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W A Wilson

Publications and source records attributed to W A Wilson.

At least 73 records · Page 4Linked to original sources
PubMed1995

Induction and reversal of long-term potentiation by low- and high-intensity theta pattern stimulation.

Reversal of long-term potentiation by low-frequency stimulation is often referred to as depotentiation. However, it is not clear whether depotentiation induced by low-frequency stimulation and long-term depression (LTD) induced by similar stimuli are distinct phenomena. We have performed a series of experiments in area CA1 of rat hippocampal slices in which a single pattern of theta-burst (TB) stimulation (Larson, et al., 1986; Staubli and Lynch, 1987) was found to produce either LTP or reversal of LTP depending on the intensity of the stimulation. TB stimulation (10 trains consisting of 4 pulses at 100 Hz, 200 msec apart) delivered at test pulse-intensity induced LTP. However, the same stimulation delivered at a higher intensity (10 times that of the test pulse, evoking a maximal response) did not induce LTP or depression of control responses, but produced lasting depression of previously potentiated responses. This reversal of LTP (TB depotentiation) was observed when the stimulus was delivered between 0.5 and 110 min after induction of LTP. TB depotentiation was reversible, cumulative and saturable when high-intensity TB trains were delivered in succession. TB depotentiation was also blocked by antagonists at NMDA receptors. Low-frequency (1 Hz) stimulation induced LTD, indicating that responses were not already maximally depressed. In addition, high-intensity TB stimulation did not reverse LTD. These results suggest that depotentiation induced by maximal TB stimulation and LTD induced by low-frequency stimulation are distinct phenomena, yet share some characteristics common to forms synaptic plasticity mediated by NMDA receptor activation.

Animals↗
PubMed1995

Familial anticardiolipin antibodies and C4 deficiency genotypes that coexist with MHC DQB1 risk factors.

OBJECTIVE: To investigate the familial basis of antiphospholipid antibodies by studying putative risk factors at the C4 and MHC class II loci. METHODS: Autoimmune diseases, anticardiolipin (aCL) and other autoantibodies were studied in 38 first and 2nd degree family members of 3 index cases selected for primary antiphospholipid syndrome (APS) and 33 controls. C4 protein phenotyping and restriction fragment length polymorphism analysis of C4 and MHC class II loci were performed. RESULTS: Nineteen family members (46%) had autoimmune diseases or autoantibodies; aCL were present in 10 family members, 4 of whom had primary APS. Each family had 2 or more subjects with aCL. Among 22 independent haplotypes in family members, there was a high frequency of C4A and C4B deficiency alleles (0.41 vs 0.18 in 66 controls, p = 0.03) and a strong trend toward an increase in MHC DQB1 putative risk factors that share the TRAELDT structural domain. This DQB1 structural domain was present in 4/5 different haplotypes that contained a C4B deficiency genotype; however, neither of 2 different haplotypes with a C4A deletion (one being a common ancestral haplotype) contained this DQB1 putative risk factor. Among the 10 family members who had aCL, 10/20 haplotypes contained a C4 deficiency genotype; moreover, the DQB1 putative risk factor was present in all 16 MHC haplotypes that did not contain a C4A deletion. CONCLUSION: In these families, expression of an autoimmunity trait as aCL antibody appears to be associated with the coexistence of C4 deficiency alleles with DQB1 alleles that contain the TRAELDT structural domain.

Adolescent↗
PubMed1995

Specificities and characteristics of beta 2 glycoprotein I-induced antiphospholipid antibodies.

