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Biomedical subjects

J J Wagner

Publications and source records attributed to J J Wagner.

At least 19 recordsLinked to original sources
PubMed2004

Modulation of long-term potentiation in the rat hippocampus following cocaine self-administration.

Long-lasting neuroadaptations that occur during drug use and remain after withdrawal are thought to contribute to the persisting and compulsive nature of drug addiction and relapse. At the molecular and cellular levels, mechanisms that have been implicated in the normal process of memory formation are increasingly being identified as potential contributors to the persistence of the addicted state. To investigate the effect of cocaine self-administration on synaptic plasticity, rats were allowed to self-administer 0.5 mg/kg/infusion cocaine or 0.9% NaCl during 90 min sessions for 15 consecutive days. These cocaine and saline self-administration subjects were then restricted to their home cages for 3, 30, or 100 days (3, 30, and 100 day cocaine/saline withdrawal groups) before the assessment of the induction and reversal of long-term potentiation (LTP) in the CA1 region of hippocampal slices. The magnitude of LTP was increased in the 3-day cocaine withdrawal group as compared with the 3-day saline withdrawal group, but this effect was short lived, as the 30-day cocaine and saline withdrawal groups exhibited similar LTP magnitudes. Interestingly, LTP was significantly decreased in the 100-day cocaine withdrawal group compared with the 100-day saline withdrawal group. These results support the hypothesis that the capacity for LTP is persistently altered after withdrawal from exposure to an addictive substance. In addition, this alteration can be differentially expressed such that depending upon the duration of the withdrawal period following the last drug exposure, LTP may be enhanced, unchanged, or suppressed.

Adaptation, Physiological↗
PubMed2001

Effects of water sulfate concentration on performance, water intake, and carcass characteristics of feedlot steers.

Two hundred forty single-source, cross-bred steers (304 kg) were used to evaluate the effects of various water sulfate concentrations on performance, water intake, and carcass characteristics of feedlot steers. Cattle were stratified by weight and assigned within weight blocks to five water treatments. Averaged over time, actual water sulfate concentrations (+/- SEM) were 136.1 (+/- 6.3), 291.2 (+/- 15.3), 582.6 (+/- 16.9), 1,219.2 (+/- 23.7), and 2,360.4 (+/- 68.2) mg/L, respectively. Weather-related data were recorded. Increasing water sulfate concentration resulted in linear decreases in ADG (P < 0.01) and gain:feed ratio (P < 0.01) and a quadratic effect on water intake (P = 0.02) and tended to quadratically increase then decrease DMI (P = 0.13). Sulfate x period interactions were evident for DMI (P = 0.01), ADG (P < 0.01), and feed efficiency (P < 0.01). Time had quadratic effects on DMI, water intake, ADG, and feed efficiency (P < 0.01 for all models). Increasing water sulfate concentration resulted in linear decreases in final weight, hot carcass weight, and dressing percentage, a linear increase in longissimus muscle area, and a quadratic effect on fat thickness over the 12th rib and predicted yield grade (P < 0.05 for all dependent variables). Mean daily temperature explained 25.7% of the observed variation in water intake. Other factors that explained a significant (P < 0.01) amount of variation in water intake were BW, DMI, water sulfate concentration, barometric pressure, wind speed, and humidity. High water sulfate concentrations had a significant and deleterious effect on performance and carcass characteristics of feedlot steers. Increasing the sulfate concentration in water may have resulted in a functional water restriction early in the trial when ambient temperatures were greatest. However, toward the latter stages of the trial, cattle supplied higher-sulfate water had higher ADG and FE. These improvements later in the trial may represent compensatory gain associated with decreased ambient temperature and water requirements. Averaged over time, a water sulfate concentration of greater than 583 mg/L, equivalent to 0.22% of the diet, decreased feedlot performance.

Age Factors↗
PubMed2001

Opioid-mediated facilitation of long-term depression in rat hippocampus.

