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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

3 loci · 8 genes with independent associations · 21 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	chr1	68674594	70751424	4	3	1.38e-08	5.97e-04	1.51e-01	Leng8 Rdh13
2	chr1	71854735	74100561	11	4	1.51e-15	2.13e-04	1.00e+00	Zfp110 Zfp329 Zfp551
3	chr5	49091753	49968409	6	1	2.82e-08	3.21e-08	1.36e-01	RGD1359108

Pleiotropic Associations

Trait	Chi2 ratio	# genes+	# genes++	% genes++	Corr	Corr P	Genes
Body weight	7.58	2	2	25	1	3.29e-12	LOC102557269 RGD1359108
Heart weight	8.79	1	0	0	0	1.00e+00	Zfp110
Left kidney weight	4.55	2	0	0	1	9.20e-17	LOC102557269 RGD1359108
Right kidney weight	4.74	2	0	0	1	4.60e-13	LOC102557269 RGD1359108
Tail length	4.68	2	0	0	0	1.00e+00	Zfp110 Zfp329
Length with tail	3.43	2	0	0	1	1.75e-13	LOC102557269 RGD1359108
Retroperitoneal fat weight	3.58	1	0	0	0	1.00e+00	Zfp329
Extensor digitorum longus weight	5.46	2	0	0	1	4.98e-12	LOC102557269 RGD1359108
Tibialis anterior weight	8	2	2	25	1	2.14e-12	LOC102557269 RGD1359108
Patch foraging indifference point 0 sec	7.02	1	0	0	0	1.00e+00	Rdh13
Indifference point function ln k	8.58	3	0	0	0	1.00e+00	Rdh13 Zfp110 Zfp329
Indifference point function log k	8.58	3	0	0	0	1.00e+00	Rdh13 Zfp110 Zfp329
Patch foraging time to switch 0 sec	12.55	5	0	0	-0.98	6.73e-09	Leng8 Rdh13 Zfp110 Zfp329 Zfp551
Patch foraging water rate 12 sec	9.87	4	0	0	0.99	1.19e-05	Leng8 Rdh13 Zfp110 Zfp329
Light reinforcement 1	7.49	1	0	0	0	1.00e+00	Rdh13
Social time	8.6	2	0	0	0.99	9.96e-03	Leng8 Zfp329
Conditioned locomotion	8.76	1	0	0	0	1.00e+00	Rdh13
Saline control response	14.29	1	0	0	0	1.00e+00	Rdh13
Pavlov. Cond. change in total contacts	8.59	1	0	0	0	1.00e+00	Rdh13
Intermitt. access day 1 inactive lever presses	13.77	5	0	0	-0.99	5.59e-10	Rdh13 Vom2r36 Zfp110 Zfp329 Zscan18
Intermitt. access day 15 inactive lever presses	12.11	6	0	0	-0.99	1.10e-12	Leng8 Rdh13 Vom2r36 Zfp110 Zfp329 Zscan18
Intermitt. access escalation Index	54.57	1	1	12.5	0	1.00e+00	Rdh13
Baseline Anxiety	10.63	2	0	0	0	1.00e+00	Zfp110 Zfp329
Incentive Sensitization - Responses	12.99	2	0	0	0	1.00e+00	Zfp110 Zscan18
Incentive Sensitization - Breakpoint	12.89	1	0	0	0	1.00e+00	Zscan18
One hour access (0.3 mA shock)	10.11	2	0	0	0	1.00e+00	Zfp329 Zscan18
One hour access (shock baseline)	9.56	4	0	0	-0.99	8.21e-07	Vom2r36 Zfp110 Zfp329 Zscan18
Number of responses in last shaping day	13.68	1	0	0	0	1.00e+00	Rdh13
Locomotion velocity, session 1	12.03	1	0	0	0	1.00e+00	Rdh13
Pavlov. Cond. intertrial magazine entries	10.61	1	0	0	0	1.00e+00	Rdh13
Bone: periosteal estimation	4.94	2	0	0	1	1.51e-16	LOC102557269 RGD1359108
Bone: trabecular tissue density	8.08	1	0	0	-0.99	6.96e-03	Zfp329
Distance traveled before self-admin	11.53	3	0	0	0.99	1.75e-05	Leng8 Zfp110 Zfp329
Distance traveled after self-admin	12.21	6	0	0	1	4.35e-17	Rdh13 Vom2r36 Zfp110 Zfp329 Zfp551 Zscan18
Delta time in open arm before/after self-admin	19.63	1	0	0	0	1.00e+00	Rdh13
Diff in mean of infusions in LGA sessions	13.15	2	0	0	0	1.00e+00	Rdh13 Zfp110
Extinction: sum of active levers before priming	18.94	1	0	0	0	1.00e+00	Rdh13
Active lever presses in extinction session 6	16.11	1	0	0	0	1.00e+00	Rdh13
Time in open arm after self-admin	15.55	1	0	0	0	1.00e+00	Rdh13
Sum of active levers in priming session hrs 5-6	14.16	2	0	0	0	1.00e+00	Rdh13 Zfp110
Time to tail flick, vehicle, after self-admin	12.61	1	0	0	0	1.00e+00	Rdh13
Time to tail flick, test, before self-admin	18.17	6	2	25	0.99	7.09e-13	Rdh13 Vom2r36 Zfp110 Zfp329 Zfp551 Zscan18
Delta time to tail flick, vehicle, before/after SA	24.61	1	0	0	0	1.00e+00	Rdh13
Delta time to tail flick, test, before/after SA	13.32	1	0	0	-1	1.78e-04	Zfp329
Ambulatory time before self-admin	13.72	1	0	0	0	1.00e+00	Rdh13
Ambulatory time after self-admin	12.35	7	0	0	0.99	1.31e-13	Leng8 Rdh13 Vom2r36 Zfp110 Zfp329 Zfp551 Zscan18
Delay disc. indifference point, 0s delay	11.42	1	0	0	0	1.00e+00	Zfp329
Bouts of movement, locomotor time 1	9.46	1	0	0	0	1.00e+00	Zfp110
Vertical activity count, locomotor time 1	13.87	1	0	0	0	1.00e+00	Rdh13
Seeking ratio, delayed vs. immediate footshock	9.85	2	0	0	1	4.36e-06	Vom2r36 Zfp329
Seeking ratio, punishment vs. effort	10.03	2	0	0	1	2.83e-09	LOC102557269 RGD1359108
Sr content in liver	15.25	6	0	0	0.99	8.21e-10	Leng8 Rdh13 Vom2r36 Zfp110 Zfp329 Zscan18

