Fig. Test Used n P value F/H/U/t/r values1 B One-way

ANOVApost hoc:

Fisher's LSD

CTL: 10SUS: 15RES: 11

ANOVA: P = 0.0009 CTL vs. SUS: P = 0.0007CTL vs. RES: P = 0.0008

ANOVA: F (2, 33) = 8.793CTL vs. SUS: t (33) = 3.718CTL vs. RES: t (33) = 3.691

1 C Pearson's r 36 XY pairs P = 0.0450 r = 0.3362

1 D Student's t test CTL: 8SUS: 10

P = 0.0088 t (16) = 2.98

1 E Pearson's r 18 XY pairs P = 0.0142 r = 0.5666

1 F One-way ANOVApost hoc:

Fisher's LSD

CTL: 15Unmediated MDD: 4Medicated MDD: 5

ANOVA: P = 0.0362CTL vs. Unmedicated MDD:

P = 0.0407CTL vs. Medicated MDD:

P = 0.0391

ANOVA: F (2, 21) = 3.904CTL vs. Unmedicated MDD:

t (21) = 2.18CTL vs. Medicated MDD:

t ( 21) = 2.201

1 G Mann-Whitney test

CTL: 12MDD: 13

P = 0.0298 U = 38

1 H Kruskal-Wallis test

CTL: 10SUS: 16RES: 11

K-W test: P = 0.8152 (approximate) K-W test: H = 0.4086

1 I Pearson's r 16 XY pairs P = 0.0007 r = -0.7546

1 J Student's t test CTL: 7SUS: 8

P = 0.0443 t (13) = 2.226

1 K Pearson's r 15 XY pairs P = 0.0270 r = -0.5686

1 L Kruskal-Wallis test

post hoc: uncorrected Dunn's test

CTL: 12Unmediated MDD: 8Medicated MDD: 5

K-W test: P = 0.0096 (approximate)CTL vs. Unmedicated MDD:

P = 0.0064CTL vs. Medicated MDD:

P = 0.0269

K-W test: H = 9.292

1 M Student's t test

CTL: 14MDD: 10

P = 0.8572 t (22) = 0.1821

2A Two-way ANOVApost hoc:

Fisher's LSD

Vgf+/+ CTL: 12Vgf+/+ Defeated: 33

Vgf+/- CTL: 9Vgf+/- Defeated: 34

Interaction: P = 0.0410 VGF level: P = 0.6554

Defeat: P < 0.0001Vgf+/+ CTL vs. Vgf+/+ Defeated:

P < 0.0001Vgf+/+ CTL vs. Vgf+/- CTL:

P = 0.3547Vgf+/- CTL vs. Vgf+/- Defeated:

P < 0.0001Vgf+/+ Defeated vs. Vgf+/- Defeated:

P = 0.0109

Interaction: F (1, 84) = 4.309VGF level: F (1, 84) = 0.2006

Defeat: F (1, 84) = 101.2Vgf+/+ CTL vs. Vgf+/+ Defeated:

t (84) = 5.97Vgf+/+ CTL vs. Vgf+/- CTL:

t (84) = 0.9306Vgf+/- CTL vs. Vgf+/- Defeated:

t (84) = 8.161Vgf+/+ Defeated vs. Vgf+/- Defeated:

t (84) = 2.603

2B Two-way ANOVApost hoc:

Fisher's LSD

Vgf+/+ Defeated/Target absent: 33

Vgf+/+ Defeated/Target present: 33

Vgf+/- Defeated/Target absent: 34

Vgf+/- Defeated/Target present: 34

Interaction: P = 0.0551VGF level: P = 0.0069

Target: P < 0.0001Vgf+/+ Defeated/Target absent vs. Vgf+/+

Defeated/Target present: P = 0.0436

Vgf+/+ Defeated/Target absent vs. Vgf+/- Defeated/Target absent:

P = 0.5674Vgf+/- Defeated/Target absent vs. Vgf+/- Defeated/Target present:

P < 0.0001Vgf+/+ Defeated/Target present vs. Vgf+/-

Defeated/Target present: P = 0.0012

Interaction: F (1, 130) = 3.747VGF level: F (1, 130) = 7.545

Target: F (1, 130) = 23.41Vgf+/+ Defeated/Target absent vs. Vgf+/+

Defeated/Target present: t (130) = 2.038

Vgf+/+ Defeated/Target absent vs. Vgf+/- Defeated/Target absent:

t (130) = 0.5734Vgf+/- Defeated/Target absent vs. Vgf+/- Defeated/Target present:

t (130) = 4.827Vgf+/+ Defeated/Target present vs. Vgf+/-

Defeated/Target present: t (130) = 3.311

2C Two-way ANOVApost hoc:

Fisher's LSD

Vgf+/+ Defeated/Target absent: 33

Vgf+/+ Defeated/Target present: 33

Vgf+/- Defeated/Target absent: 34

Vgf+/- Defeated/Target present: 34

Interaction: P = 0.1075VGF level: P = 0.0799

Target: P < 0.0001Vgf+/+ Defeated/Target absent vs. Vgf+/+

Defeated/Target present: P = 0.0003

Vgf+/+ Defeated/Target absent vs. Vgf+/- Defeated/Target absent:

P = 0.9188Vgf+/- Defeated/Target absent vs. Vgf+/-

Defeated/Target present: P < 0.0001

Vgf+/+ Defeated/Target present vs. Vgf+/- Defeated/Target present:

P = 0.0181

Interaction: F (1, 130) = 2.627VGF level: F (1, 130) = 3.116

Target: F (1, 130) = 47Vgf+/+ Defeated/Target absent vs. Vgf+/+

Defeated/Target present: t (130) = 3.674

Vgf+/+ Defeated/Target absent vs. Vgf+/- Defeated/Target absent:

t (130) = 0.1022Vgf+/- Defeated/Target absent vs. Vgf+/-

Defeated/Target present: t (130) = 6.039

Vgf+/+ Defeated/Target present vs. Vgf+/- Defeated/Target present:

t (130) = 2.394

2E Two-way ANOVApost hoc:

Fisher's LSD

Wildtype CTL: 6Wildtype Defeated: 12Syn-Cre, KO CTL: 6

Syn-Cre, KO Defeated: 6

Interaction: P = 0.0163VGF level: P = 0.1102

Defeat: P < 0.0001Wildtype CTL vs. Wildtype Defeated:

P = 0.0773Wildtype CTL vs. Syn-Cre, KO CTL:

P = 0.5500Syn-Cre, KO CTL vs. Syn-Cre, KO Defeated:

P < 0.0001Wildtype Defeated vs. Syn-Cre, KO Defeated:

P = 0.0034

Interaction: F (1, 26) = 6.602VGF level: F (1, 26) = 2.735

Defeat: F (1, 26) = 24.78Wildtype CTL vs. Wildtype Defeated:

t (26) = 1.839Wildtype CTL vs. Syn-Cre, KO CTL:

t (26) = 0.6057Syn-Cre, KO CTL vs. Syn-Cre, KO Defeated:

t (26) = 4.992Wildtype Defeatedvs. Syn-Cre, KO Defeated:

t (26) = 3.225

2F Two-way ANOVApost hoc:

Fisher's LSD

Wildtype Defeated/Target absent: 12

Wildtype Defeated/Target present: 12

Syn-Cre, KO Defeated/Target absent: 6

Syn-Cre, KO Defeated/Target present: 6

Interaction: P = 0.0708VGF level: P = 0.0020

Target: P = 0.1665Wildtype Defeated/Target absent vs. Wildtype

Defeated/Target present: P = 0.6976

Wildtype Defeated/Target absent vs. Syn-Cre, KO Defeated/Target absent:

P = 0.2989Syn-Cre, KO Defeated/Target absent vs. Syn-

Cre, KO Defeated/Target present: P = 0.0528

Wildtype Defeated/Target present vs. Syn-Cre, KO Defeated/Target present:

P = 0.0008

Interaction: F (1, 32) = 3.492VGF level: F (1, 32) = 11.3

Target: F (1, 32) = 2.005Wildtype Defeated/Target absent vs. Wildtype

Defeated/Target present: t (32) = 0.3921

Wildtype Defeated/Target absent vs. Syn-Cre, KO Defeated/Target absent:

t (32) = 1.056Syn-Cre, KO Defeated/Target absent vs. Syn-

Cre, KO Defeated/Target present:t (32) = 2.011

Wildtype Defeated/Target present vs. Syn-Cre, KO Defeated/Target present:

t (32) = 3.699

2G Two-way ANOVApost hoc:

Fisher's LSD

Wildtype Defeated/Target absent: 12

Wildtype Defeated/Target present: 12

Syn-Cre, KO Defeated/Target absent: 6

Syn-Cre, KO Defeated/Target present: 6

Interaction: P = 0.0221VGF level: P = 0.0014

Target: P = 0.0003Wildtype Defeated/Target absent vs. Wildtype

Defeated/Target present: P = 0.1513

Wildtype Defeated/Target absent vs. Syn-Cre, KO Defeated/Target absent:

P = 0.4405Syn-Cre, KO Defeated/Target absent vs. Syn-

Cre, KO Defeated/Target present: P = 0.0004

Wildtype Defeated/Target present vs. Syn-Cre, KO Defeated/Target present:

P = 0.0002

Interaction: F (1, 32) = 5.789VGF level: F (1, 32) = 12.33

Target: F (1, 32) = 16.84Wildtype Defeated/Target absent vs. Wildtype

Defeated/Target present:t (32) = 1.47

Wildtype Defeated/Target absent vs. Syn-Cre, KO Defeated/Target absent:

t (32) = 0.7811Syn-Cre, KO Defeated/Target absent vs. Syn-

Cre, KO Defeated/Target present: t (32) = 3.986

Wildtype Defeated/Target present vs. Syn-Cre, KO Defeated/Target present:

t (32) = 4.184

2H Student's t test

Wildtype: 17CaMKII-Cre, KO: 15

P = 0.6617 t (30) = 0.4419

2I Mann-Whitney test

Wildtype: 13CaMKII-Cre, KO: 12

P = 0.9043 U = 75.5

2J Student's t test

Wildtype: 13CaMKII-Cre, KO: 12

P = 0.1175 t (23) = 1.626

3B Student's t test

AAV-GFP: 4AAV-CreGFP: 4

P < 0.0001 t (6) = 15.13

3C Student's t test

AAV-GFP: 10AAV-CreGFP: 10

P = 0.0248 t (18) = 2.449

3D Mann-Whitney test

AAV-GFP: 10AAV-CreGFP: 10

P = 0.5288 U = 41

3E Two-way ANOVApost hoc:

Fisher's LSD

AAV-GFP CTL: 11AAV-GFP Defeated: 18AAV-CreGFP CTL: 12AAV-CreGFP Defeated:

21

Interaction: P = 0.5299VGF level: P = 0.0203

Defeat: P < 0.0001AAV-GFP CTL vs. AAV-GFP Defeated:

P < 0.0001AAV-GFP CTL vs. AAV-CreGFP CTL:

P = 0.2727AAV-CreGFP CTL vs. AAV-CreGFP Defeated:

P < 0.0001AAV-GFP Defeated vs. AAV-CreGFP

Defeated: P = 0.0163

Interaction: F (1, 58) = 0.3993VGF level: F (1, 58) = 5.699

Defeat: F (1, 58) = 54.59AAV-GFP CTL vs. AAV-GFP Defeated:

t (58) = 4.649AAV-GFP CTL vs. AAV-CreGFP CTL:

t (58) = 1.107AAV-CreGFP CTL vs. AAV-CreGFP Defeated:

t (58) = 5.837AAV-GFP Defeated vs. AAV-CreGFP

Defeated: t (58) = 2.475

3F Two-way ANOVApost hoc:

Fisher's LSD

AAV-GFP Defeated/Target absent:

18AAV-GFP

Defeated/Target present: 18

AAV-CreGFP Defeated/Target absent:

