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Medial prefrontal cortex (mPFC) and orbitofrontal cortex (OFC) play critical roles in cognition and behavioural control. Glutamatergic, GABAergic, and monoaminergic dysfunction in the prefrontal cortex has been hypothesised to underlie symptoms in neuropsychiatric disorders. Here we characterised electrically-evoked field potentials in the mPFC and OFC. Electrical stimulation evoked field potentials in layer V/VI of the mPFC and layer V of the OFC. The earliest component (approximately 2 ms latency) was insensitive to glutamate receptor blockade and was presumed to be presynaptic. Later components were blocked by 6,7-dinitroquinoxaline-2,3-dione (DNQX (20 μM) and were assumed to reflect monosynaptic (latency 4-6 ms) and polysynaptic activity (latency 6-40 ms) mediated by glutamate via AMPA/kainate receptor. In the mPFC, but not the OFC, the monosynaptic component was also partly blocked by 2-amino-5-phosphonopentanoic acid (AP-5 (50-100 μM) indicating the involvement of NMDA receptors. Bicuculline (3-10 μM) enhanced the monosynaptic component suggesting electrically-evoked and/or glutamate induced GABA release inhibits the monosynaptic component via GABA A receptor activation. There were complex effects of bicuculline on polysynaptic components. In the mPFC both the mono-and polysynaptic components were attenuated by 5-HT (10-100 μM) and NA (30 and 60 μM) and the monosynaptic component was attenuated by DA (100 μM). In the OFC the mono-and polysynaptic components were also attenuated by 5-HT (100 μM), NA (10-100 μM) but DA (10-100 μM) had no effect. We propose that these pharmacologically characterised electrically-evoked field potentials in the mPFC and OFC are useful models for the study of prefrontal cortical physiology and pathophysiology.

The attentional set shifting task (ASST) can be used to assess aspects of executive function, including reversal learning and set shifting. It has frequently been employed in between-subjects experimental designs: however, the clear advantages of within-subjects designs (reduction in variance, animal numbers, and cost) mean that investigation of the suitability of the ASST for within subjects designs is warranted. Rats were tested three times: test 1 (24 h after training), test 2 (24 h later), and test 3 (seven days later). On all three test days, animals showed the expected pattern of performance across the seven task stages with evidence of normal reversal learning (significant increase in trials to criterion when the rule was reversed) and intact set formation (significantly more trials to criterion for an extradimensional shift than for an intradimensional shift). There was a small decrease in total trials required to complete the task between test 1 and test 3 but this was not specific to any stage of the task. Latency to dig decreased on repeated testing suggesting some facilitation of associative learning. In conclusion, the rodent ASST is suitable for within-subject design longitudinal studies, increasing the utility and the translational value of this test and reducing numbers of animals needed in studies.

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