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Biomedical subjects

M E Corcoran

Publications and source records attributed to M E Corcoran.

At least 19 recordsLinked to original sources
PubMed2005

Anterior perirhinal cortex kindling produces long-lasting effects on anxiety and object recognition memory.

Temporal lobe epilepsy (TLE) is frequently accompanied by memory impairments and, although their bases are unknown, most research has focused on the hippocampus. The present study investigated the importance of another medial temporal lobe structure, the perirhinal cortex (Prh), in changes in memory in TLE using kindling as a model. Rats were kindled twice daily with anterior Prh stimulation until three fully generalized seizures were evoked. Beginning 7 days later and on successive days, rats were tested in an elevated plus maze, a large circular open field, an open field object exploration task and a delayed-match-to-place task in a water maze in order to assess anxiety-related and exploratory behaviour, object recognition memory and spatial cognition. Kindling increased anxiety-related behaviour in both the elevated plus and open field mazes and disrupted spontaneous object recognition but spared all other behaviours tested. These results are consistent with other findings indicating a greater role for the Prh in object memory and emotional behaviour than in spatial memory and contrast with the selective disruption of spatial memory produced by dorsal hippocampal kindling. The site-selectivity of the behavioural disruptions produced by kindling indicates that such effects are probably mediated by changes particular to the site of seizure initiation rather than to changes in the characteristic circuitry activated by limbic seizure generalization. Further investigation of the behavioural effects of Prh kindling may be useful for studying the mechanisms of mnemonic and affective dysfunction associated with TLE and offer insights into bases for variability in such dysfunction across patients.

Animals↗
PubMed2004

The relation between extent of dorsal hippocampal kindling and delayed-match-to-place performance in the Morris water maze.

Dorsal hippocampal kindling impairs subsequent performance on spatial tasks. The relation between this effect and the extent of kindling achieved prior to testing has not been clearly established. Thus, the present study investigated the effects of dorsal hippocampal kindling on performance of a delayed-match-to-place (DMTP) task in the Morris water maze by assessing performance after each of series of different points in the kindling process including 1, 6, 11, and 16 afterdischarges, 1 stage 1 seizure, and 1 stage 5 seizure. We found that kindling produced a deficit that was apparent very early into kindling in terms of both direct swim (by 1 AD) and escape distance (by 6 ADs) measures but that did not clearly change in severity with further kindling. These results illustrate that kindling of even a few localized hippocampal seizures can disrupt spatial cognition and suggest that the mechanisms mediating memory disruption either do not change substantially as kindling progresses or that compensatory processes are engaged across training that mitigate any further kindling-related deteriorations in performance.

Animals↗
PubMed2004

Further evidence for a role of the anterior claustrum in epileptogenesis.

The anatomy of the claustrum (CLA) has been well characterized, but its functional role remains uncertain. The results of recent research suggest that the CLA may be part of a network of structures involved in seizure generalization, and we set out to test this idea. To test persistence, seizures were kindled in the anterior CLA. Following a 14-day suspension of kindling, all rats required only one stimulation to evoke a stage 5 seizure. In another experiment, groups of rats received bilateral lesions of the anterior CLA before and after amygdaloid kindling. We found that small lesions of the anterior CLA retard amygdaloid kindling, but do not block the expression of generalized seizures. Lesions produced after amygdaloid kindling resulted in a shorter seizure duration, but had no marked effect on seizure expression. Another group of rats was tested for transfer of kindling between the anterior CLA and contralateral amygdala. We found an asymmetrical transfer of kindling to the CLA from the amygdala wherein amygdaloid kindling facilitated subsequent kindling of the CLA but kindling of the anterior CLA failed to facilitate kindling of the amygdala. The results add support to the notion that the CLA contributes to the development of generalized limbic seizures.

Amygdala↗
PubMed2001

Dorsal hippocampal kindling produces a selective and enduring disruption of hippocampally mediated behavior.

Kindling produces enduring neural changes that are subsequently manifest in enhanced susceptibility to seizure-evoking stimuli and alterations in some types of behavior. The present study investigated the effects of dorsal hippocampal (dHPC) kindling on a variety of behaviors to clarify the nature of previously reported effects on spatial task performance. Rats were kindled twice daily with dHPC stimulation until three fully generalized seizures were evoked. Beginning 7 d later and on successive days, rats were tested in an elevated plus maze, a large circular open field, an open field object exploration task, and a delayed-match-to-place (DMTP) task in a water maze to assess anxiety-related and activity-related behavior (tasks 1 and 2), object recognition memory (task 3), and spatial cognition (task 4). Kindling disrupted performance on the DMTP task in a manner that was not delay dependent and produced a mild enhancement of activity-related behaviors in the open field task but not the elevated plus maze. All other aspects of testing were spared. These findings indicate that dHPC kindling produces enduring and selective effects on behavior that are consistent with a restricted disruption of hippocampally mediated functions. Possible bases for these effects are changes in local NMDA receptor function and/or changes in local inhibition, which might alter the optimal conditions for experience-dependent induction of intrahippocampal plasticity. This preparation may be useful for studying the mechanisms of mnemonic dysfunction associated with temporal lobe epilepsy and may offer unique insights into the mechanisms underlying normal hippocampal function.

