TARGETED DELETION IN ASTROCYTE INTERMEDIATE FILAMENT (GFAP) ALTERS NEURONAL PHYSIOLOGY

Glial fibrillary acidic protein (GFAP) is a member of the family of in termediate filament structural proteins and is found predominantly in astrocytes of the central nervous system (CNS), To assess the function of GFAP, we created GFAP-null mice using gene targeting in embryonic stem cells, The GFAP-null mice have normal development and fertility, and show no gross alterations in behavior or CNS morphology, Astrocyte s are present in the CNS of the mutant mice, but contain a severely re duced number of intermediate filaments, Since astrocyte processes cont act synapses and may modulate synaptic function, we examined whether t he GFAP-null mice were altered in long-term potentiation in the CAI re gion of the hippocampus. The GFAP-null mice displayed enhanced long-te rm potentiation of both population spike amplitude and excitatory post -synaptic potential slope compared to control mice, These data suggest that GFAP is important for astrocyte-neuronal interactions, and that astrocyte processes play a vital role in modulating synaptic efficacy in the CNS. These mice therefore represent a direct demonstration that a primary defect in astrocytes influences neuronal physiology.