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Food seeking constrained by brief footshock

Food seeking constrained by brief footshock punishment. The last successfully completed ratio or shock intensity endured before timeout. Animals are food restricted to 85% of initial body weight, trained to lever-press for food pellets (45 mg) until stable response rates were reached, then tested either on the progressive ratio (PR) task with progressively increasing effort requirements (lever-presses required per pellet) or progressively increasing punishment (i.e., a foot-shock of increasing intensity presented 1 s after food pellet delivery, whose magnitude increases ~25% every 3 trials). In the PR task, rats time out if 2 min passed without a lever press. In the punishment task, a timeout is defined by three consecutive trials with >30 s passing without a lever press. For both tasks, the break point is the last successfully completed ratio or shock intensity endured before timeout.

Tags: Behavior · Motivation

Project: u01_tom_jhou

16 significantly associated models · 8 unique genes

Significant Loci

# chr p0 p1 # assoc genes # joint models best TWAS P best SNP P cond SNP P % var exp joint genes
1 1 68581504 69974370 1 1 3.0e-37 6.0e-04 4.2e-05 -42 Syt5
2 1 71854301 74100561 6 4 1.0e-16 2.1e-04 3.1e-14 -321 Zfp329 Zscan18 Zfp110 Vom2r35
3 5 49091753 49968409 1 1 3.6e-08 3.2e-08 1.2e-01 92 RGD1359108

p0: physical position of the start of the locus. p1: physical position of the end of the locus. # joint models: number of models selected by step-wise conditional analysis.

