Biomedical subjects

T J Teyler

Publications and source records attributed to T J Teyler.

At least 19 recordsLinked to original sources

PubMed1998

GABAa receptor-mediated field potentials are enhanced in area CA1 following prenatal cocaine exposure.

Prenatal cocaine exposure results in several documented changes in neurotransmitter receptor number and structure. Increases have been reported for cortical catecholamine and indoleamine receptor number and binding affinity, in the subunit expression of glutamatergic NMDA and AMPA receptors in the striatum, and in GABA immunoreactivity in the anterior cingulate cortex. We sought information on the functional consequences of cocaine-induced alterations in receptor structure/number. Since hippocampal amino acid neurotransmitters are of critical importance and have been shown to be affected by cocaine, we studied field potentials produced by synaptic activation of isolated glutamatergic NMDA and AMPA receptors and GABAa and GABAb responsive receptors in area CA1 of rabbit hippocampal slices. We found the GABAa receptor population produced significantly larger field potentials in cocaine-exposed offspring compared to controls, while other receptors produced responses similar to controls.

Animals↗

PubMed1998

NMDA receptor-independent LTP in basal versus apical dendrites of CA1 pyramidal cells in rat hippocampal slice.

The ability of hippocampal CA1 basal synapses to express N-methyl-D-aspartate (NMDA) receptor-independent long-term potentiation (non-NMDA LTP) was studied and compared to the simultaneously induced apical dendritic non-NMDA LTP. Non-NMDA LTP in basal and apical dendrites was induced using stimulation pattern similar to the sharp wave-associated CA3 bursts. Basal dendritic non-NMDA LTP was input-specific and displayed similar development and magnitude to the apical dendritic non-NMDA LTP. Both apical and basal dendritic non-NMDA potentiations were inhibited by the voltage-dependent calcium channel (VDCC) inhibitor verapamil and the tyrosine kinase inhibitors genistein and levandustin A. However, the difference in the degree and time course of these inhibitions suggests involvement of distinct mechanisms in the two dendritic subfields.

Animals↗

PubMed1998

Aging differentially alters forms of long-term potentiation in rat hippocampal area CA1.

Long-term potentiation (LTP) of the Schaffer collateral/commissural inputs to CA1 in the hippocampus was shown to consist of N-methyl-D-aspartate receptor (NMDAR) and voltage-dependent calcium channel (VDCC) dependent forms. In this study, the relative contributions of these two forms of LTP in in vitro hippocampal slices from young (2 mo) and old (24 mo) Fischer 344 rats were examined. Excitatory postsynaptic potentials (EPSP) were recorded extracellularly from stratum radiatum before and after a tetanic stimulus consisting of four 200-Hz, 0.5-s trains given 5 s apart. Under control conditions, a compound LTP consisting of both forms was induced and was similar, in both time course and magnitude, in young and old animals. NMDAR-dependent LTP (nmdaLTP), isolated by the application of 10 microM nifedipine (a voltage-dependent calcium channel blocker), was significantly reduced in magnitude in aged animals. The VDCC dependent form (vdccLTP), isolated by the application of 50 microM D,L-2-amino-5-phosphonvalerate (APV), was significantly larger in aged animals. Although both LTP forms reached stable values 40-60 min posttetanus in young animals, in aged animals vdccLTP increased and nmdaLTP decreased during this time. In both young and old animals, the sum of the two isolated LTP forms approximated the magnitude of the compound LTP, and application of APV and nifedipine or genestein (a tyrosine kinase inhibitor) together blocked potentiation. These results suggest that aging causes a shift in synaptic plasticity from NMDAR-dependent mechanisms to VDCC-dependent mechanisms. The data are consistent with previous findings of increased L-type calcium current and decreased NMDAR number in aged CA1 cells and may help explain age-related deficits in learning and memory.

2-Amino-5-phosphonovalerate↗

PubMed1997

The effects of anticonvulsant drugs on NMDA-EPSP, AMPA-EPSP, and GABA-IPSP in the rat hippocampus.