21AAV-CreGFP

Defeated/Target present: 21

Interaction: P = 0.2231VGF level: P = 0.1038

Target: P = 0.0438AAV-GFP Defeated/Target absent vs. AAV-

GFP Defeated/Target present: P = 0.5648

AAV-GFP Defeated/Target absent vs. AAV-CreGFP Defeated/Target absent:

P = 0.7541AAV-CreGFP Defeated/Target absent vs. AAV-

CreGFP Defeated/Target present: P = 0.0192

AAV-GFP Defeated/Target present vs. AAV-CreGFP Defeated/Target present:

P = 0.0476

Interaction: F (1, 74) = 1.446VGF level: F (1, 74) = 2.712

Target: F (1, 74) = 4.207AAV-GFP Defeated/Target absent vs. AAV-

GFP Defeated/Target present:t (74) = 0.5783

AAV-GFP Defeated/Target absent vs. AAV-CreGFP Defeated/Target absent:

t (74) = 0.3144AAV-CreGFP Defeated/Target absent vs. AAV-

CreGFP Defeated/Target present: t (74) = 2.394

AAV-GFP Defeated/Target present vs. AAV-CreGFP Defeated/Target present:

t (74) = 2.015

3H Student's t test

AAV-GFP: 4AAV-CreGFP: 4

P = 0.0038 t (6) = 4.571

3I Student's t test AAV-GFP: 10AAV-CreGFP: 11

P = 0.0164 t (19) = 2.633

3J Student's t test

AAV-GFP: 10AAV-CreGFP: 11

p = 0.6769 t (19) = 0.4232

3K Two-way ANOVApost hoc:

Fisher's LSD

AAV-GFP CTL: 10AAV-GFP Defeated: 19AAV-CreGFP CTL: 10AAV-CreGFP Defeated:

19

Interaction: P = 0.0198VGF level: P = 0.9923

Defeat: P = 0.1191AAV-GFP CTL vs. AAV-GFP Defeated:

P = 0.0067AAV-GFP CTL vs. AAV-CreGFP CTL:

P = 0.1421AAV-CreGFP CTL vs. AAV-CreGFP Defeated:

P = 0.5650AAV-GFP Defeated vs. AAV-CreGFP

Defeated: P = 0.0465

Interaction: F (1, 54) = 5.771VGF level: F (1, 54) = 9.351e-005

Defeat: F (1, 54) = 2.508AAV-GFP CTL vs. AAV-GFP Defeated:

t (54) = 2.818AAV-GFP CTL vs. AAV-CreGFP CTL:

t (54) = 1.49AAV-CreGFP CTL vs. AAV-CreGFP Defeated:

t (54) = 0.579AAV-GFP Defeated vs. AAV-CreGFP

Defeated: t (54) = 2.037

3L Two-way ANOVApost hoc:

Fisher's LSD

AAV-GFP Defeated/Target absent:

19AAV-GFP

Defeated/Target present: 19

AAV-CreGFP Defeated/Target absent:

19AAV-CreGFP

Defeated/Target present: 19

Interaction: P = 0.0593VGF level: P = 0.0765

Target: P = 0.0913AAV-GFP Defeated/Target absent vs. AAV-

GFP Defeated/Target present: P =0.0124

AAV-GFP Defeated/Target absent vs. AAV-CreGFP Defeated/Target absent:

P = 0.9330AAV-CreGFP Defeated/Target absent vs. AAV-

CreGFP Defeated/Target present: P = 0.8850

AAV-GFP Defeated/Target present vs. AAV-CreGFP Defeated/Target present:

P = 0.0105

Interaction: F (1, 72) = 3.673VGF level: F (1, 72) = 3.23

Target: F (1, 72) = 2.928AAV-GFP Defeated/Target absent vs. AAV-

GFP Defeated/Target present: t (72) = 2.565

AAV-GFP Defeated/Target absent vs. AAV-CreGFP Defeated/Target absent:

t (72) = 0.08442AAV-CreGFP Defeated/Target absent vs. AAV-

CreGFP Defeated/Target present: t (72) = 0.1452

AAV-GFP Defeated/Target present vs. AAV-CreGFP Defeated/Target present:

t (72) = 2.626

3M Student's t test IgG: 6

Anti-VGFC-term: 9

P = 0.0041 t (13) = 3.472

3N Student's t test IgG: 5

Anti-VGFC-term: 4

P = 0.4100 t (7) = 0.8762

3O Welch's t test IgG: 14

Anti-VGFC-term: 16

P = 0.0138 t (19.4) = 2.708

3P Two-way ANOVApost hoc:

Fisher's LSD; Student's t test

IgG/Target absent: 14IgG/Target present: 14

Anti-VGFC-term/Target absent: 16

Anti-VGFC-term/Target present: 16

Interaction: P = 0.0300VGF antibody: P = 0.0027

Defeat: P = 0.9821IgG/Target absent vs. IgG/Target present:

P = 0.1369

IgG/Target absent vs. Anti-VGFC-term/Target absent:

P = 0.5211

Anti-VGFC-term/Target absent vs. Anti-VGFC-

term/Target present: P = 0.1053 (Fishers' LSD); P = 0.0500

(Student's t test)

IgG/Target present vs. Anti-VGFC-term/Target present:

P = 0.0004

Interaction: F (1, 56) = 4.958VGF antibody: F (1, 56) = 9.859

Defeat: F (1, 56) = 0.0005058IgG/Target absent vs. IgG/Target present:

t (56) = 1.509

IgG/Target absent vs. Anti-VGFC-term/Target absent:

t (56) = 0.6458

Anti-VGFC-term/Target absent vs. Anti-VGFC-

term/Target present: t (56) = 1.646 (Fishers' LSD); t (30) = 2.042

(Student's t test)

IgG/Target present vs. Anti-VGFC-term/Target present:

t (56) = 3.795

4A Two-way ANOVApost hoc:

Fisher's LSD

Vgf+/+/Saline: 9Vgf+/+/Ketamine: 11

Vgf+/-/Saline: 6Vgf+/-/Ketamine: 6

Interaction: P = 0.0616VGF level: P = 0.1392Treatment: P = 0.2574

Vgf+/+/Saline vs. Vgf+/+/Ketamine: P = 0.0175

Vgf+/+/Saline vs. Vgf+/-/Saline: P = 0.7699

Vgf+/-/Saline vs. Vgf+/-/Ketamine: P = 0.6200

Vgf+/+/Ketamine vs. Vgf+/-/Ketamine: P = 0.0185

Interaction: F (1, 28) = 3.792VGF level: F (1, 28) = 2.316Treatment: F (1, 28) = 1.337

Vgf+/+/Saline vs. Vgf+/+/Ketamine: t (28) = 2.526

Vgf+/+/Saline vs. Vgf+/-/Saline: t (28) = 0.2953

Vgf+/-/Saline vs. Vgf+/-/Ketamine: t (28) = 0.5014

Vgf+/+/Ketamine vs. Vgf+/-/Ketamine: t (28) = 2.501

4B Two-way ANOVApost hoc:

Fisher's LSD

Vgf+/+/Saline: 4Vgf+/+/Ketamine: 5

Vgf+/-/Saline: 4Vgf+/-/Ketamine: 4

Interaction: P = 0.7447VGF level: P = 0.4763Treatment: P = 0.6654

Vgf+/+/Saline vs. Vgf+/+/Ketamine: P = 0.5829

Vgf+/+/Saline vs. Vgf+/-/Saline: P = 0.7867

Vgf+/-/Saline vs. Vgf+/-/Ketamine: P = 0.9408

Vgf+/+/Ketamine vs. Vgf+/-/Ketamine: P = 0.4525

Interaction: F (1, 13) = 0.1107VGF level: F (1, 13) = 0.538Treatment: F (1, 13) = 0.1958

Vgf+/+/Saline vs. Vgf+/+/Ketamine: t (13) = 0.5631

Vgf+/+/Saline vs. Vgf+/-/Saline: t (13) = 0.2762

Vgf+/-/Saline vs. Vgf+/-/Ketamine: t (13) = 0.0757

Vgf+/+/Ketamine vs. Vgf+/-/Ketamine: t (13) = 0.7745

4C Two-way ANOVApost hoc:

Fisher's LSD; Student's t test

AAV-GFP/Saline: 8AAV-GFP/Ketamine: 8AAV-CreGFP/Saline: 7

AAV-CreGFP/Ketamine: 7

Interaction: P = 0.0008VGF level: P < 0.0001Treatment: P = 0.0005

AAV-GFP/Saline vs. AAV-GFP/Ketamine: P < 0.0001

AAV-GFP/Saline vs. AAV-CreGFP/Saline: P = 0.3029 (Fisher's LSD test); P = 0.0451

(Student's t test)AAV-CreGFP/Saline vs. AAV-

CreGFP/Ketamine: P = 0.8819

AAV-GFP/Ketamine vs. AAV-CreGFP/Ketamine:

P < 0.0001

Interaction: F (1, 26) = 14.33VGF level: F (1, 26) = 27.8Treatment: F (1, 26) = 16.04

AAV-GFP/Saline vs. AAV-GFP/Ketamine: t (26) = 5.703

AAV-GFP/Saline vs. AAV-CreGFP/Saline: t (26) = 1.051 (Fisher's LSD test); t (13) =

2.216 (Student's t test)AAV-CreGFP/Saline vs. AAV-

CreGFP/Ketamine: t (26) = 0.1501

AAV-GFP/Ketamine vs. AAV-CreGFP/Ketamine:

t (26) = 6.405

4D Two-way ANOVApost hoc:

Fisher's LSD

AAV-GFP/Saline: 6AAV-GFP/Ketamine: 5AAV-CreGFP/Saline: 6

AAV-CreGFP/Ketamine: 6

Interaction: P = 0.5461VGF level: P = 0.5415Treatment: P = 0.7287

AAV-GFP/Saline vs. AAV-GFP/Ketamine: P = 0.5123

AAV-GFP/Saline vs. AAV-CreGFP/Saline: P = 0.3816

AAV-CreGFP/Saline vs. AAV-CreGFP/Ketamine:

P = 0.8512AAV-GFP/Ketamine vs. AAV-

CreGFP/Ketamine: P = 0.9961

Interaction: F (1, 19) = 0.3777VGF level: F (1, 19) = 0.3866Treatment: F (1, 19) = 0.1239

AAV-GFP/Saline vs. AAV-GFP/Ketamine: t (19) = 0.6678

AAV-GFP/Saline vs. AAV-CreGFP/Saline: t (19) = 0.8958

AAV-CreGFP/Saline vs. AAV-CreGFP/Ketamine:

t (19) = 0.1902AAV-GFP/Ketamine vs. AAV-

CreGFP/Ketamine: t (19) = 0.004967

4F Two-way ANOVApost hoc:

Fisher's LSD

Vgf+/+/Saline: 14Vgf+/+/Ketamine: 15

Vgf+/-/Saline: 11Vgf+/-/Ketamine: 19

Interaction: P = 0.5114VGF level: P = 0.0273Treatment: P = 0.0293

Vgf+/+/Saline vs. Vgf+/+/Ketamine: P = 0.0432

Vgf+/+/Saline vs. Vgf+/-/Saline: P = 0.2945

Vgf+/-/Saline vs. Vgf+/-/Ketamine: P = 0.2741

Vgf+/+/Ketamine vs. Vgf+/-/Ketamine: P = 0.0285

Interaction: F (1, 55) = 0.4368VGF level: F (1, 55) = 5.144Treatment: F (1, 55) = 5.009

Vgf+/+/Saline vs. Vgf+/+/Ketamine: t (55) = 2.07

Vgf+/+/Saline vs. Vgf+/-/Saline: t (55) = 1.058

Vgf+/-/Saline vs. Vgf+/-/Ketamine: t (55) = 1.105

Vgf+/+/Ketamine vs. Vgf+/-/Ketamine: t (55) = 2.25

4G Two-way ANOVApost hoc:

