Dentate gyrus mossy cells control spontaneous convulsive seizures and spatial memory

A way to prevent generalized seizures? Temporal lobe epilepsy is the most common form of epilepsy in adults. Patients have spontaneous seizures and risk developing serious cognitive impairment. Bui et al. studied an animal model of temporal lobe epilepsy (see the Perspective by Scharfman). Selective optogenetic inhibition of dentate gyrus mossy cells increased the likelihood of electrographic seizures generalizing to full behavioral convulsive seizures. Activation of mossy cells reduced the likelihood. Thus, the activity of mossy cells might serve to inhibit seizure propagation. Science, this issue p. 787; see also p. 740 There is a direct relationship between mossy cell activity in the dentate gyrus, convulsive seizures, and spatial memory formation in mice. Temporal lobe epilepsy (TLE) is characterized by debilitating, recurring seizures and an increased risk for cognitive deficits. Mossy cells (MCs) are key neurons in the hippocampal excitatory circuit, and the partial loss of MCs is a major hallmark of TLE. We investigated how MCs contribute to spontaneous ictal activity and to spatial contextual memory in a mouse model of TLE with hippocampal sclerosis, using a combination of optogenetic, electrophysiological, and behavioral approaches. In chronically epileptic mice, real-time optogenetic modulation of MCs during spontaneous hippocampal seizures controlled the progression of activity from an electrographic to convulsive seizure. Decreased MC activity is sufficient to impede encoding of spatial context, recapitulating observed cognitive deficits in chronically epileptic mice.