The effects of phenobarbital, phenytoin, and valproic acid on pharmacologically isolated NMDA-EPSP, AMPA-EPSP, and GABA-IPSPs were examined in rat hippocampal slices. Phenobarbital (0.05 mg/ml) had no effect on the NMDA-EPSP, but decreased the slope of the AMPA-EPSP by 13.4% and facilitated the GABA-IPSP slope by 77.12%. Phenytoin (0.02 mg/ml) had no effects on the NMDA-EPSP, AMPA-EPSP, or GABA-IPSP. Valproic acid (0.1 mg/ml) decreased the NMDA-EPSP slope by 14.3%, increased the GABA-IPSP slope by 54.34%, and had no effect on the AMPA-EPSP. These data suggest that the mechanisms of action of these anticonvulsant drugs may be via their actions on different neurotransmitter systems or ion channels.

Animals↗

PubMed1996

In utero cocaine exposure decreases dopamine D1 receptor modulation of hippocampal long-term potentiation in the rabbit.

Cocaine increases the synaptic concentration of neurotransmitters by inhibiting catecholamine transporters. Disturbances of behavior and cellular physiology have been associated with prenatal cocaine exposure and are related to changes in dopamine transmission. Recently we found the magnitude of long-term potentiation (LTP) was greater in hippocampal slices from cocaine exposed offspring. In the hippocampus, D1 dopamine receptor antagonists inhibit the expression of LTP while agonists facilitate it. To test the functionality of the D1 receptor we examined the effect of the D1 antagonist SCH-23390 on LTP using a rabbit model of gestational cocaine exposure. Tetanization during exposure to the D1 antagonist SCH-23390 resulted in a long lasting potentiation in animals prenatally exposed to cocaine while the potentiation of control slices returned to baseline.

Animals↗

PubMed1996

Prenatal cocaine exposure leads to enhanced long-term potentiation in region CA1 of hippocampus.

Cocaine use by pregnant women is currently of concern for its social and economic impact. Clinical studies of cocaine exposed offspring are limited by methodological constraints. In this study we used a rabbit model to examine the effects of gestational cocaine exposure on substrates of learning and memory. Rabbits, 30 to 40 days old, were examined for alterations in synaptic plasticity using an intact hippocampal slice preparation. Extracellular recordings revealed in utero cocaine exposure predisposed slices to larger long-term potentiation compared to controls.

Animals↗

PubMed1996

Inhibition of long-term potentiation development in rat hippocampal slice by alpha 2-macroglobulin, an acute-phase protein in the brain.

Alpha-2-macroglobulin (alpha 2M) in the rat and human brain is an acute-phase protein synthesized primarily by astrocytes, and it has been implicated in Alzheimer's disease and other neuropathological processes. The activated forms of alpha 2M, but not the native form, can suppress the neurite outgrowth of the central neurons, presumably through binding to neurotrophic factors and through direct inhibition of neurotrophic factor receptor signal transduction. Since neurotrophic factors are known to be involved in synaptic plasticity, we tested the effect of both the native and methylamine-activated (MA-alpha 2M) forms of alpha 2M on long-term potentiation (LTP) in area CA1 of adult rat hippocampal slice. Neither native alpha 2M nor MA-alpha 2M had an effect on baseline synaptic transmission. LTP induced by 200-Hz trains in the presence of 1.4 microM or 0.14 microM native alpha 2M was indistinguishable from control LTP. Although the presence of MA-alpha 2M at the same concentrations did not interfere with LTP induction, the development and maintenance of potentiation was blocked in a concentration-dependent time course. Results of this study indicate that the accumulation and activation of alpha 2M with inflammatory neuropathologies such as Alzheimer's disease can inhibit synaptic plasticity, which might partly account for the memory deficits seen in these patients.

Animals↗

PubMed1996

Protein kinase and phosphatase activity regulate the form of synaptic plasticity expressed.

