PubMed Health⌕ Search

Biomedical subjects

T V Bliss

Publications and source records attributed to T V Bliss.

At least 19 recordsLinked to original sources
PubMed1992

Persistence of individual dendritic spines in living brain slices.

A number of theories on the cellular basis of learning and memory propose that long-term changes in synaptic strength are encoded by changes in the properties of dendritic spines. Such theories imply that individual spines retain their identity over time. Using a new technique for fluorescent labelling of synaptic structures together with confocal microscopy, we have found that the appearance of individual spines on viable cells remains unchanged over observations periods of up to 5 hours. Even in slices exposed to kainic acid at concentrations that abolished synaptic transmission, groups of spines remained identifiable on cells clearly damaged by the toxin. The robust persistence of individual spines demonstrated here establishes an essential prerequisite for their potential role as mnemonic elements.

Animals↗
PubMed1991

Increase in arachidonic acid concentration in a postsynaptic membrane fraction following the induction of long-term potentiation in the dentate gyrus.

We have determined the concentration of free fatty acids in membranes of slices prepared from the dentate gyrus following the induction of long-term potentiation in the anaesthetized rat. Compared to unpotentiated tissue, there was a significant increase in the concentration of free arachidonic acid 2.5 min, 45 min and 3 h after induction of long-term potentiation. There was no corresponding increase in oleic, stearic or palmitic acids. To account for the increase in free arachidonate, the activities of phospholipase A2, phospholipase A1 and phospholipase C were determined at the same three time intervals in control and potentiated tissue. Two-and-a-half minutes after the induction of long-term potentiation, activity of phospholipase A2 was enhanced, while at 45 min, and at 3 h phospholipase C activity was increased. These results suggest that the liberation of free arachidonate is due initially to phospholipase A2 activity, but that at later stages of long-term potentiation, control switches to phospholipase C. Subcellular fractionation experiments revealed an increase in free arachidonate in the postsynaptic density fraction 45 min after induction of long-term potentiation, without significant changes in synaptosomal- or glial-enriched fractions. These results are consistent with the hypothesis that arachidonic acid, released from a postsynaptic site, acts as a trophic retrograde synaptic signal in long-term potentiation in the dentate gyrus.

Animals↗
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

A decrease in firing threshold observed after induction of the EPSP-spike (E-S) component of long-term potentiation in rat hippocampal slices.

Two components of long-term potentiation (LTP) are distinguished with extracellular recording electrodes: a synaptic and an EPSP-Spike (E-S) component. The latter consists of the enhancement produced in the population spike amplitude in excess of that predicted by EPSP potentiation alone. The experiments carried out in this study were designed to investigate intracellular correlates of E-S potentiation and to examine the hypothesis that an increased postsynaptic excitability underlies E-S potentiation. CA1 pyramidal neurons were synaptically activated from stratum radiatum. LTP, defined as a stable increase in the probability of firing to afferent stimulation, was found to be related to a decrease in the intracellular PSP peak amplitude and slope required to fire the cells at a probability of 0.5. These changes were accompanied by a decrease in threshold to direct activation. No significant changes in input resistance or resting potential were recorded. These excitability changes were only observed in cells displaying LTP; they were not related to the potentiation of the synaptic component (PSP amplitude). Our results support the hypothesis that different mechanisms underlie the two components of LTP, and that a reduction in threshold for neuronal discharge accompanies tetanus-induced E-S potentiation. It is suggested that an increase in the ratio of synaptically evoked excitation/inhibition and a reduction in tonic synaptic inhibition through GABAA channels contribute to E-S potentiation.

Action Potentials↗
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↗
PubMed1989

An in vitro study of the effect of lipoxygenase and cyclo-oxygenase inhibitors of arachidonic acid on the induction and maintenance of long-term potentiation in the hippocampus.

The effects on tetanus-induced long-term potentiation (LTP) of the lipoxygenase and phospholipase A2 inhibitor nordihydroguaiaretic acid (NDGA), and of the cyclo-oxygenase inhibitor indomethacin have been investigated in area CA1 of the hippocampal slice. In the presence of NDGA, tetanic stimulation of Schaffer collaterals produces an attenuated potentiation of the population excitatory postsynaptic potential (EPSP) lasting for less than 1 h. Indomethacin does not impair LTP of the EPSP. Neither drug significantly reduces LTP of the population spike. NDGA, but not indomethacin, reversibly reduces pre-established LTP. The results suggest a role for arachidonic acid or its lipoxygenase metabolites, but not its cyclo-oxygenase metabolites, in the induction and expression of tetanus-induced LTP in area CA1.

Action Potentials↗
PubMed1989

Arachidonic acid induces a long-term activity-dependent enhancement of synaptic transmission in the hippocampus.

