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J A Kauer

Publications and source records attributed to J A Kauer.

30 records · Page 2Linked to original sources
PubMed1988

Postsynaptic calcium is sufficient for potentiation of hippocampal synaptic transmission.

Brief repetitive activation of excitatory synapses in the hippocampus leads to an increase in synaptic strength that lasts for many hours. This long-term potentiation (LTP) of synaptic transmission is the most compelling cellular model in the vertebrate brain for learning and memory. The critical role of postsynaptic calcium in triggering LTP has been directly examined using three types of experiment. First, nitr-5, a photolabile nitrobenzhydrol tetracarboxylate calcium chelator, which releases calcium in response to ultraviolet light, was used. Photolysis of nitr-5 injected into hippocampal CA1 pyramidal cells resulted in a large enhancement of synaptic transmission. Second, in agreement with previous results, buffering intracellular calcium at low concentrations blocked LTP. Third, depolarization of the postsynaptic membrane so that calcium entry is suppressed prevented LTP. Taken together, these results demonstrate that an increase in postsynaptic calcium is necessary to induce LTP and sufficient to potentiate synaptic transmission.

Animals↗
PubMed1988

NMDA application potentiates synaptic transmission in the hippocampus.

The NMDA (N-methyl-D-aspartate) class of glutamate receptor plays a critical role in a variety of forms of synaptic plasticity in the vertebrate central nervous system. One extensively studied example of plasticity is long-term potentiation (LTP), a remarkably long-lasting enhancement of synaptic efficiency induced in the hippocampus by brief, high-frequency stimulation of excitatory synapses. LTP is a strong candidate for a cellular mechanism of learning and memory. The site of LTP induction appears to be the postsynaptic cell and induction requires both activation of NMDA receptors by synaptically released glutamate and depolarization of the postsynaptic membrane. It is proposed that this depolarization relieves a voltage-dependent Mg2+ block of the NMDA receptor channel, resulting in increased calcium influx which is the trigger for the induction of LTP. This model predicts that application of a large depolarizing dose of NMDA should be sufficient to evoke LTP. In agreement with a previous study, we have found that NMDA or glutamate application does potentiate synaptic transmission in the hippocampus. This agonist-induced potentiation is, however, decremental and short-lived, unlike LTP. It is occluded shortly after the induction of LTP and a similar short-term potentiation can be evoked by synaptically released glutamate. We thus propose that LTP has two components, a short-term, decremental component which can be mimicked by NMDA receptor activation, and a long-lasting, non-decremental component which, in addition to requiring activation of NMDA receptors, requires stimulation of presynaptic afferents.

Animals↗
PubMed1988

A persistent postsynaptic modification mediates long-term potentiation in the hippocampus.

Long-term potentiation (LTP) is a long-lasting enhancement of synaptic transmission that can be induced by brief repetitive stimulation of excitatory pathways in the hippocampus. One of the most controversial points is whether the process underlying the enhanced synaptic transmission occurs pre- or postsynaptically. To examine this question, we have taken advantage of the novel physiological properties of excitatory synaptic transmission in the CA1 region of the hippocampus. Synaptically released glutamate activates both NMDA and non-NMDA receptors on pyramidal cells, resulting in an excitatory postsynaptic potential (EPSP) with two distinct components. A selective increase in the non-NMDA component of the EPSP was observed with LTP. This result suggests that the enhancement of synaptic transmission during LTP is caused by an increased sensitivity of the postsynaptic neuron to synaptically released glutamate.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1987

Alpha bag cell peptide directly modulates the excitability of the neurons that release it.

Brief electrical or hormonal stimulation of the bag cell neurons of Aplysia triggers a long-lasting discharge during which alpha bag cell peptide (alpha-BCP) and other neuropeptides are released from the cells. We have carried out experiments, using both intact abdominal ganglia and isolated neurons, demonstrating that alpha-BCP acts directly on the bag cell neurons to influence cAMP levels and voltage-dependent potassium currents. Exposure of the bag cell neurons within intact ganglia to alpha-BCP, at concentrations greater than 1 nM, inhibited an ongoing discharge. alpha-BCP also significantly reduced both basal and forskolin-stimulated levels of cAMP in bag cell clusters. The inhibition of the discharge by alpha-BCP could be prevented and reversed by pharmacological elevation of intracellular cAMP levels. Immunohistochemical staining of neurons maintained in cell culture showed that all isolated bag cell neurons exhibit immunoreactivity with antisera against alpha-BCP. Application of the adenylate cyclase activator forskolin to such isolated cells, in the presence of a phosphodiesterase inhibitor, attenuates the amplitude of the delayed voltage-dependent outward currents measured in voltage-clamp experiments. Pretreatment of the cells with alpha-BCP significantly reduced the ability of forskolin to attenuate these currents, demonstrating that alpha-BCP acts directly at autoreceptors on bag cell neurons. Experiments with the isolated cells showed that a second autoreceptor-mediated effect of alpha-BCP was the enhancement of an inwardly rectifying potassium current that was activated at potentials more negative than -40 mV. The reversal potential and conductance of the current induced by alpha-BCP were dependent on the external K+ concentration. This response to alpha-BCP could be blocked by rubidium, cesium, and barium ions. Our data demonstrate that alpha-BCP can exert inhibitory biochemical and electrophysiological actions on the bag cell neurons that release it and suggest that autoreceptors for alpha-BCP play an important role in the termination of a discharge in the bag cell neurons.

Adenylate Cyclase Toxin↗
PubMed1985

Peptidergic neurons of Aplysia lose their response to cyclic adenosine 3':5'-monophosphate during a prolonged refractory period.