Fisher's LSD

Vgf+/+/Saline: 10Vgf+/+/Ketamine: 10

Vgf+/-/Saline: 9Vgf+/-/Ketamine: 12

Interaction: P = 0.1845VGF level: P = 0.1409Treatment: P = 0.1237

Vgf+/+/Saline vs. Vgf+/+/Ketamine: P = 0.0469

Vgf+/+/Saline vs. Vgf+/-/Saline: P = 0.9176

Vgf+/-/Saline vs. Vgf+/-/Ketamine: P = 0.8748

Vgf+/+/Ketamine vs. Vgf+/-/Ketamine: P = 0.0430

Interaction: F (1, 37) = 1.829VGF level: F (1, 37) = 2.265Treatment: F (1, 37) = 2.481

Vgf+/+/Saline vs. Vgf+/+/Ketamine: t (37) = 2.056

Vgf+/+/Saline vs. Vgf+/-/Saline: t (37) = 0.1042

Vgf+/-/Saline vs. Vgf+/-/Ketamine: t (37) = 0.1587

Vgf+/+/Ketamine vs. Vgf+/-/Ketamine: t (37) = 2.096

4H Two-way ANOVApost hoc:

Fisher's LSD

AAV-GFP/Saline: 5AAV-GFP/Ketamine: 5AAV-CreGFP/Saline: 4

AAV-CreGFP/Ketamine: 5

Interaction: P = 0.0062VGF level: P < 0.0001Treatment: P = 0.0049

AAV-GFP/Saline vs. AAV-GFP/Ketamine: P = 0.0003

AAV-GFP/Saline vs. AAV-CreGFP/Saline: P < 0.0001

AAV-CreGFP/Saline vs. AAV-CreGFP/Ketamine:

P = 0.9403AAV-GFP/Ketamine vs. AAV-

CreGFP/Ketamine: P < 0.0001

Interaction: F (1, 15) = 10.13VGF level: F (1, 15) = 336.4Treatment: F (1, 15) = 10.85

AAV-GFP/Saline vs. AAV-GFP/Ketamine: t (15) = 4.72

AAV-GFP/Saline vs. AAV-CreGFP/Saline: t (15) = 10.42

AAV-CreGFP/Saline vs. AAV-CreGFP/Ketamine: t (15) = 0.07614

AAV-GFP/Ketamine vs. AAV-CreGFP/Ketamine:

t (15) = 15.69

4I Two-way ANOVApost hoc:

Fisher's LSD

AAV-GFP/Saline: 5AAV-GFP/Ketamine: 5AAV-CreGFP/Saline: 4

AAV-CreGFP/Ketamine: 5

Interaction: P = 0.0775VGF level: P = 0.0151Treatment: P = 0.0861

AAV-GFP/Saline vs. AAV-GFP/Ketamine: P = 0.0158

AAV-GFP/Saline vs. AAV-CreGFP/Saline: P = 0.5682

AAV-CreGFP/Saline vs. AAV-CreGFP/Ketamine:

P = 0.9686AAV-GFP/Ketamine vs. AAV-

CreGFP/Ketamine: P = 0.0041

Interaction: F (1, 15) = 3.592VGF level: F (1, 15) = 7.532Treatment: F (1, 15) = 3.375

AAV-GFP/Saline vs. AAV-GFP/Ketamine: t (15) = 2.72

AAV-GFP/Saline vs. AAV-CreGFP/Saline: t (15) = 0.5835

AAV-CreGFP/Saline vs. AAV-CreGFP/Ketamine:

t (15) = 0.04009AAV-GFP/Ketamine vs. AAV-

CreGFP/Ketamine: t (15) = 3.382

4J Two-way ANOVApost hoc:

Fisher's LSD

AAV-GFP/Saline: 5AAV-GFP/Ketamine: 5AAV-CreGFP/Saline: 5

AAV-CreGFP/Ketamine: 5

Interaction: P = 0.2200VGF level: P = 0.0357Treatment: P = 0.0260

AAV-GFP/Saline vs. AAV-GFP/Ketamine: P = 0.0179

AAV-GFP/Saline vs. AAV-CreGFP/Saline: P = 0.4823

AAV-CreGFP/Saline vs. AAV-CreGFP/Ketamine:

P = 0.4179AAV-GFP/Ketamine vs. AAV-

CreGFP/Ketamine: P = 0.0225

Interaction: F (1, 16) = 1.63VGF level: F (1, 16) = 5.262Treatment: F (1, 16) = 6.015

AAV-GFP/Saline vs. AAV-GFP/Ketamine: t (16) = 2.637

AAV-GFP/Saline vs. AAV-CreGFP/Saline: t (16) = 0.7194

AAV-CreGFP/Saline vs. AAV-CreGFP/Ketamine:

t (16) = 0.8315AAV-GFP/Ketamine vs. AAV-

CreGFP/Ketamine: t (16) = 2.525

4K Two-way ANOVApost hoc:

Fisher's LSD

AAV-GFP/Saline: 5AAV-GFP/Ketamine: 5AAV-CreGFP/Saline: 5

AAV-CreGFP/Ketamine: 5

Interaction: P = 0.0116VGF level: P = 0.3556Treatment: P = 0.4963

AAV-GFP/Saline vs. AAV-GFP/Ketamine: P = 0.0234

AAV-GFP/Saline vs. AAV-CreGFP/Saline: P = 0.1986

AAV-CreGFP/Saline vs. AAV-CreGFP/Ketamine:

P = 0.1477AAV-GFP/Ketamine vs. AAV-

CreGFP/Ketamine: P = 0.0162

Interaction: F (1, 16) = 8.111VGF level: F (1, 16) = 0.9052Treatment: F (1, 16) = 0.4848

AAV-GFP/Saline vs. AAV-GFP/Ketamine: t (16) = 2.506

AAV-GFP/Saline vs. AAV-CreGFP/Saline: t (16) = 1.341

AAV-CreGFP/Saline vs. AAV-CreGFP/Ketamine:

t (16) = 1.521AAV-GFP/Ketamine vs. AAV-

CreGFP/Ketamine: t (16) = 2.687

5B Two-way ANOVApost hoc:

Fisher's LSD

AAV-GFP/SC-62: 8AAV-GFP/TLQP-62: 10AAV-CreGFP/SC-62: 9

AAV-CreGFP/TLQP-62: 9

Interaction: P = 0.0276BDNF level: P = 0.0331

Peptide: P = 0.0544AAV-GFP/SC-62 vs. AAV-GFP/TLQP-62:

P = 0.0047AAV-GFP/SC-62 vs. AAV-CreGFP/SC-62:

P = 0.9558AAV-CreGFP/SC-62 vs. AAV-CreGFP/TLQP-

62: P = 0.8265

AAV-GFP/TLQP-62 vs. AAV-CreGFP/TLQP-62:

P = 0.0024

Interaction: F (1, 32) = 5.33BDNF level: F (1, 32) = 4.962

Peptide: F (1, 32) = 3.989AAV-GFP/SC-62 vs. AAV-GFP/TLQP-62:

t (32) = 3.035AAV-GFP/SC-62 vs. AAV-CreGFP/SC-62:

t (32) = 0.05584AAV-CreGFP/SC-62 vs. AAV-CreGFP/TLQP-

62: t (32) = 0.221

AAV-GFP/TLQP-62 vs. AAV-CreGFP/TLQP-62:

t (32) = 3.301

5D Two-way ANOVApost hoc:

Fisher's LSD

Saline/SC-62: 6Saline/TLQP-62: 5NBQX/SC-62: 6

AAV-NBQX/TLQP-62: 5

Interaction: P = 0.0093NBQX Pretreatment: P = 0.0073

Peptide: P = 0.0734Saline/SC-62 vs. Saline/TLQP-62:

P = 0.0032Saline/SC-62 vs. NBQX/SC-62:

P = 0.9322NBQX/SC-62 vs. NBQX/TLQP-62:

P = 0.4848Saline/TLQP-62 vs. NBQX/TLQP-62:

P = 0.0008

Interaction: F (1, 18) = 8.468NBQX Pretreatment: F (1, 18) = 9.159

Peptide: F (1, 18) = 3.614Saline/SC-62 vs. Saline/TLQP-62:

t (18) = 3.402Saline/SC-62 vs. NBQX/SC-62:

t (18) = 0.08632NBQX/SC-62 vs. NQBX/TLQP-62:

t (18) = 0.7133Saline/TLQP-62 vs. NBQX/TLQP-62:

t (18) = 4.019

5E Two-way ANOVApost hoc:

Fisher's LSD

Saline/SC-62: 5Saline/TLQP-62: 5NBQX/SC-62: 5

AAV-NBQX/TLQP-62: 4

For p-mTOR/t-mTOR:Interaction: P = 0.0624

NBQX Pretreatment: P = 0.0355Peptide: P = 0.2860

Saline/SC-62 vs. Saline/TLQP-62: P = 0.0381

Saline/SC-62 vs. NBQX/SC-62: P = 0.8314

NBQX/SC-62 vs. NBQX/TLQP-62: P = 0.5425

Saline/TLQP-62 vs. NBQX/TLQP-62: P = 0.0095

For p-p70S6K/t-p70S6K:Interaction: P = 0.0817

NBQX Pretreatment: P = 0.1578Peptide: P = 0.0678

Saline/SC-62 vs. Saline/TLQP-62: P = 0.0136

Saline/SC-62 vs. NBQX/SC-62: P = 0.7858

NBQX/SC-62 vs. NBQX/TLQP-62: P = 0.9450

Saline/TLQP-62 vs. NBQX/TLQP-62: P = 0.0359

For p-mTOR/t-mTOR:Interaction: F (1, 15) = 4.053

NBQX Pretreatment: F (1, 15) = 5.338Peptide: F (1, 15) = 1.224

Saline/SC-62 vs. Saline/TLQP-62: t (15) = 2.274

Saline/SC-62 vs. NBQX/SC-62: t (15) = 0.2167

NBQX/SC-62 vs. NBQX/TLQP-62: t (15) = 0.6232

Saline/TLQP-62 vs. NBQX/TLQP-62: t (15) = 2.971

For p-p70S6K/t-p70S6K:Interaction: F (1, 15) = 3.483

NBQX Pretreatment: F (1, 15) = 2.21Peptide: F (1, 15) = 3.874

Saline/SC-62 vs. Saline/TLQP-62: t (15) = 2.795

Saline/SC-62 vs. NBQX/SC-62: t (15) = 0.2767

NBQX/SC-62 vs. NBQX/TLQP-62: t (15) = 0.07019

Saline/TLQP-62 vs. NBQX/TLQP-62: t (15) = 2.304

5G Two-way ANOVApost hoc:

Fisher's LSD

DMSO/SC-62: 9DMSO/TLQP-62: 9Rapamycin/SC-62: 8

Rapamycin/TLQP-62: 7

Interaction: P = 0.0284Rapamycin Pretreatment: P = 0.3789

Peptide: P = 0.0471DMSO/SC-62 vs. DMSO/TLQP-62:

P = 0.0029DMSO/SC-62 vs. Rapamycin/SC-62:

P = 0.3169Rapamycin/SC-62 vs. Rapamycin/TLQP-62:

P = 0.8753DMSO/TLQP-62 vs. Rapamycin/TLQP-62:

P = 0.0341

Interaction: F (1, 29) = 5.325Rapamycin Pretreatment: F (1, 29) = 0.7986

Peptide: F (1, 29) = 4.299DMSO/SC-62 vs. DMSO/TLQP-62:

t (29) = 3.253DMSO/SC-62 vs. Rapamycin/SC-62:

t (29) = 1.019Rapamycin/SC-62 vs. Rapamycin/TLQP-62:

t (29) = 0.1583DMSO/TLQP-62 vs. Rapamycin/TLQP-62:

t (29) = 2.223

5H Two-way ANOVApost hoc:

Fisher's LSD

DMSO/SC-62: 6DMSO/TLQP-62: 6Rapamycin/SC-62: 5

Rapamycin/TLQP-62: 6

Interaction: P = 0.0976Rapamycin Pretreatment: P = 0.0216

Peptide: P = 0.2185DMSO/SC-62 vs. DMSO/TLQP-62:

P = 0.0416DMSO/SC-62 vs. Rapamycin/SC-62:

P = 0.6052Rapamycin/SC-62 vs. Rapamycin/TLQP-62:

