Actin Isoforms in Neuronal Development and Function - International Review of Cell and Molecular Biology - page 188

Nestin-Cre expression initiates just as the neural tube is closing, the fact
that whole body Actg1 KOs and CNS- Actg1 KO mice do not exhibit any
neural tube or similar brain morphological defects ( Bunnell and Ervasti,
2010 and Fig. 4.4 ) supports the model of β-actin-specific functions in brain
morphogenesis.
6.1.3. β -Actin Contributes to the Proper Regulation of Select Behaviors
In order to determine whether β-actin specifically contributes to normal
brain function, we analyzed the behaviors of CNS- Actb KO mice using a
number of different experimental paradigms. Given the significant dis-
ruption of the hippocampus, we started by subjecting control and CNS-
Actb KO mice to the Morris water maze, which is highly dependent on
hippocampal function ( Morris et al., 1982 ; Tsien et al., 1996 ; Vorhees and
Williams, 2006 ). We found that mice lacking β-actin within the brain had
significant impairment in water maze performance, with data suggesting
that CNS- Actb KO mice actually actively avoided escape from the maze
despite a nearly normal training phase ( Cheever et al., 2012 ). This observa-
tion raises the possibility that the mice failed to learn the goal of the test
(to find the hidden platform), or that perhaps these mice had heightened
anxiety potentially confounding their spatial memory performance. We also
employed an open field activity assay, which can shed light on hippocampal
and anxiety-mediated behavioral abnormalities ( Mignogna and Viggiano,
2010 ; Viggiano, 2008 ). CNS- Actb KO mice were found to be profoundly
hyperactive, and to such an extent that it interfered with interpretation of
anxiety readouts from this assay. While this hyperactive phenotype could be
due to large number of mechanisms, we did rule out that the absence of
β-actin perturbs the regulation of circadian rhythm-mediated activity cycles
which were normal in CNS- Actb KO mice ( Fig. 4.5 ).
At present, it is unclear whether the morphological abnormalities
noted in the brains of CNS- Actb KO mice are directly responsible for the
behavioral phenotypes just described. Although the invagination of the
dentate gyrus and hippocampal fissure cuts across the normal path of the
Schaffer collateral axons in the hippocampus for example, it is possible
that the axonal tracts may be mislocalized but still intact, thus preserv-
ing the integrity of the hippocampal circuit. Given the critical role for
actin and potentially the local translation of β-actin at dendritic spines, it
would be intriguing to utilize the recently described conditional β-actin
KO mouse to ablate β-actin after hippocampal morphogenesis is com-
plete ( Zhang et al., 2012 ). Upon confirming that the hippocampus is