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Biomedical subjects

I J Urban

Publications and source records attributed to I J Urban.

At least 19 recordsLinked to original sources
PubMed1995

Temporal differences in the phosphorylation state of pre- and postsynaptic protein kinase C substrates B-50/GAP-43 and neurogranin during long-term potentiation.

The phosphorylation state of two identified neuralspecific protein kinase C substrates (the presynaptic protein B-50 and the postsynaptic protein neurogranin) was monitored after the induction of long term potentiation in the CA1 field of rat hippocampus slices by quantitative immunoprecipitation following 32Pi labeling in the recording chamber. B-50 phosphorylation was increased from 10 to 60 min, but no longer at 90 min after long term potentiation had been induced, neurogranin phosphorylation only at 60 min. Increased phosphorylation was not found when long term potentiation was blocked with the N-methyl-D-aspartate receptor antagonist D-2-amino-5-phosphonovalerate, when only low frequency stimulation was applied or tetanic stimulation failed to induce long term-potentiation. Our data show that both B-50 and neurogranin phosphorylation are increased following the induction of long term potentiation, thus providing strong evidence for pre- and postsynaptic protein kinase C activation during narrow, partially overlapping, time windows after the induction of long term potentiation.

Animals↗
PubMed1995

Long-term potentiation and synaptic protein phosphorylation.

Long-term potentiation (LTP) is a well known experimental model for studying the activity-dependent enhancement of synaptic plasticity, and because of its long duration and its associative properties, it has been proposed as a system to investigate the molecular mechanisms of memory formation. At present, there are several lines of evidence that indicate that pre- and postsynaptic kinases and their specific substrates are involved in molecular mechanisms underlying LTP. Many studies focus on the involvement of protein kinase C (PKC). One way to investigate the role of PKC in long-term potentiation is to determine the degree of phosphorylation of its substrates after in situ phosphorylation in hippocampal slices. Two possible targets are the presynaptic membrane-associated protein B-50 (a.k.a. GAP 43, neuromodulin and F1), which has been implicated in different forms of synaptical plasticity in the brain such as neurite outgrowth, hippocampal LTP and neurotransmitter release, and the postsynaptic protein neurogranin (a.k.a. RC3, BICKS and p17) which function remains to be determined. This review will focus on the protein kinase C activity in pre- and postsynaptic compartment during the early phase of LTP and the possible involvement of its substrates B-50 and neurogranin.

Animals↗
PubMed1995

A long-lasting increase and decrease in synaptic excitability in the rat lateral septum are associated with high and low shuttle box performance, respectively.

In a series of experiments with rats, using evoked field potentials, the influence of massed trial training in 2-way shuttle box avoidance and step-through passive avoidance tasks was studied on the synaptic excitability of the lateral septum (LS) neurons and on the induction of long-term potentiation in the lateral septum in vivo. The majority of rats that attained a high performance level in the shuttle box task exhibited, after the shuttle box training, a long-lasting enhancement of synaptic excitability of lateral septum neurons, whereas most of the rats with low performance in the shuttle box showed a long-lasting depression in the LS synaptic excitability. Both types of excitability changes disappeared within 24 h. Neither the first habituation session in the passive avoidance apparatus nor the subsequent one-trial learning in passive avoidance task had a marked influence on lateral septum synaptic excitability. Both high-performance and low-performance rats exhibited a long-term potentiation (LTP)-like potentiation of synaptic excitability of the lateral septum neurons after high frequency stimulation of the fimbria fibers although the amount of LTP in high performance rats was slightly higher than that in low performance animals.

Animals↗
PubMed1993

The impaired long-term potentiation in the CA1 field of the hippocampus of cognitive deficient microencephalic rats is restored by D-serine.

