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. Author manuscript; available in PMC: 2024 Jul 1.
Published in final edited form as: Biol Psychiatry. 2023 Oct 29;95(8):785–799. doi: 10.1016/j.biopsych.2023.10.016

Figure 3. Pathway-specific control of social-fear extinction impaired in Magel2KO mice.

Figure 3.

(A) Hypothalomo-septal pathways. Coronal sections showing projections in the LS from neurons targeted with AAV encoding CRE-dependent eYFP in Avp-CRE and Oxt-CRE mice.

(B) Specificity of transgene expression in Avp-CRE and Oxt-CRE mice. Scale=40 μm.

(C) Optogenetic inhibition of the PVN→LS pathway in AVP neurons had no effect. Arrows mark the onset of laser stimulation. Bold lines are means±SEM, light lines individual subjects (N). Two-way ANOVA: effect of trials F(2.6,29)=16.5 p<0.0001 post-hoc Sidak test.

(D) Optogenetic inhibition of the PVN→LS pathway in OXT neurons had no effect. Two-way ANOVA: effect of trials F(2.4,26)=11.3 p=0.0001. Post-hoc analysis with Dunnett test.

(E) Specificity of transgene expression in Avp-CRE and Oxt-CRE mice. Scale=40 μm.

(F) Optogenetic inhibition of the SON→LS pathway in AVP neurons impaired SFC extinction. Two-way ANOVA: effect of NpHR F(1,11)=27.1 p=0.0003; trials × NpHR F(5,55)=4.7 p=0.0012 post-hoc Sidak test.

(G) Optogenetic inhibition of the SON→LS pathway in OXT neurons impaired SFC extinction. Two-way ANOVA: effect of NpHR F(1,12)=10.5 p=0.007; trials × NpHR F(5,60)=7.1 p<0.0001 post-hoc Sidak test.

(H) Cumulated time of attacks on the 6 stimulus mice (means±SEM, N mice as indicated). Comparison between groups with Mann Whitney test: YFP vs NpHR in SON OXT neurons p=0.0012 and in SON AVP neurons p=0.0013.

(I) Model: loss of OXT in the SON→LS pathway prevented social-fear extinction and promoted aggressive behavior. Loss of AVP in this pathway did not completely overlap with that of OXT.

(J) Specificity of transgene expression in Magel2KO crossed with Avp-CRE and Oxt-CRE mice. Scale=40 μm.

(K) Optogenetic activation of the PVN→LS pathway in AVP neurons had no effect. Two-way ANOVA: effect of trials F(2.8,39.9)=4.9 p=0.006 post-hoc Sidak test.

(L) Optogenetic activation of the PVN→LS pathway in OXT neurons had no effect. Two-way ANOVA: effect of trials F(3.1,31.5)=3.7 p=0.018 post-hoc Sidak test.

(M) Specificity of transgene expression in Magel2KO crossed with Avp-CRE or Oxt-CRE mice. Scale=10 μm.

(N) Optogenetic activation of the SON→LS pathway in AVP neurons promoted SFC extinction in Magel2KO mice. Two-way ANOVA: effect of ChR2 F(1,11)=8.8 p=0.01 post-hoc Sidak test.

(O) Optogenetic activation of the PVN→LS pathways in OXT neurons promoted SFC extinction in Magel2KO mice. Two-way ANOVA: effect of ChR2 F(1,10)=37.65 p=0.003 post-hoc Sidak test.