Pleiotropic Associations

Trait chisq ratio # genes+ # genes++ % genes++ corr corr P genes
BMI with tail 3.0 1 0 0 1.00 7.0e-05 RGD1359108
Body weight 6.9 2 1 17 0.54 3.5e-01 RGD1359108 Syt5
Glucose 12.1 1 0 0 0.00 1.0e+00 Syt5
Left kidney weight 4.6 1 0 0 1.00 6.9e-06 RGD1359108
Right kidney weight 5.0 1 0 0 1.00 1.8e-05 RGD1359108
Length with tail 3.5 1 0 0 1.00 3.9e-05 RGD1359108
Liver weight, left 8.0 2 0 0 0.00 1.0e+00 Syt5 Zfp329
Liver weight, right 11.2 1 0 0 0.00 1.0e+00 Syt5
Retroperitoneal fat weight 3.1 3 0 0 0.00 1.0e+00 Zfp329 Zfp110 Vom2r35
Extensor digitorum longus weight 5.4 1 0 0 1.00 8.9e-05 RGD1359108
Tibialis anterior weight 8.2 1 1 17 1.00 1.7e-05 RGD1359108
Tibia length 7.5 1 0 0 0.00 1.0e+00 Syt5
Std. dev. time between licks in bursts 22.7 1 1 17 0.00 1.0e+00 Syt5
Indifference point 0 sec 6.3 1 0 0 0.00 1.0e+00 Syt5
Indifference point function ln k 7.6 2 0 0 0.00 1.0e+00 Syt5 Zfp110
Indifference point function log k 7.6 2 0 0 0.00 1.0e+00 Syt5 Zfp110
Delay discounting total patch changes 0 sec 5.8 1 0 0 0.00 1.0e+00 Syt5
Delay discounting total patch changes 24 sec 10.3 1 0 0 0.00 1.0e+00 Syt5
Delay discounting time to switch 0 sec 17.0 6 1 17 -0.98 5.4e-06 Syt5 Zfp329 Zscan18 Zfp110 Vom1r50 NA
Delay discounting water rate 0 sec 10.3 1 0 0 0.00 1.0e+00 Syt5
Delay discounting water rate 12 sec 9.3 5 1 17 0.99 3.0e-06 Syt5 Zfp329 Zfp110 Vom1r50 NA
Delay discounting water rate 18 sec 19.1 1 0 0 0.00 1.0e+00 Syt5
Delay discounting water rate 24 sec 8.0 1 0 0 0.00 1.0e+00 Syt5
Light reinforcement 1 21.6 1 1 17 0.00 1.0e+00 Syt5
Light reinforcement 2 21.6 1 1 17 0.00 1.0e+00 Syt5
Reaction time num false alarms AUC 10.6 1 0 0 0.00 1.0e+00 Syt5
Reaction time mean 6.5 2 0 0 0.00 1.0e+00 Zscan18 Zfp110
Reaction time mean AUC 6.6 1 0 0 0.00 1.0e+00 Zfp110
Median of all reaction times 7.0 1 0 0 0.00 1.0e+00 Syt5
Social response proportion 13.5 1 0 0 0.00 1.0e+00 Zfp110
Social responses 7.5 1 0 0 0.00 1.0e+00 Zfp329
Social time 12.8 2 0 0 0.00 1.0e+00 Syt5 Zfp110
Cocaine response after cond. corrected 18.2 1 0 0 0.00 1.0e+00 Syt5
Cocaine response after cond. not corrected 16.4 1 0 0 0.00 1.0e+00 Syt5
Cocaine response before conditioning 8.3 1 0 0 0.00 1.0e+00 Zfp110
Saline control response 13.2 1 0 0 0.00 1.0e+00 Syt5
Condit. Reinf. lever presses 9.9 1 0 0 0.00 1.0e+00 Syt5
Conditioned reinforcement - actives 16.9 2 0 0 0.00 1.0e+00 Syt5 Zfp110
Conditioned locomotion 14.1 2 0 0 0.00 1.0e+00 Syt5 Zfp110
Intermittent access intake escalation 9.3 1 0 0 0.00 1.0e+00 Zfp110
Intermitt. access day 1 inactive lever presses 14.2 5 0 0 -0.97 1.5e-05 Syt5 Zfp329 Zscan18 Zfp110 Vom2r35
Intermitt. access day 15 inactive lever presses 16.5 5 1 17 -0.99 1.0e-05 Syt5 Zfp329 Zscan18 Zfp110 Vom2r35
Intermitt. access escalation Index 17.2 1 0 0 0.00 1.0e+00 Syt5
Intermittent access day 15 total infusions 15.6 1 0 0 0.00 1.0e+00 Zfp110
Intermittent access terminal intake (last 3 days) 9.5 1 0 0 0.00 1.0e+00 Zfp110
Intermittent access day 15 total locomotion 9.7 1 0 0 0.00 1.0e+00 Zfp110
Intermittent access standard deviation 9.7 3 0 0 -0.97 1.8e-03 Syt5 Zfp329 Zfp110
Post-drug Anxiety 10.2 1 0 0 0.00 1.0e+00 Syt5
Baseline Anxiety 12.7 2 1 17 -1.00 3.4e-06 Syt5 Zfp329
Incentive Sensitization - Responses 14.1 3 0 0 0.00 1.0e+00 Zfp329 Zscan18 Zfp110
Incentive Sensitization - Breakpoint 15.3 2 0 0 0.00 1.0e+00 Zscan18 Zfp110
Short access day 1 total inactive lever presses 24.4 1 1 17 0.00 1.0e+00 Syt5
Short access day 10 total locomotion 11.2 1 0 0 0.00 1.0e+00 Syt5
Short access total locomotion 13.1 1 0 0 0.00 1.0e+00 Syt5
One hour access (0.3 mA shock) 11.2 3 0 0 0.00 1.0e+00 Zfp329 Zscan18 Zfp110
One hour access (shock baseline) 12.1 4 1 17 -0.99 2.0e-06 Syt5 Zfp329 Zscan18 Zfp110