Rat embryos exposed on gestational day 15 to methyl-azoxymethanol acetate develop a microencephaly characterized primarily by a hypoplasia of the neocortex and CA fields of the hippocampus that in adulthood is associated with disturbances in learning. In brain slices prepared from microencephalic rats, we have examined the field excitatory postsynaptic potentials and population spike in the CA1 field of the hippocampus evoked by stimulation of the stratum radiatum. These parameters did not differ from those obtained in slices from control rats. High frequency stimulation of the stratum radiatum afferent fibres, which readily induced long-term potentiation of the field excitatory postsynaptic potentials and population spike in the CA1 field of the hippocampus of control rats, failed to induce long-term potentiation in that of microencephalic rats. High frequency stimulation of the perforant path readily elicited long-term potentiation in the dentate gyrus of both control and microencephalic rats. Picrotoxin had no apparent effect on field excitatory postsynaptic potentials and population spike in the CA1 field of the microencephalic rats, indicating that little GABAergic inhibition was present in slices from these rats. D-2-Amino-phosphonovalerate suppressed the field potentials in slices from microencephalic rats by more than 50%, suggesting that N-methyl-D-aspartate receptors contributed markedly to the synaptic responses evoked by single stimuli. D-Serine, but not picrotoxin, restored long-term potentiation in the CA1 field of the microencephalic rats. The D-serine effect was prevented by pretreating the slices with either 7-chloro-kynurenate or D-2-amino-phosphonovalerate. The failure to induce long-term potentiation, if also found in vivo, may be among the factors related to the learning deficits displayed by these rats.

2-Amino-5-phosphonovalerate↗
PubMed1990

Vasopressin facilitates excitatory transmission in slices of the rat dorso-lateral septum.

The effect of vasopressin on neurons of the rat dorso-lateral septum (DLS) was studied in brain slices with intracellular microelectrodes. Two out of 13 neurons showed a small depolarization, spontaneous activity, and increased input resistances following a 15 min exposure to 10(-6) to 10(-8) M vasopressin (VP). These membrane effects disappeared completely within 3-5 min after the application. The remaining DLS neurons treated with these vasopressin concentrations showed an increase in glutamate-mediated excitatory postsynaptic potentials (EPSPs), evoked by stimulation of the fimbria fibers. As little as 10(-12) MVP increased these EPSPs markedly in nearly 80% of the cells studied. This increase in most of the cells disappeared within 15 min after the application period, whereas the increase in EPSPs induced by 10(-10) M VP outlasted the peptide application period for more than 30 min. Neither the blockade of GABA-ergic synaptic inhibition nor the pre-treatment of the neurons with d(CH2)5-Tyr(Me)-arginine vasopressin or 2-amino-5-phosphonovaleric acid (2-APV), antagonists for the V1 type of vasopressin receptor and NMDA receptors, respectively, interfered with the EPSPs potentiating effect of the peptide. It is concluded that a type of vasopressin receptor other then the V1 type is involved in the long-lasting potentiation of the primarily non-NMDA receptor mediated transmission in DLS neurons.

2-Amino-5-phosphonovalerate↗
PubMed1990

Two actions of vasopressin on neurons in the rat ventral hippocampus: a microiontophoretic study.

Vasopressin (VP), applied by brief iontophoretic pulses on ventral hippocampus neurons in vivo, excited approximately 30% of the neurons tested. Glutamate (Glu) and acetylcholine (ACh) excited nearly all neurons recorded. A selective antagonist of vasopressin V1 receptors suppressed the VP-induced excitation and, in addition, suppressed the excitations induced by Glu but not those by ACh. The specificity of the action in the brain of this VP antagonist must therefore be doubted. Two excitatory amino acid antagonists, D(-)-2-amino-5-phosphonovaleric acid (2APV) and glutamic acid diethyl ester (GDEE), suppressed the responses to Glu and also those to VP. ACh excitations, tested in the same neurons, were little affected by 2APV and GDEE. The remaining 70% of VH neurons were not excitable with VP. However, the responses of these neurons to Glu but not to Ach, increased markedly both while the peptide was released and for tens of minutes thereafter. The increase in Glu responses induced by VP could not be prevented by the VP or excitatory amino acid receptor antagonists applied before the peptide. The possibility that the excitation and the potentiation of Glu responses caused by VP originated from two different actions of the peptide is discussed.

Acetylcholine↗
PubMed1990

The C-terminal glycopeptide of propressophysin potentiates excitatory transmission in the rat lateral septum.

