Prefrontal neuronal morphology in kindling-prone (FAST) and kindling-resistant (SLOW) rats.

The epileptogenic-prone (FAST) and epileptogenic-resistant (SLOW) rat strains have become a valuable tool for investigating neural plasticity. The strains were generated by breeding the rats that required the fewest amygdala stimulations to elicit a stage-5 convulsive seizure (FAST) and rats requiring the most stimulations (SLOW). Previous studies have shown differences in behavior and amygdala physiology in the two strains.

Relation between startle reactivity and sucrose avidity in two rat strains bred for differential seizure susceptibility.

Rat strains selectively bred to be seizure-prone (Fast) versus seizure-resistant (Slow) show differing levels of anxiety, with Slow rats displaying relatively enhanced anxiety-like behaviors to aversive stimuli. Ample data has suggested that highly anxious rodents exhibit reduced avidity for sucrose and greater startle responses than rodents with relatively low anxiety levels. Thus, it was hypothesized that the Slow rats would have lower appetitive (sucrose consumption) and greater defensive (startle response) behaviors than Fast rats.

Caloric restriction alters seizure disposition and behavioral profiles in seizure-prone (fast) versus seizure-resistant (slow) rats.

Caloric restriction (CR), primarily known for extending life span, has proven anticonvulsant in several seizure models and antiepileptogenic in a strain of inherently seizure susceptible mice. Our animal model consisted of a seizure-prone (Fast) strain that naturally exhibits attention-deficit/hyperactivity disorder (ADHD)-like behaviors and a comparison seizure-resistant (Slow) strain; we evaluated CR's effect on the typical seizure sensitivities and behavioral profiles of each strain. Fast and Slow rats were fed ad libitum or were calorically restricted to 80% of free-feeding body weight.

Kindling as a model of human epilepsy.

The evidence supporting the suggestion that kindling is a good model of human temporal lobe epilepsy is briefly reviewed. Parallels between the human condition, involving both partial and secondarily generalized seizures, and kindling in rats and other animals are drawn and contrasted.

Postnatal epigenetic influences on seizure susceptibility in seizure-prone versus seizure-resistant rat strains.

The creation of seizure-prone (Fast) and seizure-resistant (Slow) rat strains via selective breeding implies genetic control of relative seizure vulnerability, yet ample data also advocates an environmental contribution. To investigate potential environmental underpinnings to the differential seizure sensitivities in these strains, the authors compared amygdala kindling profiles in adult male Fast and Slow rats raised by (a) their own mother, (b) a foster mother from the same strain, or (c) a foster mother from the opposing strain. Ultimately, strain-specific kindling profiles were not normalized by cross-fostering.

Assessment of anxiety-like behaviors in female rats bred for differences in kindling susceptibility and amygdala excitability.

Two rat lines bred for kindling susceptibility were previously observed to engage in different behavioral strategies in tests of emotionality. In order to extend past research on defensive behaviors in these strains which largely used males, Fast- and Slow-kindling females were assessed for anxiety-like behaviors in a number of aversive paradigms. Fast rats entered and spent more time in the open arms and spent less time in the closed arms of the elevated plus-maze (EPM) compared to Slow animals.

Mapping seizure pathways in the temporal lobe.

Interest in temporal lobe seizure pathways has a long history based initially on the human condition of temporal lobe epilepsy (TLE). This interest in TLE has extended more recently into explorations of experimental models. In this review, the network structures in the temporal lobe that are recruited in animal models during various forms of limbic seizures and status epilepticus are described.

Genetically seizure-prone or seizure-resistant phenotypes and their associated behavioral comorbidities.

It was questioned whether amygdala kindling, a model of temporal lobe epilepsy, is under genetic control, and is associated with comorbid behavioral features. Initially, rats were selectively bred for speed of amygdala kindling, and, in subsequent generations, were assessed in behavioral paradigms to measure activity, emotionality, impulsivity, and learning. Clearly kindling was under genetic control, as two strains were developed to be either Fast or Slow to kindle, and each was associated with different neurological, electrophysiological and behavioral features.

Neurodevelopment in seizure-prone and seizure-resistant rat strains: recognizing conflicts in management.

Cytoarchitectural alterations during central nervous system (CNS) development are believed to underlie aberrations in brain morphology that lead to epilepsy. We have recently reported marked reductions in hippocampal and white matter volumes along with relative ventriculomegaly in a rat strain bred to be seizure-prone (FAST) compared to a strain bred to be seizure-resistant (SLOW) (Gilby et al., 2002, American Epilepsy Society 56th Annual Meeting).