Previous studies have demonstrated that opioid substances are often inhibitors of the gamma-aminobutyric acid (GABA) transmitter system in the hippocampal formation, and that GABA-mediated inhibition is a potent modulator of synaptic plasticity. Field excitatory postsynaptic potentials were recorded from the CA1 region of rat hippocampal slices in response to stimulation of the Schaffer collateral fibers to monitor the effects of acute opioid exposure on the induction of long-term depression (LTD) at excitatory synapses in the stratum radiatum. Exogenous application of a selective mu-opioid agonist resulted in a greater than 2-fold enhancement of LTD, whereas kappa- and delta-agonists did not significantly affect LTD magnitude. Costimulation of the opioid peptide-containing stratum lacunosum-moleculare during LTD induction also resulted in a facilitation of LTD in the stratum radiatum, an effect prevented by prior administration of an opioid antagonist. These results suggest that both exogenously applied and endogenously released opioids can act to facilitate LTD of the Schaffer collateral input to CA1 pyramidal neurons.

Analgesics, Opioid↗
PubMed1999

Priming-induced shift in synaptic plasticity in the rat hippocampus.

The activity history of a given neuron has been suggested to influence its future responses to synaptic input in one prominent model of experience-dependent synaptic plasticity proposed by Bienenstock, Cooper, and Munro (BCM theory). Because plasticity of synaptic plasticity (i.e., metaplasticity) is similar in concept to aspects of the BCM proposal, we have tested the possibility that a form of metaplasticity induced by a priming stimulation protocol might exhibit BCM-like characteristics. CA1 field excitatory postsynaptic potentials (EPSPs) obtained from rat hippocampal slices were used to monitor synaptic responses before and after conditioning stimuli (3-100 Hz) of the Schaffer collateral inputs. A substantial rightward shift (>5-fold) in the frequency threshold between long-term depression (LTD) and long-term potentiation (LTP) was observed <1 h after priming. This change in the LTD/P crossover point occurred at both primed and unprimed synaptic pathways. These results provide new support for the existence of a rapid, heterosynaptic, experience-dependent mechanism that is capable of modifying the synaptic plasticity phenomena that are commonly proposed to be important for developmental and learning/memory processes in the brain.

2-Amino-5-phosphonovalerate↗
PubMed1998

N- and L-type calcium channel involvement in depolarization-induced suppression of inhibition in rat hippocampal CA1 cells.

1. We investigated depolarization-induced suppression of inhibition (DSI) under whole-cell voltage clamp in CA1 pyramidal neurons of rat hippocampal slices. DSI, a transient reduction in monosynaptic evoked GABAAergic IPSCs lasting for approximately 1 min, was induced by depolarizing the pyramidal cell to -10 or 0 mV for 1 or 2 s. 2. Raising extracellular Ca2+ concentration increased DSI, and varying the DSI-inducing voltage step showed that the voltage dependence of DSI was like that of high-voltage-activated Ca2+ channels. 3. The P- and Q-type Ca2+ channel blocker omega-agatoxin TK (200 nM and 1 microM) and the R- and T-type Ca2+ channel blocker Ni2+ (100 microM) reduced IPSCs without reducing DSI. 4. The specific N-type Ca2+ channel antagonist omega-conotoxin GVIA (250 nM) reduced IPSC amplitudes and almost completely abolished DSI. 5. Blocking L-type Ca2+ channels with nifedipine (10 microM) had no effect on IPSCs or DSI induced by our standard protocol, but reduced DSI induced by the unclamped Na+- and Ca2+-dependent spikes that occurred when 2(triethylamino)-N-(2,6-dimethylphenyl)acetamide (QX-314) was omitted from the recording pipette solution. 6. Although intracellular Ca2+ stores were not measured, DSI was not affected by cyclopiazonic acid (CPA, 20-40 microM), a blocker of Ca2+ uptake into intracellular stores. 7. We conclude that DSI is initiated by Ca2+ influx through N- and, under certain conditions, L-type Ca2+ channels.

Animals↗
PubMed1998

Primed facilitation of homosynaptic long-term depression and depotentiation in rat hippocampus.