Effects of peptides synthesized from the same precursor as vasopressin, i.e. the C-terminal 39-amino acid long glycopeptide and neurophysin II, were investigated for biological activities in electrophysiological experiments in brain slices of the rat lateral septum. These slices contained the glycopeptide as the predominant form and a fragment of it, amino acid sequence 22-39, as a minor form (8% of the glycopeptide 1-39), as shown by high performance liquid chromatography of extracts and by radioimmunoassay. None of the peptides, neurophysin II, the glycopeptide 1-39 and the fragment 22-39, tested in a concentration of 10(-12) M, had measurable effects on the resting membrane potential of the neurons. The glycopeptide and the fragment 22-39, however, increased, in some cells, for tens of minutes the excitatory postsynaptic potentials evoked in these neurons by stimulation of the fimbria fibers. The increase in input resistance, seen in many septal neurons treated with either of the peptides was not correlated with the excitatory postsynaptic potential increase. Neurophysin II affected neither the excitatory postsynaptic potentials nor the input resistance of the neurons. It is concluded that the glycopeptide 1-39 and the fragment 22-39 possess biological activities amongst which the facilitation of excitatory amino acid transmission on lateral septum neurons. Therefore, these peptides derived from the vasopressin precursor may act in concert with vasopressin to establish facilitation of excitatory transmission in the brain.

Animals↗
PubMed1989

Vasopressin maintains long-term potentiation in rat lateral septum slices.

In brain slices of normal Wistar and Long-Evans rats, brief high frequency stimulation of the fimbria fibers induced long-term potentiation (LTP) in excitatory transmission between these fimbria fibers and neurons of the lateral septum (LS). Slices prepared from diabetes insipidus (DI) Brattleboro rats, that contained no vasopressin (VP), consistently failed to maintain LTP in this excitatory transmission. Exogenous VP, administered to slices from DI Brattleboro rats shortly prior to the experiment or released from a subcutaneous depot in DI Brattleboro rats for several days prior to decapitation, corrected this failure. The maintenance of LTP in the LS in slices from Wistar and Long-Evans rats was prevented by D(CH2)5-Tyr(Me)-arginine VP, an antagonist for the V1 type of VP receptors. These results indicate an important role of VP in the maintenance of LTP in excitatory transmission in the LS. It is conjectured that the effects of VP on LS neurons are related to the role of the peptide in the maintenance of LTP and that these processes play a role in memory formation.

Action Potentials↗
PubMed1987

N-acetyl-aspartylglutamate: binding sites and excitatory action in the dorsolateral septum of rats.

In this study we examined the distribution of binding sites for [3H]N-acetyl-aspartylglutamate (NAAG) in the rat lateral septal nucleus (LSN) and the effect of iontophoretically applied NAAG on neuronal firing in this area. A high density of [3H]NAAG binding sites was found in the dorsolateral part of the LSN. Binding in the intermediate/ventral part of the LSN and medial septum was less dense. NAAG excited 75% of the dorsal neurons in the LSN, but only 36% of the cells in the intermediate/ventral part. Glutamic diethylester, an amino acid antagonist, depressed responses to NAAG to a similar extent as responses to quisqualate. The antagonist amino phosphonovaleric acid, which suppressed responses to N-methyl-D-aspartate almost completely, reduced NAAG-evoked responses only by 40%. A possible role of NAAG as excitatory transmitter in the LSN is discussed.

Action Potentials↗
PubMed1987

Rat lateral septum in slice preparation with viable transmission.

A procedure is described which makes it possible to prepare slices from the rat brain that comprise nearly the entire lateral septum together with the major part of the fimbria-fornix afferent fibers to the lateral septum. The field potentials and monosynaptic excitation of lateral septal neurons elicited by electrical stimulation of the fimbria-fornix afferent fibers were employed to demonstrate that the neurophysiological features of the lateral septal neurons in vitro are similar to those found previously in vivo, and the synaptic transmission between fimbria-fornix afferent fibers and neurons of the lateral septum could be maintained in vitro without significant alterations for at least a 6-h period of incubation.

