Too little and too much: balanced hippocampal, but not medial prefrontal, neural activity is required for intact novel object recognition in rats

Impaired GABAergic inhibition, so-called neural disinhibition, in the prefrontal cortex and hippocampus has been linked to cognitive deficits. The novel object recognition (NOR) task has been used widely to study cognitive deficits in rodents. However, the contribution of prefrontal cortex and hippocampal GABAergic inhibition to NOR task performance has not been established. Here, we investigated NOR task performance in male Lister Hooded rats following regional neural disinhibition or functional inhibition, using intra-cerebral microinfusion of the GABA-A receptor antagonist picrotoxin or agonist muscimol, respectively. Our infusion targets were the medial prefrontal cortex (mPFC), dorsal hippocampus and ventral hippocampus. Using a within-subjects design, we compared NOR task performance (1-min retention delay) following bilateral regional saline, picrotoxin or muscimol infusions made before the acquisition phase. In mPFC, neither functional inhibition nor neural disinhibition affected object recognition memory. However, in both dorsal and ventral hippocampus, neural disinhibition impaired NOR relative to saline control, mainly by reducing novel object exploration time. In addition, functional inhibition of dorsal hippocampus impaired NOR, whereas ventral hippocampal functional inhibition tended to reduce novel object exploration at the highest dose used (alongside substantial non-specific behavioural effects). Overall, our data suggest that hippocampal, but not prefrontal, GABAergic inhibition contributes to NOR at a 1-min retention delay. Moreover, such NOR performance likely requires balanced neural activity in the dorsal hippocampus, with both too little and too much dorsal hippocampal activity impairing NOR memory. Our findings support that the NOR task can be used to investigate hippocampal GABAergic dysfunction in rodent models.