A translational bridge between mouse and human models of learned safety

Figures & data

Figure 1. Experimental paradigm and pupillary and amygdala responses to the aversive stimulus. A: Training and test phase: The training phase (left) consisted of several explicitly unpaired (bottom row) or paired (top row) presentations of the CS and the US and was followed by a period of rest (middle) during which the structural MRI images were acquired. The test phase (right) consisted of five presentations of the CS alone. B: Presentation of the screams during the training phase led to significant pupillary dilation in safety and fear conditioning groups (*P < 0.05) which was comparable among the two groups (P > 0.05). C: Activity in the left and right amygdala in both groups (average effect of condition from both groups) (Montreal Neurological Institute (MNI) co-ordinates: −18, −4, −14, k = 226, t score = 5.30, P < 0.05, FWE corrected; and 20, 0, −14, k = 244, t score = 5.15, P < 0.05, FWE corrected).

Figure 2. Pupillary and neural responses to the conditioned stimulus in the test phase. A: Percentage change in pupillary diameter during the presentation of the first CS (*P < 0.05) demonstrates pupillary constriction in the learned safety group and pupillary dilation in the learned fear group. B: A cluster of differential activation in the left amygdala between safety and fear trained subjects in response to the CS is shown on a standard brain (Montreal Neurological Institute (MNI) co-ordinates: −28, 0, −16, k = 8, t score = 3.56, P < 0.05, FWE corrected). For display purposes, activity clusters are shown at P < 0.005, uncorrected in B and C. C: Differential activation in the left dlPFC between safety and fear trained groups in response to the CS (MNI: −30, 52, 32, k = 9, t score = 3.97, P < 0.001 uncorrected). D. Differential activation in the left caudate between safety and fear trained groups in response to the CS (MNI: −16, −18, 20, k = 12, t score = 2.11, P = 0.021 uncorrected). E. Group-based probabilistic tractography map between the amygdala and the dlPFC.

Supplemental Table I. Regions with greater activity (at P < 0.001, uncorrected) in the safety than in the fear conditioned group (whole brain analysis).

	Co-ordinates
Region of activation	x	y	z	k	t score
Supramarginal gyrus	−44	−28	46	44	4.56
Precuneus	16	−74	46	53	4.3
Subgyral	46	−36	−12	23	4.28
Superior frontal gyrus	−30	52	30	52	4.12
Inferior parietal lobule	60	−48	48	67	4.09
Middle frontal gyrus	−46	36	30	16	3.93
Cerebellum	2	−52	−32	35	3.92
Precuneus	−16	−70	42	30	3.89
Inferior parietal	34	−52	40	60	3.82
Inferior occipital gyrus	34	−92	−4	12	3.72
Frontal superior medial	6	34	56	11	3.62
Inferior frontal gyrus	34	36	16	11	3.61
Middle frontal gyrus	34	36	26	7	3.54
Subgyral	−26	−48	36	8	3.42

Supplemental Table II. Number of streamlines (waytotals) for each subject.

Subject	Waytotal
1	0
2	0
3	6
4	1
5	0
6	367
7	0
8	3
9	0
10	1
11	17
12	12
13	4
14	8
15	4
16	8
17	24
18	2
19	0
20	45
21	4
22	14
23	2
24	167
25	1
26	68
27	1
28	114