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E M Schuman

Publications and source records attributed to E M Schuman.

17 recordsLinked to original sources
PubMed1997

Visualization of the distribution of autophosphorylated calcium/calmodulin-dependent protein kinase II after tetanic stimulation in the CA1 area of the hippocampus.

Autophosphorylation of calcium/calmodulin-dependent protein kinase II (CaMKII) at threonine-286 produces Ca2+-independent kinase activity and has been proposed to be involved in induction of long-term potentiation by tetanic stimulation in the hippocampus. We have used an immunocytochemical method to visualize and quantify the pattern of autophosphorylation of CaMKII in hippocampal slices after tetanization of the Schaffer collateral pathway. Thirty minutes after tetanic stimulation, autophosphorylated CaM kinase II (P-CaMKII) is significantly increased in area CA1 both in apical dendrites and in pyramidal cell somas. In apical dendrites, this increase is accompanied by an equally significant increase in staining for nonphosphorylated CaM kinase II. Thus, the increase in P-CaMKII appears to be secondary to an increase in the total amount of CaMKII. In neuronal somas, however, the increase in P-CaMKII is not accompanied by an increase in the total amount of CaMKII. We suggest that tetanic stimulation of the Schaffer collateral pathway may induce new synthesis of CaMKII molecules in the apical dendrites, which contain mRNA encoding its alpha-subunit. In neuronal somas, however, tetanic stimulation appears to result in long-lasting increases in P-CaMKII independent of an increase in the total amount of CaMKII. Our findings are consistent with a role for autophosphorylation of CaMKII in the induction and/or maintenance of long-term potentiation, but they indicate that the effects of tetanus on the kinase and its activity are not confined to synapses and may involve induction of new synthesis of kinase in dendrites as well as increases in the level of autophosphorylated kinase.

Animals↗
PubMed1997

Neurotrophins and time: different roles for TrkB signaling in hippocampal long-term potentiation.

We examined the role of TrkB ligands in hippocampal long-term potentiation (LTP) using function-blocking TrkB antiserum (Ab) and Trk-IgG fusion proteins. Incubation of hippocampal slices with TrkB Ab had no effect on basal synaptic transmission, short-term plasticity, or LTP induced by several trains of tetanic stimulation. The TrkB Ab-treated slices, however, showed significant deficits in LTP induced by either theta-burst stimulation (TBS) or "pairing." Slices exposed to the same number of inducing stimuli, delivered either as TBS or as a single 100 Hz epoch, only exhibited TrkB-sensitive LTP when TBS was used, indicating that the temporal pattern of stimulation determines the neurotrophin dependence. The late phase of LTP (2-3 hr) was also significantly impaired in slices pretreated with TrkB Ab or a TrkB-IgG. The application of a TrkB-IgG 30 min after LTP induction caused previously potentiated synaptic transmission to return to baseline levels, indicating that TrkB ligands are required to maintain LTP for up to 1 hr after induction. Taken together, these results indicate that both the temporal patterns of synaptic activity and the different temporal phases of synaptic enhancement are important in determining the neurotrophin dependence of plasticity in the hippocampus.

3T3 Cells↗
PubMed1996

A role for endothelial NO synthase in LTP revealed by adenovirus-mediated inhibition and rescue.

Pharmacological studies support the idea that nitric oxide (NO) serves as a retrograde messenger during long-term potentiation (LTP) in area CA1 of the hippocampus. Mice with a defective form of the gene for neuronal NO synthase (nNOS), however, exhibit normal LTP. The myristoyl protein endothelial NOS (eNOS) is present in the dendrites of CA1 neurons. Recombinant adenovirus vectors containing either a truncated eNOS (a putative dominant negative) or an eNOS fused to a transmembrane protein were used to demonstrate that membrane-targeted eNOS is required for LTP. The membrane localization of eNOS may optimally position the enzyme both to respond to Ca2+ influx and to release NO into the extracellular space during LTP induction.

Adenoviridae↗
PubMed1996

A requirement for local protein synthesis in neurotrophin-induced hippocampal synaptic plasticity.

Two neurotrophic factors, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), are able to produce a long-lasting enhancement of synaptic transmission in the hippocampus. Unlike other forms of plasticity, neurotrophin-induced plasticity exhibited an immediate requirement for protein synthesis. Plasticity in rat hippocampal slices in which the synaptic neuropil was isolated from the principal cell bodies also required early protein synthesis. Thus, the neurotrophins may stimulate the synthesis of proteins in either axonal or dendritic compartments, allowing synapses to exert local control over the complement of proteins expressed at individual synaptic sites.