P = 0.7490DMSO/TLQP-62 vs. Rapamycin/TLQP-62:

P = 0.0062

Interaction: F (1, 19) = 3.036Rapamycin Pretreatment: F (1, 19) = 6.267

Peptide: F (1, 19) = 1.62DMSO/SC-62 vs. DMSO/TLQP-62:

t (19) = 2.185DMSO/SC-62 vs. Rapamycin/SC-62:

t (19) = 0.5257Rapamycin/SC-62 vs. Rapamycin/TLQP-62:

t (19) = 0.3246DMSO/TLQP-62 vs. Rapamycin/TLQP-62:

t (19) = 3.077

5I Two-way ANOVApost hoc:

Fisher's LSD

DMSO/SC-62: 10DMSO/TLQP-62: 10Rapamycin/SC-62: 7

Rapamycin/TLQP-62: 7

Interaction: P = 0.0035Rapamycin Pretreatment: P = 0.2843

Peptide: P = 0.3299DMSO/SC-62 vs. DMSO/TLQP-62:

P = 0.0029DMSO/SC-62 vs. Rapamycin/SC-62:

P = 0.1528Rapamycin/SC-62 vs. Rapamycin/TLQP-62:

P = 0.1666DMSO/TLQP-62 vs. Rapamycin/TLQP-62:

P = 0.0053

Interaction: F (1, 30) = 10.02Rapamycin Pretreatment: F (1, 30) = 1.189

Peptide: F (1, 30) = 0.9808DMSO/SC-62 vs. DMSO/TLQP-62:

t (30) = 3.238DMSO/SC-62 vs. Rapamycin/SC-62:

t (30) = 1.467Rapamycin/SC-62 vs. Rapamycin/TLQP-62:

t (30) = 1.418DMSO/TLQP-62 vs. Rapamycin/TLQP-62:

t (30) = 3.009

5J Two-way ANOVApost hoc:

Fisher's LSD

DMSO/SC-62: 5DMSO/TLQP-62: 6Rapamycin/SC-62: 5

Rapamycin/TLQP-62: 5

Interaction: P = 0.0252Rapamycin Pretreatment: P = 0.0538

Peptide: P = 0.3253DMSO/SC-62 vs. DMSO/TLQP-62:

P = 0.0226DMSO/SC-62 vs. Rapamycin/SC-62:

P = 0.7945Rapamycin/SC-62 vs. Rapamycin/TLQP-62:

P = 0.3324DMSO/TLQP-62 vs. Rapamycin/TLQP-62:

P = 0.0045

Interaction: F (1, 17) = 6.023Rapamycin Pretreatment: F (1, 17) = 4.292

Peptide: F (1, 17) = 1.026DMSO/SC-62 vs. DMSO/TLQP-62:

t (17) = 2.507DMSO/SC-62 vs. Rapamycin/SC-62:

t (17) = 0.2647Rapamycin/SC-62 vs. Rapamycin/TLQP-62:

t (17) = 0.9977DMSO/TLQP-62 vs. Rapamycin/TLQP-62:

t (17) = 3.272

SI 1A One-way ANOVApost hoc:

Fisher's LSD

CTL: 10SUS: 16RES: 11

ANOVA: P = 0.0291CTL vs. SUS: P = 0.0187CTL vs. RES: P = 0.0175

ANOVA: F (2, 34) = 3.933CTL vs. SUS: t (34) = 2.469CTL vs. RES: t (34) = 2.497

SI 1B Pearson's r 37 XY pairs P = 0.1031 r = 0.2722SI 1C One-way

ANOVApost hoc:

Fisher's LSD

CTL: 10SUS: 16RES: 11

ANOVA: P <0.0001CTL vs. SUS: P < 0.0001SUS vs. RES: P < 0.0001

ANOVA: F (2, 34) = 44.27CTL vs. SUS: t (34) = 8.384SUS vs. RES: t (34) = 7.241

SI 1D Two-way ANOVApost hoc:

Fisher's LSD

CTL/Target absent: 10CTL/Target present: 10SUS/Target absent: 16SUS/Target present: 16RES/Target absent: 11RES/Target present: 11

Interaction: P < 0.0001Susceptibility: P < 0.0001

Target: P = 0.0085CTL/Target absent vs. CTL/Target present:

P < 0.0001SUS/Target absent vs. SUS/Target present:

P < 0.0001RES/Target absent vs. RES/Target present:

P < 0.0001CTL/Target present vs. SUS/Target present:

P < 0.0001SUS/Target present vs. RES/Target present:

P < 0.0001

Interaction: F (2, 68) = 32.1Susceptibility: F (2, 68) = 15.99

Target: F (1, 68) = 7.351CTL/Target absent vs. CTL/Target present:

t (68) = 4.169SUS/Target absent vs. SUS/Target present:

t (68) = 5.267RES/Target absent vs. RES/Target present:

t (68) = 4.522CTL/Target present vs. SUS/Target present:

t (68) = 7.129SUS/Target present vs. RES/Target present:

t (68) = 8.691

SI 1E Two-way ANOVApost hoc:

Fisher's LSD

CTL/Target absent: 10CTL/Target present: 10SUS/Target absent: 16SUS/Target present: 16RES/Target absent: 11RES/Target present: 11

Interaction: P < 0.0001Susceptibility: P < 0.0001

Target: P = 0.1118CTL/Target absent vs. CTL/Target present:

P = 0.1151SUS/Target absent vs. SUS/Target present:

P < 0.0001RES/Target absent vs. RES/Target present:

P = 0.0655CTL/Target present vs. SUS/Target present:

P < 0.0001SUS/Target present vs. RES/Target present:

P < 0.0001

Interaction: F (2, 68) = 26.51Susceptibility: F (2, 68) = 14.49

Target: F (1, 68) = 2.595CTL/Target absent vs. CTL/Target present:

t (68) = 1.596SUS/Target absent vs. SUS/Target present:

t (68) = 7.52RES/Target absent vs. RES/Target present:

t (68) = 1.872CTL/Target present vs. SUS/Target present:

t (68) = 6.899SUS/Target present vs. RES/Target present:

t (68) = 7.938

SI 1F Two-way ANOVApost hoc:

Fisher's LSD

CTL/Target absent: 10CTL/Target present: 10SUS/Target absent: 16SUS/Target present: 16RES/Target absent: 11RES/Target present: 11

Interaction: P = 0.4785Susceptibility: P < 0.0001

Target: P < 0.0001CTL/Target absent vs. CTL/Target present:

P < 0.0001SUS/Target absent vs. SUS/Target present:

P < 0.0001RES/Target absent vs. RES/Target present:

P < 0.0001CTL/Target absent vs. SUS/Target absent:

P = 0.0002CTL/Target absent vs. RES/Target absent:

P = 0.0007

Interaction: F (2, 68) = 0.7452Susceptibility: F (2, 68) = 24.93

Target: F (1, 68) = 123.5CTL/Target absent vs. CTL/Target present:

t (68) = 5.075SUS/Target absent vs. SUS/Target present:

t (68) = 7.412RES/Target absent vs. RES/Target present:

t (68) = 7.087CTL/Target absent vs. SUS/Target absent:

t (68) = 4.003CTL/Target absent vs. RES/Target absent:

t (68) = 3.541

SI 1G Welch's t test CTL: 8SUS: 10

P = 0.0022 t (7.917) = 4.463

SI 1H Two-way ANOVApost hoc:

Fisher's LSD

CTL/Target absent: 8CTL/Target present: 8SUS/Target absent: 10SUS/Target present: 10

Interaction: P = 0.0002Susceptibility: P = 0.0004

Target: P = 0.7752CTL/Target absent vs. CTL/Target present:

P = 0.0043CTL/Target absent vs. SUS/Target absent:

P = 0.8025SUS/Target absent vs. SUS/Target present:

P = 0.0052CTL/Target present vs. SUS/Target present:

P < 0.0001

Interaction: F (1, 32) = 18.42Susceptibility: F (1, 32) = 15.49

Target: F (1, 32) = 0.08294CTL/Target absent vs. CTL/Target present:

t (32) = 3.073CTL/Target absent vs. SUS/Target absent:

t (32) = 0.2521SUS/Target absent vs. SUS/Target present:

t (32) = 3.003CTL/Target present vs. SUS/Target present:

t (32) = 5.818

SI 1I Two-way ANOVApost hoc:

Fisher's LSD

CTL/Target absent: 8CTL/Target present: 8SUS/Target absent: 10SUS/Target present: 10

Interaction: P = 0.0321Susceptibility: P = 0.0005

Target: P = 0.0176CTL/Target absent vs. CTL/Target present:

P = 0.8618CTL/Target absent vs. SUS/Target absent:

P = 0.2553SUS/Target absent vs. SUS/Target present:

P = 0.0012CTL/Target present vs. SUS/Target present:

P = 0.0001

Interaction: F (1, 32) = 5.02Susceptibility: F (1, 32) = 15.04

Target: F (1, 32) = 6.261CTL/Target absent vs. CTL/Target present:

t (32) = 0.1755CTL/Target absent vs. SUS/Target absent:

t (32) = 1.158SUS/Target absent vs. SUS/Target present:

t (32) = 3.557CTL/Target present vs. SUS/Target present:

t (32) = 4.327

SI 1J Two-way ANOVApost hoc:

Fisher's LSD

CTL/Target absent: 8CTL/Target present: 8SUS/Target absent: 10SUS/Target present: 10

Interaction: P = 0.2968Susceptibility: P = 0.0003

Target: P < 0.0001CTL/Target absent vs. CTL/Target present:

P = 0.0002SUS/Target absent vs. SUS/Target present:

P = 0.0037CTL/Target absent vs. SUS/Target absent:

P = 0.0011

Interaction: F (1, 32) = 1.125Susceptibility: F (1, 32) = 16.06

Target: F (1, 32) = 27.36CTL/Target absent vs. CTL/Target present:

t (32) = 4.22SUS/Target absent vs. SUS/Target present:

t (32) = 3.127CTL/Target absent vs. SUS/Target absent:

t (32) = 3.583

SI 2B Student's t test CTL: 8SCVS: 8

P = 0.0390 t (14) = 2.277

SI 2C Welch's t test CTL: 8SCVS: 8

P = 0.0130 t (8.747) = 3.109

SI 2D Student's t test CTL: 8SCVS: 8

P = 0.0115 t (14) = 2.904

SI 2E Mann-Whitney test

CTL: 8SCVS: 8

P = 0.0148 U = 9

SI 3A Two-way ANOVApost hoc:

Fisher's LSD

Vgf+/+ CTL/Target absent: 12

Vgf+/+ CTL/Target present: 12

Vgf+/+ Defeated/Target absent: 33

Vgf+/+ Defeated/Target present: 33

Vgf+/- CTL/Target absent: 9

Vgf+/- CTL/Target present: 9

Vgf+/- Defeated/Target absent: 34

Vgf+/- Defeated/Target present: 34

Interaction: P < 0.0001VGF level: P < 0.0001

Target: P = 0.0369Vgf+/+ CTL/Target absent vs. Vgf+/+

CTL/Target present: P = 0.0024

Vgf+/+ Defeated/Target absent vs. Vgf+/+ Defeated/Target present:

P = 0.0353 Vgf+/- CTL/Target absent vs. Vgf+/-

CTL/Target present: P < 0.0001

Vgf+/- Defeated/Target absent vs. Vgf+/- Defeated/Target present:

P < 0.0001Vgf+/+ CTL/Target present vs. Vgf+/+

Defeated/Target present: P = 0.0005

Vgf+/+ Defeated/Target present vs. Vgf+/- Defeated/Target present:

