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Biomedical subjects

M G Weisskopf

Publications and source records attributed to M G Weisskopf.

16 recordsLinked to original sources
PubMed2001

Misidentification of Onchocerca volvulus as guinea worm.

Over the past 10 years, the status of human infection with guinea worm (Dracunculus medinensis) in the Central African Republic (CAR) has been difficult to ascertain. It is unclear if indigenous cases are occurring and whether cases are migrating into the CAR from surrounding countries. A team of investigators visited the CAR in July-August 2000, to attempt to ascertain the presence of indigenous transmission. No cases of true guinea-worm infection (i.e. dracunculiasis) were detected, but three cases of human infection with Onchocerca volvulus, each of which had been misidentified as dracunculiasis, were detected. The unusual presentation of skin blisters and extraction of an intact female O. volvulus are described. As a result of this investigation, and the confusion of onchocerciasis being misidentified as dracunculiasis, the presence of endemic transmission of guinea worm in the CAR remains in question.

Adult↗
PubMed2000

Wisconsin, July 1999 heat wave: an epidemiologic assessment.

OBJECTIVE: To assess the characteristics of heat-related deaths in Wisconsin during the summer of 1999. METHODS: Review of death certificates indicating heat as an underlying or contributing cause of death. RESULTS: Heat-related illness led to 21 deaths during the summer of 1999 in Wisconsin. The rate of death was highest in the elderly, particularly those aged 65-84 years (2.2/100,000). Heat was the underlying cause for 12 of the 21 deaths. Cardiovascular conditions were the underlying cause in 8 of the deaths, and a contributing cause for another 7. CONCLUSIONS: The elderly, persons taking psychotropic medications, and persons with chronic diseases, particularly cardiovascular conditions, are at increased risk of death from heat during heat waves. Prevention messages and weather advisories during heat emergencies must target these groups. Care givers and medical personnel must be on heightened awareness for the signs and symptoms of heat exhaustion and heat stroke during these periods.

Age Factors↗
PubMed2000

Hazardous ammonia releases in Wisconsin: trends and risk factors for evacuation and injury.

OBJECTIVE: To assess trends in hazardous ammonia releases and risk factors for subsequent evacuation and injury. METHODS: Analysis of the Wisconsin Hazardous Substances Emergency Events Surveillance system data during 1993 through 1998. RESULTS: Ammonia releases (291) accounted for 13% of all reported chemical releases, but 26% of all releases that led to evacuations. The majority of non-transportation-related ammonia releases are the result of equipment failure or operator error (85.5%). Few ammonia releases are transportation-related (6.5%) or occur during extreme weather (14.4%). Extreme weather is not a risk factor for evacuation or injury following ammonia releases. CONCLUSIONS: Ammonia releases are frequently the result of equipment failure or operator error and thus preventable. The majority of ammonia releases that lead to evacuation and injury are not the result of transportation accidents or weather factors beyond human control. Prevention efforts that focus on preventive maintenance, and worker training and awareness could reduce the burden of hazardous ammonia releases.

Accidents, Occupational↗
PubMed1999

L-type voltage-gated calcium channels mediate NMDA-independent associative long-term potentiation at thalamic input synapses to the amygdala.

Long-term potentiation (LTP) in the amygdala is a leading candidate mechanism to explain fear conditioning, a prominent model of emotional memory. LTP occurs in the pathway from the auditory thalamus to the lateral amygdala, and during fear conditioning LTP-like changes occur in the synapses of this pathway. Nevertheless, LTP has not been investigated in the thalamoamygdala pathway using in vitro recordings; hence little is known about the underlying mechanisms. We therefore examined thalamoamygdala LTP in vitro using visualized whole-cell patch recording. LTP at these synapses was dependent on postsynaptic calcium entry, similar to synaptic plasticity in other regions of the brain. However, unlike many forms of synaptic plasticity, thalamoamygdala LTP was independent of NMDA receptors, despite their presence at these synapses, and instead was dependent on L-type voltage-gated calcium channels. This was true when LTP was induced by pairing presynaptic activity with either action potentials or constant depolarization in the postsynaptic cell. In addition, the LTP was associative, in that it required concurrent pre- and postsynaptic activity, and it was synapse specific. Thus, although this LTP is different from that described at other synapses in the brain, it is nonetheless well suited to mediate classical fear conditioning.

Afferent Pathways↗
PubMed1999

Distinct populations of NMDA receptors at subcortical and cortical inputs to principal cells of the lateral amygdala.

