Journal: Neurobiology of disease
Article Title: α-Synuclein aggregation decreases cortico-amygdala connectivity and impairs social behavior in mice.
doi: 10.1016/j.nbd.2024.106702
Figure Lengend Snippet: Fig. 5. Social interaction behavior was impaired by α-Syn pathology and rescued by chemogenetic activation of mPFC-BLA pathway. A) Diagram showing overall behavioral experimental design. B) Representative heatmap plots showing social interaction behavior of controls and PFFs-injected mice in Session 1 when S1 was paired with an empty cage for sociability. C) Representative heatmap plots showing social interaction behavior of controls and PFFs-injected mice in Session 2 when familiar S1 was paired with a novel stimulus S2 for social novelty preference. D-E) Summarized graphs showing normal sociability (D, controls empty = 177 [147, 191] sec, control S1 = 309 [273, 326] sec, n = 9 mice, p < 0.0001; PFFs empty = 181 [142, 211] sec, PFFs S1 = 290 [245, 331] sec, n = 10 mice, p = 0.001, MWU) but impaired social novelty preference behavior of PFFs-injected mice relative to controls (E, control S1 = 179 [170, 207] sec, control S2 = 256 [210, 298] sec, n = 9 mice, p = 0.01, MWU; PFFs S1 = 213 [179, 251] sec, PFFs S2 = 182 [146, 276] sec, n = 10 mice, p = 0.49, MWU). F) Representative image showing AAV-fDIO-hM3D (Gq)-mCherry infection site in the mPFC and the mCherry-labeled mPFC-BLA axon terminal field. G) Representative heatmap plots showing sociability of PFFs- injected mice receiving either saline or DCZ (DREADDs agonist) administration. H) Representative heatmap plots showing social novelty preference of PFFs- injected mice receiving either saline or DCZ (DREADDs agonist) administration. I-J) Summarized graphs showing that PFFs-injected mice receiving saline in- jections exhibit impairment in their social novelty preference behavior of (I, saline-injected control, S1 = 198 [178, 220] sec, S2 = 275 [260, 338] sec, n = 5 mice, p = 0.008; saline-injected PFFs, S1 = 294 [244, 335] sec, S2 = 214 [168, 278] sec, n = 5 mice, p = 0.09, MWU), which was rescued by DREADDs agonist DCZ injection (J, DCZ-injected controls, S1 = 180 [166, 213] sec, S2 = 294 [284, 347] sec, n = 5 mice, p = 0.008; DCZ-injected PFFs, S1 = 176 [134, 201] sec, S2 = 371 [280, 438] sec, n = 5 mice, p = 0.008, MWU).
Article Snippet: An intersectional approach was used for selective activation of mPFC to BLA projection using chemogenetics: 1) retrograde AAV encoding FlpO (0.3 μL, titer ≥7 × 1012 GC/ml, Addgene# 55637; RRID: Addgene_55,637) were bilaterally injected into BLA (A-P, − 1.3 mm from bregma; M-L,± 3.3 mm from the middle; D–V, − 4.4 mm from the brain surface), and 2) AAVs encoding FlpO-dependent excitatory designer receptors exclusively activated by designer drugs (DREADDs) (titer = 2.5 × 1013 GC/mL, Addgene 154,868; RRID:Addgene_154,868) were injected into infralimbic subregion of mPFC (IL-mPFC) (A-P, +2.1 mm from bregma; M-L,± 0.3 mm from the midline; D–V, − 2.6 mm from the brain surface).
Techniques: Activation Assay, Injection, Control, Infection, Labeling, Saline