Beth Adams

Long-term potentiation trains induce mossy fiber sprouting

It has been shown that both amygdaloid and hippocampal kindling induce sprouting of the mossy fibers in the dentate gyrus. In this study, we investigated whether non-epileptogenic stimulation could also induce mossy fiber sprouting. Long-term potentiation (LTP) was induced in the dentate gyrus by the application of brief, high frequency trains to the perforant path. The potentiating stimulation was applied each day for 10 days, and the tissue was prepared for Timm labelling 7 days later. Sprouting was significantly increased in the LTP group compared to the implanted control rats. These results suggest that mossy fiber sprouting is not damage-induced and is dependent on neuronal activation.

Brain-derived neurotrophic factor infusion delays amygdala and perforant path kindling without affecting paired-pulse measures of neuronal inhibition in adult rats

Kindling is an animal model of human temporal lobe epilepsy in which excitability in limbic structures is permanently enhanced by repeated stimulations. Kindling also increases the expression of nerve growth factor, brain-derived neurotrophic factor, and brain-derived neurotrophic factor receptor messenger RNAs in both the hippocampus and cerebral cortex and causes structural changes in the hippocampus including hilar hypertrophy. We have recently shown that intraventricular nerve growth factor infusion enhances the development of kindling, whereas blocking nerve growth factor activity retards amygdaloid kindling. Furthermore, we have shown that nerve growth factor protects against kindling-induced hilar hypertrophy. The physiological role of brain-derived neurotrophic factor in kindling is not as clear. Acute injection of brain-derived neurotrophic factor increases neuronal excitability and causes seizures, whereas chronic brain-derived neurotrophic factor infusion in rats slows hippocampal kindling. In agreement with the latter, we show here that intrahilar brain-derived neurotrophic factor infusion delays amygdala and perforant path kindling. In addition, we show that brain-derived neurotrophic factor, unlike nerve growth factor, does not protect against kindling-induced increases in hilar area. To test the hypothesis that brain-derived neurotrophic factor suppresses kindling by increasing inhibition above normal levels, we performed paired-pulse measures in the perforant path-dentate gyrus pathway. Brain-derived neurotrophic factor infused into the hippocampus had no effect on the stimulus intensity function (input/output curves); there was also no significant effect on paired-pulse inhibition. We then kindled the perforant path 10 days after the end of brain-derived neurotrophic factor treatment. Once again, kindling was retarded, showing that the brain-derived neurotrophic factor effect is long-lasting. These results indicate that prolonged in vivo infusion of brain-derived neurotrophic factor reduces, rather than increases, excitability without increasing inhibitory neuron function, at least as assessed by paired-pulse protocols. This effect may be mediated by long-lasting effects on brain-derived neurotrophic factor receptor regulation.

Infants’ and adults’ use of duration and intensity cues in the segmentation of tone patterns

Adults and 8-month-olds were presented with sequences in which every third complex tone was either longer or more intense. Segmentation was measured by comparing the detection of silent gaps inserted into three possible locations in each pattern: Silent gaps inserted at perceived segmentation boundaries are harder to detect than gaps within perceived phrases or groups. A go/no-go conditioned head-turn (hand-raising for adults) procedure was used. In Experiment 1, detection was worse for the gaps following the longer complex tones than for the gaps at the other locations, suggesting that the longer tones marked the ends of perceived groups for both infants and adults. Experiment 2 showed that an increase in intensity did not result in any systematic grouping at either age.

Time course for kindling-induced changes in the hilar area of the dentate gyrus: reactive gliosis as a potential mechanism

Recurrent seizure activity induced during kindling has been reported to cause an increase in the hilar area of the dentate gyrus of the hippocampus. To date, very little is known about the mechanism of this increase. This study investigated the time course for kindling-induced changes in the hilar area of the dentate gyrus at seven days, one month, and two months post-kindling. Hilar area of the dentate gyrus was significantly increased by approximately 46% at seven days and remained elevated at one month, but declined back to control levels by two months. Glial fibrillary acidic protein (GFAP) immunostaining was also evaluated at the same time points to determine whether kindling-induced changes in the hilar area of the dentate gyrus are related to kindling-induced glial cell changes. Increases in hilar GFAP immunostaining by approximately 57% were observed at seven days and at one month post-kindling, but not at two months post-kindling. These findings indicate that kindling-induced changes in the hilar area of the dentate gyrus and kindling-induced glial cell changes follow a similar time course, and that kindling-induced glial cell changes may mediate the observed changes in the hilar area of the dentate gyrus.

Neural Growth, Neural Damage and Neurotrophins in the Kindling Model of Epilepsy

Do seizures change the brain? Studies on the kindling model--a widely used animal model of epilepsy--suggest that they do. Dr. Racine, one of the pioneers in the kindling field, describes the basic phenomena of kindling, and discusses the possible roles of cell growth and cell death in this model.

Neuronal Growth and Neuronal Loss in Kindling Epileptogenesis

Goddard published his first brief description of the kindling phenomenon in 196736. Although we have learned quite a lot about this model of epilepsy in the last 30 years, the underlying mechanisms continue to elude us. Part of the difficulty arises from the fact that various patterns of neural activation, we now know, can trigger a wide variety of long-lasting post-activation effects. Excess neural activation (e.g. epileptiform events) can produce an even greater number of effects, and any of these could contribute to the development of an epileptogenic state.