Fear conditioning involves the transmission of sensory stimuli to the amygdala from the thalamus and cortex. These input synapses are prime candidates for sites of plasticity critical to the learning in fear conditioning. Because N-methyl-D-aspartate (NMDA)-dependent mechanisms have been implicated in fear learning, we investigated the contribution of NMDA receptors to synaptic transmission at putative cortical and thalamic inputs using visualized whole cell recording in amygdala brain slices. Whereas NMDA receptors are present at both of these pathways, differences were observed. First, the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-receptor-mediated component of the synaptic response, relative to the NMDA component, is smaller at thalamic than cortical input synapses. Second, thalamic NMDA responses are more sensitive to Mg2+. These findings suggest that there are distinct populations of NMDA receptors at cortical and thalamic inputs to the lateral amygdala. Differences such as these might underlie unique contributions of the two pathways to fear conditioning.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1996

Characterizing the site and mode of action of dynorphin at hippocampal mossy fiber synapses in the guinea pig.

Extracellular field potential recordings from the CA3 region in guinea pig hippocampal slices were used to study the release and action of dynorphin at the mossy fiber synapse. Dynorphin A(1-17) or U69593 inhibited mossy fiber synaptic responses in preparations in which the CA3 region was surgically isolated from the rest of the hippocampus. This inhibition was completely reversed by the kappa 1 selective antagonist nor-BNI, thus establishing the presence of functional kappa 1 receptors in CA3. Inhibitory effects of dynorphin on mossy fiber responses were unaltered in the presence of the N- or P-type Ca2+ channel blockers, omega-CgTx or omega-Aga IVA, respectively. This indicates that the action of dynorphin is independent of the particular type of Ca2+ channel that mediates transmitter release at the mossy fiber terminal. Heterosynaptic inhibition of mossy fiber responses was observed in the presence of nifedipine, omega-CgTx, or omega-Aga IVA, indicating that dynorphin release does not depend specifically on L-, N-, or P-type Ca2+ channels. The blockade of heterosynaptic inhibition by the membrane-permeant Ca2+ chelator EGTA-AM suggests the involvement of a slow Ca(2+)-dependent process in dynorphin release. On the basis of a variety of experimental evidence, we propose that the time course of heterosynaptic inhibition is determined primarily by the time course of clearance of dynorphin in the extracellular space.

Animals↗
PubMed1995

Presynaptic changes during mossy fibre LTP revealed by NMDA receptor-mediated synaptic responses.

Activity-dependent changes in synaptic strength are important for learning and memory. Long-term potentiation (LTP) of glutamatergic excitatory synapses following brief repetitive stimulation provides a compelling cellular model for such plasticity. In the CA1 region of the hippocampus, anatomical studies have revealed large numbers of NMDA (N-methyl-D-aspartate) receptor sites at excitatory synapses, which express primarily an NMDA receptor-dependent form of LTP. In contrast, these studies have suggested that mossy fibre synapses activate primarily or exclusively alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and, indeed, these synapses express a form of LTP that is entirely independent of NMDA receptors. Here we present physiological data demonstrating that mossy fibres activate a substantial NMDA receptor synaptic component that expresses LTP. The presence of an NMDA receptor response allowed us to use the open-channel NMDA receptor antagonist MK-801 to establish directly that the probability of transmitter release is enhanced during the expression of mossy fibre LTP.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1995

A comparison of the role of dynorphin in the hippocampal mossy fiber pathway in guinea pig and rat.

Several behavioral studies in rat (Gallagher, 1988) have suggested that opioids in the hippocampus could play an important role in learning and memory. However, in this species, very few reports specifically address the issue of physiological actions of opioids released by the mossy fibers which constitute the principal source of dynorphin and enkephalin in the hippocampus. In the guinea pig high frequency stimulation of mossy fibers causes a transient heterosynaptic inhibition of neighboring mossy fibers (Weisskopf et al., 1993) or perforant path synapses in the dentate (Wagner et al., 1993), which is mediated by the synaptic release of dynorphin that activates presynaptic kappa receptors. We show here that neither exogenous nor endogenous dynorphin affect mossy fiber excitatory postsynaptic potentials in the Sprague-Dawley rat, which is consistent with the finding that kappa receptor binding in the mossy fiber termination zone is dense in the guinea pig and sparse in this rat. More surprisingly, although kappa receptor binding is found in the rat dentate gyrus molecular layer and in the CA3 pyramidal cell layer, dynorphin had no action on perforant path field responses, somatic potassium currents or evoked monosynaptic inhibitory postsynaptic currents in CA3 cells. This lack of action appears to be an exception among rodents as dynorphin significantly inhibited mossy fiber responses in the hamster, mouse, and even another strain of rat, Long-Evans. Unlike the kappa mediated actions, the mu opioid receptor agonist DAMGO inhibited Sprague-Dawley mossy fiber responses, as it does in guinea pig. In contrast to other investigators, however, we found that the opioid receptor antagonist naloxone had no effect on Sprague-Dawley mossy fiber LTP.

Animals↗
PubMed1994

Mediation of hippocampal mossy fiber long-term potentiation by cyclic AMP.