P = 0.0007Vgf+/- CTL/Target present vs. Vgf+/-

Defeated/Target present: P < 0.0001

Interaction: F (3, 168) = 17.74VGF level: F (3, 168) = 11.67

Target: F (1, 168) = 4.424Vgf+/+ CTL/Target absent vs. Vgf+/+

CTL/Target present: t (168) = 3.078

Vgf+/+ Defeated/Target absent vs. Vgf+/+ Defeated/Target present:

t (168) = 2.123 Vgf+/- CTL/Target absent vs. Vgf+/-

CTL/Target present: t (168) = 4.211

Vgf+/- Defeated/Target absent vs. Vgf+/- Defeated/Target present:

t (168) = 5.028Vgf+/+ CTL/Target present vs. Vgf+/+

Defeated/Target present: t (168) = 3.559

Vgf+/+ Defeated/Target present vs. Vgf+/- Defeated/Target present:

t (168) = 3.449Vgf+/- CTL/Target present vs. Vgf+/-

Defeated/Target present: t (168) = 8.15

SI 3B Two-way ANOVApost hoc:

Fisher's LSD

Vgf+/+ CTL/Target absent: 12

Vgf+/+ CTL/Target present: 12

Vgf+/+ Defeated/Target absent: 33

Vgf+/+ Defeated/Target present: 33

Vgf+/- CTL/Target absent: 9

Vgf+/- CTL/Target present: 9

Vgf+/- Defeated/Target absent: 34

Vgf+/- Defeated/Target present: 34

Interaction: P < 0.0001VGF level: P < 0.0001

Target: P = 0.0047Vgf+/+ CTL/Target absent vs. Vgf+/+

CTL/Target present: P = 0.9782

Vgf+/+ Defeated/Target absent vs. Vgf+/+ Defeated/Target present:

P < 0.0001Vgf+/- CTL/Target absent vs. Vgf+/-

CTL/Target present: P = 0.2176

Vgf+/- Defeated/Target absent vs. Vgf+/- Defeated/Target present:

P < 0.0001Vgf+/+ CTL/Target present vs. Vgf+/+

Defeated/Target present: P = 0.0003

Vgf+/+ Defeated/Target present vs. Vgf+/- Defeated/Target present:

P = 0.0090Vgf+/- CTL/Target present vs. Vgf+/-

Defeated/Target present: P < 0.0001

Interaction: F (3, 168) = 7.815VGF level: F (3, 168) = 10.48

Target: F (1, 168) = 8.203Vgf+/+ CTL/Target absent vs. Vgf+/+

CTL/Target present: t (168) = 0.02737

Vgf+/+ Defeated/Target absent vs. Vgf+/+ Defeated/Target present:

t (168) = 4.054Vgf+/- CTL/Target absent vs. Vgf+/-

CTL/Target present: t (168) = 1.238

Vgf+/- Defeated/Target absent vs. Vgf+/- Defeated/Target present:

t (168) = 6.663Vgf+/+ CTL/Target present vs. Vgf+/+

Defeated/Target present: t (168) = 3.716

Vgf+/+ Defeated/Target present vs. Vgf+/- Defeated/Target present:

t (168) = 2.642Vgf+/- CTL/Target present vs. Vgf+/-

Defeated/Target present: t (168) = 5.854

SI 3C Two-way ANOVApost hoc:

Fisher's LSD

Vgf+/+ CTL/Target absent: 12

Vgf+/+ CTL/Target present: 12

Vgf+/+ Defeated/Target absent: 33

Vgf+/+ Defeated/Target present: 33

Vgf+/- CTL/Target absent: 9

Vgf+/- CTL/Target present: 9

Vgf+/- Defeated/Target absent: 34

Vgf+/- Defeated/Target present: 34

Interaction: P = 0.0444VGF level: P < 0.0001

Target: P < 0.0001Vgf+/+ CTL/Target absent vs. Vgf+/+

CTL/Target present: P < 0.0001

Vgf+/+ Defeated/Target absent vs. Vgf+/+ Defeated/Target present:

P < 0.0001Vgf+/- CTL/Target absent vs. Vgf+/-

CTL/Target present: P < 0.0001

Vgf+/- Defeated/Target absent vs. Vgf+/- Defeated/Target present:

P < 0.0001Vgf+/+ CTL/Target absent vs. Vgf+/+

Defeated/Target absent: P = 0.0002

Vgf+/- CTL/Target absent vs. Vgf+/- Defeated/Target absent:

P = 0.0014

Interaction: F (3, 168) = 2.75VGF level: F (3, 168) = 8.231

Target: F (1, 168) = 163.4Vgf+/+ CTL/Target absent vs. Vgf+/+

CTL/Target present: t (168) = 6.302

Vgf+/+ Defeated/Target absent vs. Vgf+/+ Defeated/Target present:

t (168) = 8.511Vgf+/- CTL/Target absent vs. Vgf+/-

CTL/Target present: t (168) = 6.062

Vgf+/- Defeated/Target absent vs. Vgf+/- Defeated/Target present:

t (168) = 6.544Vgf+/+ CTL/Target absent vs. Vgf+/+

Defeated/Target absent: t (168) = 3.763

Vgf+/- CTL/Target absent vs. Vgf+/- Defeated/Target absent:

t (168) = 3.249

SI 3D Two-way ANOVApost hoc:

Fisher's LSD

Wildtype CTL/Target absent: 6

Wildtype CTL/Target present: 6

Wildtype Defeated/Target absent: 12

Wildtype Defeated/Target present: 12

Syn-Cre, KO CTL/Target absent: 6

Syn-Cre, KO CTL/Target present: 6

Syn-Cre, KO Defeated/Target absent: 6

Syn-Cre, KO Defeated/Target present: 6

Interaction: P = 0.0074VGF level: P = 0.0002

Target: P = 0.1676Wildtype CTL/Target absent vs. Wildtype

CTL/Target present: P = 0.0280

Wildtype Defeated/Target absent vs. Wildtype Defeated/Target present:

P = 0.6727Syn-Cre, KO CTL/Target absent vs. Syn-Cre,

KO CTL/Target present: P = 0.0296

Syn-Cre, KO Defeated/Target absent vs. Syn-Cre, KO Defeated/Target present:

P = 0.0338Wildtype CTL/Target present vs. Wildtype

Defeated/Target present: P = 0.0269

Wildtype Defeated/Target present vs. Syn-Cre, KO Defeated/Target present:

P = 0.0002Syn-Cre, KO CTL/Target present vs. Syn-Cre,

KO Defeated/Target present: P < 0.0001

Interaction: F (3, 52) = 4.447VGF level: F (3, 52) = 7.784

Target: F (1, 52) = 1.958Wildtype CTL/Target absent vs. Wildtype

CTL/Target present: t (52) = 2.26

Wildtype Defeated/Target absent vs. Wildtype Defeated/Target present:

t (52) = 0.4249Syn-Cre, KO CTL/Target absent vs. Syn-Cre,

KO CTL/Target present: t (52) = 2.237

Syn-Cre, KO Defeated/Target absent vs. Syn-Cre, KO Defeated/Target present:

t (52) = 2.18Wildtype CTL/Target present vs. Wildtype

Defeated/Target present: t (52) = 2.278

Wildtype Defeated/Target present vs. Syn-Cre, KO Defeated/Target present:

t (52) = 4.008Syn-Cre, KO CTL/Target present vs. Syn-Cre,

KO Defeated/Target present: t (52) = 4.697

SI 3E Two-way ANOVApost hoc:

Fisher's LSD

Wildtype CTL/Target absent: 6

Wildtype CTL/Target present: 6

Wildtype Defeated/Target absent: 12

Wildtype Defeated/Target present: 12

Syn-Cre, KO CTL/Target absent: 6

Syn-Cre, KO CTL/Target present: 6

Syn-Cre, KO Defeated/Target absent: 6

Syn-Cre, KO Defeated/Target present: 6

Interaction: P = 0.0053VGF level: P = 0.0001

Target: P = 0.0014Wildtype CTL/Target absent vs. Wildtype

CTL/Target present: P = 0.5892

Wildtype Defeated/Target absent vs. Wildtype Defeated/Target present:

P = 0.0879Syn-Cre, KO CTL/Target absent vs. Syn-Cre,

KO CTL/Target present: P = 0.8506

Syn-Cre, KO Defeated/Target absent vs. Syn-Cre, KO Defeated/Target present:

P < 0.0001Wildtype CTL/Target present vs. Wildtype

Defeated/Target present: P = 0.3355

Wildtype Defeated/Target present vs. Syn-Cre, KO Defeated/Target present:

P < 0.0001Syn-Cre, KO CTL/Target present vs. Syn-Cre,

KO Defeated/Target present: P < 0.0001

Interaction: F (3, 52) = 4.752VGF level: F (3, 52) = 8.539

Target: F (1, 52) = 11.34Wildtype CTL/Target absent vs. Wildtype

CTL/Target present: t (52) = 0.5434

Wildtype Defeated/Target absent vs. Wildtype Defeated/Target present:

t (52) = 1.739Syn-Cre, KO CTL/Target absent vs. Syn-Cre,

KO CTL/Target present: t (52) = 0.1893

Syn-Cre, KO Defeated/Target absent vs. Syn-Cre, KO Defeated/Target present:

t (52) = 4.716Wildtype CTL/Target present vs. Wildtype

Defeated/Target present: t (52) = 0.9721

Wildtype Defeated/Target present vs. Syn-Cre, KO Defeated/Target present:

t (52) = 4.949Syn-Cre, KO CTL/Target present vs. Syn-Cre,

KO Defeated/Target present: t (52) = 5.441

SI 3F Two-way ANOVApost hoc:

Fisher's LSD

Wildtype CTL/Target absent: 6

Wildtype CTL/Target present: 6

Wildtype Defeated/Target absent: 12

Wildtype Defeated/Target present: 12

Syn-Cre, KO CTL/Target absent: 6

Syn-Cre, KO CTL/Target present: 6

Syn-Cre, KO Defeated/Target absent: 6

Syn-Cre, KO Defeated/Target present: 6

Interaction: P = 0.0111VGF level: P < 0.0001

Target: P < 0.0001Wildtype CTL/Target absent vs. Wildtype

CTL/Target present: P < 0.0001

Wildtype Defeated/Target absent vs. Wildtype Defeated/Target present:

P = 0.0006Syn-Cre, KO CTL/Target absent vs. Syn-Cre,

KO CTL/Target present: P < 0.0001

Syn-Cre, KO Defeated/Target absent vs. Syn-Cre, KO Defeated/Target present:

P = 0.2197Wildtype CTL/Target absent vs. Wildtype

Defeated/Target absent: P = 0.0020

Syn-Cre, KO CTL/Target absent vs. Syn-Cre, KO Defeated/Target absent:

P < 0.0001Wildtype CTL/Target absent vs. Syn-Cre, KO

CTL/Target absent: P = 0.0053

Interaction: F (3, 52) = 4.093VGF level: F (3, 52) = 27.52

Target: F (1, 52) = 56.41Wildtype CTL/Target absent vs. Wildtype

CTL/Target present: t (52) = 4.574

Wildtype Defeated/Target absent vs. Wildtype Defeated/Target present:

t (52) = 3.678Syn-Cre, KO CTL/Target absent vs. Syn-Cre,

KO CTL/Target present: t (52) = 5.635

Syn-Cre, KO Defeated/Target absent vs. Syn-Cre, KO Defeated/Target present:

t (52) = 1.242Wildtype CTL/Target absent vs. Wildtype

Defeated/Target absent: t (52) = 3.262

Syn-Cre, KO CTL/Target absent vs. Syn-Cre, KO Defeated/Target absent:

t (52) = 8.186Wildtype CTL/Target absent vs. Syn-Cre, KO

CTL/Target absent:t (52) = 2.907

SI 3G Two-way ANOVApost hoc:

Fisher's LSD

Wildtype Defeated/Target absent: 17

Wildtype Defeated/Target present: 17

αCaMKII-Cre, KO Defeated/Target absent:

15αCaMKII-Cre, KO

Defeated/Target present: 15

Interaction: P = 0.8686VGF level: P = 0.2035

Target: P = 0.7247Wildtype Defeated/Target absent vs. Wildtype

Defeated/Target present: P = 0.8914

αCaMKII-Cre, KO Defeated/Target absent vs. αCaMKII-Cre, KO Defeated/Target present:

P = 0.7225Wildtype Defeated/Target absent vs.