Previous studies have demonstrated that prior synaptic activity can influence the subsequent induction of synaptic plasticity in the brain. Such temporal modulation of synaptic plasticity has been called "metaplasticity." In this report, we describe the facilitatory effects of high-frequency stimulation on the induction of homosynaptic long-term depression (LTD) in the CA1 region of the rat hippocampus. The LTD induced by low-frequency stimulation (1 Hz) protocols was found to be homosynaptic and NMDA receptor-dependent. The facilitatory effects of the high-frequency stimulation-induced priming event itself were found to be NMDA receptor-independent and to have a duration of at least 90 min. The effects of priming also were heterosynaptic, because the induction of synaptic plasticity by low-frequency stimulation was enhanced at an unprimed synaptic pathway after the priming of an independent pathway. In addition to enhancing LTD, priming also enhanced the reversal of long-term potentiation elicited by a 5 Hz depotentiation protocol. Our results provide examples of how metaplasticity may play a key role in the ongoing modulation of the induction and stabilization of alterations in synaptic strength.

2-Amino-5-phosphonovalerate↗
PubMed1996

Retrograde signalling in depolarization-induced suppression of inhibition in rat hippocampal CA1 cells.

1. We have investigated the phenomenon of 'depolarization-induced suppression of inhibition' (DSI) using whole-cell voltage-clamp techniques in Ca1 pyramidal cells of rat hippocampal slices. DSI was induced by eliciting voltage-dependent calcium (Ca2+) currents with 1 s voltage steps of +60 to +90 mV from the holding potential. DSI was apparent as a reduction in synaptic GABAA responses for a period of about 1 min following the voltage step. 2. TTX-sensitive spontaneous IPSCs (sIPSCs) were susceptible to DSI, while TTX-resistant miniature inhibitory postsynaptic current (mIPSCs) were not. Miniature IPSCs are ordinarily infrequent and independent of external Ca2+ in the CA1 region. To increase the frequency of mIPSCs and to induce a population of Ca(2+)-sensitive mIPSCs, we increased the bath K+ concentration to 15 mM. The increased mIPSCs were also insensitive to DSI, however. 3. T whole-cell pipette-filling solution contained 5 mM 2(triethylamino-N-(2,6-dimethyl-phenyl)acetamide (QX-314) to block voltage-dependent Na+ currents and caesium to block K+ currents. Nevertheless, bath application of 50 microM 4-aminopyridine (4-AP) or 250 nM veratridine both clearly reduced DSI, evidently by acting at presynaptic sites. 4. The amplitudes of monosynaptically evoked IPSCs (elicited in the presence of 10 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 50 microM 2-amino-5-phosphonovaleric acid (APV)) were dramatically reduced during the DSI period. Weak stimulation produced small IPSCs and occasional 'failures' of transmission during the control period. The percentage of failures increased markedly during the DSI period. Moderate-intensity stimulation produced larger IPSCs that were often composed of distinguishable multiquantal components. All-or-none failures of multiquantal IPSC components also occurred during DSI. 5. The degree of paired-pulse IPSC depression did not change during DSI, whereas it was decreased, as expected, by baclofen. 6. We conclude that the data represent novel evidence that DSI is mediated by a retrograde signalling process possibly involving presynaptic axonal conduction block.

Animals↗
PubMed1996

Increased neuronal excitability during depolarization-induced suppression of inhibition in rat hippocampus.

1. Depolarization-induced suppression of inhibition (DSI) is a form of plasticity of gamma-amino-butyric acid (GABAA)-mediated (henceforth 'GABAergic') responses in the CNS. We made whole-cell recordings from CA1 pyramidal neurons to investigate the effects of DSI on excitatory synaptic transmission in the hippocampal slice preparation. 2. Significant enhancement of the voltage-clamped excitatory postsynaptic current (EPSC) occurs during DSI of the temporally overlapping inhibitory postsynaptic current. With high levels of calcium chelators in the pipette solution, or bath application of bicuculline, EPSC enhancement is blocked, suggesting that it results from DSI and that the DSI process selectively affects GABAergic, but not glutamatergic, transmission. 3. The probability of synaptically evoked action potential firing is increased during DSI under current clamp. DSI could influence other excitatory phenomena as well.

Animals↗
PubMed1996

Homosynaptic LTD and depotentiation: do they differ in name only?

