Search PubMed⌕ Search

Biomedical subjects

R Racine

Publications and source records attributed to R Racine.

17 recordsLinked to original sources
PubMed1998

Selective loss of early suppression in the dentate gyrus precedes kainic acid induced electrographic seizures.

The role of inhibitory and facilitatory processes in the induction of seizures was studied in a kainic acid (KA) model of epilepsy. The dentate gyrus (DG) response to paired-pulse stimulation of the perforant path (PP) was monitored prior to and immediately following the initial KA induced afterdischarge (AD) in rats chronically prepared with stimulation recording electrodes. The subjects received a 1-h program of stimulation consisting of repeated sequences of pulse pairs at a short (20-30 ms), intermediate (45-90 ms), and long (200-300 ms) interpulse interval (IPIs). The stimulation program was administered both under control conditions and immediately following systemic injection of KA. During the control condition, stable suppression of population spike measures was obtained at the short (early phase) and long (late phase) IPIs, while facilitation was observed at the intermediate IPI. Administration of KA resulted in a progressive loss of suppression prior to the initial AD at the short IPI; neither facilitation nor the late phase of suppression were significantly affected. The early phase decreased further following the initial discharge. Since the early phase most likely reflects recurrent inhibition, these results provide evidence that inhibitory loss precedes the occurrence of KA induced AD, and that this inhibitory loss is increased further following the initial evoked AD. A use-dependent disinhibition is one possible explanation for the change in responsiveness that precedes the AD. This disinhibition could result from a depressed response at GABA-A receptors, an increased responsiveness at GABA-B receptors or possibly both.

Animals↗
PubMed1997

Electrical stimulation of the septal region of aged rats improves performance in an open-field maze.

Memory deficits of age and disease may result from dysfunction of septohippocampal structures. Electrical brain stimulation might ameliorate these memory deficits. We show here that septal stimulation of very old rats leads to a marked and progressive improvement in performance in an open-field maze task. Unilateral stimulation of the perforant path is less effective. The frequency of stimulation is important: stimulation at 5 Hz and 50 Hz is effective, whereas stimulation at 0.5 Hz is less effective (though still significantly better than control). Hippocampal (dentate) EEG does not change significantly with septal stimulation frequency. These results may bear on the memory deficit of old age in humans. The results may also bear on the memory deficits seen in human disease states such as Alzheimer's disease.

Aging↗
PubMed1995

Development of spontaneous seizures over extended electrical kindling. II. Persistence of dentate inhibitory suppression.

The effect of an extended program of perforant path or amygdala kindling on paired-pulse suppression in the dentate gyrus was studied in male hooded rats. Repeated kindling stimulations were delivered twice or three times daily until either 300 stimuli had been delivered or generalized convulsions had been observed to occur spontaneously. Paired-pulse suppression was monitored prior to and over the course of kindling using a standard variable interval paradigm. We also used a variable intensity paradigm in which the intensity of the conditioning pulse was varied while the test pulse intensity was fixed at 600 microA and the interpulse interval was fixed at 30 ms. Both procedures revealed progressive increases in paired-pulse suppression which persisted over the course of kindling. This increased inhibition also persisted in animals which developed spontaneous seizures. The variable intensity paired-pulse procedure also allowed us to monitor facilitation effects which were relatively uncontaminated by recurrent inhibition (when the conditioning pulse intensity was low). Kindling was found to increase paired-pulse facilitation. With the standard variable interval paradigm, these increases in facilitation masked the increases in suppression.

Amygdala↗
PubMed1994

Hippocampal stimulation of fornical-lesioned rats improves working memory.

Intrinsic rhythmic electrical activity in the brain, such as the hippocampal theta rhythm, might serve important roles in normal cognition. Lesions to the medial septal nuclei, or to the fimbria/fornix, disrupt the hippocampal theta rhythm and lead to memory impairment. We have superimposed an artificial stimulating rhythm to the hippocampus of rats with prior lesion of the fornix, during testing in the Morris water maze. This intervention improves performance in a test of working memory, and lends support to the view that intrinsic rhythmic activity may play an important role in normal physiology, and in certain disease states.

Analysis of Variance↗
PubMed1991

Changes in inhibitory processes in the hippocampus following recurrent seizures induced by systemic administration of kainic acid.

Rats were chronically prepared with stimulation electrodes in the angular bundle and recording electrodes in the dentate gyrus under electrophysiological guidance. Following testing of dentate gyrus field potentials, the animals were given a single injection of kainic acid which caused repeated seizures and led to status epilepticus. The seizures were stopped by administration of a barbiturate anesthetic after 60 min. Changes in inhibition during seizure development were monitored by administering pulse pairs at regular intervals. The results revealed a progressive kainic acid-induced loss in inhibition that preceded the occurrence of seizures. This breakdown of inhibition was transient, and generally disappeared within 24 h. Over subsequent testing, recurrent inhibition, as measured by the double pulse test, increased beyond baseline levels. This increase persisted for at least one month and was restricted to the early phase of inhibition with a conditioning/test pulse interval of less than 50 ms. A later phase of inhibition, measured at interpulse intervals between 200 and 300 ms, showed a transient decrease which lasted about a week. These results contrast with previous reports of a long-term period of hyperexcitability following recurrent seizures. Procedural differences which might account for such discrepancies are discussed.