Animals↗
PubMed1995

Long-lasting neurotrophin-induced enhancement of synaptic transmission in the adult hippocampus.

The neurotrophins are signaling factors important for the differentiation and survival of distinct neuronal populations during development. To test whether the neurotrophins also function in the mature nervous system, the effects of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and neurotrophic factor 3 (NT-3) on the strength of synaptic transmission in hippocampal slices were determined. Application of BDNF or NT-3 produced a dramatic and sustained (2 to 3 hours) enhancement of synaptic strength at the Schaffer collateral-CA1 synapses; NGF was without significant effect. The enhancement was blocked by K252a, an inhibitor of receptor tyrosine kinases. BDNF and NT-3 decreased paired-pulse facilitation, which is consistent with a possible presynaptic modification. Long-term potentiation could still be elicited in slices previously potentiated by exposure to the neurotrophic factors, which implies that these two forms of plasticity may use at least partially independent cellular mechanisms.

2-Amino-5-phosphonovalerate↗
PubMed1995

Neurotrophin-induced modulation of synaptic transmission in the adult hippocampus.

The NGF-family of neurotrophic factors including NGF, BDNF and NT-3,4/5 is known to be crucial for neuronal survival and differentiation during development. However, recent studies suggest that the neurotrophins are also widely expressed and play a dynamic role in the mature nervous system. One of the major sites of expression of the neurotrophins in the adult brain is the hippocampus which has been also popular as an important structure for the adult plasticity. Moreover, the level of expression of the neurotrophins in the hippocampus can be regulated by a variety of neuronal inputs, such as experimentally-induced seizures, injection of glutamate receptor agonists, and LTP-inducing stimulation. The possibility that the neurotrophins modulate synaptic transmission in the mature brain has been investigated at the Schaffer collateral-CA1 synapses in the adult rat hippocampus. We report that transient application of BDNF and NT-3, but not NGF induces a long-lasting increase of synaptic transmission, which is likely to be mediated by Trk family of receptor tyrosine kinases. Both BDNF and NT-3 decrease paired pulse facilitation, suggesting a possible presynaptic modification. Interestingly, previous potentiation of synaptic activity by the application of neurotrophic factors does not occlude the induction of long-term potentiation. These results suggest that the neurotrophins may locally regulate synaptic plasticity in the adult nervous system.

Animals↗
PubMed1994

An ADP-ribosyltransferase as a potential target for nitric oxide action in hippocampal long-term potentiation.

Recent studies of long-term potentiation (LTP) in the CA1 region of the hippocampus have demonstrated that nitric oxide (NO) may be involved in some forms of LTP and have suggested that postsynaptically generated NO is a candidate to act as a retrograde messenger. However, the molecular target(s) of NO in LTP remain to be elucidated. The present study examined whether either of two potential NO targets, a soluble guanylyl cyclase or an ADP-ribosyltransferase (ADPRT; EC 2.4.2.31) plays a role in LTP. The application of membrane-permeant analogs of cGMP did not produce any long-lasting alterations in synaptic strength. In addition, application of a cGMP-dependent protein kinase inhibitor did not prevent LTP. We found that the CA1 tissue from hippocampus possesses an ADPRT activity that is dramatically stimulated by NO and attenuated by two different inhibitors of mono-ADPRT activity, phylloquinone and nicotinamide. The extracellular application of these same inhibitors prevented LTP. Postsynaptic injection of nicotinamide failed to attenuate LTP, suggesting that the critical site of ADPRT activity resides at a nonpostsynaptic locus. These results suggest that ADP-ribosylation plays a role in LTP and are consistent with the idea that an ADPRT may be a target of NO action.

2-Amino-5-phosphonovalerate↗
PubMed1994

Locally distributed synaptic potentiation in the hippocampus.

The long-lasting increase in synaptic strength known as long-term potentiation has been advanced as a potential physiological mechanism for many forms of both developmental and adult neuronal plasticity. In many models of plasticity, intercellular communication has been proposed to account for observations in which simultaneously active neurons are strengthened together. The data presented here indicate that long-term potentiation can be communicated between synapses on neighboring neurons by means of a diffusible messenger. This distributed potentiation provides a mechanism for the cooperative strengthening of proximal synapses and may underlie a variety of plastic processes in the nervous system.

Animals↗
PubMed1994

Molecular consequences of diffusible signaling: locally distributed synaptic enhancement in hippocampal neurons.