Autoimmune antiphospholipid antibodies are associated with thrombosis, thrombocytopenia, and recurrent fetal death. These antibodies are thought to be directed against an epitope formed by phospholipids complexed with beta 2 glycoprotein I (beta 2GPI), a plasma protein with affinity for phospholipids. By immunizing mice and rabbits with heterologous beta 2GPI, we produced antibodies that bind strongly to acidic phospholipids in addition to binding to beta 2GPI. To evaluate the specificities of these antibodies, we passed the serum of a rabbit immunized with beta 2GPI through a cardiolipin (CL) affinity column and studied the bound and fall-through antibodies for binding to CL and beta 2GPI by ELISA. The results demonstrated the presence of two populations of antibodies, one with specificity for beta 2GPI alone without binding to phospholipids and the other with specificities for both CL and beta 2GPI. These dual-specificity antibodies are similar to the antiphospholipid antibodies present in autoimmune diseases because they bind to other acidic phospholipids in addition to CL and because their binding to phospholipids is enhanced by beta 2GPI and blocked by placental anticoagulant protein I (annexin V).

Animals↗
PubMed1994

Temporally distinct mechanisms of use-dependent depression at inhibitory synapses in the rat hippocampus in vitro.

1. Gamma-aminobutyric acid-B (GABAB) autoreceptor-dependent and -independent components of paired-pulse depression (PPD) at inhibitory synapses in area CA3 of the rat hippocampus were studied using whole-cell recording techniques. Inhibitory fibers were activated directly in the presence of the ionotropic glutamate receptor antagonists 6,7-dinitroquinoxaline-2,3,dione (20 microM) and D-2-amino-5-phosphonovalerate (20 microM). 2. When pairs of monosynaptic inhibitory postsynaptic currents (eIPSCs) were evoked with an interstimulus interval of 200 ms, the amplitude of the second response (eIPSC2) was depressed when compared with the first (eIPSC1). The GABAB receptor agonist baclofen (10 microM) depressed both responses, but eIPSC1 was depressed more than eIPSC2, resulting in PPD that was comparatively smaller. Addition of the GABAB receptor antagonist CGP 55845A (1 microM) completely reversed depression of eIPSC1 by baclofen and increased the amplitude of eIPSC2 above the control value, such that PPD in the combination of baclofen and CGP 55845A was equivalent to that in baclofen alone. The ratio eIPSC2/eIPSC1 was 0.64 under control conditions, 0.77 in the presence of baclofen, and 0.79 in the presence of baclofen and CGP 55845A. These results demonstrate the existence of two components of PPD at inhibitory synapses, one that depends on activation of GABAB autoreceptors (GABAB receptor-dependent PPD) and one that does not (GABAB receptor-independent PPD). 3. When the number of inhibitory fibers activated was lowered by decreasing the stimulus intensity, eIPSC2/eIPSC1 was 0.76 under control conditions, 0.75 in the presence of baclofen, and 0.76 in the presence of baclofen and CGP 55845A. These results indicate that GABAB receptor-dependent PPD requires activation of several presynaptic inhibitory neurons, whereas GABAB receptor-independent PPD does not. 4. The time-courses of the GABAB-dependent and -independent components of PPD were compared by varying the interstimulus interval in the absence and presence of CGP 55845A. GABAB-dependent PPD was maximal at an interstimulus interval of 100 ms and was undetectable at 1 s. In contrast, GABAB-independent PPD was maximal at 5 ms and 1 s, was slightly less pronounced at intermediate intervals (50-200 ms), and was present at intervals as long as 5 s. 5. GABAB-independent PPD was not blocked by antagonists at opioid receptors (10 microM naloxone) or muscarinic acetylcholine receptors (10 microM atropine). GABAB-independent PPD could not be accounted for by a decrease in driving force because of Cl- redistribution.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Seizure-like activity disrupts LTP in vitro.

Amnesia is one of the most common consequences of seizures. We modelled this phenomenon in the in vitro hippocampal slice preparation by examining effects of seizure-like activity on long-term potentiation (LTP). LTP is an expression of neuronal plasticity which has been correlated with learning. Electrographic seizures (EGSs) were induced in area CA1 by electrical stimulation of CA3. Trains of tetanic stimuli were then immediately delivered to the Schaffer collateral-CA1 pathway in order to induce LTP. The subsequent LTP in these test slices was significantly lower in magnitude compared to LTP in control slices (with no EGSs). LTP could be successfully induced in test slices 1 h after the EGS. EGSs alone produced no long-lasting effect on baseline responses. These results indicate that the hippocampal slice preparation may serve as a model system in which to study the mechanisms by which seizures can disrupt neuronal plasticity.

