in spinal cord neurons. Blockade of the NMDA receptor had no effect on immediate early gene induction in the spinal cord.

Animals↗
PubMed1990

Increases in glutamate release and phosphoinositide metabolism associated with long-term potentiation and classical conditioning.

Long-term potentiation (LTP) is a widely studied model of the kind of activity-dependent modulation of synaptic efficacy which is assumed to provide the physical basis for learning. Whether LTP, in the hippocampus or elsewhere in the brain, does in fact serve such a role is still a matter for debate. One approach to answering this question is to identify physiological or biochemical changes which are common to both learning and LTP; in the hippocampus, for example, one can ask whether the biochemical changes associated with LTP are also associated with learning. In this chapter we summarize the results which we have obtained in a study of glutamate release and phosphoinositide turnover in the dentate gyrus of rats trained in a classical conditioning task. The similarity between the changes occurring after classical conditioning and those associated with LTP is consistent with the hypothesis that LTP is one of the mechanisms by which a neural trace of the learned association is formed. We discuss this interpretation in the light of the observation that classical conditioning does not appear to affect synaptic responses in the hippocampus.

Animals↗