αCaMKII-Cre, KO Defeated/Target absent:P = 0.4317

Wildtype Defeated/Target present vs.αCaMKII-Cre, KO Defeated/Target present:

P = 0.3087

Interaction: F (1, 60) = 0.02761VGF level: F (1, 60) =1.653Target: F (1, 60) = 0.1252

Wildtype Defeated/Target absent vs. Wildtype Defeated/Target present:

t (60) = 0.1371αCaMKII-Cre, KO Defeated/Target absent vs. αCaMKII-Cre, KO Defeated/Target present:

t (60) = 0.3567Wildtype Defeated/Target absent vs.

αCaMKII-Cre, KO Defeated/Target absent:t (60) = 0.7917

Wildtype Defeated/Target present vs.αCaMKII-Cre, KO Defeated/Target present:

t (60) = 1.027

SI 3H Two-way ANOVApost hoc:

Fisher's LSD

Wildtype Defeated/Target absent: 17

Wildtype Defeated/Target present: 17

αCaMKII-Cre, KO Defeated/Target absent:

15αCaMKII-Cre, KO

Defeated/Target present: 15

Interaction: P = 0.5623VGF level: P = 0.1017

Target: P = 0.0461Wildtype Defeated/Target absent vs. Wildtype

Defeated/Target present: P = 0.2925

αCaMKII-Cre, KO Defeated/Target absent vs. αCaMKII-Cre, KO Defeated/Target present:

P = 0.0774Wildtype Defeated/Target absent vs.

αCaMKII-Cre, KO Defeated/Target absent:P = 0.4483

Wildtype Defeated/Target present vs.αCaMKII-Cre, KO Defeated/Target present:

P = 0.1177

Interaction: F (1, 60) = 0.3395VGF level: F (1, 60) =2.763

Target: F (1, 60) = 4.149Wildtype Defeated/Target absent vs. Wildtype

Defeated/Target present: t (60) = 1.062

αCaMKII-Cre, KO Defeated/Target absent vs. αCaMKII-Cre, KO Defeated/Target present:

t (60) = 1.797Wildtype Defeated/Target absent vs.

αCaMKII-Cre, KO Defeated/Target absent:t (60) = 0.7633

Wildtype Defeated/Target present vs.αCaMKII-Cre, KO Defeated/Target present:

t (60) = 1.587

SI 3I Two-way ANOVApost hoc:

Fisher's LSD

Wildtype Defeated/Target absent: 17

Wildtype Defeated/Target present: 17

αCaMKII-Cre, KO Defeated/Target absent:

15αCaMKII-Cre, KO

Defeated/Target present: 15

Interaction: P = 0.6267VGF level: P = 0.0998

Target: P < 0.0001Wildtype Defeated/Target absent vs. Wildtype

Defeated/Target present: P < 0.0001

αCaMKII-Cre, KO Defeated/Target absent vs. αCaMKII-Cre, KO Defeated/Target present:

P = 0.0001Wildtype Defeated/Target absent vs.

αCaMKII-Cre, KO Defeated/Target absent:P = 0.1319

Wildtype Defeated/Target present vs.αCaMKII-Cre, KO Defeated/Target present:

P = 0.4064

Interaction: F (1, 60) = 0.239VGF level: F (1, 60) = 2.794

Target: F (1, 60) = 43.05Wildtype Defeated/Target absent vs. Wildtype

Defeated/Target present: t (60) = 5.149

αCaMKII-Cre, KO Defeated/Target absent vs. αCaMKII-Cre, KO Defeated/Target present:

t (60) = 4.166Wildtype Defeated/Target absent vs.

αCaMKII-Cre, KO Defeated/Target absent:t (60) = 1.528

Wildtype Defeated/Target present vs.αCaMKII-Cre, KO Defeated/Target present:

t (60) = 0.8362

SI 3J Mann-Whitney test

Wildtype Defeated: 7αCaMKII-Cre, KO

Defeated: 8

P > 0.9999 U = 28

SI 3K Student's t test Vgf+/+: 8Vgf+/-: 9

P = 0.0218 t (15) = 2.559

SI 3L Welch's t test Vgf+/+: 8Vgf+/-: 9

P = 0.0072 t (11.14) = 3.278

SI 4A Two-way ANOVApost hoc:

Fisher's LSD

AAV-GFP CTL/Target absent: 11

AAV-GFP CTL/Target present: 11AAV-GFP

Defeated/Target absent: 18

AAV-GFP Defeated/Target present:

18AAV-CreGFP CTL/Target

absent: 12AAV-CreGFP CTL/Target

present: 12AAV-CreGFP

Defeated/Target absent: 21

AAV-CreGFP Defeated/Target present:

21

Interaction: P < 0.0001VGF level: P < 0.0001

Target: P = 0.0055AAV-GFP CTL/Target absent vs. AAV-GFP

CTL/Target present: P < 0.0001

AAV-GFP Defeated/Target absent vs. AAV-GFP Defeated/Target present:

P = 0.5363AAV-CreGFP CTL/Target absent vs. AAV-

CreGFP CTL/Target present: P = 0.0030

AAV-CreGFP Defeated/Targer absent vs. AAV-CreGFP Defeated/Target present:

P = 0.0115AAV-GFP CTL/Target present vs. AAV-GFP

Defeated/Target present: P < 0.0001

AAV-CreGFP CTL/Target present vs. AAV-CreGFP Defeated/Target present:

P < 0.0001AAV-GFP Defeated/Target present vs. AAV-

CreGFP Defeated/Target present: P = 0.0328

Interaction: F (3, 116) = 11.17VGF level: F (3, 116) = 20.34

Defeat: F (1, 116) = 7.989AAV-GFP CTL/Target absent vs. AAV-GFP

CTL/Target present: t (116) = 4.379

AAV-GFP Defeated/Target absent vs. AAV-GFP Defeated/Target present:

t (116) = 0.6202AAV-CreGFP CTL/Target absent vs. AAV-

CreGFP CTL/Target present: t (116) = 3.031

AAV-CreGFP Defeated/Targer absent vs. AAV-CreGFP Defeated/Target present:

t (116) = 2.568AAV-GFP CTL/Target present vs. AAV-GFP

Defeated/Target present: t (116) = 5.87

AAV-CreGFP CTL/Target present vs. AAV-CreGFP Defeated/Target present:

t (116) = 7.197AAV-GFP Defeated/Target present vs. AAV-

CreGFP Defeated/Target present: t (116) = 2.161

SI 4B Two-way ANOVApost hoc:

Fisher's LSD

AAV-GFP CTL/Target absent: 11

AAV-GFP CTL/Target present: 11AAV-GFP

Defeated/Target absent: 18

AAV-GFP Defeated/Target present:

18AAV-CreGFP CTL/Target

absent: 12AAV-CreGFP CTL/Target

present: 12AAV-CreGFP

Defeated/Target absent: 21

AAV-CreGFP Defeated/Target present:

21

Interaction: P = 0.1286VGF level: P < 0.0001

Target: P = 0.7971AAV-GFP CTL/Target absent vs. AAV-GFP

CTL/Target present: P = 0.3905

AAV-GFP Defeated/Target absent vs. AAV-GFP Defeated/Target present:

P = 0.4248AAV-CreGFP CTL/Target absent vs. AAV-

CreGFP CTL/Target present: P = 0.3807

AAV-CreGFP Defeated/Targer absent vs. AAV-CreGFP Defeated/Target present:

P = 0.0369AAV-GFP CTL/Target present vs. AAV-GFP

Defeated/Target present: P = 0.0203

AAV-CreGFP CTL/Target present vs. AAV-CreGFP Defeated/Target present:

P < 0.0001AAV-GFP Defeated/Target present vs. AAV-

CreGFP Defeated/Target present: P = 0.1065

Interaction: F (3, 116) = 1.93VGF level: F (3, 116) = 8.154

Defeat: F (1, 116) = 0.0664AAV-GFP CTL/Target absent vs. AAV-GFP

CTL/Target present: t (116) = 0.8619

AAV-GFP Defeated/Target absent vs. AAV-GFP Defeated/Target present:

t (116) = 0.8009AAV-CreGFP CTL/Target absent vs. AAV-

CreGFP CTL/Target present: t (116) = 0.8799

AAV-CreGFP Defeated/Targer absent vs. AAV-CreGFP Defeated/Target present:

t (116) = 2.112AAV-GFP CTL/Target present vs. AAV-GFP

Defeated/Target present: t (116) = 2.352

AAV-CreGFP CTL/Target present vs. AAV-CreGFP Defeated/Target present:

t (116) = 4.494AAV-GFP Defeated/Target present vs. AAV-

CreGFP Defeated/Target present: t (116) = 1.627

SI 4C Two-way ANOVApost hoc:

Fisher's LSD

AAV-GFP CTL/Target absent: 11

AAV-GFP CTL/Target present: 11AAV-GFP

Defeated/Target absent: 18

AAV-GFP Defeated/Target present:

18AAV-CreGFP CTL/Target

absent: 12AAV-CreGFP CTL/Target

present: 12AAV-CreGFP

Defeated/Target absent: 21

AAV-CreGFP Defeated/Target present:

21

Interaction: P = 0.1823VGF level: P = 0.2388

Target: P < 0.0001AAV-GFP CTL/Target absent vs. AAV-GFP

CTL/Target present: P < 0.0001

AAV-GFP Defeated/Target absent vs. AAV-GFP Defeated/Target present:

P = 0.0021AAV-CreGFP CTL/Target absent vs. AAV-

CreGFP CTL/Target present: P < 0.0001

AAV-CreGFP Defeated/Targer absent vs. AAV-CreGFP Defeated/Target present:

P = 0.0047

Interaction: F (3, 116) = 1.648VGF level: F (3, 116) = 1.426

Defeat: F (1, 116) = 54.44AAV-GFP CTL/Target absent vs. AAV-GFP

CTL/Target present: t (116) = 4.199

AAV-GFP Defeated/Target absent vs. AAV-GFP Defeated/Target present:

t (116) = 3.146AAV-CreGFP CTL/Target absent vs. AAV-

CreGFP CTL/Target present: t (116) = 4.33

AAV-CreGFP Defeated/Targer absent vs. AAV-CreGFP Defeated/Target present:

t (116) = 2.88

SI 4D Two-way ANOVApost hoc:

Fisher's LSD

AAV-GFP CTL/Target absent: 10

AAV-GFP CTL/Target present: 10AAV-GFP

Defeated/Target absent: 19

AAV-GFP Defeated/Target present:

19AAV-CreGFP CTL/Target

absent: 10AAV-CreGFP CTL/Target

present: 10AAV-CreGFP

Defeated/Target absent: 19

AAV-CreGFP Defeated/Target present:

19

Interaction: P = 0.0493VGF level: P = 0.0148

Target: P = 0.9230AAV-GFP CTL/Target absent vs. AAV-GFP

CTL/Target present: P = 0.1649

AAV-GFP Defeated/Target absent vs. AAV-GFP Defeated/Target present:

P = 0.0115AAV-CreGFP CTL/Target absent vs. AAV-

CreGFP CTL/Target present: P = 0.8473

AAV-CreGFP Defeated/Targer absent vs. AAV-CreGFP Defeated/Target present:

P = 0.8845AAV-GFP CTL/Target present vs. AAV-GFP

Defeated/Target present:P = 0.0002

AAV-CreGFP CTL/Target present vs. AAV-CreGFP Defeated/Target present:

P = 0.4447AAV-GFP Defeated/Target present vs. AAV-

CreGFP Defeated/Target present:P = 0.0097

Interaction: F (3, 108) = 2.7VGF level: F (3, 108) = 3.657Defeat: F (1, 108) = 0.009375

AAV-GFP CTL/Target absent vs. AAV-GFP CTL/Target present:

t (108) = 1.398AAV-GFP Defeated/Target absent vs. AAV-

GFP Defeated/Target present: t (108) = 2.572

AAV-CreGFP CTL/Target absent vs. AAV-CreGFP CTL/Target present:

t (108) = 0.1931AAV-CreGFP Defeated/Targer absent vs. AAV-

CreGFP Defeated/Target present: t (108) = 0.1456

AAV-GFP CTL/Target present vs. AAV-GFP Defeated/Target present:

t (108) = 3.911AAV-CreGFP CTL/Target present vs. AAV-

CreGFP Defeated/Target present:t (108) = 0.7671

AAV-GFP Defeated/Target present vs. AAV-CreGFP Defeated/Target present:

t (108) = 2.633

SI 4E Two-way ANOVApost hoc:

