Fig. 4: Enhancing LHb autophagy facilitates synaptic GluRs degradation for normalizing neuronal hyperactivity and depression-like behaviours.
From: Stress dynamically modulates neuronal autophagy to gate depression onset
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 GABAA receptor subunit (d,h) (a–c, nnaive/CRS = 5 per group; d, nnaive/CRS = 4; e–h, nCRS+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 (nACSF/0.5/1/5 = 8, 8, 9 neurons, nACSF/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, nACSF/tBP = 8 neurons, nACSF/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, nACSF/Dyngo+tBP = 8 neurons, nACSF/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, nACSF/Dyngo+tBP = 8 neurons, nACSF/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–GluA23Y reverses this effect (x, nVeh/Dyngo/tBP/tBP+TAT–GluA23y/Dyngo+tBP = 8, 10, 12, 10, 7; y, nVeh/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. 31, Elsevier.
