Fig. 8: 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 hippocampus (HPC). 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 FWE-correction and 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, corrected p < 0.05; light blue, corrected p < 0.1). AP antero-posterior from Bregma in mm. C Average functional connectivity of the HPC with the rest of the brain. Sagital 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 HPC 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: Amg amygdala, CPu caudate putamen, Cg cingulate cortex, DR dorsal raphe nucleus, ECIC external cx inferior coll, Ect ectorhinal cortex, GP globus pallidus, Hb habenular commissure, Hyp hypothamus, IL infralimbic cortex, M1 primary motor cortex, Pir piriform cortex, PrL prelimbic cortex, PRh perirhinal cortex, RS retrosplenial cortex, Rt reticular nucleus, S1 primary somatosensorial cortex, SNr substantia nigra reticulate, ST bed nucleus of stria terminalis, Th thalamus, V1 primary visual cortex.