Amnesia↗
PubMed1993

Proconvulsant and anticonvulsant properties of ethanol: studies of electrographic seizures in vitro.

Recent studies have demonstrated that ethanol is a potent blocker of N-methyl-D-aspartate (NMDA) receptor mediated responses. It is well known that neuroplasticity processes depend on the activation of the NMDA type of excitatory amino acid receptor. We have used an in vitro model of electrographic seizures (EGS), a neuroplasticity process, to examine the effect of varying ethanol concentrations. In the present experiment, slices of rat hippocampus were electrically stimulated to produce stimulus train-induced epileptiform bursting in area CA3. EGS duration and intensity was enhanced by 10 mM ethanol, whereas increasing the concentration of ethanol (60-300 mM) attenuated established EGSs. Ethanol also raised the threshold to elicit an EGS. Removal of low ethanol concentrations resulted in a hyperexcitable state, with increased EGS duration and intensity. These results reflect acute biphasic effects of ethanol across concentrations, and withdrawal hyperexcitability. The effects of ethanol on EGSs, at concentrations which elicit intoxication but not anesthesia (< 75 mM), resemble the actions produced by NMDA antagonists on EGSs. Therefore the effects of ethanol on stimulus train-induced EGSs may be mediated through an action at the NMDA receptor complex.

2-Amino-5-phosphonovalerate↗
PubMed1993

Antiepileptic effects of GABAb receptor activation in area CA3 of rat hippocampus.

The role of GABAb receptor activation in the expression of both interictal and ictal phenomena was investigated in slices of area CA3 of the rat hippocampal formation. Interictal-like bursts occurred following application of high frequency trains to the Schaffer collaterals. When two bursts were triggered using paired stimuli, profound depression of the second burst was seen 150-600 ms following the first burst. GABAb receptor antagonists potently reversed the paired pulse depression of the interictal-like bursts. Reversal of the paired depression was also accomplished by increasing the extracellular concentration of K+ by 2-3 mM. Additional experiments were performed in area CA3 to determine the role of GABAb receptor activation on the expression of ictal phenomena. Electrographic seizures (EGSs) were induced by application of high frequency trains. 2-Hydroxy-saclofen (200 microM) significantly decreased the duration of trains required to elicit EGSs. Taken together, these data suggest that GABAb receptor activation has potent inhibitory effects on both ictal and interictal-like events.

Animals↗
PubMed1993

Heterogeneity in presynaptic regulation of GABA release from hippocampal inhibitory neurons.

Release of GABA from the terminals of hippocampal inhibitory neurons is inhibited by activation of GABAB autoreceptors and mu opioid receptors. However, it is not known whether these presynaptic processes affect all inhibitory synapses equally. We examined the effects of the GABAB receptor agonist baclofen and the mu opioid receptor agonist DAGO on postsynaptic currents evoked by minimal stimulation of inhibitory fibers (meIPSCs) in area CA3. Baclofen reversibly depressed approximately half of the meIPSCs evoked in the stratum pyramidale. The remaining meIPSCs were unaffected despite a coincident depression of spontaneous IPSCs. In contrast, all meIPSCs were depressed by DAGO. In addition, minimal stimulation in the stratum radiatum evoked meIPSCs that were always depressed by baclofen. These results indicate that regulation of GABA release by GABAB autoreceptors occurs at a subset of inhibitory synapses and that GABAB-resistant inhibitory synapses are located on pyramidal neuron somata. Hippocampal inhibitory neurons may be heterogeneous with respect to presynaptic receptor-mediated regulation of GABA release.