Fisher's LSD

AAV-GFP CTL/Target absent: 10

AAV-GFP CTL/Target present: 10AAV-GFP

Defeated/Target absent: 19

AAV-GFP Defeated/Target present:

19AAV-CreGFP CTL/Target

absent: 10AAV-CreGFP CTL/Target

present: 10AAV-CreGFP

Defeated/Target absent: 19

AAV-CreGFP Defeated/Target present:

19

Interaction: P = 0.8420VGF level: P = 0.6967

Target: P = 0.0048AAV-GFP CTL/Target absent vs. AAV-GFP

CTL/Target present: P = 0.3283

AAV-GFP Defeated/Target absent vs. AAV-GFP Defeated/Target present:

P = 0.0178AAV-CreGFP CTL/Target absent vs. AAV-

CreGFP CTL/Target present: P = 0.1568

AAV-CreGFP Defeated/Targer absent vs. AAV-CreGFP Defeated/Target present:

P = 0.2289AAV-GFP CTL/Target present vs. AAV-GFP

Defeated/Target present:P = 0.2077

AAV-CreGFP CTL/Target present vs. AAV-CreGFP Defeated/Target present:

P = 0.8341AAV-GFP Defeated/Target present vs. AAV-

CreGFP Defeated/Target present:P = 0.3117

Interaction: F (3, 108) = 0.2768VGF level: F (3, 108) = 0.4802

Defeat: F (1, 108) = 8.295AAV-GFP CTL/Target absent vs. AAV-GFP

CTL/Target present: t (108) = 0.9821

AAV-GFP Defeated/Target absent vs. AAV-GFP Defeated/Target present:

t (108) = 2.407AAV-CreGFP CTL/Target absent vs. AAV-

CreGFP CTL/Target present: t (108) = 1.426

AAV-CreGFP Defeated/Targer absent vs. AAV-CreGFP Defeated/Target present:

t (108) = 1.21AAV-GFP CTL/Target present vs. AAV-GFP

Defeated/Target present:t (108) = 1.267

AAV-CreGFP CTL/Target present vs. AAV-CreGFP Defeated/Target present:

t (108) = 0.2099AAV-GFP Defeated/Target present vs. AAV-

CreGFP Defeated/Target present:t (108) = 1.016

SI 4F Two-way ANOVApost hoc:

Fisher's LSD

AAV-GFP CTL/Target absent: 10

AAV-GFP CTL/Target present: 10AAV-GFP

Defeated/Target absent: 19

AAV-GFP Defeated/Target present:

19AAV-CreGFP CTL/Target

absent: 10AAV-CreGFP CTL/Target

present: 10AAV-CreGFP

Defeated/Target absent: 19

AAV-CreGFP Defeated/Target present:

19

Interaction: P = 0.1731VGF level: P = 0.1375

Target: P < 0.0001AAV-GFP CTL/Target absent vs. AAV-GFP

CTL/Target present: P = 0.0396

AAV-GFP Defeated/Target absent vs. AAV-GFP Defeated/Target present:

P < 0.0001AAV-CreGFP CTL/Target absent vs. AAV-

CreGFP CTL/Target present: P = 0.0016

AAV-CreGFP Defeated/Targer absent vs. AAV-CreGFP Defeated/Target present:

P < 0.0001

Interaction: F (3, 108) = 1.692VGF level: F (3, 108) = 1.879

Defeat: F (1, 108) = 58.62AAV-GFP CTL/Target absent vs. AAV-GFP

CTL/Target present: t (108) = 2.083

AAV-GFP Defeated/Target absent vs. AAV-GFP Defeated/Target present:

t (108) = 6.541AAV-CreGFP CTL/Target absent vs. AAV-

CreGFP CTL/Target present: t (108) = 3.241

AAV-CreGFP Defeated/Targer absent vs. AAV-CreGFP Defeated/Target present:

t (108) = 4.56

SI 4H Two-way ANOVApost hoc:

Fisher's LSD

IgG/Target absent: 14IgG/Target present: 14

Anti-VGFC-term/Target absent: 16

Anti-VGFC-term/Target present: 16

Interaction: P = 0.0199VGF antibody: P = 0.1291

Defeat: P = 0.0118IgG/Target absent vs. IgG/Target present:

P = 0.8882

IgG/Target absent vs. Anti-VGFC-term/Target absent:

P = 0.5476

Anti-VGFC-term/Target absent vs. Anti-VGFC-

term/Target present: P = 0.0006

IgG/Target present vs. Anti-VGFC-term/Target present:

P = 0.0073

Interaction: F (1, 56) = 5.742VGF antibody: F (1, 56) = 2.373

Defeat: F (1, 56) = 6.773IgG/Target absent vs. IgG/Target present: t (56)

= 0.1412

IgG/Target absent vs. Anti-VGFC-term/Target absent:

t (56) = 0.605

Anti-VGFC-term/Target absent vs. Anti-VGFC-

term/Target present: t (56) = 3.659

IgG/Target present vs. Anti-VGFC-term/Target present:

t (56) = 2.784SI 4I Two-way

ANOVApost hoc:

Fisher's LSD

IgG/Target absent: 14IgG/Target present: 14

Anti-VGFC-term/Target absent: 16

Anti-VGFC-term/Target present: 16

Interaction: P = 0.3529VGF antibody: P = 0.0027

Defeat: P < 0.0001IgG/Target absent vs. IgG/Target present:

P < 0.0001

Anti-VGFC-term/Target absent vs. Anti-VGFC-

term/Target present: P < 0.0001

Interaction: F (1, 56) = 0.8774VGF antibody: F (1, 56) = 9.841

Defeat: F (1, 56) = 78.26IgG/Target absent vs. IgG/Target present:

t (56) = 6.698

Anti-VGFC-term/Target absent vs. Anti-VGFC-

term/Target present: t (56) = 5.789

SI 5B Welch's t test

AAV-GFP: 4AAV-VGF: 4

P = 0.0012 t (3.103) = 11.42

SI 5C Welch's t test

AAV-GFP: 7AAV-VGF: 7

P = 0.0099 t (7.352) = 3.451

SI 5D Student's t test

AAV-GFP: 7AAV-VGF: 7

P = 0.7316 t (12) = 0.3511

SI 6B Student'st test

AAV-GFP: 4AAV-VGF: 3

P = 0.0017 t (5) = 6.145

SI 6C Student's t test

AAV-GFP: 9AAV-VGF: 9

P = 0.0011 t (16) = 3.989

SI 6D Student's t test

AAV-GFP: 9AAV-VGF: 9

P = 0.4803 t (16) = 0.7227

SI 7B Two-way ANOVApost hoc:

Fisher's LSD

Vgf+/+/Saline: 8Vgf+/+/Imipramine: 10

Vgf+/-/Saline: 9Vgf+/-/Imipramine: 11

Interaction: P = 0.0656VGF level: P = 0.1186Treatment: P = 0.0943

Vgf+/+/Saline vs. Vgf+/+/Imipramine: P = 0.0176

Vgf+/-/Saline vs. Vgf+/-/Imipramine: P = 0.8961

Vgf+/+/Imipramine vs. Vgf+/-/Imipramine:P = 0.0131

Interaction: F (1, 34) = 3.619VGF level: F (1, 34) = 2.563Treatment: F (1, 34) = 2.963

Vgf+/+/Saline vs. Vgf+/+/Imipramine: t (34) = 2.496

Vgf+/-/Saline vs. Vgf+/-/Imipramine: t (34) = 0.1316

Vgf+/+/Imipramine vs. Vgf+/-/Imipramine:t (34) = 2.62

SI 7C Two-way ANOVApost hoc:

Fisher's LSD

Vgf+/+/Saline: 5Vgf+/+/Imipramine: 6

Vgf+/-/Saline: 5Vgf+/-/Imipramine: 6

Interaction: P = 0.6154VGF level: P = 0.5298Treatment: P = 0.0524

Vgf+/+/Saline vs. Vgf+/+/Imipramine: P = 0.0838

Vgf+/-/Saline vs. Vgf+/-/Imipramine: P = 0.2828

Vgf+/+/Imipramine vs. Vgf+/-/Imipramine:P = 0.9246

Interaction: F (1, 18) = 0.2614VGF level: F (1, 18) = 0.4105Treatment: F (1, 18) = 4.314

Vgf+/+/Saline vs. Vgf+/+/Imipramine: t (18) = 1.83

Vgf+/-/Saline vs. Vgf+/-/Imipramine: t (18) = 1.107

Vgf+/+/Imipramine vs. Vgf+/-/Imipramine:t (18) = 0.09598

SI 7D Two-way ANOVApost hoc:

Fisher's LSD

AAV-GFP/Saline: 13AAV-GFP/Imipramine: 13AAV-CreGFP/Saline: 13

AAV-CreGFP/Imipramine: 12

Interaction: P = 0.1944VGF level: P = 0.0721Treatment: P = 0.0081

AAV-GFP/Saline vs. AAV-GFP/Imipramine: P = 0.0054

AAV-CreGFP/Saline vs. AAV-CreGFP/Imipramine:

P = 0.3161AAV-GFP/Imipramine vs. AAV-

CreGFP/Imipramine:P = 0.0320

Interaction: F (1, 47) = 1.733VGF level: F (1, 47) = 3.386Treatment: F (1, 47) = 7.64

AAV-GFP/Saline vs. AAV-GFP/Imipramine: t (47) = 2.915

AAV-CreGFP/Saline vs. AAV-CreGFP/Imipramine:

t (47) = 1.013AAV-GFP/Imipramine vs. AAV-

CreGFP/Imipramine:t (47) = 2.21

SI 7E Two-way ANOVApost hoc:

Fisher's LSD

AAV-GFP/Saline: 9AAV-GFP/Imipramine: 9AAV-CreGFP/Saline: 9

AAV-CreGFP/Imipramine: 9

Interaction: P = 0.3493VGF level: P = 0.6942Treatment: P = 0.2140

AAV-GFP/Saline vs. AAV-GFP/Imipramine: P = 0.8235

AAV-CreGFP/Saline vs. AAV-CreGFP/Imipramine:

P = 0.1267AAV-GFP/Imipramine vs. AAV-

CreGFP/Imipramine:P = 0.3481

Interaction: F (1, 32) = 0.9024VGF level: F (1, 32) = 0.1574Treatment: F (1, 32) = 1.608

AAV-GFP/Saline vs. AAV-GFP/Imipramine: t (32) = 0.2249

AAV-CreGFP/Saline vs. AAV-CreGFP/Imipramine:

t (32) = 1.568AAV-GFP/Imipramine vs. AAV-

CreGFP/Imipramine:t (32) = 0.9523

SI 8A Two-way ANOVApost hoc:

Fisher's LSD

Vgf+/+ /Saline/Target absent: 14

Vgf+/+ /Saline/Target present: 14

Vgf+/+ /Ketamine/Target absent: 15

Vgf+/+ /Ketamine/Target present: 15

Vgf+/- /Saline/Target absent: 11

Vgf+/- /Saline/Target present: 11

Vgf+/- /Ketamine/Target absent: 19

Vgf+/- /Ketamine/Target present: 19

Interaction: P = 0.4470VGF level: P = 0.0375Treatment: P < 0.0001

Vgf+/+/Saline/Target absent vs. Vgf+/+/Saline/Target present:

P = 0.0030Vgf+/+/Ketamine/Target absent vs. Vgf+/+/Ketamine/Target present:

P = 0.0512Vgf+/-/Saline/Target absent vs. Vgf+/-

/Saline/Target present:P = 0.0010

Vgf+/-/Ketamine/Target absent vs. Vgf+/-/Ketamine/Target present:

P < 0.0001Vgf+/+/Saline/Target present vs. Vgf+/+/Ketamine/Target present:

