Biomedical subjects

Nandor Ludvig

Publications and source records attributed to Nandor Ludvig.

5 recordsLinked to original sources

PubMed2006

Elevated lactate suppresses neuronal firing in vivo and inhibits glucose metabolism in hippocampal slice cultures.

Glucose is well accepted as the major fuel for neuronal activity, while it remains controversial whether lactate also supports neural activity. In hippocampal slice cultures, synaptic transmission supported by glucose was reversibly suppressed by lactate. To test whether lactate had a similar inhibitory effect in vivo, lactate was perfused into the hippocampi of unanesthetized rats while recording the firing of nearby pyramidal cells. Lactate perfusion suppressed pyramidal cell firing by 87.5+/-8.3% (n=6). Firing suppression was slow in onset and fully reversible and was associated with increased lactate concentration at the site of the recording electrode. In vivo suppression of neural activity by lactate occurred in the presence of glucose; therefore we tested whether suppression of neural firing was due to lactate interference with glucose metabolism. Competition between glucose and lactate was measured in hippocampal slice cultures. Lactate had no effect on glucose uptake. Lactate suppressed glucose oxidation when applied at an elevated, pathological concentration (10 mM), but not at its physiological concentration (1 mM). Pyruvate (10 mM) also inhibited glucose oxidation but was significantly less effective than lactate. The greater suppressive effect of lactate as compared to pyruvate suggests that alteration of the NAD(+)/NADH ratio underlies the suppression of glucose oxidation by lactate. ATP in slice culture was unchanged in glucose (1 mM), but significantly reduced in lactate (1 mM). ATP in slice culture was significantly increased by combination of glucose (1 mM) and lactate (1 mM). These data suggest that alteration of redox ratio underlies the suppression of neural discharge and glucose metabolism by lactate.

Action Potentials↗

PubMed2006

Epidural pentobarbital delivery can prevent locally induced neocortical seizures in rats: the prospect of transmeningeal pharmacotherapy for intractable focal epilepsy.

PURPOSE: To determine whether epidural pentobarbital (PB) delivery can prevent and/or terminate neocortical seizures induced by locally administered acetylcholine (Ach) in freely moving rats. METHODS: Rats were implanted permanently with an epidural cup placed over the right parietal cortex with intact dura mater. Epidural screw-electrodes, secured to the cup, recorded local neocortical EEG activity. In the seizure-termination study, Ach was delivered into the epidural cup, and after the development of electrographic and behavioral seizures, the Ach solution was replaced with either PB or artificial cerebrospinal fluid (aCSF; control solution). In the seizure-prevention study, the epidural Ach delivery was preceded by a 10-min exposure of the delivery site to PB or aCSF. Raw EEG recordings, EEG power spectra, and behavioral events were analyzed. RESULTS: Ach-induced EEG seizures associated with convulsions, which were unaffected by epidural aCSF applications, were terminated by epidurally delivered PB within 2-2.5 min. Epidural deliveries of PB before Ach applications completely prevented the development of electrographic and behavioral seizures, whereas similar deliveries of aCSF exerted no influence on the seizure-generating potential of Ach. CONCLUSIONS: This study showed for the first time that epidural AED delivery can prevent, as well as terminate, locally induced neocortical seizures. The findings support the viability of transmeningeal pharmacotherapy for the treatment of intractable neocortical epilepsy.

Acetylcholine↗

PubMed2004

Detecting location-specific neuronal firing rate increases in the hippocampus of freely-moving monkeys.

