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C F Stevens

Publications and source records attributed to C F Stevens.

At least 73 records · Page 4Linked to original sources
PubMed1994

Changes in reliability of synaptic function as a mechanism for plasticity.

Synaptic transmission in the hippocampus is rather unreliable, with many presynaptic action potentials failing to release neurotransmitter. How is this unreliability affected by the alterations in synaptic strength seen in long-term potentiation (LTP) and long-term depression (LTD)? We find that LTP increases synaptic reliability, and LTD decreases it, both without a change in the size of those postsynaptic currents that do occur. Thus LTD is a functional inverse of LTP.

Animals↗
PubMed1994

The role of calcium-calmodulin kinase II in three forms of synaptic plasticity.

BACKGROUND: Calcium influx into postsynaptic dendritic spines can, depending on circumstances, activate three forms of synaptic plasticity: long-term potentiation (LTP), short-term potentiation (STP) and long-term depression (LTD). The increased postsynaptic calcium concentrations that trigger all three forms of plasticity should activate the alpha isoform of calcium-calmodulin kinase type II (alpha CaMKII), which is present at high levels just below the postsynaptic membrane. Earlier experiments have implicated alpha CaMKII in the regulation or induction of LTP, but no information is available on the possible role of this enzyme in the two other forms of synaptic plasticity, STP and LTD. RESULTS: We used mice that lack the gene for alpha CaMKII to investigate the role of this enzyme in synaptic plasticity. Field potential recordings from hippocampal slices taken from mutant mice show that STP and LTD are, like LTP, absent or markedly attenuated in the absence of alpha CaMKII. A brief form of synaptic modification--post-tetanic potentiation (PTP)--is, however, intact in the absence of this enzyme. CONCLUSIONS: It appears likely that alpha CaMKII is involved in the production or global regulation of all three forms of synaptic plasticity. We propose that the activation of this enzyme is a common step in the induction of LTP and STP, and that alpha CaMKII activity is required for the normal production of LTD.

2-Amino-5-phosphonovalerate↗
PubMed1994

Memory. A model with good CREdentials.

The sea snail Aplysia provides a relatively simple model system for studying both short-term and long-term memory; a known transcriptional mechanism is implicated in establishment of the latter.

Animals↗
PubMed1994

Increased transmitter release at excitatory synapses produced by direct activation of adenylate cyclase in rat hippocampal slices.

The field EPSP recorded in the CA1 region of rat hippocampal slices is potentiated by bath application of the direct adenylate cyclase activator forskolin (Chavez-Noriega and Stevens, 1992a). We have now used the whole-cell patch-clamp technique to analyze the effect of forskolin on evoked synaptic currents and on spontaneous and miniature excitatory postsynaptic currents (sEPSCs and mEPSCs) recorded in rat hippocampal slices in order to determine the relative contributions of pre- and postsynaptic mechanisms to this increased synaptic strength. Application of 50 microM forskolin in the presence of 3-isobutyl-1-methylxanthine (IBMX; a phosphodiesterase inhibitor) enhanced the evoked EPSC (eEPSC) peak amplitude to 230 +/- 43% of control (n = 13). No significant change in sEPSC or in mEPSC amplitude was detected after forskolin addition (106 +/- 7%, n = 9), indicating that postsynaptic receptor sensitivity at synaptic junctions is not greatly affected. In contrast, a large increase in sEPSC and mEPSC frequency was noted in all cells (299 +/- 81%). Following forskolin application, the amplitude distribution of evoked synaptic currents shifted to larger values, but more significantly, a sharp decrease in failure rate was produced in all cells tested. Also, a significant correlation was found between the potentiation produced by forskolin in IBMX on the eEPSC and the ratio of the squared coefficient of variation (CV = SD/mean). Finally, a quantal analysis of four cells was consistent with the hypothesis that transmitter release was increased by forskolin/IBMX with, if anything, a concomitant decrease in quantal size. Together, these observations indicate that presynaptic mechanisms significantly contribute to the enhancement produced by this diterpene.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗
PubMed1994

Both open and closed NMDA receptor channels desensitize.

Desensitization of NMDA receptors was studied at the single-channel level using outside-out patches taken from rat hippocampus CA neurons maintained short term in culture. The amount of desensitization that accumulated as a function of time during the application of NMDA (2.5 microM) was measured by the response to the rapid application of NMDA at a high concentration (100 microM). Records were sorted into two classes: those in which no openings were detected during the application of 2.5 microM NMDA, and those in which some channel openings occurred. Analysis of these data reveals that some desensitization accumulated when no channels opened, but that more desensitization developed when channels opened. The observations indicate that channels can pass from the closed state to the desensitized state, but that desensitization occurs more rapidly from the open state.

Animals↗
PubMed1993

Modified hippocampal long-term potentiation in PKC gamma-mutant mice.

Calcium-phospholipid-dependent protein kinase (PKC) has long been suggested to play an important role in modulating synaptic efficacy. We have created a strain of mice that lacks the gamma subtype of PKC to evaluate the significance of this brain-specific PKC isozyme in synaptic plasticity. Mutant mice are viable, develop normally, and have synaptic transmission that is indistinguishable from wild-type mice. Long-term potentiation (LTP), however, is greatly diminished in mutant animals, while two other forms of synaptic plasticity, long-term depression and paired-pulse facilitation, are normal. Surprisingly, when tetanus to evoke LTP was preceded by a low frequency stimulation, mutant animals displayed apparently normal LTP. We propose that PKC gamma is not part of the molecular machinery that produces LTP but is a key regulatory component.