Analgesics↗
PubMed1993

Discrimination of post- and presynaptic GABAB receptor-mediated responses by tetrahydroaminoacridine in area CA3 of the rat hippocampus.

1. The effects of the K+ channel blocker 9-amino-1,2,3,4-tetrahydroacridine (THA) on the actions of baclofen and gamma-aminobutyric acid (GABA) at post- and presynaptic GABAB receptors were studied with whole-cell voltage-clamp recording in area CA3 of rat hippocampal slices. 2. The effect of THA on postsynaptic GABAB receptor-mediated responses was studied in neurons perfused internally with potassium gluconate and guanosine triphosphate (GTP). At a holding potential of -70 mV, the GABAB receptor agonist (+/-)-baclofen (30 microM) induced an outward current and increased membrane conductance. In the presence of the excitatory amino acid receptor antagonists 6,7-dinitroquinoxaline-2,3-dione (DNQX) and (+/-)-2-amino-5-phosphonovalerate (APV), stimulation in stratum pyramidale or proximal stratum radiatum evoked GABAA receptor-mediated, fast monosynaptic inhibitory postsynaptic currents (IPSCs) and GABAB receptor-mediated, late monosynaptic IPSCs. THA (0.3 mM) blocked the baclofen-induced current and conductance increase and GABAB receptor-mediated IPSCs. 3. The effect of THA on presynaptic GABAB receptor-mediated responses was studied in neurons perfused internally with Cs+ and lidocaine N-ethyl bromide (QX-314), which blocked post-synaptic GABAB receptor-mediated responses. Stimulation in the presence of DNQX and APV evoked GABAA receptor-mediated IPSCs; when pairs of stimuli were delivered 200 ms apart the second IPSC was depressed. Baclofen reversibly depressed IPSCs, and partially occluded paired-pulse depression of IPSCs. The GABAB receptor antagonist CGP 35348 (0.5-1.0 mM) reversed baclofen-induced depression of IPSCs and partially blocked paired-pulse depression. Baclofen-induced and paired-pulse depression of IPSCs were not by affected by THA (0.3 mM). 4. Baclofen reversibly decreased the amplitude and frequency of spontaneous monosynaptic IPSCs (sIPSCs). Depression of sIPSCs by baclofen was unchanged by THA. 5. These results indicate that THA blocks the actions of baclofen and GABA at post- but not presynaptic GABAB receptors. We conclude that post- and presynaptic GABAB receptors in area CA3 of the rat hippocampus couple to different effector mechanisms; postsynaptic GABAB receptors activate THA-sensitive K+ channels, and presynaptic GABAB receptors decrease neurotransmitter release through a THA-insensitive mechanism.

2-Amino-5-phosphonovalerate↗
PubMed1993

GABAB autoreceptors mediate activity-dependent disinhibition and enhance signal transmission in the dentate gyrus.