Ruling out postnatal origins to attention-deficit/hyperactivity disorder (ADHD)-like behaviors in a seizure-prone rat strain.

Adult Fast (seizure-prone) and Slow (seizure-resistant) kindling rat strains exhibit divergent behaviors in paradigms relevant to attention-deficit/hyperactivity disorder (ADHD) in humans. Similar dissociations in rodent behavior have been linked to disparities in early life experience, suggesting that differential maternal care or postnatal interactions may underlie these behaviors. Consequently, the authors compared maternal behavior and preweaning pup weights in these 2 strains under control and cross-fostered conditions and examined its effects on subsequent adult offspring behavior.

Effect of focal low-frequency stimulation on amygdala-kindled afterdischarge thresholds and seizure profiles in fast- and slow-kindling rat strains.

Purpose: To determine whether low-frequency, 1-Hz sine-wave stimulation (LFS) applied to a fully kindled amygdala focus would show antiepileptic properties in rats that were either naturally seizure prone (Fast) or seizure resistant (Slow).

Methods: Normal twisted and/or "spanning" bipolar electrode configurations were implanted in the amygdalae of adult male Fast and Slow rats. In experiment one, rats were kindled daily to stage-5 levels through one electrode type until stable afterdischarge thresholds (ADTs) were obtained.

Temporal sequence of ictal discharges propagation in the corticolimbic basal ganglia system during amygdala kindled seizures in freely moving rats.

We used a multiple channel, single unit recording technique to investigate the neural activity in different corticolimbic and basal ganglia regions in freely moving rats before and during generalized amygdala kindled seizures. Neural activity was recorded simultaneously in the sensorimotor cortex (Ctx), hippocampus, amygdala, substantia nigra pars reticulata (SNr) and the subthalamic nucleus (STN). We observed massive synchronized activity among neurons of different brain regions during seizure episodes.

Differential noradrenergic influence on seizure expression in genetically Fast and Slow kindling rat strains during massed trial stimulation of the amygdala.

The involvement of alpha(2) noradrenergic receptors during amygdala 'massed' stimulation (MS) was examined in rats that were selectively bred to be seizure-prone (Fast) or seizure-resistant (Slow) to amygdala kindling. The selective alpha(2) noradrenergic agonist guanfacine, or the antagonist idazoxan, was intraperitoneally injected during the MS procedure to study subsequent changes in afterdischarge (AD) threshold, AD duration and behavioral seizure expression. These measurements were again assessed weekly for 2 weeks after the MS treatment.

Play fighting between kindling-prone (FAST) and kindling-resistant (SLOW) rats.

Differences in the play behavior of 2 strains of rats suggest that different components of play fighting can be modified independently. The development of play fighting in cross-strain pairs of familiar and unfamiliar rats was examined to determine whether interacting with a non-congruent pair-mate would alter the pattern of play typical for each strain. In both strains, changes in play fighting were observed throughout development, but partner identity appeared to influence play fighting in different ways depending on age.

Parahippocampal networks, intractability, and the chronic epilepsy of kindling.

Clearly, the root cause of intractability in epilepsy is currently unknown. Whereas the aforementioned findings may shed light on putative underpinnings, they are by no means an exhaustive list of possibilities. However, new and more effective animal models are continually being created or discovered that take into account genetic predisposition for seizure.

Differential GABA(A) subunit expression following status epilepticus in seizure-prone and seizure-resistant rats: a putative mechanism for refractory drug response.

Purpose: Two rat strains were selectively bred to be prone (Fast) or resistant (Slow) to amygdala kindling. The first objective of this experiment was to determine whether that selection was specific to kindling or was sensitive more broadly to another seizure induction agent, kainic acid (KA). Second, we investigated whether these strains exhibit distinct molecular responses to KA with respect to GABA(A) receptor subunit expression.

Neurosteroids exhibit differential effects on mIPSCs recorded from normal and seizure prone rats.

