Evaluation of tracing techniques in the rat spinal cord using a custom MATLAB application.

The objective of this research project is to evaluate the efficiency of traditional chemical tracing compared to dual-viral tracing for labeling long ascending propriospinal neurons (LAPNs) in the uninjured rat spinal cord, and to develop a MATLAB program which will accurately quantify this labeling. To evaluate chemical tracing, Fluoro-Ruby (FR) was injected at the level of the axon terminals, and the number of ipsilateral labeled cell bodies at lumbar level was quantified. Similarly, two dual-viral systems were evaluated, by either injecting retro-AAV-Cre or HiRet-Lenti-Cre unilaterally in combination with a Cre-dependent adeno-associated virus. The HiRet-Lenti and FR groups labeled significantly greater numbers of LAPNs than the retro-AAV group, showing that dual-viral systems utilizing retro-AAVs do not provide robust labeling when tracing LAPNs. Additionally, dual-viral tracing utilizing the HiRet-lentivirus provides more specificity than traditional chemical tracing with FR. Thus, dual-viral labeling utilizing HiRet-lentiviruses is preferred due to greater specificity and more prominent labeling. To automate the cell counting process, a MATLAB program was developed to accurately determine the number of ipsilateral cell bodies labeled by each of the tracing techniques. To validate the accuracy of the MATLAB program, the number of labeled cells counted for each tracing technique by manual counting was compared to the number generated by the MATLAB program. The number of LAPNs counted manually did not significantly differ from the number of LAPNs counted by the MATLAB application between labeling groups, and there was a highly significant correlation between the two methods

Genetic and environmental influences on focal brain density in bipolar disorder

Structural neuroimaging studies suggest the presence of subtle abnormalities in the brains of patients with bipolar disorder. The influence of genetic and/or environmental factors on these brain abnormalities is unknown. To investigate the contribution of genetic and environmental factors on grey and white matter brain densities in bipolar disorder, monozygotic and dizygotic twins concordant and discordant for bipolar disorder were scanned using 1.5 Tesla magnetic resonance imaging and compared with healthy twin pairs. A total of 232 subjects: 49 affected twin pairs (8 monozygotic concordant, 15 monozygotic discordant, 4 dizygotic concordant, 22 dizygotic discordant) and 67 healthy twin pairs (39 monozygotic and 28 dizygotic) were included. After correcting for the effect of lithium, the liability for bipolar disorder was associated with decreased grey matter density in widespread areas of the brain, but most prominent in frontal and limbic regions, and with decreased white matter density in (frontal parts of) the superior longitudinal fasciculi. The genetic risk to develop bipolar disorder was related to decreased grey matter density in the right medial frontal gyrus, precentral gyrus and insula and with decreased white matter density in the superior longitudinal fasciculi bilaterally. In conclusion, pathology in the frontal lobe, especially in parts of the superior longitudinal fasciculus, may be central to the genetic risk to develop bipolar disorder, while widespread grey matter abnormalities appear related to the illness itself. © 2010 The Author