EEG tracings from the two amygdalae (right) during daily amygdala kindling (one low intensity stimulation/day). In the top pair, the first electrical kindling stimulus has been applied to the right amygdala (lower trace). Note the brief, low frequency monophasic discharge triggered in the stimulated hemisphere, but not the contralateral side. The next pair of traces are taken from the 8th stimulation. Note the discharge is longer, of higher frequency and affects both amygdalae. The last pair of traces are taken during the first fully generalize seizure (15th stimulation), where a frank convulsion occurs during the arrow heads. This developed epileptic disposition to kindled seizures remains for the life of the rat.

Our experiments on functional neuroanatomy of the rat brain are depicted in this schematic figure (left). Here we describe the pathways (with arrows) that carry kindled seizure activity from limbic sites in one hemisphere, like the hippocampus (blue), amygdala (yellow), perirhinal cortex (orange) or piriform cortex (pink), to the ipsilateral motor cortex and then to the contralateral motor cortex via the corpus callosum. From the motor cortices, the seizure discharge projects to the convulsive seizure mechanisms in the brainstem and spinal cord through crossed motor pathways.

In our electrical model of status epilepticus (SE), we trigger prolonged seizures (which characterize the SE condition) by applying 60 min of low intensity stimulation to a previously kindled site one amygdala (in the right temporal lobe, in this example). Depicted here (right) is the incorporation of glucose (the brain's fuel) in a radioactive form (14C-2-deoxyglucose), which appears dark on the x-ray film, and clearly defines the structures of the brain that are actively using glucose during SE. Note that ipsilateral structures are more involved in the mild form of 'ambulatory SE' shown here, while bilateral incorporation is observed in our more serious model forms of SE (masticatory and generalized) that are not shown.

This figure (right) is a colour enhancement of figure 4, which readily draws your attention to the areas of more intense glucose utilization.

As SE develops more fully over time, neuropathological changes begin to appear. For example, in the dorsal hippocampus (left), many living cells in the CA1 field begin to show a dramatic stress responses, represented here by the expression of 'heat shock protein' immunocytochemistry (black cells). The red cells are counter-stained with neutral red and are healthy.

While many cells are stressed during SE, other cells are dying. In this photograph (left), silver deposition (in black) is observed in many cells in the CA1 field of the dorsal hippocampus, where active degeneration is ongoing. Depending upon the form of SE, this degeneration can develop rapidly (within a few hours) or over several days.

SE, initiated with a chemical injection of a convulsant like kainic acid, invariably results in complete loss of temporal lobe structures like the piriform and perirhinal cortices, basal amygdala and many parts of the hippocampus. In this 'Timm's stained' brain section (right), collected within a 10 days of the SE experience, the basal amygdala and piriform and perirhinal cortices have completely degenerating in both hemispheres.

In our studies on neuroprotection, we have discovered that amygdala kindling can protect parts of the brain against the ravages of kainic acid induced SE. This remarkable observation is depicted here (right), where the kindled amygdala (left hemisphere) is completely protected (and is intact) one month after kainic acid SE, while in the non-kindled, right hemisphere, the entire amygdala and piriform cortex has degenerated, leaving a large hole; much of the dorsal hippocampus also has died bilaterally (resulting in severe shrinkage).

Many of our studies make use of in vitro brain slice preparations where brain sections can be kept alive for many hours in a dish for electrophysiological and other observations. Shown here (right) is our amygdala-piriform-perirhinal cortex preparation (abbrev. BLa = basal amygdala; Pir = piriform cortex; Prh - perirhinal cortex, etc.)

The slice preparation shown in figure 9 can easily be made epileptic by subjecting it to a bath perfusion with the magnesium ion removed (O Mg2+). Here (left) we show paired recordings of epileptic bursts responses in the perirhinal and piriform cortices (top pair) and the piriform and basal amygdala (bottom pair). Note the perirhinal response is much larger and longer than the piriform and basal amygdala response. This result has drawn our attention to the perirhinal area as an important player in convulsive seizure development.

Shown here (right) is a biocytin filled layer V pyramidal cell in the perirhinal cortex. We routinely fill our cells in this manner after recording a variety of electrophysiological responses from them.

Here (left) is the intracellular response of the perirhinal cell in figure 11 to current injection with depolarizing and hyperpolarizing current pulses. Each cell has its own unique profile, which has significance for its impact on its neuronal network.

Microarray gene chip analysis of differences between our epileptic prone (Fast) and epileptic resistant (Slow) rat strains. In this figure (right), many genes are assessed in one Slow rat (indicated by dots) as paired against another Slow rat. Note that the dots primarily fall along a single straight line, which indicates that one Slow is expressing the same genes at the same level as another Slow rat. Thus the genes expressed in each strain are internally quite consistent.

The microarray chip shown in this figure (left) compares a Slow rat to a Fast rat. Importantly, here we see many expressed genes that do not fall along a single line, but rather along two or more lines. Those genes around the lower line are genes that are under expressed in the Fast relative to the Slow rats.

Here (right) the differential display technique is used to show genetic differences between our Fast and Slow rat strains as compared to one of their two outbred parent phenotypes (controls). The arrow is pointing to a gene that is expressed in all 6 of the Slow rats, 4 of the 6 control rats and none of the Fast rats.

This is another differential display (right) showing a different gene that is expressed in all 4 of the Slow rats, 2 of the 4 control rats, and none of the Fast rats. In all experiments, the genes subsequently are identified by molecular techniques.