Animals↗
PubMed1986

Effect of vasopressin, oxytocin and peptides derived from these hormones on field potential induced in lateral septum of rats by stimulation of the fimbria fornix.

Superfusion of the dorsal surface of the septum with artificial cerebrospinal fluid containing 10(-10) M [Arg8]-vasopressin (VP) significantly increased the negative (N) wave in field potentials (FPs) elicited in the lateral septum (LS) of rats by stimulation of the fimbria-fornix. A similar increase in the FPs negativity was also observed following superfusion of the septum with [pGlu4, Cyt6] VP(4-9), [pGlu4, Cyt6] VP(4-8), [Cyt6] VP (5-9), desglycinamide9-VP and 1-deamino, 8-D-arginine-VP. However, for obtaining the effect with these peptides 10(3-4) times higher concentrations had to be used. Superfusion of the septum with 10(-8) M oxytocin (OX) elicited nearly the same N-wave increase as the 10(-8) M VP septal superfusion. The 10(-10) M concentration of OX as well as 10(-7) M [pGlu4, Cyt6] OX(4-9) and [pGlu4, Cyt6] OX(4-8) had little effect on the FPs negativity. The significance of these findings for the elucidation of the VP function in the LS is discussed.

Animals↗
PubMed1985

Monoamine-induced responses in lateral septal neurons: influence of iontophoretically applied vasopressin.

We examined the effect of iontophoretically applied noradrenaline (NA), dopamine (DA) and serotonin (5-HT) on the spontaneous activity of lateral septal neurons in rats and subsequently investigated if the observed responses to these monoamines were altered in the presence of arginine8-vasopressin (AVP). NA, DA and 5-HT induced a depression of the spontaneous activity in 70% of the spontaneously active neurons on which they were tested. Of the remaining neurons the majority was not affected by the monoamines. The responding cells differed from the non-responding cells in their localization in those parts of the lateral septum where dense monoamine-containing terminal networks have been visualized and in their significantly lower spontaneous activity. The effect of AVP on monoamine-induced responses was tested in neurons in which the spontaneous activity was not affected by the peptide itself. It appeared that in about 30% of these neurons, monoamine-induced inhibitions were reduced in presence of the peptide whereas in the majority of the neurons responses to the monoamines were not markedly altered by AVP. In contrast to this rather low occurrence of a clear AVP-effect on the monoamine responses, the peptide enhanced excitatory responses to glutamate in more than 75% of neurons tested during the same experiments. It was concluded that under these experimental conditions the effect of AVP on excitatory amino acid neurotransmission is more pronounced than on responses to putative monoaminergic neurotransmitters in the lateral septum.

Animals↗
PubMed1985

Topographic organization of fimbria-fornix fibers projecting to the lateral septum of rats: a single and field response analysis.

Single-unit and field potential responses, evoked by stimulation of restricted fimbria-fornix (fi-fx) segments, were recorded over the entire extent of the lateral septal complex (LSC) of rats in order to examine electrophysiologically the topographic organization of fi-fx fibers projecting to the LSC. We confirmed earlier studies showing that fi-fx fibers constitute a bilateral, monosynaptic excitatory projection to the LSC. The projection appeared to be topographically ordered in that medial fi-fx fibers innervated neurons in the mediodorsal part of the LSC whereas fibers coursing through progressively more lateral positions in the fi-fx activated neurons in gradually more lateral and ventral parts of the LSC. In addition to the topographic organization, a marked convergence of the fi-fx fibers on neurons located in the dorsolateral part of the LSC was apparent from both the single-unit and field potential experiments.

Animals↗
PubMed1984

Arginine-vasopressin enhances the responses of lateral septal neurons in the rat to excitatory amino acids and fimbria-fornix stimuli.