Associations by panel

Tissue	RNA modality	# hits	% hits/tests	Avg chisq
Adipose	alternative polyA	0	0	1.24
Adipose	alternative TSS	2	0.1	1.27
Adipose	gene expression	3	0	1.24
Adipose	isoform ratio	1	0	1.23
Adipose	intron excision ratio	0	0	1.16
Adipose	mRNA stability	0	0	1.23
BLA	alternative polyA	0	0	1.17
BLA	alternative TSS	0	0	1.2
BLA	gene expression	1	0	1.24
BLA	isoform ratio	0	0	1.2
BLA	intron excision ratio	0	0	1.1
BLA	mRNA stability	1	0	1.29
Brain	alternative polyA	0	0	1.25
Brain	alternative TSS	0	0	1.2
Brain	gene expression	2	0	1.23
Brain	isoform ratio	1	0	1.24
Brain	intron excision ratio	0	0	1.15
Brain	mRNA stability	0	0	1.26
Eye	alternative polyA	0	0	1.11
Eye	alternative TSS	0	0	1.25
Eye	gene expression	0	0	1.35
Eye	isoform ratio	0	0	1.41
Eye	intron excision ratio	0	0	1.2
Eye	mRNA stability	0	0	1.36
IL	alternative polyA	0	0	1.35
IL	alternative TSS	0	0	1.24
IL	gene expression	0	0	1.25
IL	isoform ratio	0	0	1.32
IL	intron excision ratio	0	0	1.11
IL	mRNA stability	0	0	1.26
LHb	alternative polyA	0	0	1.21
LHb	alternative TSS	0	0	1.16
LHb	gene expression	0	0	1.24
LHb	isoform ratio	0	0	1.22
LHb	intron excision ratio	0	0	1.13
LHb	mRNA stability	0	0	1.29
Liver	alternative polyA	1	0	1.25
Liver	alternative TSS	0	0	1.26
Liver	gene expression	1	0	1.2
Liver	isoform ratio	0	0	1.23
Liver	intron excision ratio	1	0	1.12
Liver	mRNA stability	0	0	1.22
NAcc	alternative polyA	2	0.1	1.32
NAcc	alternative TSS	3	0.1	1.26
NAcc	gene expression	2	0	1.27
NAcc	isoform ratio	0	0	1.27
NAcc	intron excision ratio	0	0	1.15
NAcc	mRNA stability	1	0	1.29
OFC	alternative polyA	0	0	1.18
OFC	alternative TSS	0	0	1.13
OFC	gene expression	0	0	1.24
OFC	isoform ratio	0	0	1.29
OFC	intron excision ratio	0	0	1.08
OFC	mRNA stability	0	0	1.31
PL	alternative polyA	6	0.2	1.39
PL	alternative TSS	1	0	1.13
PL	gene expression	2	0	1.24
PL	isoform ratio	1	0	1.29
PL	intron excision ratio	0	0	1.16
PL	mRNA stability	0	0	1.29
pVTA	alternative polyA	0	0	1.29
pVTA	alternative TSS	0	0	1.28
pVTA	gene expression	1	0	1.25
pVTA	isoform ratio	1	0	1.3
pVTA	intron excision ratio	0	0	1.15
pVTA	mRNA stability	0	0	1.2
RMTg	alternative polyA	0	0	1.26
RMTg	alternative TSS	0	0	1.28
RMTg	gene expression	0	0	1.2
RMTg	isoform ratio	0	0	1.38
RMTg	intron excision ratio	0	0	1.31
RMTg	mRNA stability	0	0	1.34