The spatial properties of the firing of hippocampal neurons have mainly been studied in (a) freely moving rodents, (b) non-human primates seated in a moveable primate chair with head fixed, and (c) epileptic patients subjected to virtual navigation. Although these studies have all revealed the ability of hippocampal neurons to generate spatially selective discharges, the detected firing patterns have been found to be considerably different, even conflicting, in many respects. The present cellular electrophysiological study employed squirrel monkeys (Saimiri sciureus), which moved freely on the walls and floor of a large test chamber. This permitted the examination of the spatial firing of hippocampal neurons in nearly ideal conditions, similar to those used in rodents, yet in a species that belongs to the primate Suborder Anthropoidea. The major findings were that: (1) a group of slow-firing complex-spike cells increased their basal, awake firing rate more than 20-fold, often above 30 spikes/s, when the monkey was in a particular location in the chamber, (2) these location-specific discharges occurred consistently, forming 4-25 s action potential volleys, and (3) fast-firing cells displayed no such electrical activity. Thus, during free movement in three dimensions, primate hippocampal complex-spike cells do generate high-frequency, location-specific action potential volleys. Since these cells are components of the medial temporal lobe memory system, their uncovered firing pattern may well be involved in the formation of declarative memories on places.

Action Potentials↗

PubMed2003

Spatial memory performance of freely-moving squirrel monkeys.

Few experiments have addressed the problem of cognitive map formation in non-human primates. Therefore, a paradigm was developed to assess spatial memory formation in squirrel monkeys (Saimiri sciureus) moving freely in three dimensions. While moving on the walls and floor of a large test chamber, the animals learned to collect pieces of cereal from baited food-ports interspersed among non-baited ports. The cereal-pellets were not visible to the monkeys, so the animals needed to develop spatial memory to visit only the baited ports for food and avoid the non-baited ones. A session consisted of ten consecutive trials, and 3 successive sessions were conducted on each day for a 5-day period. For each trial, correct choices (CC; number of visited baited-ports) and incorrect choices (IC; number of visited non-baited ports) were registered, and spatial memory performance index (SMPI; ranging from 0.00 to 1.00) was calculated as follows: SMPI=(CC-IC)/CC. For each session, mean SMPI, session duration, total reaches into the non-baited ports, and total reaches into the baited ports were documented. In an 8-port task, where 4 food-ports were baited and 4 were non-baited, the mean SMPI was higher than 0 in the first session (day 1), indicating the development of short-term spatial memory. By the fifth session (day 2), this index was significantly higher than in the first session, indicating the build-up of long-term spatial memory. These changes were related to a significant decrease in the total reaches into the non-baited ports. At the same time, the duration of the sessions and the total reaches into the baited ports did not change significantly. This paradigm can be used for (1) studying cognitive map formation in primates, (2) examining the underlying cellular and molecular mechanisms in integrative neurobiological experiments, and (3) screening cognition-enhancer drugs in a monkey model.

Analysis of Variance↗

PubMed2002

The use of a remote-controlled minivalve, carried by freely moving animals on their head, to achieve instant pharmacological effects in intracerebral drug-perfusion studies.

Intracerebral drug-perfusion studies in animals can be very efficiently performed with the 'reverse-dialysis' procedure. In this procedure, drugs are delivered into the brain via an intracerebrally implanted microdialysis probe. Traditionally, in reverse-dialysis studies the flow of control and drug solutions in the microdialysis site is alternated by large and heavy valves placed far from the experimental animal. In this arrangement, the drugs travel from the fluid-alternating device for a long (20--60 min) period before reaching the brain. This can obscure the onset of drug action, makes it difficult to deliver drugs into the extracellular space during short-lasting behavioral episodes, and considerably limits the number of drug solutions that can be perfused within an experimental session. This report describes the use of a miniature (15 mm long and 8 mm diameter), lightweight (1.4 g) minivalve (patent pending) for combined neuronal recording--intracerebral microdialysis studies in freely moving rats. The device is activated remotely and carried by the animals on their head. This allows the experimenter to alternate the control and drug solutions in the intracerebral recording/dialysis site rapidly and to detect the drug-induced neuronal firing pattern changes instantly, without interfering with the animal's behavior. It is demonstrated that with this novel device the onset of drug actions on hippocampal neurons can be clearly defined and that these actions occur within 2 min after minivalve activation. Furthermore, it is demonstrated that the minivalve allows one to test a large number of drug solutions, successively, within the same experimental session. The described protocol offers a high-throughput method for testing the neuron-specific pharmacological effects of intracerebrally perfused drugs during various behaviors.

Action Potentials↗