1. Activity-dependent depression (fading) of polysynaptic inhibition and the effects of this disinhibition on signal transmission were studied in the dentate gyrus of the rat hippocampal slice with the use of intracellular and extracellular recordings. 2. Polysynaptic inhibitory postsynaptic potentials/currents (IPSP/Cs) were evoked in dentate granule cells by stimulation of mossy fibers in stratum lucidum of area CA3b/c. These mossy fiber-evoked IPSP/Cs consisted of an early GABAA receptor-mediated component (IPSP/CA) and a late GABAB receptor-mediated component (IPSP/CB). 3. When paired stimuli were delivered 200 ms apart under voltage clamp, the amplitude of the IPSCA and IPSCB evoked by the second stimulus was reduced by 37.0 +/- 4.0 and 61.6 +/- 7.8% (mean +/- SE), respectively. Paired-pulse depression of both IPSCA and IPSCB was greatest at interstimulus intervals of 100-400 ms with a maximal effect when stimuli were delivered 200 ms apart. 4. (+/-) Baclofen, a GABAB receptor agonist, suppressed both components of the mossy fiber-evoked IPSP in a concentration-dependent fashion. At a concentration that only partially suppressed the initial IPSP, baclofen occluded paired-pulse depression of IPSPA. In addition, paired-pulse depression of IPSPA was blocked in a concentration-dependent fashion by 2-hydroxy-saclofen (10-400 microM), a GABAB receptor antagonist. 5. The contribution of the IPSPB conductance increase to paired-pulse depression of IPSPA was evaluated. Paired-pulse depression of IPSPA was significantly greater than was the depression of the response to a current pulse delivered 200 ms after the mossy fiber stimulus. In addition, injection of granule cells with GTP gamma S, a nonhydrolyzable guanosine triphosphate (GTP) analogue, occluded both IPSPB as well as the effects of baclofen on the granule cell membrane by activating G proteins but did not reduce paired-pulse depression of IPSPA or suppression of IPSPA by baclofen. Finally, examination of the first and second IPSCA evoked by paired stimuli 200 ms apart revealed no significant differences in response kinetics. Taken together, these results indicate that postsynaptic GABAB receptors on the granule cells are not responsible for paired-pulse depression of IPSPA. 6. Monosynaptic IPSPs were evoked by direct stimulation of inhibitory neurons in the inner molecular layer of the dentate gyrus during pharmacological blockade of excitatory transmission with D(-)-2-amino-5-phosphonovaleric acid (D-APV), an N-methyl-D-aspartate (NMDA) receptor antagonist and 6,7-dinitroquinoxaline-2,3-dione (DNQX), a non-NMDA glutamate receptor antagonist.(ABSTRACT TRUNCATED AT 400 WORDS)

2-Amino-5-phosphonovalerate↗
PubMed1993

Axon terminal hyperexcitability associated with epileptogenesis in vitro. I. Origin of ectopic spikes.

1. Intracellular and extracellular recording techniques were used to study the increase in ectopic (i.e., nonsomatic) action-potential generation occurring among CA3 pyramidal cells during the kindling-like induction of electrographic seizures (EGSs) in this subpopulation of the hippocampal slice. Kindling-like stimulus trains (60 Hz, 2 s) were delivered to s. radiatum of CA3 at 10-min intervals. As EGSs developed, the frequency of ectopic firing increased markedly (by 10.33 +/- 3.29 spikes/min, mean +/- SE, P << 0.01). Several methods were applied to determine the initiation site for these action potentials within the cell (axons vs. dendrites). 2. Collision tests were conducted between known antidromic and orthodromic action potentials in CA3 cells to determine the critical period, c, for collision. Attempts were then made to collide ectopic spikes with known antidromic action potentials. At intervals less than c, ectopic spikes failed to collide with antidromic ones, in 5 of 10 cases. In these cells, this clearly indicates that the ectopic spikes were themselves of axonal origin. In the remaining five cases, ectopic spikes collided with antidromic action potentials at intervals approximately equal to c, most likely because of interactions within the complex system of recurrent axon collaterals in CA3. 3. Action potentials of CA3 pyramidal cells were simulated with the use of a compartmental computer model, NEURON. These simulations were based on prior models of CA3 pyramidal neurons and of the motoneuron action potential. Simulated action potentials generated in axonal compartments possessed a prominent inflection on their rising phase (IS-SD break), which was difficult to appreciate in those spikes generated in somatic or dendritic compartments. 4. An analysis of action potentials recorded experimentally from CA3 pyramidal cells also showed that antidromic spikes possess a prominent IS-SD break that is not present in orthodromic spikes. In addition to identified antidromic action potentials, ectopic spikes also possess such an inflection. Together with the predictions of computer simulations, this analysis also indicates that ectopic spikes originate in the axons of CA3 cells. 5. Tetrodotoxin (TTX, 50 microM) was locally applied by pressure injection while monitoring ectopic spike activity. Localized application of TTX to regions of the slice that could include the axons but not the dendrites of recorded cells abolished or markedly reduced the frequency of ectopic spikes (n = 5), further confirming the hypothesis that these action potentials arise from CA3 axons.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Axon terminal hyperexcitability associated with epileptogenesis in vitro. II. Pharmacological regulation by NMDA and GABAA receptors.

