Brain Metabolism of the P/Q type calcium channel deficient mice, an fMRI study

H. W. MORENO, D. VELA-DUARTE, S. CHOI, F. J. URBANO, T. LEE, H.-S. SHIN, S. SMALL, R. R. LLINÁS.

San Diego, USA.

Conferencia; San Diego Convention Center: Halls B-H; 2007

Cerebral blood volumes (CBV) maps were generated by an in vivo high spatial resolution fMRI contrasted based technique in a 9,4T magnet in same age mice lacking P/Q-type calcium channels (α1A-deficient mice, α1A-/-) and its wildtype littermates. CBV is a measure of basal brain metabolism. Structural volumetric analysis was also preformed. The α1A-deficient mice (α1A-/-) are characterized for being smaller than their wild-type littermates, living up to 3 weeks after birth. The α1A-/- developed several neurological symptoms during the last two weeks of life. From 10 days after birth, the α1A-/- mice started to loss balance during walking. The other dystonic phenotypes, such as twisting movements of trunk and limbs and abnormal postures, were also observed in α1A-/- mice. In addition, α1A-/- showed severe absence seizure, which were characterized by 3~5 Hz spike-wave discharges (SWDs) in EEG accompanied by behavioral arrest were occurred ~160 times per hour in these animals. We found higher CBV values in all brain regions analyzed using 5 wildtypes and 5 knockouts. The areas with statistically significant increased CBV values were: cerebellum (P=0.019), frontal cortex (P=0.044), anterior thalamus (P=0.046), caudate/putamen (P=0.046). Differences in other areas such as parietal cortex, occipital cortex, olfactory bulb, hippocampus, or posterior thalamus, did not reach significance. On the other hand, structural volumetric analysis showed a significant decreased only in caudate/ putamen in KO mice as compare to wildtypes (1.86 +/-0.11 mm3 and 0.89+/-0.13 mm3, P<0.05 for KO and WT, respectively). Other areas measured had also lower values, though were not significantly different. These findings suggests that the absence of P/Q type calcium channels provoked an abnormal increment of activity in motor related areas as basal ganglia and cerebellum, consistent with the pathological phenotype showed by these knockouts.