Journal: Nature

Article Title: Stress dynamically modulates neuronal autophagy to gate depression onset

doi: 10.1038/s41586-025-08807-4

Figure Lengend Snippet: a – h , Western blot analysis showing that CRS ( a – d ) increased, whereas activating LHb autophagy by local infusion of tBP ( e – h ) decreased, the expression of GluA1 ( a , e ), GluA2 ( b , f ) and GluN1 ( c , g ), without affecting the GABA A receptor subunit ( d , h ) ( a – c , n naive/CRS = 5 per group; d , n naive/CRS = 4; e – h , n CRS+tBP-scm/CRS+tBP = 4 per group). α-tub, α-tubulin i , Experimental design. j , k , Representative traces ( j ) and quantification ( k ) show the acute effect of tBP perfusion on spontaneous firing patterns and firing frequency of LHb neurons ( n ACSF/0.5/1/5 = 8, 8, 9 neurons, n ACSF/0.5/1/5 = 7, 6, 6 mice). l – p , Representative traces ( l ) and quantification (frequency ( m , o ) and amplitude ( n , p ) of sEPSC and sIPSC) showing spontaneous neural transmission before and right after tBP perfusion in LHb neurons of CRS mice (1 μM tBP, n ACSF/tBP = 8 neurons, n ACSF/tBP = 6 mice). q – u , Representative traces ( q ) and quantification ( r – u ) showing spontaneous neural transmission before and right after coperfusion of tBP and Dyngo-4a in LHb neurons of CRS mice (Dyngo-4a + 1 μM tBP, n ACSF/Dyngo+tBP = 8 neurons, n ACSF/Dyngo+tBP = 3 mice): sEPSC frequency ( r ), sEPSC amplitude ( s ), sIPSC frequency ( t ) and sIPSC amplitude ( u ). v , Bar graph showing spontaneous firing frequency before and after coperfusion of tBP and Dyngo-4a (Dyngo-4a + 1 μM tBP, n ACSF/Dyngo+tBP = 8 neurons, n ACSF/Dyngo+tBP = 3 mice). w , Experimental design. x , y , tBP decreases immobile duration in FST ( x ) and increases sucrose preference in SPT ( y ) whereas co-application of tBP with Dyngo-4a or TAT–GluA2 3Y reverses this effect ( x , n Veh/Dyngo/tBP/tBP+TAT–GluA23y/Dyngo+tBP = 8, 10, 12, 10, 7; y , n Veh/Dyngo/tBP/tBP+TAT–GluA23y/Dyngo+tBP = 9, 10, 10, 11, 8. Two-sided Mann–Whitney test ( a – h ), two-sided paired t -test ( k , m – p , r – v ), two-sided Wilcoxon test ( k ), one-way ANOVA with uncorrected Fisher’s LSD test ( x , y ). Data are mean ± s.e.m. Schematic in w adapted from ref. , Elsevier.

Article Snippet: For pharmacological experiments, drugs (SBI, 0.5 μM, Selleck; tBP, 0.1, 1 and 5 μM, Selleck; TAT–GluA2 3Y peptide, 10 μM, MCE; a designed tBP-scrambled (YGRKKRRQRRRGGVGNDFFINHETTGFATEW), 1 μM, MCE; TAT–GluA2 3Y -scrambled, 10 μM, MCE; dyngo-4a, 5 μM, MCE) were bath applied after 10 min of stable baseline recordings.

Techniques: Western Blot, Expressing, Transmission Assay, MANN-WHITNEY

Journal: Nature

Article Title: Stress dynamically modulates neuronal autophagy to gate depression onset

doi: 10.1038/s41586-025-08807-4

Figure Lengend Snippet: a , Experimental design. b,c , Representative images (left) and quantification (right) of p62 or Beclin-1 western blot showing LTD induction protocol instantly enhances autophagy level in LHb of naïve mice (i.e., decreased p62 and increased Beclin-1 ( b , n mCherry/oChIEF = 3/group for p62, n mCherry/oChIEF = 4/group for Beclin-1) but not CRS mice ( c , n mCherry/oChIEF = 3/group for p62, n mCherry/oChIEF = 4/group for Beclin-1). d , LFS fails to induce LTD in the LHb of CRS mice (n naïve = 9 neurons, 7 mice; n CRS = 11 neurons, 7 mice). e , SBI abolishes the LTD induction and induces a slight but significant LTP in LHb neurons (n = 7 neurons, 6 mice). f , Schematics of stereotaxic surgeries. g , Conditional knock-out of Atg7 abolishes LTD in LHb neurons (n Atg7+/+ = 11 neurons, 6 mice; n Atg7−/− = 10 neurons, 7 mice). h , Kinetics and representative traces showing conditional knock-out of Atg7 increases the LTP magnitude in LHb neurons (n Atg7+/+ = 8 neurons, 3 mice; n Atg7−/− = 10 neurons, 8 mice). i , tBP, but not tBP-scm, directly induces dose-dependent pharmacological LTD in the LHb of CRS mice (1 μΜ tBP, n = 10 neurons, 8 mice; 5 μΜ tBP, n = 11 neurons, 7 mice; 1 μΜ tBP-scm, n = 10 neurons, 7 mice). j , TAT-GluA2 3Y peptide, but not its scrambled analog (TAT-GluA2 3Y -scm), disrupts the tBP-induced LTD in the LHb of CRS mice (TAT-GluA2 3Y , n = 9 neurons, 6 mice; TAT-GluA2 3Y -scm, n = 9 neurons, 7 mice). k , tBP fails to induce LTD in the LHb of Atg7 LHb−/− mice (n = 11 neurons, 7 mice). Two-sided Unpaired t -test for all. Data are mean ± s.e.m. Schematics in a , f adapted from ref. , Elsevier.

Article Snippet: For pharmacological experiments, drugs (SBI, 0.5 μM, Selleck; tBP, 0.1, 1 and 5 μM, Selleck; TAT–GluA2 3Y peptide, 10 μM, MCE; a designed tBP-scrambled (YGRKKRRQRRRGGVGNDFFINHETTGFATEW), 1 μM, MCE; TAT–GluA2 3Y -scrambled, 10 μM, MCE; dyngo-4a, 5 μM, MCE) were bath applied after 10 min of stable baseline recordings.

Techniques: Western Blot, Knock-Out