1. The preceding report presented evidence that the kindling-like induction of electrographic seizures (EGSs) in the hippocampal slice is accompanied by a lasting increase in the excitability of CA3 axon terminals, which is manifested by an increase in action-potential initiation at this site. In this report we explore the role of the N-methyl-D-aspartate (NMDA) receptor in the induction and maintenance of this antidromic firing, as well as the role of the gamma-aminobutyric acid type A (GABAA) receptor in regulating this activity once it has been induced. 2. Kindling-like stimulus trains (60 Hz, 2 s) were delivered to s. radiatum of CA3 at 10-min intervals. As EGSs developed in control artificial cerebrospinal fluid (ACSF), the frequency of axon terminal firing increased markedly (by 10.33 +/- 3.29 spikes/min, mean +/- SE P << 0.01). The prior application of the competitive NMDA antagonist D-2-amino-5-phosphonovaleric acid (D-APV, 50 or 100 microM) prevented the induction of EGSs and suppressed the increase in terminal firing seen in control ACSF (mean increase 1.06 +/- 1.11 spikes/min, P < 0.02). However, when D-APV was applied only after EGSs and antidromic spikes were induced in control ACSF, it failed to alter the frequency of terminal firing (mean 6.44 +/- 2.03 in control ACSF, 8.89 +/- 2.31 in APV; P >> 0.1). Thus the NMDA receptor is required for the induction but not maintenance of increased axon terminal firing, as we previously have shown to be the case for EGSs.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Amino-5-phosphonovalerate↗
PubMed1992

Suppression of interictal bursting in hippocampus unleashes seizures in entorhinal cortex: a proepileptic effect of lowering [K+]o and raising [Ca2+]o.

The relation between interictal bursts (IIBs) and seizures in epilepsy is obscure. Results from some human and animal studies suggest that IIBs may actually suppress seizure activity. This appears particularly true in the zero magnesium in vitro seizure model. Here we provide new evidence in support of this and new insight into the mechanisms of seizure suppression in this model. Brain slices containing hippocampus and entorhinal cortex were bathed in zero magnesium medium. Electrographic seizures appeared, then were replaced by IIBs. Upon lowering [K+]o and raising [Ca2+]o the IIBs disappeared and the seizures reappeared. Repeated stimuli mimicking IIBs then suppressed seizures again. Selective knife cuts revealed that the IIBs originated in the hippocampus (area CA3) whereas the seizures originated in entorhinal cortex. These results confirm that IIBs suppress seizures in the zero magnesium model. They also show that an important aspect of the interaction between IIBs and seizures in this model is the anatomical segregation of their respective sites of origin. This may apply in other models and in human epilepsy as well. Finally, these results illustrate that one consequence of the anatomical segregation and mutual interaction of IIBs and seizures is that influences which are locally pro- or antiepileptic can have opposite effects in a broader region.

Action Potentials↗
PubMed1992

The GABAB receptor antagonist, CGP-35348, inhibits paired-pulse disinhibition in the rat dentate gyrus in vivo.

Extracellular field potentials were recorded from the dentate gyrus of adult rats during electrical stimulation of the angular bundle in vivo. Paired pulses produced inhibition of the second population spike (PS2) at 25 ms, and potentiation at inter-stimulus intervals from 50 to 200 ms. The GABAB receptor antagonist, CGP 35348, reduced the amplitude of PS2 at each of these inter-stimulus intervals while producing no effect on the first population spike of the pair (PS1). Under control conditions, the duration of the second population EPSP (pEPSP2) was increased relative to the first at inter-stimulus intervals from 100 to 400 ms, and CGP 35348 reduced these durations to baseline levels. These results demonstrate that GABAB receptors modulate synaptic inhibition in vivo.

Animals↗