Number of responses in last shaping day 9.8 1 0 0 0.00 1.0e+00 Syt5
Locomotion velocity, session 1 61.5 1 1 17 0.00 1.0e+00 Syt5
Locomotion distance, session 1 22.4 1 1 17 0.00 1.0e+00 Syt5
Locomotion velocity, session 2 20.6 1 0 0 0.00 1.0e+00 Syt5
Locomotion distance, session 3 8.7 1 0 0 0.00 1.0e+00 Syt5
Locomotion distance, session 7 10.2 1 0 0 0.00 1.0e+00 Syt5
Locomotion velocity, session 8 15.7 1 0 0 0.00 1.0e+00 Syt5
Locomotion distance, session 8 9.2 1 0 0 0.00 1.0e+00 Syt5
Time in familiar zone, hab. session 1 10.4 3 0 0 0.97 3.4e-02 Syt5 Zfp329 Zfp110
Total zone transitions, hab. session 1 10.7 2 1 17 0.03 9.6e-01 RGD1359108 Syt5
Total locomotion distance, hab. session 1 19.3 1 1 17 0.00 1.0e+00 Syt5
Locomotion velocity, hab. session 1 12.3 1 0 0 0.00 1.0e+00 Syt5
Time in familiar zone, hab. session 2 14.1 1 0 0 0.00 1.0e+00 Syt5
Total zone transitions, hab. session 2 7.9 1 0 0 0.00 1.0e+00 Syt5
Total locomotion distance, hab. session 2 10.7 1 0 0 0.00 1.0e+00 Syt5
Locomotion velocity, hab. session 2 13.6 1 0 0 0.00 1.0e+00 Syt5
Pavlov. Cond. magazine entry latency 10.4 1 0 0 0.00 1.0e+00 Syt5
Pavlov. Cond. intertrial magazine entries 19.5 1 0 0 0.00 1.0e+00 Syt5
Pavlov. Cond. response bias 13.4 1 0 0 0.00 1.0e+00 Syt5
Bone: periosteal estimation 5.0 1 0 0 1.00 4.4e-05 RGD1359108
Bone: post-yield work 11.6 1 0 0 0.00 1.0e+00 Syt5
Bone: tissue strength 11.4 2 0 0 0.00 1.0e+00 Syt5 Zfp329
Bone: trabecular tissue density 8.3 3 0 0 -0.95 5.3e-02 Syt5 Zfp329 Zfp110
Distance traveled before self-admin 22.1 3 1 17 0.98 1.6e-02 Syt5 Zfp329 Zfp110
Distance traveled after self-admin 19.4 5 1 17 0.99 6.3e-08 Syt5 Zfp329 Zscan18 Zfp110 Vom2r35
Delta time in open arm before/after self-admin 18.0 1 0 0 0.00 1.0e+00 Syt5
Diff in mean of infusions in LGA sessions 20.4 1 0 0 0.00 1.0e+00 Syt5
Extinction: sum of active levers before priming 36.5 1 1 17 0.00 1.0e+00 Syt5
Active lever presses in extinction session 6 17.9 1 0 0 0.00 1.0e+00 Syt5
Time in closed arm after self-admin 22.3 1 0 0 0.00 1.0e+00 Syt5
Time in open arm before self-admin 12.1 1 0 0 0.00 1.0e+00 Zfp110
Time in open arm after self-admin 17.1 1 0 0 0.00 1.0e+00 Syt5
Sum of active levers in priming session hrs 5-6 17.2 1 0 0 0.00 1.0e+00 Syt5
Time to tail flick, vehicle, after self-admin 10.3 1 0 0 0.00 1.0e+00 Zfp110
Time to tail flick, test, before self-admin 20.6 6 2 33 1.00 1.7e-10 Syt5 Zfp329 Zscan18 Zfp110 Vom1r50 NA
Delta time to tail flick, test, before/after SA 18.7 3 1 17 -1.00 3.4e-06 Syt5 Zfp329 Zscan18
Ambulatory time before self-admin 36.6 1 1 17 0.00 1.0e+00 Syt5
Ambulatory time after self-admin 17.3 6 1 17 0.99 5.0e-08 Syt5 Zfp329 Zscan18 Zfp110 Vom1r50 NA
Delay disc. indifference point, 0s delay 14.3 4 1 17 1.00 4.3e-07 Syt5 Zfp329 Zscan18 Zfp110
Delay disc. indifference point, 16s delay 24.1 1 0 0 0.00 1.0e+00 Syt5
Delay disc. indifference point, 24s delay 9.6 1 0 0 0.00 1.0e+00 Syt5
Bouts of movement, locomotor time 1 18.2 2 1 17 0.97 5.5e-03 Syt5 Zfp329
Total resting periods, locomotor time 1 37.3 1 1 17 0.00 1.0e+00 Syt5
Vertical activity count, locomotor time 1 24.2 1 0 0 0.00 1.0e+00 Syt5
Rest time, locomotor task time 2 9.1 1 0 0 0.00 1.0e+00 Syt5
Weight adjusted by age 8.3 1 0 0 0.00 1.0e+00 Syt5
Seeking ratio, delayed vs. immediate footshock 12.4 4 1 17 1.00 5.6e-07 Syt5 Zfp329 Zscan18 Zfp110
Locomotion in novel chamber 12.7 1 0 0 0.00 1.0e+00 Syt5
Progressive ratio 7.6 1 0 0 0.00 1.0e+00 Syt5
Seeking ratio, punishment vs. effort 10.3 2 0 0 0.98 3.3e-03 RGD1359108 Syt5
Co content in liver 19.4 1 0 0 0.00 1.0e+00 Syt5
Sr content in liver 23.0 4 1 17 0.98 8.0e-04 Syt5 Zfp329 Zscan18 Vom2r35
Zn content in liver 12.4 1 0 0 0.00 1.0e+00 Syt5