Long-term potentiation (LTP) and long-term depression (LTD) are calcium-dependent forms of synaptic plasticity observed in area CA1 of the hippocampus. Low-frequency tetani (1-5 Hz) activates protein phosphatases to induce LTD, whereas high-frequency tetani (> 25 Hz) activates protein kinases to induce LTP. A tetanus at an intermediate frequency (10 Hz), however, does not result in a change in synaptic efficacy [Dudek and Bear, (1992), Proc. Natl. Acad. Sci. USA, 89:4363-4367]. We hypothesized that the 10-Hz tetanus results in no long-term change in synaptic efficacy due to a balance of the activity of protein phosphatases and protein kinases. We manipulated protein kinase/phosphatase activity at a 10-Hz tetanus to test this hypothesis. A 10-Hz tetanus under normal conditions results in a transient depression which returns to baseline in 25 min. However, inhibiting kinase activity with the protein kinase inhibitor H-7, or decreasing extracellular calcium concentration, results in the 10-Hz tetanus, inducing LTD. Conversely, inhibiting phosphatase activity with the protein phosphatase inhibitor tautomycin, or increasing extracellular calcium concentration, results in the 10-Hz tetanus, inducing LTP. These results suggest that the relative balance of protein kinase and phosphatase activity (and/or the calcium levels activating them) determines the expression of specific forms of synaptic plasticity, and that these forms lie on a continuum.

Animals↗

PubMed1996

The effects of anticonvulsant drugs on long-term potentiation (LTP) in the rat hippocampus.

In hippocampal CA1 area, there are at least two forms of long-term potentiation (LTP): one is N-methyl-D-aspartate (NMDA) receptor-dependent LTP (NMDA LTP), which is induced with a 25 Hz tetanus and blocked by 50 microM 2-amino-5-phosphonovaleric acid (APV); the other is NMDA receptor-independent LTP (VDCC LTP), which is induced by 200 Hz tetanus stimulation in the presence of APV and blocked by nifedipine, a voltage-dependent Ca++ channel (VDCC) blocker, or by the intracellular injection of 1,2-bis(2-Aminophenoxoy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). The effects of anticonvulsant drugs phenobarbital, phenytoin, and valproic acid on both NMDA LTP and VDCC LTP were investigated in rat hippocampal slices. The results showed that 0.1 mg/ml valproic acid significantly altered baseline population spike amplitude by 34.6%, but the other drugs had no significant effect on the baseline population spike amplitude. Phenobarbital (0.025 mg/ml) potently blocked NMDA LTP and inhibited VDCC LTP. Phenytoin (0.02 mg/ml) had no effect on NMDA LTP but reduced VDCC LTP. Valproic acid did not inhibit VDCC LTP, but it abolished the expression of NMDA LTP in a similar manner as H-7, a nonspecific protein kinase C inhibitor. These data suggest that the anti-convulsant effects of these three drugs may be via different cellular mechanisms.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1995

Metabotropic glutamate receptor antagonist, (R,S)-alpha-methyl-4-carboxyphenyglycine, blocks two distinct forms of long-term potentiation in area CA1 of rat hippocampus.

The necessity of metabotropic glutamate receptors (mGluRs) in the induction of long-term potentiation (LTP) has recently been questioned. We examined the effect of (R,S)-alpha-methyl-4-caboxyphenylglycine (MCPG), a selective mGluR antagonist, on two independent forms of LTP. One form induced by a 25 Hz/1 s tetanus is solely N-methyl-D-aspartate (NMDA) receptor-dependent. The other form induced by four 200 Hz/0.5 s bursts in the presence of APV is NMDA receptor-independent. In both paradigms the presence of MCPG prevented the induction of LTP by afferent activation.

Animals↗

PubMed1995

Spermine increases paired-pulse facilitation in area CA1 of hippocampus in a calcium-dependent manner.

The effect of spermine on neurotransmission was studied in area CA1 of the hippocampal slice preparation. Paired-pulse stimulation (20 ms interpulse interval) was delivered to stratum radiatum; the evoked field potential responses were recorded simultaneously from stratum radiatum and from stratum pyramidale. At mM and sub-mM concentrations, spermine decreased the slope of pEPSP in stratum radiatum and the area of the conditioning population spike in stratum pyramidale. Short-latency paired-pulse inhibition of the population spike was converted to facilitation by spermine. These effects of spermine resembled those observed at low calcium concentration. In addition, dose-response and input-output curves determined at various Ca2+ concentrations demonstrated that the depressant effects of spermine were larger at low Ca2+ levels. The results support the notion that spermine competitively blocks presynaptic voltage-sensitive Ca2+ channels, thus causing a decreased release of neurotransmitter. Since spermine is present in brain, it is likely that it is a natural modulator of Ca2+ channels.