In the present study we investigated the effect of arginine-vasopressin (AVP) on responses induced in lateral septal neurons of the rat by iontophoretically administered excitatory and inhibitory amino acids and by synaptical stimuli delivered through fimbria-fornix (fi-fx) fibers. In the majority of the lateral septal neurons, iontophoretically applied AVP induced a marked increase in the excitatory responses to glutamate, aspartate, quisqualate and N-methyl-D-aspartate. The responses to excitatory amino acids frequently remained elevated several minutes after termination of the peptide administration. Inhibitory responses induced by GABA were not affected by AVP. The responsiveness of lateral septal single units to fi-fx stimuli was enhanced during iontophoretic administration of AVP. The enhanced responsiveness also appeared from experiments in which topically applied AVP induced a prolonged increase in the negative but not the positive wave of field potentials evoked in the lateral by fi-fx stimuli. The possible physiological significance of these findings is discussed.

Amino Acids↗
PubMed1984

Electrophysiological and pharmacological evidence in favor of amino acid neurotransmission in fimbria-fornix fibers innervating the lateral septal complex of rats.

Electrical stimulation of fimbria-fornix (fi-fx) fibers monosynaptically activated many of the neurons tested in the lateral septal complex (LSC) of the rat. The orthodromically activated LSC neurons were classified as "strongly" orthodromically activated (SOA) or "weakly" orthodromically activated ( WOA ) cells according to their threshold for eliciting a response, stability of the response latency, frequency following and the stimulus-response ratio. Microiontophoretically applied glutamate (GLU) could excite both SOA and WOA neurons. However, the expelling currents needed to activate the SOA cells were often considerably lower than those necessary to excite the WOA cells suggesting higher sensitivity to GLU of those cells which receive a strong fi-fx innervation. Iontophoretically administered glutamic acid diethylester (GDEE) in general reversibly attenuated excitatory responses of LSC cells to GLU but not to acetylcholine. GDEE was also effective in blocking the synaptic responses of SOA septal cells to fi-fx stimuli. In addition, GDEE administered topically reversibly suppressed the field potential induced in the LSC by fi-fx stimulation. These electrophysiological and pharmacological results support recent biochemical observations suggesting that the excitatory innervation of LSC neurons by fi-fx fibers is mediated by GLU or a closely related excitatory amino acid.

Animals↗
PubMed1984

Amino acid neurotransmission between fimbria-fornix fibers and neurons in the lateral septum of the rat: a microiontophoretic study.

We investigated the nature of the excitatory amino acid and the type of amino acid receptor involved in the projection of fimbria-fornix (fi-fx) fibers on neurons in the lateral septal complex (LSC) of the rat. It appeared that neurons which were strongly orthodromically activated (SOA) by stimulation of fi-fx fibers were excited by glutamate (GLU) and aspartate (ASP) at much lower ejecting currents than neurons which were only weakly orthodromically excited. In addition, GLU was a stronger agent than ASP, particularly in SOA septal cells. Two amino acid antagonists tested, glutamic acid diethylester (GDEE) and 2-amino-5-phosphonovaleric acid (2-APV), selectively antagonized responses to the amino acid agonists quisqualate (QUIS) and N-methyl-D-aspartate (NMDA), respectively. They also depressed GLU- and ASP-induced responses, although in that case the antagonists frequently had to be expelled with currents higher than those needed to block QUIS- and NMDA-evoked excitations. Furthermore, GDEE frequently antagonized GLU-induced responses better than ASP-evoked excitations, whereas 2-APV often blocked responses to ASP more effectively than those to GLU. It was observed that GDEE, ejected with currents that blocked responses to QUIS reversibly, decreased the number of synaptic responses induced in SOA cells by fi-fx stimuli. Synaptically induced excitation in these neurons was consistently unaffected by 2-APV, even when the antagonist was expelled with high currents. According to these results, LSC neurons, in particular the SOA neurons, are more readily activated by GLU than by ASP. Monosynaptic excitations elicited in SOA septal cells by fi-fx stimuli appear to be predominantly if not exclusively mediated by QUIS receptors. There are indications that GLU-induced responses in the LSC neurons are presumably mediated by the QUIS receptors. From these data it may be inferred that GLU rather than ASP is the transmitter involved in the projection of fi-fx fibers on LSC neurons.

2-Amino-5-phosphonovalerate↗