Fig. 6: Overexpressing of h-α-Syn in raphe 5-HT neurons in mice results in rsfMRI hypoconnectivity.
From: Early synaptic changes and reduced brain connectivity in PD-like mice with depressive phenotype
Seed-based analysis from medial prefrontal cortex (mPFC). Male mice received 1 μl of AAV2/5-CBh-WPRE3 construct to boost h-α-Syn expression (AAV-h-α-Syn) or empty AAV2/5-CBh-WPRE3 vector containing non-coding (null) fill DNA (AAV-EV) in the dorsal raphe nucleus (DR) and were analyzed 8 weeks later. A, B Map of significant differences identified by voxel-wise statistical analysis (randomize with threshold-free cluster enhancement). In blue areas where a decreased connectivity was observed in the AAV-h-α-Syn compared to AAV-EV-injected mice (dark blue, p < 0.005; light blue, p < 0.01). AP: antero-posterior from Bregma in mm. C Average functional connectivity of the mPFC with the rest of the brain. Sagittal slices from the left hemisphere are represented. D For each cluster of voxels with significantly decreased connectivity in the AAV-h-α-Syn compared to AAV-EV-injected mice, average functional connectivity with mPFC is computed as the average of the seed-based correlation map in the specific area. Each gray point represents data from an individual mouse (n = 8 mice/group; ****p < 0.0001 versus controls). Values are presented as mean ± SEM. Abbreviations: AcbC accumbens nucleus core, B9 serotonin cells, HPC hippocampus, Hyp hypothamus, MG medial geniculate nucleus, OB olfactory bulb, PAG periaqueductal gray, Pn,pontine nucleus, SNr substantia nigra reticulata, VDB nucleus of the vertical limb of the diagonal band.