Action Potentials↗
PubMed1981

Effects of diazepam on hippocampal excitability in the rat: action in the dentate area.

Acute and chronic experiments were performed on rats to examine the effects of diazepam (Valium) on recurrent inhibition in the monosynaptic perforant path-dentate synapse of the dentate area of the dorsal hippocampus. Evidence was obtained which indicated that diazepam facilitated a presumably GABA mediated post synaptic recurrent inhibition in both acute and chronic preparations at 1 and 2 mg/kg doses (IP). Acute studies also revealed that diazepam prolonged recurrent inhibition, possibly by lengthening the IPSP. An effect of the drug on cholinergically mediated positive feedback from the septum could not be ruled out, however. Taken together, this study extends the evidence that diazepam acts centrally on GABA mediated inhibition in the limbic system. Furthermore, the limbic action of diazepam revealed here suggests a mechanism for the anticonvulsant properties of diazepam in epilepsy involving subcortical (limbic) circuitry.

Animals↗
PubMed1979

The effect of procaine hydrochloride and diazepam, separately or in combination, on cortico-generalized kindled seizures.

The effects of cortically kindled seizure responses of procaine hydrochloride, diazepam and combinations of these two drugs were tested in this study. The cortex was stimulated until seizure responses developed past the focal stage (accompanied primarily by brief tonic convulsions) to the cortico-generalized stage (accompanied, typically, by an early brief tonus followed by a longer clonic seizure that is characteristic of subcortically triggered seizures). Diazepam was found to block the generalized component of the cortico-generalized electrographic and motor seizure leaving the tonus only slightly suppressed. Procaine blocked the tonus leaving the clonic seizure and discharge that is characteristic of the generalized response relatively intact. Combinations of half doses of the two drugs completely blocked all electrographic and motor seizure responses in about half the animals. The remaining animals had a very brief discharge with no convulsive responses.

Animals↗
PubMed1979

The effects of atropine and reserpine on cortical kindling in the rat.

The effects on cortical kindling of atropine (a muscarinic, cholinergic blocking agent) and reserpine (a depleter of catecholamines and 5 hydroxytryptamine) were tested in this study. Atropine, which had previously been found to retard amygdaloid kindling, had similar but somewhat weaker effects on cortical kindling. Reserpine also had similar effects on cortical kindling compared to subcortical kindling in that it potentiated seizure responses.

Animals↗
PubMed1977

Afterdischarge thresholds and kindling rates in dorsal and ventral hippocampus and dentate gyrus.

Electrodes were implanted to dorsal hippocampus (CA1), ventral CA1, DOrsal dentate gyrus or ventral dentate gyrus. Epileptiform afterdischarge (AD) thresholds were lower in dorsal areas than in ventral areas. Dorsal areas, however, required a greater number of stimulations to develop ("kindle") a fully generalized convulsion than did ventral areas. Thresholds and kindling rates in the dentate gyrus were intermediate between dorsal and ventral CA1, except for the ventral dentate which had higher AD thresholds than ventral CA1. Secondary sites within the hippocampus subsequently kindled within a few stimulations following completion of kindling in the primary site, regardless of which hippocampal area served as the primary site.

Animals↗
PubMed1975

Post-activation potentiation and the kindling phenomenon.

Potentials evoked in the hippocampus and preoptic region of rats by single biphasic pulses applied to the amygdala were compared during recruiting, after post-tetanic potentiation (PTP) and after amygdaloid kindling. The same components were enhanced temporarily by recruiting and PTP as were enhanced permanently by kindling. Trains of tetanic stimulation with parameters which partially mimicked the cellular discharge parameters during an amygdaloid afterdischarge (AD) were applied to the amygdala at a frequency of 1 per 5 sec continuously for 2.5 h or for 15 min a day for 10 days to produce a total of 1800 trains. Amygdaloid kindling rates were then measured and compared with control groups. Animals pretreated with tetanic stimulation required significantly fewer ADs to develop maximal seizures. Further experiments showed that tetanic stimulation, but not recruiting stimulation (10 c/sec), low frequency stimulation (1 c/sec), or handling, would produce a permanent change in potentials evoked in secondary sites by single pulses applied to the amygdala. This change in evoked potential amplitude was significant but smaller than that produced by kindling. Also tetanic stimulation, but not recruiting or single pulses, facilitated subsequent kindling.

Amygdala↗
PubMed1975

Effects of procaine hydrochloride, diazepam, and diphenylhydantoin on seizure development in cortical and subcortical structures in rats.

