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The synaptic Ras/Rap-GTPase-activating protein (SynGAP) regulates specific intracellular events following N-methyl-d-aspartate receptor (NMDAR) activation. Here, the impact of SynGAP heterozygous knockout (SG+/-) on NMDAR-dependent functions was assessed using different positive reinforcement schedules in instrumental conditioning. The knockout did not affect the temporal control of operant responding under a fixed interval (FI) schedule, but led to a putative enhancement in response vigor and/or disinhibition. When examined on differential reinforcement of low rates of response (DRL) schedules, SG+/- mice showed increased responding under DRL-4s and DRL-8s, without impairing the response efficiency (total rewards/total lever presses) because both rewarded and nonrewarded presses were elevated. Motivation was unaffected as evaluated using a progressive ratio (PR) schedule. Yet, SG+/- mice persisted in responding during extinction at the end of PR training, although an equivalent phenotype was not evident in extinction learning following FI-20s training. This extinction phenotype is therefore schedule-specific and cannot be generalized to Pavlovian conditioning. In conclusion, constitutive SynGAP reduction increases vigor in the execution of learned operant behavior without compromising its temporal control, yielding effects readily distinguishable from NMDAR blockade.

Appetitively motivated instrumental learning in SynGAP heterozygous knockout mice.