Fig. 6: Chronic chemogenetic activation of the BLA-DMS circuit increases ERK phosphorylation levels and synaptic plasticity in the DMS. | Nature Communications

Fig. 6: Chronic chemogenetic activation of the BLA-DMS circuit increases ERK phosphorylation levels and synaptic plasticity in the DMS.

From: Persistent enhancement of basolateral amygdala-dorsomedial striatum synapses causes compulsive-like behaviors in mice

Fig. 6

a Scheme of virus injection for optical stimulation-evoked excitatory postsynaptic current (oEPSC) measurement. b Representative oEPSC traces measured in D1-MSNs (tdTomato+). Blue rectangles indicate times of light stimulation (470 nm, 1 ms) and arrows indicate sampling time of AMPA receptor- and NMDA receptor-mediated currents. c AMPA/NMDA ratio in control (n = 9 cells from 3 mice) and CNO-treated mice (n = 5 cells from 4 mice) (two-sided Student’s t-test, t = 2.6989, df = 12, P = 0.0193). d−h Immunohistochemistry using pERK antibody performed on D13−D16 (Saline, n = 3 mice; CNO, n = 4 mice; CNO + SL327, n = 3 mice). Representative images are shown in (d) where enlarged images showing the colocalization of pERK with BLA axons (hM3Dq-mCherry) are displayed in insets. Scale bars indicate 50 µm. Quantified data of pERK puncta and BLA axons are shown in (e) and (g), respectively (two-sided Friedman test with post hoc Dunn’s multiple comparisons test, pERK: Saline vs CNO, P = 1.0e−15; CNO vs CNO + SL327, P = 1.0e−15; Saline vs CNO + SL327, P = 0.4911; Axon: Saline vs CNO: P = 1.0e−15; CNO vs CNO + SL327, P = 1.0e−15; Saline vs CNO + SL327, P = 7.286e−08). The pERK puncta and BLA axons data shown in (e) and (g) are represented in a cumulative probability plot in (f) and (h), respectively (two-sided Kolmogorov−Smirnov test, pERK: Saline vs CNO, P = 0.0259; CNO vs CNO + SL327, P = 0.002; Saline vs CNO + SL327, P = 0.8186; Axons: Saline vs CNO, P = 1.621e−12; CNO vs CNO + SL327, P = 1.0e−15; Saline vs CNO + SL327, P = 0.0028). i−m Immunohistochemistry using a pERK antibody performed after CMI administration (D31-D32) (Axon terminals analysis: Saline/Water, n = 4 mice; CNO/Water, n = 4 mice; CNO/CMI, n = 4 mice, pERK analysis: Saline/Water, n = 4 mice; CNO/Water, n = 4 mice; CNO/CMI, n = 3 mice). Representative images are shown in (i) in which enlarged images showing the colocalization of pERK signals with BLA axons (hM3Dq-mCherry) are displayed in insets. Scale bars indicate 50 µm. Quantified data of pERK puncta and BLA axons are shown in (j) and (l), respectively (two-sided Friedman test with post hoc Dunn’s multiple comparisons test, pERK: Saline/Water vs CNO/Water, P = 1.0e−15; CNO/Water vs CNO/CMI, P = 1.0e−15; Saline/Water vs CNO/CMI, P = 0.4550; Axon: Saline/Water vs CNO/Water, P = 1.0e−15; CNO/Water vs CNO/CMI, P = 1.0e−15; Saline/Water vs CNO/CMI, P = 0.0290). The pERK puncta and BLA axons data shown in (j) and (l) are represented in a cumulative probability plot in (k) and (m), respectively (two-sided Kolmogorov−Smirnov test, pERK: Saline/Water vs CNO/Water, P = 8.184e−09; CNO/Water vs CNO/CMI, P = 9.225e−08; Saline/Water vs CNO/CMI, P = 0.0222; Axon: Saline/Water vs CNO/Water, P = 3.72e−09; CNO/Water vs CNO/CMI, P = 1.564e−08; Saline/Water vs CNO/CMI, P = 0.0062).

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