Procaine HCl and diphenylhydantoin (DPH) increased the duration and propagation of epileptiform afterdischarges (ADs) produced by electrical stimulation of the amygdala in rats. Procaine and DPH also increased the rate of seizure development (kindling) produced by repeated stimulation of the amygdala. Procaine and to a limited extentDPH would themselves act as convulsants in well kindled subjects. Diazepam, on the other hand, retarded or blocked amygdaloid kindling. Diazepam trigered a high frequency (20-30 c/sec) rhtthm in the amygdala, hippocampus and preoptic area. None of these drugs had any significant effect on potentials evoked in secondary limbic sites by single electrical pulses applied to the amygdala. Also, none of these drugs had any effect on recruiting or post-tetanic potentiation (PTP) in secondary sites produced by amygdala stimulation and none of the drugs had any effect on amygdaloid AD thresholds. The effects of these drugs on the responses evoked by anterior neocortex stimulation were quite different. Diazepam had no effect on any of the characteristics of the discharge or convulsion even at twice the dose levels used for the amygdala group. Procaine and DPH, however, blocked not only the eonvulsion but the AD as well. Eighty percent of the procaine- and DPH-treated rats failed to respond with neocortical AD even at current levels as high as 2000 muA. The few cortically stimulated subjects that did respond with an AD showed a subcortical rather than a neocortical seizure response. DPH had no effect on recruiting or PTP of the transcallosal response. Both procaine and DPH produced a weak but significant increase in the amplitude of the transcallosal evoked potential, while diazepam produce a weak decrement in that response.

Amygdala↗
PubMed1975

Kindling, unit discharge patterns and neural plasticity.

Two approaches to the study of the kindling phenomenon were discussed: 1) an attempt to identify the pattern of neural activity required to produce the changes underlying kindling and 2) an investigation into the nature of those changes. Three experiments were reported that used the neocortical transcallosal system as a monosynaptic model system in which to study possible synaptic mechanisms of the kindling effect. Experiment I showed an increase in the transcallosal evoked potential following neocortical kindling. Experiment II showed an increase in the strength of the transcallosal evoked cell discharge following neocortical kindling. Experiment III reported the results of an histological examination of neocortical tissue in kindled and non-kindled animals using the Golgi-Cox technique. Spine density, spine dimension and branching were measured for pyramidal cell apical dendrites. No differences were found between primary and secondary (contralateral) foci or between kindled and non-kindled animals.

Animals↗
PubMedDate not supplied

Effects of midbrain raphe lesions or systemic p-chlorophenylalanine on the development of kindled seizures in rats.

Previous research has suggested that brain serotonin (5-hydroxytryptamine or 5-HT) neurons inhibit epileptiform seizure activity. To test further this possibility, experiments were performed to determine if brain 5-HT depletion would enhance the occurrence and/or magnitude of seizures "kindled" from the amygdala or neocortex of rats. Two modes of 5-HT depletion were used: (1) radiofrequency heat lesions of the midbrain dorsal and median raphe nuclei, and (2) systemic injection of the 5-HT synthesis inhibitor, p-chlorophenylalanine (pCPA). Both modes of 5-HT depletion reliably enhanced the strength of motor convulsions kindled from the cortex. Systemic pCPA also reduced the duration of after-discharges (ADs) in cortically-stimulated rats. However, pCPA reduced rather than enhanced convulsions kindled from the amygdala. In contrast to this, raphe lesions appeared to sensitize rats to the effects of amygdaloid kindling, i.e., lesions lowered AD thresholds, AD durations and number of ADs to elicit motor convulsions. Viewed together, these data support the hypothesis that 5-HT neurons can serve to inhibit seizures. However, the lack of robustness across parameters of epileptogenesis as well as discrepant findings related to 5-HT depletion mode additionally suggest that kindled seizures affect other neuronal populations in addition to those under serotonergic influence.

Amygdala↗
PubMedDate not supplied

Kindling: the first decade.

The kindling phenomenon is a progressive increase in the strength of epileptiform activity evoked by spaced (in time) and repeated electrical stimulation of certain brain structures. The work that has been done on the kindling phenomenon is reviewed, with an emphasis on those studies that deal with underlying mechanisms. Based on the work that has been done thus far, it is clear that the kindling effect is not due to any type of gross tissue damage. It is also clear that at least some of the effects are due to changes at the synapse and that these changes are widely distributed in the brain. The changes might be due to an increasing efficacy at excitatory synapses or a decreased effectiveness at inhibitory synapses, or both. The long term post-tetanic potentiation data and some preliminary electron microscopic studies support the former mechanism, whereas the depletions of catecholamines in kindled tissue support the latter. In addition to these transynaptic changes, there may be other changes that occur at the site of the stimulating electrode, and these changes may be based on a different mechanism. These ideas and the relevant data are discussed.

Animals↗