Long-term depression (LTD) now occupies a major place in theories of the cellular basis of learning and memory and other nervous system phenomena involving persistent changes in synaptic responsiveness. LTD can be induced using a variety of stimulation paradigms. Homosynaptic LTD in this review refers to a depression of basal responses that is restricted to the pathway that has been stimulated by a low-frequency (1 Hz) stimulus train. Despite the intensive interest in LTD, there has been controversy about the ease with which LTD can be induced and reports range from no success to routine success. There has been much less controversy about a related form of response depression now called "depotentiation" which shares many similarities with LTD. Depotentiation is the response reduction that affects, not the basal responses affected by LTD, but responses that have been increased by the process of long-term potentiation (LTP). LTD and depotentiation can be induced by similar stimulation and have many biochemical properties in common, but it has not been clear whether or not they represent the same phenomenon, in part because it often occurs that the same preparation that does not undergo LTD readily expresses depotentiation. We review work that indicates that the major differences between LTD and depotentiation involve age-dependence, the need for priming stimulation and sensitivity to GABA receptor antagonists. We present a hypothetical model that can reconcile the apparent disparities between LTD and depotentiation.

Animals↗
PubMed1996

Whole-cell voltage-clamp investigation of the role of PKC in muscarinic inhibition of IAHP in rat CA1 hippocampal neurons.

Muscarinic, cholinergic inputs, largely from the medial septum, have pronounced effects on hippocampal cell excitability. A major effect of synaptically released ACh is block of the slow Ca(2+)-dependent potassium current, called IAHP. Protein kinase C exists in the hippocampus in high concentrations, its activation blocks IAHP, and it has been suggested as a mediator of the muscarinic-receptor-(mAChR)-mediated actions. Using conditions that produce a stable postspike afterhyperpolarizing current (IAHP) in whole-cell recordings from CA1 hippocampal pyramidal neurons in the slice preparation, we have investigated the role of PKC in the cholinergic inhibition of IAHP mediated by mACHRs. Bath application of the general kinase inhibitor, H7, had no effect on inhibition of IAHP by carbachol, although H7 dramatically reduced inhibition of IAHP by the phorbol ester, phorbol-12, 13-diacetate (PDA). Another muscarinic response thought to be mediated by PKC-inhibition of GABAB-mediated hyperpolarization-was reduced by extracellular H7 treatment, suggesting that the coupling between mAChRs and protein kinase activity was maintained in whole-cell recordings. We also discovered that PDA does not mediate its effects on IAHP directly. Intracellular perfusion of high concentrations of H7 (10 mM) or the specific PKC inhibitor, PKCI(19-31) (1 mM), did not prevent inhibition of IAHP by PDA. These results are consistent with an indirect, presynaptic action of phorbol esters on IAHP, possibly mediated through enhanced release of neurotransmitter from surrounding cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1995

GABAergic and developmental influences on homosynaptic LTD and depotentiation in rat hippocampus.

Low-frequency (1 Hz) stimulation (LFS) was used to elicit long-term depression (LTD) or depotentiation of excitatory transmission of the Schaffer collateral pathway in the CA1 region of the rat hippocampus. Both LTD and depotentiation were found to be homosynaptic and NMDA receptor (NMDAR) dependent. As NMDAR activation can be modulated by the inhibitory GABAergic system, we tested the hypothesis that GABA plays a role in regulating these phenomena. The GABAB antagonist CGP 35348 significantly inhibited LTD, but not depotentiation, in slices from young animals (indicating that the GABAB-mediated contribution was altered following HFS). The ability to express LTD was found to be developmentally dependent, as young animals (16-22 d) consistently expressed LTD, whereas LTD was not expressed in naive slices taken from mature (5-10 weeks) animals. The GABAA antagonist bicuculline did not affect LTD in the young animals, but did enhance LTD expression in slices from mature animals. LFS was also effective in decreasing, or depotentiating, responses that had undergone long-term potentiation (LTP) by high-frequency stimulation (HFS). In contrast to LTD, depotentiation was consistently expressed in slices from both the young and mature groups. Moreover, following an HFS train, LTD (compared to initial baseline response) could be induced in mature slices previously unable to express LTD in the naive state. Thus, the role of GABA in modulating the effects of LFS varied with the prior synaptic activity in the slice as well as with the maturity of the animal. Our results suggest that the influence of both age and prior synaptic activity (i.e., HFS) on LTD induction can be explained by changes in GABAergic systems in young versus mature, and naive versus tetanized slices.

