Figure 9. The ‘irritable mossy cell’ hypothesis.

A, schematic diagram of the connectivity of the control dentate gyrus. Stimulation of the perforant path (INPUT) discharges both interneurones (IN) and granule cells (GC), and granule cells excite the mossy cells (MC) (perforant path inputs may also directly activate mossy cells; not indicated). The granule cell discharge is the main signal that leaves the dentate gyrus (OUTPUT). Neuronal discharge is schematically indicated next to the INPUT, the OUTPUT and the three cell types. B, the ‘dormant basket cell’ hypothesis (DBCH; Sloviter, 1991) proposes that the loss of mossy cells is the central event leading to the development of hyperexcitability (hyperexcitability is indicated by the increased number of action potentials in granule cells). C, the ‘irritable mossy cell’ hypothesis (IMCH) suggests that the key event is the survival of mossy cells, which form a hyperexcitable excitatory feedback pathway to granule cells. Note that the loss of some mossy cells is not indicated for clarity. Also note that although enhanced firing of interneurones is indicated in C (since this is a likely prediction of the IMCH), in this paper the issue of the excitatory drive to GABAergic cells after FPI is not directly addressed (however, in other models of hyperexcitability, enhanced excitatory drive to interneurones has been observed, e.g. Buhl et al. 1996).