Animals↗
PubMed2001

Susceptibility to kindling and neuronal connections of the anterior claustrum.

The claustrum has been implicated in the kindling of generalized seizures from limbic sites. We examined the susceptibility of the anterior claustrum itself to kindling and correlated this with an anatomical investigation of its afferent and efferent connections. Electrical stimulation of the anterior claustrum resulted in a pattern of rapid kindling with two distinct phases. Early kindling involved extremely rapid progression to bilaterally generalized seizures of short duration. With repeated daily kindling stimulations, early-phase generalized seizures abruptly became more elaborate and prolonged, resembling limbic-type seizures as triggered from the amygdala. We suggest that the rapid rate of kindling from the anterior claustrum is an indication that the claustrum is functionally close to the mechanisms of seizure generalization. In support of our hypothesis, we found significant afferent, efferent, and often reciprocal connections between the anterior claustrum and areas that have been implicated in the generation of generalized seizures, including frontal and motor cortex, limbic cortex, amygdala, and endopiriform nucleus. Additional connections were found with various other structures, including olfactory areas, nucleus accumbens, midline thalamus, and brainstem nuclei including the substantia nigra and the dorsal raphe nucleus. The anatomical connections of the anterior claustrum are consistent with its very high susceptibility to kindling and support the view that the claustrum is part of a forebrain network of structures participating in the generalization of seizures.

Afferent Pathways↗
PubMed2001

Dorsal hippocampal kindling selectively impairs spatial learning/short-term memory.

Kindling with electrical stimulation of the dorsal hippocampus has been shown to disrupt spatial task performance in rats. The present study investigated the specificity of this effect in terms of the possible contribution of nonmnemonic effects, the presence of a more general mnemonic deficit, and the involvement of learning/short-term memory and/or long-term memory processes. Rats were fully kindled with stimulation of the dorsal hippocampus and subsequently tested for acquisition, 7-day retention, and 28-day retention of a hidden platform (HP) location in the Morris water maze and an object discrimination problem in a modified water maze. To control for nonmnemonic behavioral impairments, testing on both tasks was preceded by training on visible platform control tasks. Kindling impaired acquisition of the HP location but spared performance on all other aspects of testing, indicating a specific impairment of spatial learning/short-term memory. These results suggest that epileptogenesis induced by hippocampal stimulation is indeed associated with a selective disruption of the mechanisms mediating spatial learning/short-term memory.

Animals↗
PubMed2001

Kindling of claustrum and insular cortex: comparison to perirhinal cortex in the rat.

The perirhinal cortex has recently been implicated in the kindling of limbic generalized seizures. The following experiments in rats tested the selectivity of the perirhinal cortex's epileptogenic properties by comparing its kindling profile with those of the adjacent insular cortex, posterior (dorsolateral) claustrum and amygdala. The first experiment examined the kindling and EEG profiles, and found that both the claustrum and insular cortex demonstrated rapid epileptogenic properties similar to the perirhinal cortex, including very rapid kindling rates and short latencies to convulsion. Furthermore, electrical stimulation of all three structures led to a two-phase progression through stage-5 seizures which had characteristics of both neocortical and amygdaloid kindling. In a second experiment rats were suspended in a harness to allow for more detailed documentation of both forelimb and hindlimb convulsions. With this procedure we were able to detect subtle yet unique differences in convulsion characteristics from each of the kindled sites and stage-5 seizure phases. Some of these convulsive parameters were correlated with changes in FosB/DeltaFosB protein and BDNF mRNA expression measured two hours after the last convulsion. Overall, it appears that the perirhinal cortex is not unique in its property of rapid epileptogenesis. Moreover, the posterior claustrum exhibited the fastest kindling and most vigorous patterns of clonus, suggesting that it may be even more intimately associated with the motor substrates responsible for limbic seizure generalization than is the perirhinal cortex.

Animals↗
PubMed2001

Food insufficiency and the physical and mental health of low-income women.

