Genetically altered AMPA-type glutamate receptor kinetics in interneurons disrupt long-range synchrony of gamma oscillation

Gamma oscillations synchronized between distant neuronal populations may be critical for binding together brain regions devoted to common processing t asks. Network modeling predicts that such synchrony depends in part on the fast time course of excitatory postsynaptic potentials (EPSPs) in interneur ons, and that even moderate slowing of this time course will disrupt synchr ony. We generated mice with slowed interneuron EPSPs by gene targeting, in which the gene encoding the 67-kDa form of glutamic acid decarboxylase (GAD 67) was altered to drive expression of the alpha -amino-3-hydroxy-5-methyl- 4-isoxazolepropionic acid (AMPA) glutamate receptor subunit GluR-B, GluR-B is a determinant of the relatively slow EPSPs in excitatory neurons and is normally expressed at low levels in gamma -aminobutyric acid (GABA)ergic in terneurons, but at high levels in the GAD-GluR-B mice. In both wild-type an d GAD-GluR-B mice, tetanic stimuli evoked gamma oscillations that were indi stinguishable in local field potential recordings. Remarkably, however, osc illation synchrony between spatially separated sites was severely disrupted in the mutant, in association with changes in interneuron firing patterns. The congruence between mouse and model suggests that the rapid time course of AMPA receptor-mediated EPSPs in interneurons might serve to allow gamma oscillations to synchronize over distance.