Repetitive activation of hippocampal mossy fibers evokes a long-term potentiation (LTP) of synaptic responses in pyramidal cells in the CA3 region that is independent of N-methyl-D-aspartate receptor activation. Previous results suggest that the site for both the induction and expression of this form of LTP is presynaptic. Experimental elevation of cyclic adenosine 3',5'-monophosphate (cAMP) both mimics and interferes with tetanus-induced mossy fiber LTP, and blockers of the cAMP cascade block mossy fiber LTP. It is proposed that calcium entry into the presynaptic terminal may activate Ca(2+)-calmodulin-sensitive adenylyl cyclase I which, through protein kinase A, causes a persistent enhancement of evoked glutamate release.

Animals↗
PubMed1994

MCPG antagonizes metabotropic glutamate receptors but not long-term potentiation in the hippocampus.

In the CA1 and CA3 regions of the guinea pig hippocampus, we have tested the ability of the new antagonist (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG) to inhibit the well-known effects of (trans)-1-amino-cyclopentyl-1,3-dicarboxylate (ACPD), a specific agonist of glutamate metabotropic receptors. Whole-cell recordings showed that MCPG was able to antagonize the blocking action of ACPD on IAHP in the CA1 region. In addition, we report here that MCPG also antagonized the presynaptic inhibitory actions of ACPD on field excitatory postsynaptic potentials in both areas CA1 and CA3. Thus, MCPG proved to be an effective tool for determining physiological roles of the glutamate metabotropic receptors in synaptic transmission in the hippocampus. We next tested the possible effects of this antagonist on long-term potentiation (LTP). In completely blind experiments MCPG was without effect on LTP in both areas CA1 and CA3. In conclusion, our results suggest that, although MCPG is a valuable antagonist of the ACPD-sensitive receptors, it has no inhibitory effect on LTP.

Animals↗
PubMed1994

The role of Ca2+ channels in hippocampal mossy fiber synaptic transmission and long-term potentiation.

We have addressed the role of Ca2+ channels in mossy fiber synaptic transmission and long-term potentiation (LTP). Whereas the induction of mossy fiber LTP is entirely normal when synaptic transmission is blocked by the glutamate receptor antagonist kynurenate, LTP is blocked in the absence of extracellular Ca2+. These findings suggest that presynaptic Ca2+ entry is essential for mossy fiber LTP. Therefore, the role of different types of presynaptic Ca2+ channels in synaptic transmission and LTP was investigated. Mossy fiber responses were little affected by the L-type Ca2+ channel blocker nifedipine. They were blocked partially by omega-conotoxin-GVIA (N-type) and almost entirely by omega-agatoxin-IVA (P-type). None of these antagonists blocked mossy fiber LTP, nor was its expression associated with a change in sensitivity of synaptic transmission to either of the two toxins. These results, together with previous findings, suggest that the induction of mossy fiber LTP is critically dependent on the entry of Ca2+ into the presynaptic terminal to trigger a series of steps resulting in the long lasting enhancement of evoked glutamate release. Whereas P-type Ca2+ channels are of primary importance in mossy fiber synaptic transmission, both the induction and expression of mossy fiber LTP can occur in the absence of P-type (or N-type) Ca2+ channels.

Animals↗
PubMed1993

The opioid peptide dynorphin mediates heterosynaptic depression of hippocampal mossy fibre synapses and modulates long-term potentiation.

The mossy fibre pathway in the hippocampus uses glutamate as a neurotransmitter, but also contains the opioid peptide dynorphin. Synaptic release of dynorphin causes a presynaptic inhibition of neighbouring mossy fibres and inhibits the induction and expression of mossy fibre long-term potentiation. These findings demonstrate a physiological role for a neuropeptide in the central nervous system, provide a functional basis for the coexistence of a neuropeptide with classic neurotransmitters and demonstrate the very different roles played by these two classes of signalling molecules.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1991

Horizontal long-term potentiation of responses in rat somatosensory cortex.

The search for mechanisms in neocortex that change synaptic efficacy and produce associative learning through activity-dependent processes has focused on the role of glutamate receptors of the N-methyl-D-aspartate (NMDA) type. NMDA receptor activation is necessary for the induction of long-term potentiation (LTP) in hippocampus and in neocortex. The effect of NMDA receptor activation is modulated in several ways, including Mg2+ block of the NMDA-dependent channel which prevents Ca2+ entry until neurons become partially depolarized. We report that when NMDA receptor activation is facilitated by lowering the extracellular [Mg2+] in the bathing medium, a low-frequency train presented in layer VI induces potentiated responses throughout a wide horizontal extent of layer II/III in neocortical slices. The response amplitudes potentiated by 34-200% over baseline values depending on the intensity of the repetitive conditioning stimulus and the distance of the recording site from the stimulus. At the same time that pre-existing evoked responses were potentiated, horizontal spread of activity in layer II/III was facilitated resulting in responses appearing at sites more than 1 mm from the stimulus. This enhanced transmission of responses persisted for greater than 2 h, and its induction was prevented by selective NMDA receptor antagonists. The results show that the horizontal spread of activity can be increased by altering the conditions of the stimulus presentation. We conclude that the mechanisms supporting LTP could determine the area of neocortex that is activated by a sensory input.

Animals↗