Animals↗

PubMed1995

Different mechanisms may be required for maintenance of NMDA receptor-dependent and independent forms of long-term potentiation.

In hippocampal area CA1, long-term potentiation (LTP) is induced by tetanic stimulation protocols that activate N-methyl-D-aspartate (NMDA) receptors. In addition, some stimulation protocols can induce LTP during NMDA receptor blockade. An initial signal in both NMDA receptor-dependent and independent LTPs is increased intracellular Ca2+ concentration in postsynaptic neurons. It therefore seems possible that subsequent steps leading to expression and maintenance of potentiation are shared whether or not LTP is induced through NMDA receptor activation. We tested this hypothesis by applying a broad spectrum protein kinase inhibitor, previously shown to inhibit NMDA receptor-dependent LTP. In agreement with earlier reports, we found that H-7 inhibited NMDA receptor-dependent LTP when applied either during tetanic stimulation, or beginning 30 min following tetanic stimulation. In contrast, NMDA receptor-independent LTP was not inhibited by H-7 applied during or following tetanic stimulation. We also tested for mutual occlusion between NMDA receptor-dependent and independent LTPs. Although induction of NMDA receptor-independent LTP did not occlude later induction of NMDA receptor-dependent LTP, induction of NMDA receptor-dependent LTP did occlude NMDA receptor-independent LTP. While the kinase inhibitor experiment showed a clear difference between NMDA receptor-dependent and independent LTPs, the occlusion experiments suggest an interaction between the signalling pathways for the two LTPs.

Action Potentials↗

PubMed1995

Synaptic plasticity in the hippocampal slice: functional consequences.

There are 3 known forms of synaptic plasticity at CNS synapses: long-term potentiation (LTP) mediated by NMDA receptor activation, LTP mediated by voltage-dependent calcium channel (VDCC) activation, and long-term depression (LTD) mediated by the NMDA receptor. All 3 forms of synaptic plasticity can be observed in hippocampal CAl cells, all are induced by afferent activation, all involve Ca2+ influx, and all activate Ca(2+)-dependent mechanisms. We consider the functional consequences of the presence of 3, sometime opposing, forms of synaptic plasticity at the same synapse. We suggest that the 2 forms of LTP have different consequences for the synapse. We postulate that the co-existence of potentiating and depressing capabilities influences the network processing capabilities of neural networks.

Animals↗

PubMed1994

Spermine depresses NMDA, K/AMPA and GABAA-mediated synaptic transmission in the rat hippocampal slice preparation.

The effects of spermine, an endogenous polyamine, were examined in area CA1 of the rat hippocampal slice preparation. Spermine, at low millimolar concentrations, rapidly and potently depressed NMDA and K/AMPA-mediated population EPSPs, and GABA-mediated monosynaptic population IPSPs. These effects contrast with its well-known potentiation of NMDA currents at lower concentrations. Our results raise the possibility that the large intracellular stores of spermine that are released after various neural insults could act as an endogenous neuroprotective mechanism by limiting excessive calcium entry.

Animals↗

PubMed1994

Antiepileptics inhibit cortical N-methyl-D-aspartate-evoked [3H]norepinephrine efflux.

The antiepileptic drugs phenytoin, valproic acid and phenobarbital were examined for their ability to inhibit N-methyl-D-aspartate (NMDA)-stimulated [3H]norepinephrine efflux from rat brain cortical slices. All three drugs inhibited efflux at varying concentrations. Valproic acid was the most potent and inhibited efflux at 0.01 mg/ml. Phenytoin and phenobarbital inhibited efflux at 0.1 mg/ml. These results indicate that some antiepileptic drugs are capable of inhibiting NMDA receptor function in the therapeutic range.

