Fig. 6: Optogenetic stimulation of adBNST GABAergic terminals in sNAc produces an anxiolytic effect, which is mediated by sNAcPV neurons. | Molecular Psychiatry

Fig. 6: Optogenetic stimulation of adBNST GABAergic terminals in sNAc produces an anxiolytic effect, which is mediated by sNAcPV neurons.

From: A new GABAergic somatostatin projection from the BNST onto accumbal parvalbumin neurons controls anxiety

Fig. 6

a Schematic showing optogenetic manipulation of adBNST GABAergic afferent fibers that innervate NAcPV neurons. b Representative image showing adBNST GABAergic afferent axons innervating the PV neurons within NAc shell. Scale bar, 10 μm. c–d Mean time spent in the center and average velocity in OFT (n = 8 mice per group, unpaired t -test, for c, ChR2: OFF vs. ON, t = 4.244, P = 0.0008; ON: mCherry vs. ChR2, t = 4.484, P = 0.0263; for d, t = 0.6661, P = 0.5162) with or without optogenetic stimulation of adBNST GABAergic afferent axons innervating PV neurons within NAc shell. e Mean time spent in the open arms in EPM (n = 8 mice per group, unpaired t test, ChR2: OFF vs. ON, t = 3.009, P = 0.0094; ON: mCherry vs. ChR2, t = 3.160, P = 0.0070). f Representative mouse tracks during the novelty object interaction for both mCherry and ChR2 groups. g–h Mean interaction time and approaches in mCherry and ChR2 groups (n = 8 per group, unpaired t test, for g, t = 2.286, P = 0.0372; for h, t = 2.343, P = 0.0333). (i) Schematic showing three-chamber social interaction tests. (j) Time in each chamber in habituation trials, L: Left; M: Middle; R: Right (n = 8 per group, paired t test, mCherry: t = 1.543, P = 0.1572; ChR2: t = 0.1754, P = 0.8657). k Interaction time with a stranger mouse (S1) or an empty cage (E) in sociability trials (n = 8 per group, paired t test, mCherry: t = 3.245, P = 0.0101; ChR2: t = 4.514, P = 0.0028). l Interaction time with the stranger mouse (S1) or the second stranger mouse (S2) in social novelty trials (n = 8 per group, paired t test, mCherry: t = 6.541, P = 0.0001; ChR2: t = 1.565, P = 0.1615). m Schematic showing viruses injected into the adBNST and NAc shell. Three groups: Control, BNSTmCherry-NAcGFP; GFP, BNSTChR2-NAcGFP; taCasp3, BNSTChR2-NActaCasp3. In each mouse, an optical fiber was implanted above the NAc shell for optogenetic illumination of adBNST GABAergic outputs. n Representative images showing selective deletion of PV neurons in the NAc shell; scale bar, 100 μm. o–p Mean time spent in the center (n = 6–7 mice per group, unpaired t test, GFP vs. Control: t = 2.410, P = 0.0346; taCasp3 vs. Control: t = 2.460, P = 0.0317) and in open arms (n = 6–7 mice per group, unpaired t test, GFP vs. Control: t = 2.660, P = 0.0222; taCasp3 vs. Control: t = 2.880, P = 0.0150). q Schematic showing PPR of eIPSPs recorded from PV neurons within the NAc shell in wild-type and stressed PV-Cre mice during optogenetic stimulation of adBNST GABAergic afferents around PV neurons. r PPR of eIPSPs plotted as a function of interspike intervals (ISIs); s mean PPR measured at 50 ms interspike interval. (n = 4 from 3 mice per group, unpaired t test, t = 3.247, P = 0.0175). t Schematic showing optogenetic stimulation of adBNST GABAergic afferents around PV neurons in the sNAc on stressed mice. u–v Mean time in the center and open arms (n = 9 mice per group, unpaired t test, for u, ChR2: OFF vs. ON, t = 5.540, P < 0.0001; ON: mCherry vs. ChR2, t = 2.396, P = 0.0292; for v, ChR2: OFF vs. ON, t = 3.961, P = 0.0011; ON: mCherry vs. ChR2, t = 3.047, P = 0.0077).

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