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

3 loci · 6 genes with independent associations · 8 total associated genes

Significant Loci

#	Chr	Start pos	End pos	# assoc genes	# joint models	Best TWAS P	Best GWAS P	Cond GWAS P	Joint genes
1	1	68581504	69974370	1	1	3.03e-37	5.97e-04	4.23e-05	Syt5
2	1	71854301	74100561	6	4	1.05e-16	2.13e-04	3.10e-14	Zfp329 Zscan18 Zfp110 Vom2r35
3	5	49091753	49968409	1	1	3.57e-08	3.21e-08	1.21e-01	RGD1359108

Pleiotropic Associations

Trait	Chi² ratio	# genes⁺	# genes⁺⁺	% genes⁺⁺	Corr	Corr P	Genes
BMI with tail	3.02	1	0	0	1	7.04e-05	RGD1359108
Body weight	6.88	2	1	16.7	0.54	3.51e-01	RGD1359108 Syt5
Glucose	12.08	1	0	0	0	1.00e+00	Syt5
Left kidney weight	4.58	1	0	0	1	6.92e-06	RGD1359108
Right kidney weight	5.04	1	0	0	1	1.84e-05	RGD1359108
Length with tail	3.48	1	0	0	1	3.91e-05	RGD1359108
Liver weight, left	7.95	2	0	0	0	1.00e+00	Syt5 Zfp329
Liver weight, right	11.2	1	0	0	0	1.00e+00	Syt5
Retroperitoneal fat weight	3.11	3	0	0	0	1.00e+00	Zfp329 Zfp110 Vom2r35
Extensor digitorum longus weight	5.43	1	0	0	1	8.92e-05	RGD1359108
Tibialis anterior weight	8.15	1	1	16.7	1	1.72e-05	RGD1359108
Tibia length	7.53	1	0	0	0	1.00e+00	Syt5
Std. dev. time between licks in bursts	22.72	1	1	16.7	0	1.00e+00	Syt5
Indifference point 0 sec	6.32	1	0	0	0	1.00e+00	Syt5
Indifference point function ln k	7.62	2	0	0	0	1.00e+00	Syt5 Zfp110
Indifference point function log k	7.62	2	0	0	0	1.00e+00	Syt5 Zfp110
Delay discounting total patch changes 0 sec	5.75	1	0	0	0	1.00e+00	Syt5
Delay discounting total patch changes 24 sec	10.35	1	0	0	0	1.00e+00	Syt5
Delay discounting time to switch 0 sec	16.97	6	1	16.7	-0.98	5.45e-06	Syt5 Zfp329 Zscan18 Zfp110 Vom1r50 ENSRNOG00000070456
Delay discounting water rate 0 sec	10.34	1	0	0	0	1.00e+00	Syt5
Delay discounting water rate 12 sec	9.28	5	1	16.7	0.99	2.98e-06	Syt5 Zfp329 Zfp110 Vom1r50 ENSRNOG00000070456
Delay discounting water rate 18 sec	19.1	1	0	0	0	1.00e+00	Syt5
Delay discounting water rate 24 sec	7.99	1	0	0	0	1.00e+00	Syt5
Light reinforcement 1	21.59	1	1	16.7	0	1.00e+00	Syt5
Light reinforcement 2	21.57	1	1	16.7	0	1.00e+00	Syt5
Reaction time num false alarms AUC	10.57	1	0	0	0	1.00e+00	Syt5
Reaction time mean	6.55	2	0	0	0	1.00e+00	Zscan18 Zfp110
Reaction time mean AUC	6.62	1	0	0	0	1.00e+00	Zfp110
Median of all reaction times	6.98	1	0	0	0	1.00e+00	Syt5
Social response proportion	13.48	1	0	0	0	1.00e+00	Zfp110
Social responses	7.52	1	0	0	0	1.00e+00	Zfp329
Social time	12.78	2	0	0	0	1.00e+00	Syt5 Zfp110
Cocaine response after cond. corrected	18.2	1	0	0	0	1.00e+00	Syt5
Cocaine response after cond. not corrected	16.42	1	0	0	0	1.00e+00	Syt5
Cocaine response before conditioning	8.29	1	0	0	0	1.00e+00	Zfp110
Saline control response	13.17	1	0	0	0	1.00e+00	Syt5
Condit. Reinf. lever presses	9.91	1	0	0	0	1.00e+00	Syt5
Conditioned reinforcement - actives	16.9	2	0	0	0	1.00e+00	Syt5 Zfp110
Conditioned locomotion	14.1	2	0	0	0	1.00e+00	Syt5 Zfp110
Intermittent access intake escalation	9.34	1	0	0	0	1.00e+00	Zfp110
Intermitt. access day 1 inactive lever presses	14.24	5	0	0	-0.97	1.52e-05	Syt5 Zfp329 Zscan18 Zfp110 Vom2r35
Intermitt. access day 15 inactive lever presses	16.54	5	1	16.7	-0.99	1.01e-05	Syt5 Zfp329 Zscan18 Zfp110 Vom2r35
Intermitt. access escalation Index	17.22	1	0	0	0	1.00e+00	Syt5
Intermittent access day 15 total infusions	15.58	1	0	0	0	1.00e+00	Zfp110
Intermittent access terminal intake (last 3 days)	9.49	1	0	0	0	1.00e+00	Zfp110
Intermittent access day 15 total locomotion	9.66	1	0	0	0	1.00e+00	Zfp110
Intermittent access standard deviation	9.67	3	0	0	-0.97	1.79e-03	Syt5 Zfp329 Zfp110
Post-drug Anxiety	10.17	1	0	0	0	1.00e+00	Syt5
Baseline Anxiety	12.72	2	1	16.7	-1	3.44e-06	Syt5 Zfp329
Incentive Sensitization - Responses	14.13	3	0	0	0	1.00e+00	Zfp329 Zscan18 Zfp110
Incentive Sensitization - Breakpoint	15.3	2	0	0	0	1.00e+00	Zscan18 Zfp110
Short access day 1 total inactive lever presses	24.45	1	1	16.7	0	1.00e+00	Syt5
Short access day 10 total locomotion	11.18	1	0	0	0	1.00e+00	Syt5