P = 0.0136Vgf+/-/Saline/Target present vs. Vgf+/-

/Ketamine/Target present:P = 0.4875

Vgf+/+/Ketamine/Target present vs. Vgf+/-/Ketamine/Target present:

P = 0.1360

Interaction: F (3, 110) = 0.8936VGF level: F (3, 110) = 2.916Treatment: F (1, 110) = 40.32

Vgf+/+/Saline/Target absent vs. Vgf+/+/Saline/Target present:

t (110) = 3.04Vgf+/+/Ketamine/Target absent vs. Vgf+/+/Ketamine/Target present:

t (110) = 1.972Vgf+/-/Saline/Target absent vs. Vgf+/-

/Saline/Target present:t (110) = 3.384

Vgf+/-/Ketamine/Target absent vs. Vgf+/-/Ketamine/Target present:

t (110) = 4.481Vgf+/+/Saline/Target present vs. Vgf+/+/Ketamine/Target present:

t (110) = 2.509Vgf+/-/Saline/Target present vs. Vgf+/-

/Ketamine/Target present:t (110) = 0.6967

Vgf+/+/Ketamine/Target present vs. Vgf+/-/Ketamine/Target present:

t (110) = 1.502

SI 8B Two-way ANOVApost hoc:

Fisher's LSD

Vgf+/+ /Saline/Target absent: 14

Vgf+/+ /Saline/Target present: 14

Vgf+/+ /Ketamine/Target absent: 15

Vgf+/+ /Ketamine/Target present: 15

Vgf+/- /Saline/Target absent: 11

Vgf+/- /Saline/Target present: 11

Vgf+/- /Ketamine/Target absent: 19

Vgf+/- /Ketamine/Target present: 19

Interaction: P = 0.2997VGF level: P = 0.0606Treatment: P < 0.0001

Vgf+/+/Saline/Target absent vs. Vgf+/+/Saline/Target present:

P = 0.0001Vgf+/+/Ketamine/Target absent vs. Vgf+/+/Ketamine/Target present:

P = 0.0553Vgf+/-/Saline/Target absent vs. Vgf+/-

/Saline/Target present:P = 0.0003

Vgf+/-/Ketamine/Target absent vs. Vgf+/-/Ketamine/Target present:

P = 0.0045Vgf+/+/Saline/Target present vs. Vgf+/+/Ketamine/Target present:

P = 0.0067Vgf+/-/Saline/Target present vs. Vgf+/-

/Ketamine/Target present:P = 0.0836

Vgf+/+/Ketamine/Target present vs. Vgf+/-/Ketamine/Target present:

P = 0.2901

Interaction: F (3, 110) = 1.238VGF level: F (3, 110) = 2.534Treatment: F (1, 110) = 39.58

Vgf+/+/Saline/Target absent vs. Vgf+/+/Saline/Target present:

t (110) = 3.955Vgf+/+/Ketamine/Target absent vs. Vgf+/+/Ketamine/Target present:

t (110) = 1.937Vgf+/-/Saline/Target absent vs. Vgf+/-

/Saline/Target present:t (110) = 3.7

Vgf+/-/Ketamine/Target absent vs. Vgf+/-/Ketamine/Target present:

t (110) = 2.903Vgf+/+/Saline/Target present vs. Vgf+/+/Ketamine/Target present:

t (110) = 2.765Vgf+/-/Saline/Target present vs. Vgf+/-

/Ketamine/Target present:t (110) = 1.746

Vgf+/+/Ketamine/Target present vs. Vgf+/-/Ketamine/Target present:

t (110) = 1.063

SI 8C Two-way ANOVApost hoc:

Fisher's LSD

Vgf+/+ /Saline/Target absent: 14

Vgf+/+ /Saline/Target present: 14

Vgf+/+ /Ketamine/Target absent: 15

Vgf+/+ /Ketamine/Target present: 15

Vgf+/- /Saline/Target absent: 11

Vgf+/- /Saline/Target present: 11

Vgf+/- /Ketamine/Target absent: 19

Vgf+/- /Ketamine/Target present: 19

Interaction: P = 0.8230VGF level: P = 0.0062Treatment: P < 0.0001

Vgf+/+/Saline/Target absent vs. Vgf+/+/Saline/Target present:

P < 0.0001Vgf+/+/Ketamine/Target absent vs. Vgf+/+/Ketamine/Target present:

P < 0.0001Vgf+/-/Saline/Target absent vs. Vgf+/-

/Saline/Target present:P < 0.0001

Vgf+/-/Ketamine/Target absent vs. Vgf+/-/Ketamine/Target present:

P < 0.0001

Interaction: F (3, 110) = 0.3032VGF level: F (3, 110) = 4.345Treatment: F (1, 110) = 140.8

Vgf+/+/Saline/Target absent vs. Vgf+/+/Saline/Target present:

t (110) = 6.568Vgf+/+/Ketamine/Target absent vs. Vgf+/+/Ketamine/Target present:

t (110) = 6.265Vgf+/-/Saline/Target absent vs. Vgf+/-

/Saline/Target present:t (110) = 4.909

Vgf+/-/Ketamine/Target absent vs. Vgf+/-/Ketamine/Target present:

t (110) = 6.29

SI 9A Two-way ANOVApost hoc:

Fisher's LSD; Student's t test

Vgf+/+/PBS: 6Vgf+/+/BDNF: 7

Vgf+/-/PBS: 6Vgf+/-/BDNF: 7

Interaction: P = 0.4301VGF level: P = 0.5392Treatment: P = 0.0018

Vgf+/+/PBS vs. Vgf+/+/BDNF: P = 0.0054

Vgf+/-/PBS vs. Vgf+/-/BDNF:P = 0.0644 (Fisher's LSD); P = 0.0310

(Student's t test)

Interaction: F (1, 22) = 0.646VGF level: F (1, 22) = 0.3891Treatment: F (1, 22) = 12.65

Vgf+/+/PBS vs. Vgf+/+/BDNF: t (22) = 3.083

Vgf+/-/PBS vs. Vgf+/-/BDNF:t (22) = 1.947 (Fisher's LSD); t (11) = 2.472

SI 9B Two-way ANOVApost hoc:

Fisher's LSD

Vgf+/+/DMSO: 10Vgf+/+/7, 8 - DHF: 10

Vgf+/-/DMSO: 8Vgf+/-/7, 8 - DHF: 9

Interaction: P = 0.7713VGF level: P = 0.3707Treatment: P = 0.0015

Vgf+/+/DMSO vs. Vgf+/+/7, 8 - DHF: P = 0.0254

Vgf+/-/DMSO vs. Vgf+/-/7, 8 - DHF:P = 0.0155

Interaction: F (1, 33) = 0.0859VGF level: F (1, 33) = 0.8237

Treatment: F (1, 33) = 12Vgf+/+/DMSO vs. Vgf+/+/7, 8 - DHF:

t (33) = 2.341Vgf+/-/DMSO vs. Vgf+/-/7, 8 - DHF:

t (33) = 2.553

SI 10A Two-way ANOVApost hoc:

Fisher's LSD

Saline/SC-62: 5Saline/TLQP-62: 5NBQX/SC-62: 5

NBQX/TLQP-62: 4

Interaction: P = 0.0424NBQX pretreatment: P = 0.1651

Peptide: P = 0.0231Saline/SC-62 vs. Saline/TLQP-62:

P = 0.0035Saline/SC-62 vs. NBQX/SC-62:

P = 0.5882NBQX/SC-62 vs. NBQX/TLQP-62:

P = 0.8334Saline/TLQP-62 vs. NBQX/TLQP-62:

P = 0.0232

Interaction: F (1, 15) = 4.922NBQX pretreatment: F (1, 15) = 2.13

Peptide: F (1, 15) = 6.402Saline/SC-62 vs. Saline/TLQP-62:

t (15) = 3.461Saline/SC-62 vs. NBQX/SC-62:

t (15) = 0.5534NBQX/SC-62 vs. NBQX/TLQP-62:

t (15) = 0.2141Saline/TLQP-62 vs. NBQX/TLQP-62:

t (15) = 2.527

SI 10B Two-way ANOVApost hoc:

Fisher's LSD

DMSO/SC-62: 6DMSO/TLQP-62: 6Rapamycin/SC-62: 5

Rapamycin/TLQP-62: 6

Interaction: P = 0.0071Rapamycin pretreatment: P = 0.6792

Peptide: P = 0.1578DMSO/SC-62 vs. DMSO/TLQP-62:

P = 0.0042DMSO/SC-62 vs. Rapamycin/SC-62:

P = 0.0887Rapamycin/SC-62 vs. Rapamycin/TLQP-62:

P = 0.2986DMSO/TLQP-62 vs. Rapamycin/TLQP-62:

P = 0.0222

Interaction: F (1, 19) = 9.105Rapamycin pretreatment: F (1, 19) = 0.1764

Peptide: F (1, 19) = 2.162DMSO/SC-62 vs. DMSO/TLQP-62:

t (19) = 3.252DMSO/SC-62 vs. Rapamycin/SC-62:

t (19) = 1.794Rapamycin/SC-62 vs. Rapamycin/TLQP-62:

t (19) = 1.069DMSO/TLQP-62 vs. Rapamycin/TLQP-62:

t (19) = 2.491

SI 11A Student's t test AAV-GFP: 8AAV-CreGFP: 8

P = 0.0019 t (14) = 3.806

SI 11B Two-way ANOVApost hoc:

Fisher's LSD

AAV-GFP/SC-62: 3AAV-GFP/TLQP-62: 4AAV-CreGFP/SC-62: 3

AAV-CreGFP/TLQP-62: 4

Interaction: P = 0.0456BDNF level: P = 0.1289

Peptide: P = 0.0876AAV-GFP/SC-62 vs. AAV-GFP/TLQP-62:

P = 0.0145AAV-GFP/SC-62 vs. AAV-CreGFP/SC-62:

P = 0.6868AAV-CreGFP/SC-62 vs. AAV-CreGFP/TLQP-

62:P = 0.7885

AAV-GFP/TLQP-62 vs. AAV-CreGFP/TLQP-62:

P = 0.0132

Interaction: F (1, 10) = 5.211BDNF level: F (1, 10) = 2.74

Peptide: F (1, 10) = 3.584AAV-GFP/SC-62 vs. AAV-GFP/TLQP-62:

t (10) = 2.953AAV-GFP/SC-62 vs. AAV-CreGFP/SC-62:

t (10) = 0.4151AAV-CreGFP/SC-62 vs. AAV-CreGFP/TLQP-

62:t (10) = 0.2756

AAV-GFP/TLQP-62 vs. AAV-CreGFP/TLQP-62:

t (10) = 3.008

SI 11C Two-way ANOVApost hoc:

Fisher's LSD; Student's t test

AAV-GFP/SC-62: 3AAV-GFP/TLQP-62: 3AAV-CreGFP/SC-62: 3

AAV-CreGFP/TLQP-62: 4

Interaction: P = 0.1689BDNF level: P = 0.0285

Peptide: P = 0.2170AAV-GFP/SC-62 vs. AAV-GFP/TLQP-62:

P = 0.0852 (Fisher's LSD); P = 0.0198 (Student's t test)

AAV-GFP/SC-62 vs. AAV-CreGFP/SC-62:P = 0.4668

AAV-CreGFP/SC-62 vs. AAV-CreGFP/TLQP-62:

P = 0.9048AAV-GFP/TLQP-62 vs. AAV-CreGFP/TLQP-

62: P = 0.0149

Interaction: F (1, 9) = 2.238BDNF level: F (1, 9) = 6.79

Peptide: F (1, 9) = 1.763AAV-GFP/SC-62 vs. AAV-GFP/TLQP-62:t (9) = 1.933 (Fisher's LSD); t (4) = 3.758

(Student's t test)AAV-GFP/SC-62 vs. AAV-CreGFP/SC-62:

t (9) = 0.7598AAV-CreGFP/SC-62 vs. AAV-CreGFP/TLQP-

62:t (9) = 0.1231

AAV-GFP/TLQP-62 vs. AAV-CreGFP/TLQP-62:

t (9) = 3.002