Animals↗
PubMed1993

Calcium permeability of the N-methyl-D-aspartate receptor channel in hippocampal neurons in culture.

We have developed a quantitative description for calcium permeability of the N-methyl-D-aspartate receptor channel to permit predictions of the reversal potential and calcium influx at different voltages for different extracellular calcium concentrations. Increasing the external calcium concentration markedly shifted the reversal potential to positive values and simultaneously decreased the single-channel conductance at potentials negative to the reversal potential. Very simple quantitative descriptions of calcium permeation and channel block by calcium ions accurately characterize our data and permit the prediction of reversal potentials and magnitudes of calcium influx for a wide range of conditions.

Animals↗
PubMed1993

Reversal of long-term potentiation by inhibitors of haem oxygenase.

Evidence that carbon monoxide can serve as an intercellular messenger in brain, a role much like that demonstrated for nitric oxide in various tissue, prompted us to investigate whether carbon monoxide participates in long-term potentiation (LTP), the cellular mechanism that may underlie certain forms of learning and memory. Although LTP is triggered in the postsynaptic neuron, at least some fraction of LTP is expressed presynaptically as an increase in the quantity of neurotransmitter released. Thus, a retrograde signal must form the communication link between the postsynaptic site of induction and the presynaptic site of expression. To test whether carbon monoxide might act as a retrograde signal in LTP, we have investigated the effect on LTP of inhibitors of the enzyme haem oxygenase-2, which catalyses the production of carbon monoxide in the brain. We find that these inhibitors prevent the induction of LTP and have no effect on one form of long-term depression. Furthermore, they will reverse LTP that is already established.

Animals↗
PubMed1993

NMDA receptors at excitatory synapses in the hippocampus: test of a theory of magnesium block.

Excitatory postsynaptic currents (EPSCs) were studied using the whole-cell patch-clamp technique to record from rat hippocampal pyramidal neurons in both slices and dissociated cultures. The voltage- and magnesium-dependence of the N-methyl-D-aspartate (NMDA) component of the EPSCs was quantified by measuring the amplitude of this component at a range of holding potentials (-80 mV to 60 or 80 mV) in several bath magnesium concentrations (0.2 microM, 0.1, 1 and 10 mM). All of our results were well-fitted by a theory of magnesium block developed from single-channel studies of extrajunctional NMDA channels in culture. It is concluded that extrasynaptic and subsynaptic NMDA channels both in culture and in situ have identical properties of magnesium block.

Animals↗
PubMed1992

Adenosine decreases neurotransmitter release at central synapses.

Adenosine, at concentrations ranging from 5 to 100 microM, decreases the efficacy of transmission at the perforant path synapses on dentate granule cells. We have used whole cell recording from these cells in slices to determine the mechanism of the reduced synaptic strength. We find that size of miniature excitatory postsynaptic currents (mepscs) is unaffected by adenosine at concentrations up to 100 microM, an observation that indicates adenosine's mode of action is not through a decreased postsynaptic sensitivity to neurotransmitter. A quantal analysis indicates, however, that the quantity of neurotransmitter released is sufficiently diminished by adenosine to account entirely for the adenosine-produced decrease in synaptic strength. Application of 3-isobutyl-1-methylxanthine (IBMX), a drug that antagonizes the effects of endogenous adenosine, produces an increase in synaptic strength. This observation suggests that the resting level of adenosine in our slices is appreciable, and an analysis of the adenosine dose-response relation is consistent with endogenous adenosine levels of about 10 microM. IBMX application produces only slight changes in the amplitude of mepscs, whereas a quantal analysis demonstrates that the drug significantly increases the amount of neurotransmitter released. Thus IBMX acts as an "anti-adenosine" in our experiments. In some experiments we have been able to record excitatory and inhibitory synaptic currents produced by the same perforant path stimulus. In these instances we find that inhibitory transmission is unaffected by concentrations of adenosine that produce a marked decrease in the strength of excitatory synapses.

1-Methyl-3-isobutylxanthine↗
PubMed1992

Deficient hippocampal long-term potentiation in alpha-calcium-calmodulin kinase II mutant mice.

As a first step in a program to use genetically altered mice in the study of memory mechanisms, mutant mice were produced that do not express the alpha-calcium-calmodulin-dependent kinase II (alpha-CaMKII). The alpha-CaMKII is highly enriched in postsynaptic densities of hippocampus and neocortex and may be involved in the regulation of long-term potentiation (LTP). Such mutant mice exhibited mostly normal behaviors and presented no obvious neuroanatomical defects. Whole cell recordings reveal that postsynaptic mechanisms, including N-methyl-D-aspartate (NMDA) receptor function, are intact. Despite normal postsynaptic mechanisms, these mice are deficient in their ability to produce LTP and are therefore a suitable model for studying the relation between LTP and learning processes.

Animals↗