Animals↗

PubMed1994

The development of GABAB-mediated activity in the rat dentate gyrus.

We examined the effects of GABAB receptor activation in the dentate gyrus of hippocampal slices prepared from 6-8-day-old rat pup. Baclofen (0.25-1.0 microM), a GABAB agonist, rapidly and potently disinhibited the developing dentate, similar to its effect in the mature organism. CGP 35348, a GABAB antagonist, quickly reversed the baclofen-induced disinhibition. However, GABAB antagonists did not reverse long-latency (500-1000 ms IPI) paired-pulse depression, suggesting that it is not caused by a late GABAB-mediated IPSP. GABAB-mediated disinhibition of the dentate gyrus can occur by postnatal day 6, providing a powerful mechanism for altering excitability in the developing hippocampus.

Animals↗

PubMed1994

Laminar pattern of synaptic activity in rat primary visual cortex: comparison of in vivo and in vitro studies employing the current source density analysis.

In the present study we employed current source density analysis to study the major excitatory/inhibitory pathways in rat primary visual cortex in vivo and in vitro. A natural photic stimulus was used in vivo and served as a baseline for understanding the results obtained from in vivo and in vitro studies employing electrical stimulation of the white matter. The temporal pattern of synaptic activity in the cortex revealed an early excitation, characterized by sinks of short duration and high amplitude, that was followed by inhibition, characterized by long lasting, low amplitude active sources. The spatial pattern of this synaptic activity displayed early excitatory inputs to layer IV and lower layer III. Supragranular layers exhibited synaptic activity of longer latency at more superficial layers. The excitatory activity of the infragranular layers was delayed relative to that in layer IV. This spatial and temporal pattern of synaptic activity supports the model of sequential information processing in visual cortex. Based on the results of electrical and photic stimulations in vivo we conclude that electrical stimulation of white matter activate the thalamo-cortical input which results in a similar laminar pattern of postsynaptic activity evoked by photic stimulation. Electrical stimulation revealed additional antidromic and anti-orthodromic activity (collaterals of descending axons to white matter), resulting in the early fast components and the additional activity in layer VI. The major differences between in vivo and in vitro laminar pattern of synaptic activity (applying electrical stimulation) were reduced synaptic activity in layer IV and increased synaptic activity in the infragranular layers in the in vitro preparation. We concluded that the visual cortex slice preparation preserves the major pathways and electrophysiological function of this area. The technical advantages of the cortical slice preparation will facilitate studies and provide additional insight into this complex cortical network.

Animals↗

PubMed1994

Development of inhibitory and excitatory synaptic transmission in the rat dentate gyrus.

We studied the ontogeny of inhibitory and excitatory processes in the rat dentate gyrus by examining paired-pulse plasticity in the hippocampal slice preparation. The mature dentate gyrus produces characteristic paired-pulse responses across a wide range of interpulse intervals (IPI). Paired-pulse effects on population excitatory postsynaptic potential (EPSP) slope and population spike (PS) amplitude were analyzed at postnatal day 6 (PN6), PN7/8, PN9/10, PN15/16, and PN > 60. The synaptic paired-pulse profile (10-5,000 ms IPI) matured by PN7/8. The triphasic pattern of short-latency depression, a relative facilitation at intermediate intervals, and long-latency depression was present at all ages tested. Paired-pulse effects on granule cell discharge indicated the presence of weak short-latency (20 ms IPI) inhibition at PN6, the earliest day that a population spike could be evoked. By PN7/8, short-latency inhibition was statistically equivalent to the mature dentate gyrus. Long-latency (500-2,000 ms IPI) PS inhibition was present, and equal to the mature dentate gyrus by PN6. The most consistent difference between the mature and developing dentate gyrus occurred at intermediate IPIs (40-120 ms) where spike facilitation was significantly depressed in the development groups. The studies indicate that short-term plasticity matures rapidly in the dentate gyrus and suggest that the inhibitory circuitry can function at a surprisingly early age.

Action Potentials↗