Hippocampal phenotypes in kalirin-deficient mice.
Regulation of forebrain cellular structure and function by small GTPase pathways is crucial for normal and pathological brain development and function. Kalirin is a brain-specific activator of Rho-like small GTPases implicated in neuropsychiatric disorders. We have recently demonstrated key roles for kalirin in cortical synaptic transmission, dendrite branching, spine density, and working memory. However, little is known about the impact of the complete absence of kalirin on the hippocampus in mice. We thus investigated hippocampal function, structure, and associated behavioral phenotypes in KALRN knockout (KO) mice we have recently generated. Here we show that KALRN KO mice had modest impairments in hippocampal LTP, but normal hippocampal synaptic transmission. In these mice, both context and cue-dependent fear conditioning were impaired. Spine density and dendrite morphology in hippocampal pyramidal neurons were not significantly affected in the KALRN KO mice, but small alterations in the gross morphology of the hippocampus were detected. These data suggest that hippocampal structure and function are more resilient to the complete loss of kalirin, and reveal impairments in fear learning. These studies allow the comparison of the phenotypes of different kalirin mutant mice and shed light on the brain region-specific functions of small GTPase signaling.
Xie
Zhong
Z
Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Cahill
Michael E
ME
Radulovic
Jelena
J
Wang
Jing
J
Campbell
Susan L
SL
Miller
Courtney A
CA
Sweatt
J David
JD
Penzes
Peter
P
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002478:Cells, Cultured; D005239:Fear / Q000502:physiology; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D006801:Humans; D017774:Long-Term Potentiation / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000502:physiology; D010641:Phenotype; D009435:Synaptic Transmission / Q000502:physiology
D020662:Guanine Nucleotide Exchange Factors; C548820:KALRN protein, mouse