Aging↗
PubMed1994

GTP modulates run-up of whole-cell Ca2+ channel current in a Ca(2+)-dependent manner.

1. Whole-cell voltage-clamp recordings were obtained from CA1 neurons acutely dissociated from rat hippocampus to study the effects of guanosine 5'-triphosphate (GTP) on the gradual increase in Ca2+ channel current amplitude that takes place over several minutes after breaking in to whole-cell mode ("run-up"). 2. Including GTP (500 microM) in the patch pipette significantly prolonged the duration of run-up of peak Ca2+ channel current to its maximum value compared with controls without GTP when the recording solutions contained Ca2+. On the other hand, GTP significantly enhanced run-up when Mg2+ and Ba2+ were substituted for intracellular and extracellular Ca2+, respectively. 3. The enhancement of run-up of the current in the Mg/Ba condition appeared to be due both to an initial increase in current amplitude that was complete within 30 s after break in and to a more rapid initial rate of run-up when compared with the Ca2+ condition. GTP did not affect the absolute maximum amplitudes of the currents in either Ca2+ or Ba2+ conditions. 4. We conclude that an early GTP-dependent modulation of Ca2+ channel current is qualitatively altered, depending on whether Ca2+ or Ba2+ is used as the charge carrier. Evidence of this modulation is apparent within seconds after rupture of the membrane patch. Conceivably, influences occurring during the period of "equilibration" with electrode contents could alter subsequent regulatory steps.

Animals↗
PubMed1994

Kappa opioids inhibit induction of long-term potentiation in the dentate gyrus of the guinea pig hippocampus.

NMDA receptor-mediated long-term potentiation (LTP) of dentate granule cell responses to perforant path stimulation was inhibited by the kappa 1 opioid receptor agonist U69,593. This inhibition was reversed stereospecifically by naloxone and blocked by the selective kappa 1 antagonist norbinaltorphimine (NBNI). NBNI, by itself, had no effect on LTP induced by threshold stimulation but significantly enhanced LTP from more prolonged stimulation. This effect of NBNI suggests that endogenous opioids can regulate LTP in the dentate gyrus. In support of this hypothesis, stimulation of dynorphin-containing fibers also blocked LTP production in an NBNI-sensitive manner. Finally, dynorphin-mediated inhibition of LTP acts primarily on mechanisms of induction rather than maintenance or expression, since dynorphin released immediately before, but not immediately after, perforant path stimulation blocked LTP. Thus, exogenous and endogenous kappa opioids can inhibit induction of long-term potentiation at the perforant path-granule cell synapse and may therefore regulate plastic changes in synaptic transmission in a brain region thought to play an important role in processes of both learning and memory and epileptogenesis.

Animals↗
PubMed1993

Endogenous dynorphins inhibit excitatory neurotransmission and block LTP induction in the hippocampus.

Although anatomical and neurochemical studies suggest that endogenous opioids act as neurotransmitters, their roles in normal and pathophysiological regulation of synaptic transmission are not defined. Here we examine the actions of prodynorphin-derived opioid peptides in the guinea-pig hippocampus and show that physiological stimulation of the dynorphin-containing dentate granule cells can release endogenous dynorphins, which then activate kappa 1 opioid receptors present in the molecular layer of the dentate gyrus. Activation of kappa 1 receptors by either pharmacologically applied agonist or endogenously released peptide reduces excitatory transmission in the dentate gyrus, as shown by a reduction in the excitatory postsynaptic currents evoked by stimulation of the perforant path, a principal excitatory afferent. In addition, released dynorphin peptides were found to block the induction of long-term potentiation (LTP) at the granule cell-perforant path synapse. The results indicate that endogenous dynorphins function in this hippocampal circuit as retrograde, inhibitory neurotransmitters.

Action Potentials↗
PubMed1992

Endogenous opioid regulation of norepinephrine release in guinea pig hippocampus.