In the perirhinal cortex of seizure prone (SP) rats, GABA(A)-mediated miniature inhibitory postsynaptic currents (mIPSCs) are smaller in amplitude but have longer deactivation phases than mIPSCs recorded in normal control (NC; outbred) rats. These differences in mIPSCs are correlated to the relatively higher alpha1 subunit expression in the NC rat strains and the higher alpha2, alpha3, and alpha5 subunit expression in the SP strain. Using patch-clamp recording, we investigated how the neurosteroids tetrahydrodeoxcorticosterone (THDOC) and allopregnanolone at physiological and pharmacological concentrations may differentially affect the mIPSCs in the perirhinal cortex of brain slices isolated from SP and NC rats.

Development of play fighting in kindling-prone (FAST) and kindling-resistant (SLOW) rats: how does the retention of phenotypic juvenility affect the complexity of play?

Rats selectively bred for susceptibility to amygdala kindling (FAST) have been shown to retain neural and behavioral features of the juvenile phase into adulthood. In contrast, rats selectively bred for resistance to amygdala kindling (SLOW) are neurobehaviorally more typically adult. The development of play fighting in male and female rats of both selected lines was studied.

Amygdala amino acid and monoamine levels in genetically Fast and Slow kindling rat strains during massed amygdala kindling: a microdialysis study.

We investigated the neurochemistry of epileptic seizures in rats selectively bred to be seizure-prone (Fast) vs. seizure-resistant (Slow) to amygdala kindling. Microdialysis was used to measure levels of amino acids [glutamate, aspartate and gamma-aminobutyric acid (GABA)] and monoamines (noradrenaline, dopamine and serotonin) during 'massed' stimulation (MS) (every 6 min) of the ipsilateral amygdala for a total of 40 stimulation trials.

Activin mRNA induced during amygdala kindling shows a spatiotemporal progression that tracks the spread of seizures.

The progressive development of seizures in rats by amygdala kindling, which models temporal lobe epilepsy, allows the study of molecular regulators of enduring synaptic changes. Neurotrophins play important roles in synaptic plasticity and neuroprotection. Activin, a member of the transforming growth factor-beta superfamily of growth and differentiation factors, has recently been added to the list of candidate synaptic regulators.

Differential neuroplastic changes in neocortical movement representations and dendritic morphology in epilepsy-prone and epilepsy-resistant rat strains following high-frequency stimulation.

The epileptogenic-prone (FAST) and epileptogenic-resistant (SLOW) rat strains have become a valuable tool for investigating the neurochemical and neurophysiological basis of epilepsy. This study examined the two strains with respect to their neocortical movement representations and cortical layer III pyramidal cell dendritic morphology in both control and potentiated conditions. FAST and SLOW rats received high-frequency stimulation of the corpus callosum in order to induce long-term polysynaptic potentiation of the transcallosal pathway to the sensorimotor neocortex.

Anxiety in rats selectively bred for Fast and Slow kindling rates: situation-specific outcomes.

Rats selectively bred for amygdala excitability, realized by fast or slow kindling epileptogenesis, were previously reported to exhibit differential levels of anxiety. Although the Slow kindling rats generally appeared more anxious in several behavioral tests, under certain test conditions the Fast kindling rats displayed greater anxiety or stressor reactivity. The present investigation confirmed that in a test of anxiety comprising suppression of consumption of a palatable snack in an unfamiliar environment, the Slow kindling rats exhibited greater anxiety and that this effect was attenuated by diazepam.

Differential sensitivity of genetically Fast vs. Slow kindling rats strains to GABAergic convulsive agents.

Following selective breeding for seizure-proneness vs. seizure-resistance to amygdala kindling, two strains of rats were developed with non-overlapping kindling rates, i.e.

Secondary generalization of hippocampal kindled seizures in rats: examining the role of the piriform cortex.

A primary feature of epilepsy is the potential for focal seizures to recruit distant structures and generalize into convulsions. Key to understanding generalization is to identify critical structures facilitating the transition from focal to generalized seizures. In kindling, development of a primary site leads progressively to secondarily generalized convulsions.

Divergent GABA(A) receptor-mediated synaptic transmission in genetically seizure-prone and seizure-resistant rats.

Recent evidence suggests that abnormal expression of GABA(A) receptors may underlie epileptogenesis. We observed previously that rats selectively bred to be seizure-prone naturally overexpressed, as adults, GABA alpha subunits (alpha2, alpha3, and alpha5) seen at birth, whereas those selected to be seizure-resistant overexpressed the adult, alpha1 subunit. In this experiment, we gathered GABA miniature IPSCs (mIPSCs) from these strains and correlated their attributes with the subunit expression profile of each strain compared with a normal control strain.