Long-term potentiation (LTP) is a widely studied model of the synaptic basis of information storage in the mammalian brain. The induction of LTP is triggered by the postsynaptic entry of calcium through the channel associated with the N-methyl-D-aspartate (NMDA) receptor, whereas its maintenance is mediated, at least in part, by presynaptic mechanisms. To explain how postsynaptic events can lead to an increase in transmitter release, we have postulated the existence of a retrograde messenger to carry information from the postsynaptic side of the synapse to recently active presynaptic terminals. Candidates for a retrograde messenger include arachidonic acid or one of its lipoxygenase metabolites. Here we report that weak activation of the perforant path, when given in the presence of arachidonic acid, leads to a slow-onset persistent increase in synaptic efficacy both in vivo and in vitro. The activity-dependent potentiation thus produced is accompanied by an increase in the release of glutamate, and is non-additive with tetanus-induced LTP. These observations indicate a role for arachidonic acid as a retrograde messenger in the later, but not the initial, stages of LTP.

2-Amino-5-phosphonovalerate↗
PubMed1989

The EPSP-spike (E-S) component of long-term potentiation in the rat hippocampal slice is modulated by GABAergic but not cholinergic mechanisms.

Long-term potentiation of synaptic efficacy (LTP) can be shown to consist of two components: a synaptic and an excitatory postsynaptic potential (EPSP)-spike (E-S) component. The E-S component is expressed as a leftward shift in the curve relating population spike amplitude as a function of EPSP slope. The participation of cholinergic and GABAergic processes in E-S potentiation was studied in field CA1 of rat hippocampal slices. Atropine, a muscarinic antagonist, did not prevent tetanus-induced E-S potentiation. The cholinergic agonist carbachol and the GABAA antagonist picrotoxin produced a leftward shift in the E-S relation; picrotoxin, but not carbachol, prevented the expression of tetanus-induced E-S potentiation. These observations indicate that an increase in the ratio of evoked excitation to inhibition and/or a reduction in tonic inhibition mediated by the activation of GABAA receptors contribute to E-S potentiation produced by high-frequency stimulation.

Action Potentials↗
PubMed1989

The increase in [3H]glutamate release associated with long-term potentiation in the dentate gyrus is blocked by commissural stimulation.

Previous findings have indicated that long-term potentiation (LTP) in the perforant path-granule cell synapses is accompanied by an increase in K+-stimulated, calcium-dependent release of [3H]glutamate 45 min after the induction of LTP. Here we report that release of [3H]glutamate is increased at 3 time intervals following induction of LTP, 2.5 min, 45 min and 3 h. Stimulation of the commissural input to the granule cells blocks the induction of LTP and the increase in [3H]glutamate release.

Animals↗
PubMed1989

Nordihydroguaiaretic acid blocks the synaptic component of long-term potentiation and the associated increases in release of glutamate and arachidonate: an in vivo study in the dentate gyrus of the rat.

The dentate gyrus of anaesthetized rats was perfused with artificial cerebrospinal fluid while field responses evoked by stimulation of the perforant path were monitored. Perfusates were collected for analysis of endogenous glutamate, aspartate and arachidonate. In animals in which long-term potentiation was induced by tetanic stimulation, there was a sustained increase in the concentration of glutamate in the perfusate, and, less reliably, in aspartate, as previously reported by Bliss et al. (J. Physiol., Lond. 377, 391-408, 1986) and Errington et al. (Neuroscience 20, 279-284, 1987). The lipoxygenase and phospholipase A2 inhibitor nordihydroguaiaretic acid, when added to the perfusate 30 min before the tetanus, abolished both long-term potentiation of the population excitatory postsynaptic potential and the tetanus-induced increase in glutamate release. Long-term potentiation of the population spike was reduced but not abolished. There was also a sustained increase in the release of arachidonic acid following the induction of long-term potentiation which did not occur when induction was blocked by nordihydroguaiaretic acid. These results are discussed in the light of the possibility that arachidonic acid or one of its lipoxygenase metabolites may be the retrograde messenger which we have postulated is released from postsynaptic sites following tetanic stimulation to trigger increased transmitter release from presynaptic terminals.

Action Potentials↗
PubMed1988

Long-term potentiation in the dentate gyrus of the anaesthetized rat is accompanied by an increase in protein efflux into push-pull cannula perfusates.

Changes in protein content of push-pull cannula perfusates from the dentate gyrus of anaesthetized rats were analyzed before and after the induction of long-term potentiation (LTP). LTP, induced by either high-frequency stimulation of the perforant path or raising the extracellular calcium concentration, was associated with increases in the protein content of the perfusates. Tetanically induced LTP was accompanied with a large but delayed increase (apparent in the second hour after the stimulation) in protein efflux. In contrast, when LTP was induced by the elevation of extracellular calcium concentration, a smaller but more immediate increase in protein efflux was observed. When 5-D-aminophosphonovalerate was used to block the induction of LTP, no increase was observed in either case. These results indicate that LTP in the dentate gyrus is accompanied by an increase in the efflux of proteins into push-pull cannula perfusates. The possible origins of these proteins and their role in LTP are discussed.

2-Amino-5-phosphonovalerate↗