Release of endogenous norepinephrine was detected in guinea pig hippocampal slices using a radioligand displacement assay. Focal electrical stimulation released endogenous norepinephrine and caused a calcium-dependent reduction in specific [3H]propranolol binding at beta-adrenergic receptors in the brain slice. The mu-opioid agonist PL017 decreased norepinephrine release, and the inhibition by PL017 could be blocked by the opioid antagonist naloxone. Endogenous opioid peptides concomitantly released by tissue stimulation also decreased norepinephrine release in a naloxone-sensitive manner. These results support the hypothesis that endogenous opioids can regulate excitability in the hippocampus by presynaptic modulation of norepinephrine release.

Animals↗
PubMed1992

GnRH in the infundibular stalk-median eminence is related to percentage body fat in carcasses of beef cows.

Mature Hereford cows (n = 28) were used to determine the effect of percentage body fat on secretion of LH and content of GnRH in the infundibular stalk-median eminence (ISME). Cows were fed to maintain, lose, or gain weight to achieve body condition scores (BCS; 1 = emaciated; 9 = obese) of 3 to 7. Then cows were fed to maintain weight and body condition. Before slaughter, estrus was synchronized using two injections of prostaglandin F2 alpha(PGF) 11 d apart. Five d after the second PGF injection, cows were given 100 micrograms of GnRH (im) and serum samples were obtained. LH was quantified using RIA. The anterior pituitary and ISME were obtained within 45 min of death. Anterior pituitary weight and LH concentration, total GnRH in the ISME, total carcass fat, and percentage carcass fat were determined. BCS of cows at the time of slaughter influenced percentage carcass fat (P less than .001), total GnRH in the ISME (P less than .02), and maximum LH after GnRH treatment (P less than .09), but did not influence pituitary weight or concentration of LH in the pituitary. Content of GnRH in the ISME averaged 76 +/- 12, 32 +/- 14, 27 +/- 13, and 24 +/- 13 ng for cows with BCS of 3, 5, 6, and 7, respectively. BCS was correlated (P less than .001) with percentage carcass fat (r = .94) and total fat in the carcass (r = .92). Total GnRH in the ISME was negatively correlated (P less than .005) with BCS (r = -.54), percentage carcass fat (r = -.55), and total carcass fat (r = -.49).(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1992

Kappa-opioids decrease excitatory transmission in the dentate gyrus of the guinea pig hippocampus.

In the guinea pig hippocampus, kappa 1-opioid binding sites were primarily localized in the molecular layer of the dentate gyrus as shown by autoradiography using either the kappa 1-selective radioligand 3H-U69,593 or the nonselective radioligand 3H-diprenorphine in the presence of unlabeled mu- and delta-blocking ligands. In this region, the electrophysiological effects of kappa 1-receptor activation were identified using extracellular and intracellular recordings of dentate granule cell responses. The amplitude of the extracellularly recorded population spike was reduced by U69,593 with an EC50 of 26 nM; this effect was reversible and blocked by the opioid antagonist naloxone. The kappa 1-selective antagonist norbinaltorphimine also blocked the effect of U69,593 with an apparent equilibrium dissociation constant (Ki) of 0.26 nM determined by Schild analysis in the physiologic assay. This value agreed well with the Ki for norbinaltorphimine at kappa 1-binding sites measured by radioligand binding displacement (0.24 nM). These results indicate that the electrophysiologic response observed was likely mediated by kappa 1-receptors. As seen with U69,593, dynorphin B, an endogenous opioid peptide that is present in the dentate gyrus, also inhibited the population spike response. mu- and delta-selective opioid agonists had no effect on the amplitude of the maximally evoked response. Intracellular recordings of dentate granule cells showed no direct effects of U69,593 on the granule cells themselves. However, analysis of synaptic potentials revealed that U69,593 significantly reduced the amplitude of glutaminergic EPSPs evoked by afferent stimulation without affecting IPSP amplitudes. The specific effect of U69,593 application on granule cell EPSPs indicates that presynaptic kappa 1-receptor activation inhibits glutamate release from perforant path terminals in the molecular layer of the dentate gyrus. These results suggest that endogenous dynorphins present in the granule cells may act as feedback inhibitors of the major excitatory input to the dentate gyrus.

Action Potentials↗