Although the peptidergic bag cell neurons of Aplysia are ordinarily silent, they respond to brief electrical stimulation by producing an afterdischarge of about 30 min duration. This afterdischarge is followed by a refractory period lasting many hours during which electrical stimulation either fails to initiate afterdischarges or produces discharges of much shorter duration. Previous work has demonstrated that cyclic AMP plays a role in the genesis of afterdischarge, both in intact bag cell clusters and in isolated cultured bag cells. We have now examined the hypothesis that in the refractory period either the synthesis of cyclic AMP or the response to cyclic AMP is attenuated. Direct measurements of cyclic AMP showed that cyclic AMP levels in the bag cell neurons are elevated to a similar extent after stimulation in refractory and nonrefractory clusters of neurons. We have found, however, that the response to cyclic AMP is altered during the refractory period. The electrophysiological responses of bag cell neurons were first examined in intact clusters of cells within the abdominal ganglion. Cyclic AMP levels were elevated using the adenylate cyclase activator, forskolin, in the presence of theophylline (FT). The duration of a first bag cell afterdischarge could be greatly increased if FT was added before stimulation. The duration of a stimulated second bag cell afterdischarge could also be significantly increased if FT was added within a brief period following the end of the first afterdischarge. Furthermore, at these times the addition of FT often resulted in the onset of spontaneous afterdischarges.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Neural control of hatching: fate of the pattern generator for the leg movements of hatching in post-hatching chicks.

Chicks from 0 to 61 days post-hatching were gently folded into the hatching position and placed in artificial glass eggs. Within 0 to 2 min they began to produce a behavior that qualitatively resembled normal hatching. Furthermore, quantitative analysis of electromyographic records showed that under these conditions the intralimb and interlimb leg motor output patterns produced during each hatching episode (the episode motor program) were those typical of normal hatching. The only major change associated with increasing post-hatching age was a gradual increase in inter-episode interval. Therefore, we conclude that the neural pattern-generating circuitry which produces the motor program for the leg movements of hatching remains functional in post-hatching chicks despite the fact that, under normal conditions, hatching behavior is never used again.

Animals↗
PubMed1983

Calcium entry causes a prolonged refractory period in peptidergic neurons of Aplysia.

A brief train of electrical stimuli to the pleuroabdominal connective of Aplysia produces a cumulative depolarization in the peptidergic bag cell neurons within the abdominal ganglion. This response is followed by an afterdischarge which lasts for about 30 min, and then by a prolonged refractory period lasting for several hours. During the refractory period the cumulative depolarization in response to stimulation is attenuated, and stimulation either fails to initiate afterdischarges or produces discharges of much shorter duration. We have used the cationophore X537A to test the hypothesis that the prolonged refractory period is caused by calcium entry into the bag cell neurons during the afterdischarge. Exposure of intact bag cell clusters to X537A at concentrations from 1 to 10 microM for a period of 20 min in calcium-containing media produced no change in their resting potentials or in their ability to generate action potentials, but induced a state resembling natural refractoriness in response to subsequent stimulation. Both natural refractoriness and that induced by X537A could be overcome by extracellular tetraethylammonium ions (90 mM). Dose response data showed that concentrations of ionophore of 2.5 to 5.0 microM produce an attenuation of afterdischarge that is similar to that following a stimulated afterdischarge. These concentrations of X537A also produced an enhancement of 3H-labeled peptide release from these cells that is comparable to that observed on stimulation of an afterdischarge. Moreover, the time course of recovery from exposure to 5.0 microM X537A parallels that of natural refractoriness, recovery being essentially complete about 20 hr after X537A exposure or stimulation. The ionophore did not affect the mean duration of afterdischarge when applied in calcium-deficient media. The electrical effects of X537A were investigated using isolated bag cell neurons in cell culture. After treatment with the adenylate cyclase activator, forskolin, and theophylline, such isolated cells show many of the electrical changes occurring in intact bag cell clusters at the onset of afterdischarge, including the enhancement of action potentials, as well as increased input resistance and the emergence of oscillations in membrane potential. None of these parameters was significantly affected by concentrations of ionophore that induce refractoriness. In response to repetitive intracellular stimulation, however, some forskolin-treated cells undergo a cumulative depolarization which is similar to that seen at the onset of afterdischarge in intact clusters. This cumulative depolarization was found to be attenuated or abolished by 5.0 microM X537A.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMedDate not supplied

Long-term potentiation in mice lacking the neural cell adhesion molecule L1.

Genetic evidence indicates that cell adhesion molecules of the immunoglobulin superfamily (IgCAMs) are critical for activity-dependent synapse formation at the neuromuscular junction in Drosophila and have also been implicated in synaptic remodelling during learning in Aplysia (see [1] for review). In mammals, a widely adopted model for the process of learning at the cellular level is long-term potentiation (LTP) in the hippocampal formation. Studies in vitro have shown that antibodies to the IgCAMs L1 and NCAM reduce LTP in CA1 neurons of rat hippocampus, suggesting a role for these molecules in the modulation of synaptic efficacy, perhaps by regulating synaptic remodelling [2]. A role for NCAM in LTP has been confirmed in mice lacking NCAM [3] (but see [4]), but similar studies have not been reported for L1. Here we examine LTP in the hippocampus of mice lacking L1 [5,6], using different experimental protocols in three different laboratories. In tests of LTP in vitro and in vivo we found no significant differences between mutant animals and controls. Thus, contrary to expectation, our data suggest that L1 function is not necessary for the establishment or maintenance of LTP in the hippocampus. Impaired performance in spatial learning exhibited by L1 mutants may therefore not be due to hippocampal dysfunction [6].

Animals↗