A central role for the small GTPase Rac1 in hippocampal plasticity and spatial learning and memory.
Rac1 is a member of the Rho family of small GTPases that are important for structural aspects of the mature neuronal synapse including basal spine density and shape, activity-dependent spine enlargement, and AMPA receptor clustering in vitro. Here we demonstrate that selective elimination of Rac1 in excitatory neurons in the forebrain in vivo not only affects spine structure, but also impairs synaptic plasticity in the hippocampus with consequent defects in hippocampus-dependent spatial learning. Furthermore, Rac1 mutants display deficits in working/episodic-like memory in the delayed matching-to-place (DMP) task suggesting that Rac1 is a central regulator of rapid encoding of novel spatial information in vivo.
Haditsch
Ursula
U
Department of Neurosurgery, Stanford School of Medicine, 1201 Welch Rd, MSLS P304, Stanford, California 94305, USA. ursula.haditsch@stanford.edu
Leone
Dino P
DP
Farinelli
Mélissa
M
Chrostek-Grashoff
Anna
A
Brakebusch
Cord
C
Mansuy
Isabelle M
IM
McConnell
Susan K
SK
Palmer
Theo D
TD
D000704:Analysis of Variance; D000818:Animals; D001703:Biophysics / Q000379:methods; D000076122:Disks Large Homolog 4 Protein; D004558:Electric Stimulation / Q000379:methods; D049452:Green Fluorescent Proteins / Q000235:genetics; D051528:Guanylate Kinases; D006624:Hippocampus / Q000166:cytology* / Q000502:physiology / Q000648:ultrastructure; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007858:Learning / Q000502:physiology*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D018782:Maze Learning / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000502:physiology / Q000648:ultrastructure; D018408:Patch-Clamp Techniques / Q000379:methods; D011930:Reaction Time / Q000235:genetics; D013037:Spatial Behavior / Q000502:physiology*; D001616:beta-Galactosidase / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000172:deficiency / Q000502:physiology*
D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D051528:Guanylate Kinases; D001616:beta-Galactosidase; D020830:rac1 GTP-Binding Protein