Poor women with children are disproportionately represented among the food insufficient. Recent research has linked food insufficiency with dietary deficiencies, but further research linking this problem to health and mental health problems is needed to inform health and social policy. We analyzed the relationship between food insufficiency and physical and mental health in a random sample of 724 single women who were welfare recipients in February, 1997. Food insufficiency was significantly associated with poor or fair self-rated health and physical limitations, and with respondents' meeting DSM-III-R criteria for recent major depression. Although the cross-sectional design of this study precludes causal inference, these findings add to a growing body of evidence that food insufficiency is associated with serious adverse physical and mental health consequences.

Adult↗
PubMed2000

Mossy fiber sprouting is dissociated from kindling of generalized seizures in the guinea-pig.

Controversy surrounds whether aberrant mossy fiber sprouting in the hippocampus is necessary for the establishment of seizure states. We investigated the association between mossy fiber sprouting and kindling in guinea-pigs, using either single-site or alternate-site stimulation. Kindling with single-site amygdaloid stimulation did not induce significant sprouting, despite the development of partial seizures. In contrast, single-site septal and alternating amygdaloid-septal stimulation produced moderate but significant sprouting in about 60% of animals that failed to develop stage 5 generalized seizures. Since the magnitude of sprouting was similar despite striking differences in the intensity of seizures that developed, we conclude that mossy sprouting is not causally associated with seizure development.

Amygdala↗
PubMed2000

The mnemonic effects of kindling.

Kindling produces enduring changes in the brain that are evident in not only enhanced susceptibility to seizure-evoking stimuli but also alterations in non-epileptic behaviors or functions. The present review examines the effects of kindling on one class of non-epileptic functions, learning and memory, and explores the dependence of these effects on variables such as the site of kindling, extent of kindling, and interval between kindling and testing. Current research shows that kindling is capable of altering performance on a variety of tasks including those that require spatial cognition, aversive conditioning, and object-related cognition and that non-mnemonic effects are unlikely, in at least some cases, to underlie these effects. Consideration of the conditions under which these effects are observed indicates a distinct relation between specific mnemonic effects and both the site and extent of kindling. Continued characterization of the mnemonic effects of kindling should provide a theoretical framework to guide discovery of their underlying mechanisms, which, in turn, may lead to rational therapy for mnemonic dysfunction associated with epilepsy and insights into the mechanisms of learning and memory.

Animals↗
PubMed2000

Hippocampal kindled seizures impair spatial cognition in the Morris water maze.

We investigated the effects of hippocampally kindled seizures on spatial performance of rats in the Morris water maze (MWM). Seizures were elicited with stimulation of field CA1 of dorsal hippocampus 25-45 min prior to daily testing in the water maze. One group of rats was naive to the MWM (acquisition groups), while another group received pretraining in the MWM (retention groups). These groups were further subdivided into rats that experienced non-convulsive seizures prior to daily testing and rats that experienced fully generalized convulsive seizures prior to daily testing. We found that CA1 seizures significantly disrupted water maze performance during both acquisition and retention, and the effects were similar when either non-convulsive or fully generalized convulsive seizures were evoked. Our findings are consistent with previous reports suggesting that epileptiform activity in the hippocampus acutely impairs performance in tasks sensitive to spatial learning and memory deficits and suggest that both new learning and demonstration of an established place response are susceptible to such disruption.

Animals↗
PubMed2000

Claustral lesions delay amygdaloid kindling in the rat.

PURPOSE: Lesions of the claustrum in cats and primates have been shown to disrupt the development and expression of amygdaloid-kindled seizures in cats and primates. Because the structure and connectivity of the claustrum can vary between species, we wanted to examine the effects of claustral lesions on kindling in rats. METHODS: One group of rats received bilateral radiofrequency lesions of both anterior and posterior regions of the claustrum before amygdaloid kindling. Another group of rats received bilateral anterior and posterior radiofrequency lesions of the claustrum after amygdaloid kindling. Some rats were tested for transfer of kindling to the contralateral amygdala after claustral lesions. RESULTS: Small lesions that destroyed 13% of the claustrum were capable of delaying, but not blocking, amygdaloid kindling. The delay in kindling was due to an increase in the stimulation trials required to kindle to stage 5 seizures. The lesions had no effect on established kindled seizures or on transfer to the contralateral amygdala. CONCLUSIONS: As in other species, the claustrum in the rat appears to play a role in kindling from the amygdala. Because of the restricted size of our claustral lesions, however, we were unable to conclusively assess the full extent of the claustrum's participation in limbic kindling.

Amygdala↗
PubMed1998

Dissociation between mossy fiber sprouting and rapid kindling with low-frequency stimulation of the amygdala.

