Abstract

To study the heritability of different training stages of appetitive operant conditioning, we carried out behavioral screening of 5 standard inbred mouse strains, 28 recombinant-inbred (BxD) mouse lines and their progenitor strains C57BL/6J and DBA/2J. We also computed correlations between successive training stages to study whether learning deficits at an advanced stage of operant conditioning may be dissociated from normal performance in preceding phases of training. The training consisted of two phases: an operant nose poking (NP) phase, in which mice learned to collect a sucrose pellet from a food magazine by NP, and an operant lever press and NP phase, in which mice had to execute a sequence of these two actions to collect a food pellet. As a measure of magazine oriented exploration, we also studied the nose poke entries in the food magazine during the intertrial intervals at the beginning of the first session of the nose poke training phase. We found significantly heritable components in initial magazine checking behavior, operant NP and lever press–NP. Performance levels in these phases were positively correlated, but several individual strains were identified that showed poor lever press–NP while performing well in preceding training stages. Quantitative trait loci mapping revealed suggestive likelihood ratio statistic peaks for initial magazine checking behavior and lever press–NP. These findings indicate that consecutive stages toward more complex operant behavior show significant heritable components, as well as dissociability between stages in specific mouse strains. These heritable components may reside in different chromosomal areas.

Highlights

  • Appetitive operant learning is often studied in a conditioning chamber in which animals learn to lever press and nose poke in order to receive a food or liquid reward delivered at a specific reward site

  • Operant learning usually results in complex behavior that depends on a multitude of capacities such as forming place-reward and action-outcome associations, and chaining actions such as lever pressing and nose poking (NP) into a food magazine together

  • Initial magazine checking behavior The average nose poke rate during intertrial intervals (ITI) of the first 10 trials of reward collection training varied from 0.53 pokes/min (129S1/ Sv) to 10.28 pokes/min of ITI (NOD/Ltj), the mean + SEM being 3.35 ± 0.34 pokes/min of ITI (Figure 2A)

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Summary

Introduction

Appetitive operant learning is often studied in a conditioning chamber in which animals learn to lever press and nose poke in order to receive a food or liquid reward delivered at a specific reward site. For genetic mouse models of learning and memory, it would be an asset to identify strains that show a dissociation between poor performance at advanced training stages but good performance at preceding stages. Such dissociations may indicate which mouse strains present models targeting more complex operant learning, or alternatively show deficits in more basic behaviors and learning processes

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