FIGURE 1.

Hypothesis of zinc-induced collapse of inhibition after mossy fiber reorganization. In control dentate granule cells (DGCs), the GABA receptors (GABARs) are insensitive to zinc (left). In DGCs from tissue of animals or humans with temporal lobe epilepsy, the subsynaptic GABARs are hypothetically altered and inhibition is enhanced (right). One hypothetical mechanism for the altered inhibition is an epilepsy-associated change in the subunit composition of the GABARs, which results in new receptors that are sensitive to zinc. The reorganized mossy fiber (MF) terminals release zinc that can hypothetically block the new GABARs, particularly during intense activity (i.e., seizures). Modified with permission from Coulter ²⁶.