Targeted deletion in astrocyte intermediate filament (Gfap) alters neuronal physiology.
Glial fibrillary acidic protein (GFAP) is a member of the family of intermediate 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. Astrocytes are present in the CNS of the mutant mice, but contain a severely reduced number of intermediate filaments. Since astrocyte processes contact synapses and may modulate synaptic function, we examined whether the GFAP-null mice were altered in long-term potentiation in the CA1 region of the hippocampus. The GFAP-null mice displayed enhanced long-term 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.
McCall
M A
MA
Department of Pathobiological Sciences, University of Wisconsin-Madison, 53706, USA.
Gregg
R G
RG
Behringer
R R
RR
Brenner
M
M
Delaney
C L
CL
Galbreath
E J
EJ
Zhang
C L
CL
Pearce
R A
RA
Chiu
S Y
SY
Messing
A
A
D000818:Animals; D001253:Astrocytes / Q000648:ultrastructure; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics*; D006624:Hippocampus / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure; D006720:Homozygote; D017774:Long-Term Potentiation; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure; D012583:Schwann Cells / Q000648:ultrastructure; D017384:Sequence Deletion; D009435:Synaptic Transmission
D005904:Glial Fibrillary Acidic Protein