chisq ratio: Average Chi2 statistic for the selected genes in the secondary trait, divided by the average statistic for all genes in the secondary trait. # genes+: Shared significant genes at Bonferroni correction. # genes++: Shared significant genes at transcriptome-wide significance. % genes++: Number of [++] genes as a percentage of primary trait’s total joint genes. corr: Correlation of effect sizes across the [+] genes.

Associations by panel

tissue modality # hits % hits/tests avg chisq
Adipose alternative polyA 1 0.047 1.14
Adipose alternative TSS 0 0.000 1.28
Adipose gene expression 2 0.024 1.24
Adipose isoform ratio 0 0.000 1.17
Adipose intron excision ratio 0 0.000 1.19
Adipose mRNA stability 0 0.000 1.28
BLA alternative polyA 0 0.000 1.21
BLA alternative TSS 0 0.000 1.31
BLA gene expression 1 0.016 1.27
BLA isoform ratio 1 0.057 1.27
BLA intron excision ratio 0 0.000 1.14
BLA mRNA stability 1 0.049 1.36
Brain alternative polyA 0 0.000 1.19
Brain alternative TSS 0 0.000 1.23
Brain gene expression 1 0.011 1.23
Brain isoform ratio 2 0.063 1.24
Brain intron excision ratio 0 0.000 1.18
Brain mRNA stability 0 0.000 1.25
Eye alternative polyA 0 0.000 1.10
Eye alternative TSS 0 0.000 1.30
Eye gene expression 0 0.000 1.35
Eye isoform ratio 0 0.000 1.21
Eye intron excision ratio 0 0.000 1.17
Eye mRNA stability 0 0.000 1.48
IL alternative polyA 0 0.000 1.19
IL alternative TSS 0 0.000 1.30
IL gene expression 0 0.000 1.22
IL isoform ratio 0 0.000 1.20
IL intron excision ratio 0 0.000 1.07
IL mRNA stability 0 0.000 1.19
LHb alternative polyA 0 0.000 0.98
LHb alternative TSS 0 0.000 1.24
LHb gene expression 0 0.000 1.23
LHb isoform ratio 0 0.000 1.21
LHb intron excision ratio 0 0.000 1.23
LHb mRNA stability 0 0.000 1.30
Liver alternative polyA 0 0.000 1.18
Liver alternative TSS 0 0.000 1.26
Liver gene expression 0 0.000 1.21
Liver isoform ratio 0 0.000 1.22
Liver intron excision ratio 0 0.000 1.15
Liver mRNA stability 0 0.000 1.22
NAcc alternative polyA 0 0.000 1.21
NAcc alternative TSS 0 0.000 1.36
NAcc gene expression 1 0.016 1.24
NAcc isoform ratio 0 0.000 1.22
NAcc intron excision ratio 0 0.000 1.17
NAcc mRNA stability 1 0.044 1.33
OFC alternative polyA 0 0.000 1.02
OFC alternative TSS 0 0.000 0.94
OFC gene expression 0 0.000 1.23
OFC isoform ratio 0 0.000 1.27
OFC intron excision ratio 0 0.000 1.09
OFC mRNA stability 0 0.000 1.28
PL alternative polyA 0 0.000 1.25
PL alternative TSS 0 0.000 1.24
PL gene expression 1 0.014 1.22
PL isoform ratio 2 0.091 1.23
PL intron excision ratio 2 0.056 1.15
PL mRNA stability 0 0.000 1.30

avg chisq: Average Chi2 (squared Z-score) across all models in this panel for this trait.