Short access total locomotion	13.05	1	0	0	0	1.00e+00	Syt5
One hour access (0.3 mA shock)	11.2	3	0	0	0	1.00e+00	Zfp329 Zscan18 Zfp110
One hour access (shock baseline)	12.06	4	1	16.7	-0.99	2.01e-06	Syt5 Zfp329 Zscan18 Zfp110
Number of responses in last shaping day	9.84	1	0	0	0	1.00e+00	Syt5
Locomotion velocity, session 1	61.51	1	1	16.7	0	1.00e+00	Syt5
Locomotion distance, session 1	22.42	1	1	16.7	0	1.00e+00	Syt5
Locomotion velocity, session 2	20.55	1	0	0	0	1.00e+00	Syt5
Locomotion distance, session 3	8.71	1	0	0	0	1.00e+00	Syt5
Locomotion distance, session 7	10.24	1	0	0	0	1.00e+00	Syt5
Locomotion velocity, session 8	15.73	1	0	0	0	1.00e+00	Syt5
Locomotion distance, session 8	9.21	1	0	0	0	1.00e+00	Syt5
Time in familiar zone, hab. session 1	10.37	3	0	0	0.97	3.44e-02	Syt5 Zfp329 Zfp110
Total zone transitions, hab. session 1	10.66	2	1	16.7	0.03	9.62e-01	RGD1359108 Syt5
Total locomotion distance, hab. session 1	19.26	1	1	16.7	0	1.00e+00	Syt5
Locomotion velocity, hab. session 1	12.27	1	0	0	0	1.00e+00	Syt5
Time in familiar zone, hab. session 2	14.1	1	0	0	0	1.00e+00	Syt5
Total zone transitions, hab. session 2	7.86	1	0	0	0	1.00e+00	Syt5
Total locomotion distance, hab. session 2	10.72	1	0	0	0	1.00e+00	Syt5
Locomotion velocity, hab. session 2	13.63	1	0	0	0	1.00e+00	Syt5
Pavlov. Cond. magazine entry latency	10.45	1	0	0	0	1.00e+00	Syt5
Pavlov. Cond. intertrial magazine entries	19.53	1	0	0	0	1.00e+00	Syt5
Pavlov. Cond. response bias	13.37	1	0	0	0	1.00e+00	Syt5
Bone: periosteal estimation	4.96	1	0	0	1	4.44e-05	RGD1359108
Bone: post-yield work	11.59	1	0	0	0	1.00e+00	Syt5
Bone: tissue strength	11.36	2	0	0	0	1.00e+00	Syt5 Zfp329
Bone: trabecular tissue density	8.31	3	0	0	-0.95	5.34e-02	Syt5 Zfp329 Zfp110
Distance traveled before self-admin	22.08	3	1	16.7	0.98	1.55e-02	Syt5 Zfp329 Zfp110
Distance traveled after self-admin	19.45	5	1	16.7	0.99	6.34e-08	Syt5 Zfp329 Zscan18 Zfp110 Vom2r35
Delta time in open arm before/after self-admin	18.04	1	0	0	0	1.00e+00	Syt5
Diff in mean of infusions in LGA sessions	20.43	1	0	0	0	1.00e+00	Syt5
Extinction: sum of active levers before priming	36.46	1	1	16.7	0	1.00e+00	Syt5
Active lever presses in extinction session 6	17.94	1	0	0	0	1.00e+00	Syt5
Time in closed arm after self-admin	22.26	1	0	0	0	1.00e+00	Syt5
Time in open arm before self-admin	12.07	1	0	0	0	1.00e+00	Zfp110
Time in open arm after self-admin	17.09	1	0	0	0	1.00e+00	Syt5
Sum of active levers in priming session hrs 5-6	17.22	1	0	0	0	1.00e+00	Syt5
Time to tail flick, vehicle, after self-admin	10.34	1	0	0	0	1.00e+00	Zfp110
Time to tail flick, test, before self-admin	20.63	6	2	33.3	1	1.65e-10	Syt5 Zfp329 Zscan18 Zfp110 Vom1r50 ENSRNOG00000070456
Delta time to tail flick, test, before/after SA	18.74	3	1	16.7	-1	3.35e-06	Syt5 Zfp329 Zscan18
Ambulatory time before self-admin	36.65	1	1	16.7	0	1.00e+00	Syt5
Ambulatory time after self-admin	17.31	6	1	16.7	0.99	5.03e-08	Syt5 Zfp329 Zscan18 Zfp110 Vom1r50 ENSRNOG00000070456
Delay disc. indifference point, 0s delay	14.31	4	1	16.7	1	4.29e-07	Syt5 Zfp329 Zscan18 Zfp110
Delay disc. indifference point, 16s delay	24.13	1	0	0	0	1.00e+00	Syt5
Delay disc. indifference point, 24s delay	9.61	1	0	0	0	1.00e+00	Syt5
Bouts of movement, locomotor time 1	18.16	2	1	16.7	0.97	5.51e-03	Syt5 Zfp329
Total resting periods, locomotor time 1	37.3	1	1	16.7	0	1.00e+00	Syt5
Vertical activity count, locomotor time 1	24.22	1	0	0	0	1.00e+00	Syt5
Rest time, locomotor task time 2	9.12	1	0	0	0	1.00e+00	Syt5
Weight adjusted by age	8.26	1	0	0	0	1.00e+00	Syt5
Seeking ratio, delayed vs. immediate footshock	12.44	4	1	16.7	1	5.59e-07	Syt5 Zfp329 Zscan18 Zfp110
Locomotion in novel chamber	12.66	1	0	0	0	1.00e+00	Syt5
Progressive ratio	7.56	1	0	0	0	1.00e+00	Syt5
Seeking ratio, punishment vs. effort	10.28	2	0	0	0.98	3.29e-03	RGD1359108 Syt5
Co content in liver	19.37	1	0	0	0	1.00e+00	Syt5
Sr content in liver	22.99	4	1	16.7	0.98	7.95e-04	Syt5 Zfp329 Zscan18 Vom2r35
Zn content in liver	12.43	1	0	0	0	1.00e+00	Syt5