In an attempt to determine whether sprouting of mossy fibers is invariably correlated with kindling of seizures, we subjected rats to rapid kindling with long trains of low-frequency stimulation of the amygdala that resulted in development of generalized seizures within a mean of five stimulations. For comparison, we subjected other rats to conventional kindling with short trains of high-frequency stimulation of the amygdala that resulted in development of generalized seizures within a mean of 13 stimulations. We found no evidence of mossy fiber sprouting in the dentate gyrus of rats killed one day after completion of rapid kindling, as compared to yoked controls, although significant sprouting was seen in rats killed one day after completion of conventional kindling. When we examined tissue from rats killed 20 days after rapid kindling, however, we did find significant sprouting, suggesting that mossy fiber sprouting can be triggered by rapid kindling if sufficient survival time is allowed. The observed disparity between completion of rapid low-frequency kindling and detection of mossy fiber sprouting suggests that mossy fiber sprouting may be associated more with sustained survival time after neuronal activation than with kindling per se. Furthermore, the similar time course of conventional kindling and of mossy fiber sprouting obscures the determination of a causal role of mossy fiber sprouting in conventional kindling.

Amygdala↗
PubMed1997

The effects of fimbria/fornix transections on perforant path kindling and mossy fiber sprouting.

Various clinical and experimental studies of epilepsy have described synaptic reorganization in the dentate gyrus of hippocampus, in the form of collateral sprouting of the mossy fibers. These reports have led to the hypothesis that reorganized mossy fibers form a functional excitatory feedback circuit that contributes to local circuit hyperexcitability and chronic seizures. Much of the evidence supporting the sprouting hypothesis has been derived from kindling. We recently reported that transection of the fimbria/fornix (FF), which produces chronic epileptiform activity in the hippocampus, also induces mossy fiber sprouting in the inner molecular layer of the dentate gyrus. In the present study, we attempted to determine whether mossy fiber sprouting contributes to epileptiform activity, by examining the effects FF transections on perforant path (PP) kindling and associated mossy fiber sprouting. We found that FF transections and PP kindling produced moderate levels of sprouting, whereas the combination of the two treatments produced significantly denser sprouting. FF transections had mixed effects on kindling: afterdischarge thresholds were decreased and clonus and afterdischarge durations were increased, suggesting increased local excitation, whereas the kindling of behavioral seizures was delayed, suggesting decreased epileptogenesis.

Analysis of Variance↗
PubMed1997

Time course of mossy fiber sprouting following bilateral transection of the fimbria/fornix.

Lesions of the fimbria/fornix (FF) lead to a variety of epileptiform changes in hippocampal activity. In epilepsy, as well as in several experimental preparations of epilepsy, aberrant sprouting of the dentate gyrus mossy fibers (MF) is observed and has been hypothesized to play a critical role in the generation of seizure activity. We therefore sought to determine whether MF sprouting also follows FF transections. FF transections did indeed lead to MF sprouting, which became apparent at 14 days and reached asymptotic levels at 28 days post-lesion. These results indicate a possible mechanism for the epileptiform activity seen following FF lesions and provide an additional example of the diverse epileptogenic treatments that are accompanied by MF sprouting.

Animals↗
PubMed1996

Kindling antagonism: interactions of the amygdala with the piriform, perirhinal, and insular cortices.

We employed the kindling antagonism paradigm to characterize the role of the amygdala (AM), piriform cortex (PIR), perirhinal cortex (PRH), and insular cortex (INS) in the propagation and expression of generalized seizures. Alternating kindling stimulation was delivered to the AM and either the PIR, PRH, or INS. We found that kindling from the AM was retarded by stimulation only of the deep layers of both the INS and anterior PRH. Kindling antagonism was specific to the anterior cortical regions, since neither the posterior PRH or PIR were capable of antagonizing AM kindling. The results strongly implicate the deep layers of anterior limbic cortex in establishment of antagonism of AM kindling.

Amygdala↗
PubMed1996

Kindling of hippocampal field CA1 impairs spatial learning and retention in the Morris water maze.

We used two procedures to assess the spatial learning and memory of rats in the Morris water maze task subsequent to kindling of hippocampal field CA1: (1) seizures were kindled with stimulation of CA1 prior to training in the water maze (acquisition); and (2) maze training was imposed until performance stabilized, seizures were kindled with stimulation of CA1, and then performance in the maze was reassessed (retention). In both conditions, behavioral testing occurred 24 h after the last kindled seizure. When the effects of CA1 kindling on acquisition were tested, we found that kindling of generalized seizures with stimulation of field CA1 (kindling), but not kindling of non-convulsive or partial seizures (partial kindling), produced deficits in the water maze. When the effects of CA1 kindling on retention were tested, however, we found that kindling of either partial or generalized seizures produced deficits in the water maze. The results suggest that the processing of spatial information is vulnerable to the long-lasting changes in neural excitability associated with kindling.

Animals↗