In the normal granule cells of the dentate gyrus glutamate, GABA and glutam
ic acid decarboxylase (GAD(67)) coexist. After kindled seizures, this enzym
e is transiently overexpressed and simultaneous glutamatergic and GABAergic
transmission in the mossy fiber projection occurs. Since this dual transmi
ssion is also seen after acutely-induced seizures, we decided to study the
relationship between the expression of GAD(67) and the induction of simulta
neous glutamatergic and GABAergie transmission by kindled or acutely induce
d seizures. We also explored whether kindling of the dentate gyrus in vitro
, that does not induce epileptiform activity, could induce the expression o
f GAD(67). We confirm that kindling epilepsy induces the expression of GAD(
67) in the dentate gyrus. Despite the emergence of GABAergic transmission i
n the mossy fiber projection after a single seizure, GAD(67) expression in
the dentate gyrus appeared similar to controls, however, in the mossy fiber
s an enhanced immunostaining was evident. Interestingly, kindling the denta
te gyrus in vitro induces a marked GAD(67) staining in the granule cells. O
ur results show that after the activity-dependent emergence of simultaneous
glutamatergic and GABAergic transmission from the mossy fibers, GAD(67) is
expressed in the mossy fibers and, upon long-lasting enduring stimulation
periods, also in the dentate gyrus. Thus, this phenomenon does not depend o
n the presence of epileptic activity, but rather, on increased excitatory i
nput onto the dentate gyrus, This can represent a protective mechanism that
can sustain GABA synthesis in an activity-dependent manner. (C) 2001 Elsev
ier Science B.V. All rights reserved.