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But they can also stimulate an opposing class of cells that inhibit these excitatory cells. Whether the net effect of mossy-cell activity is to promote or counter overall output of the excitatory nerve cells has, until now, been an open question. To answer the question, Soltesz, who holds the James R. Doty Professorship of Neurosurgery and Neurosciences, and his colleagues turned to a mouse model of temporal lobe epilepsy. The mice the Stanford investigators used were bioengineered so that their mossy cells responded to pulses of light, conveyed to those cells via an implanted optical fiber. Blue light caused mossy cells to fire, while amber light caused them to resist firing.

Medial Temporal Lobe Epilepsy: Evaluation

So, by flipping a laser switch, the scientists could activate or inhibit the mice's mossy cells at will. This increasingly widespread experimental technique, called optogenetics, is noteworthy for its capacity to target specific sets of nerve cells in order to reveal their function.

Specific set of nerve cells controls epileptic seizures' spread through brain

The scientists also recorded activity in the hippocampal region where mossy cells reside. Soltesz, Bui and their colleagues showed that inhibiting mossy cells, while not increasing the frequency of spontaneous episodes of hyperactivity in the focus of the chronically epileptic mice, did lead to a substantial increase in the number of seizures that spread from the focus to larger areas of the brain. Conversely, excitation of mossy cells in these mice diminished the number of generalized, outwardly visible seizures while having no effect, or merely a minor one, on the frequency of purely focal seizures.

In a memory test that gauges a mouse's recognition of unfamiliar objects, the epileptic mice, despite having lost more than half of their mossy cells, did fine. But they failed another test that assesses their ability to notice when a familiar object has been moved -- a gauge of spatial memory, which suffers a decline in chronic temporal lobe epilepsy.

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When the Stanford scientists also subjected optogenetically engineered but otherwise normal mice to these tests, they did great -- until the researchers inhibited their mossy cells, at which point these animals' spatial recall headed south, too. Such interventions might serve as an alternative to demanding surgical procedures now employed to excise the seizure focus from patients' brains, Soltesz said. Materials provided by Stanford Medicine.

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