John J. Wagner

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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(More)
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(More)
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(More)
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(More)
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(More)
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(More)
Physiological release of endogenous opioids in guinea pig hippocampal slices was detected in an in vitro competition binding assay using [3H]U69,593, a kappa 1-selective radioligand. Veratridine-induced opioid release caused a decrease in [3H]U69,593 binding that was blocked by either tetrodotoxin addition or the removal of calcium from the incubation(More)
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(More)
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(More)
The neural adaptations involved in initiating and maintaining the long-term consequences of utilizing drugs of abuse are the subject of intense investigation. It is commonly suggested that the neural plasticity mechanisms underlying physiological phenomena such as learning and memory may also be engaged when drug addiction occurs. The effect of cocaine on(More)