The long-lasting increase in synaptic strength known as long-term potentiation is regarded as a potential physiological mechanism for many forms of both developmental and adult neuronal plasticity. In many models of plasticity, intercellular communication has been proposed to account for observations in which simultaneously active neurons are strengthened together. Recent studies indicate that long-term potentiation can be communicated between synapses on neighboring neurons, perhaps via a diffusible messenger. This distributed potentiation provides a potential mechanism for the cooperative strengthening of proximal synapses that underlie common neuronal functions and contribute to a variety of plastic processes in the nervous system.

Animals↗
PubMed1994

Inhibition of hippocampal heme oxygenase, nitric oxide synthase, and long-term potentiation by metalloporphyrins.

Four potent metalloporphyrin inhibitors of heme oxygenase were used to assess whether carbon monoxide production was required for induction of LTP in the CA1 region of the hippocampus. Although the metalloporphyrins produced a similar and substantial inhibition of heme oxygenase activity in hippocampal slices, only two compounds reduced the amount of LTP elicited by tetanic stimulation (chromium mesoporphyrin IX and zinc protoporphyrin IX). Both chromium mesoporphyrin IX and zinc protoporphyrin IX inhibited nitric oxide synthase in the hippocampus; tin mesoporphyrin IX and zinc deuteroporphyrin IX bis glycol neither reduced LTP induction nor inhibited NOS activity, although they did inhibit heme oxygenase. None of these metalloporphyrins reversed established LTP. Thus, together these data do not support carbon monoxide as a mediator in either LTP induction or expression/maintenance and emphasize further the nonselectivity of some metalloporphyrins.

Amino Acid Oxidoreductases↗
PubMed1994

Synaptic facilitation at connections of Hermissenda type B photoreceptors.

The enhancement of excitability in type B photoreceptors is an important neural mechanism underlying classically conditioned suppression of phototaxis in the marine mollusk Hermissenda crassicornis. However, the possibility that type B photoreceptors also exhibit synaptic plasticity has not previously been explored. We now report that connections of type B photoreceptors onto type A photoreceptors exhibit synaptic facilitation, and that this facilitation involves the same first messenger (5-HT) and second messenger (protein kinase C) previously implicated in the learning-produced excitability changes. In brief, we found that application of 5-HT dramatically facilitates synaptic potentials evoked by type B cells in type A cell cells, and that this facilitation is blocked by preincubation with staurosporine, a protein kinase inhibitor. Furthermore, activation of protein kinase C also induces synaptic facilitation, whereas activation of the cAMP-dependent protein kinase has no effect. Changes in synaptic strength produced by these manipulations are paralleled by changes in type B cell input resistance (a simple index of cellular excitability), whereas type A cell input resistance is unaffected. These findings indicate a previously unrecognized form of neuronal plasticity in Hermissenda that may contribute importantly to the learned changes in behavior, and thereby highlight general principles of learning-related neuronal plasticity shared by different preparations and species.

Alkaloids↗
PubMed1991

A requirement for the intercellular messenger nitric oxide in long-term potentiation.

Long-term potentiation (LTP) of synaptic transmission is a widely studied model of neuronal plasticity. The induction of LTP is known to require processes in the postsynaptic neuron, while experimental evidence suggests that the expression of LTP may occur in the presynaptic terminal. This has led to speculation that a retrograde messenger travels from the post- to the presynaptic cell during induction of LTP. Extracellular application or postsynaptic injection of two inhibitors of nitric oxide synthase, N-nitro-L-arginine or NG-methyl-L-arginine, blocks LTP. Extracellular application of hemoglobin, which binds nitric oxide, also attenuates LTP. These findings suggest that nitric oxide liberated from postsynaptic neurons may travel back to presynaptic terminals to cause LTP expression.

Amino Acid Oxidoreductases↗
PubMed1991

LTP, post or pre? A look at the evidence for the locus of long-term potentiation.

It seems self-evident that changes in the cellular synaptic function of the brain must underlie the formation and storage of cognitive memories. Because it has been identified as a brain area important in the formation of memory, the hippocampus has been a focus in the study of such synaptic changes. An activity-induced increase in hippocampal synaptic efficacy, known as long-term potentiation (LTP), has been widely studied as a potential substrate for memory. This paper briefly reviews some of the significant progress that has been made in understanding the cellular mechanisms that underlie LTP, including recent experiments dealing with its synaptic locus, or the question of whether the mechanism regulating LTP is pre- or postsynaptic.

Animals↗