Associations by panel

Tissue	RNA modality	# hits	% hits/tests	Avg chisq
Adipose	alternative polyA	1	0	1.14
Adipose	alternative TSS	0	0	1.28
Adipose	gene expression	2	0	1.24
Adipose	isoform ratio	0	0	1.17
Adipose	intron excision ratio	0	0	1.19
Adipose	mRNA stability	0	0	1.28
BLA	alternative polyA	0	0	1.21
BLA	alternative TSS	0	0	1.31
BLA	gene expression	1	0	1.27
BLA	isoform ratio	1	0.1	1.27
BLA	intron excision ratio	0	0	1.14
BLA	mRNA stability	1	0	1.36
Brain	alternative polyA	0	0	1.19
Brain	alternative TSS	0	0	1.23
Brain	gene expression	1	0	1.23
Brain	isoform ratio	2	0.1	1.24
Brain	intron excision ratio	0	0	1.18
Brain	mRNA stability	0	0	1.25
Eye	alternative polyA	0	0	1.1
Eye	alternative TSS	0	0	1.3
Eye	gene expression	0	0	1.35
Eye	isoform ratio	0	0	1.21
Eye	intron excision ratio	0	0	1.17
Eye	mRNA stability	0	0	1.48
IL	alternative polyA	0	0	1.19
IL	alternative TSS	0	0	1.3
IL	gene expression	0	0	1.22
IL	isoform ratio	0	0	1.2
IL	intron excision ratio	0	0	1.07
IL	mRNA stability	0	0	1.19
LHb	alternative polyA	0	0	0.98
LHb	alternative TSS	0	0	1.24
LHb	gene expression	0	0	1.23
LHb	isoform ratio	0	0	1.21
LHb	intron excision ratio	0	0	1.23
LHb	mRNA stability	0	0	1.3
Liver	alternative polyA	0	0	1.18
Liver	alternative TSS	0	0	1.26
Liver	gene expression	0	0	1.21
Liver	isoform ratio	0	0	1.22
Liver	intron excision ratio	0	0	1.15
Liver	mRNA stability	0	0	1.22
NAcc	alternative polyA	0	0	1.21
NAcc	alternative TSS	0	0	1.36
NAcc	gene expression	1	0	1.24
NAcc	isoform ratio	0	0	1.22
NAcc	intron excision ratio	0	0	1.17
NAcc	mRNA stability	1	0	1.33
OFC	alternative polyA	0	0	1.02
OFC	alternative TSS	0	0	0.94
OFC	gene expression	0	0	1.23
OFC	isoform ratio	0	0	1.27
OFC	intron excision ratio	0	0	1.09
OFC	mRNA stability	0	0	1.28
PL	alternative polyA	0	0	1.25
PL	alternative TSS	0	0	1.24
PL	gene expression	1	0	1.22
PL	isoform ratio	2	0.1	1.23
PL	intron excision ratio	2	0.1	1.15
PL	mRNA stability	0	0	1.3