Characterization of electrically evoked field potentials in the medial prefrontal cortex and orbitofrontal cortex of the rat: Modulation by monoamines

Abstract

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.

Ethanol Dependence Abolishes Monoamine and GIRK (Kir3) Channel Inhibition of Orbitofrontal Cortex Excitability

“…In the lOFC of adult rats, D1 receptor activation increases the amplitude of NMDA EPSCs and D2 receptor agonists decrease NMDA EPSCs (Thompson et al, 2016). In contrast, Wallace et al (2014) reported that DA had no effect on mono-or polysynaptic responses of electrically evoked field responses recorded from slices containing caudal areas of the OFC. In this study, we found that DA or the D1 agonist SKF81297 had no effect on sIPSCs but increased a tonic current that was suppressed by picrotoxin.…”

Conditional inactivation of Npy1r gene in mice induces behavioural inflexibility and orbitofrontal cortex hyperactivity that are reversed by escitalopram

“…On the other hand, evidence from studies in rodents and primates demonstrate that 5-HT is implicated in the modulation of reversal learning in the OFC. Electrophysiological studies have shown that 5-HT inhibits pyramidal cell firing in the OFC (Rueter et al, 2000;Wallace et al, 2014). The depletion of brain 5-HT or chronic intermittent stress, which reduces frontal cortex 5-HT release, impairs the ability of animals to adapt their response to changes in reward contingencies in the environment, resulting in perseverative behaviour (Bondi et al, 2008;Clarke et al, 2007;Man et al, 2012).…”

Toward a theoretical role for tonic norepinephrine in the orbitofrontal cortex in facilitating flexible learning

“…This seems particularly plausible, as tonic NE has been specifically implicated in functional connectivity changes that might lead to remapping-like effects by changing the relative strength of afferent vs. local, intrinsic input to a region (Hasselmo et al, 1997). Indeed, increases in NE tone can induce sudden changes in both local (Wallace et al, 2014) and global (Hermans et al, 2011) network connectivity and directly facilitate sensory cortical remapping (Greuel et al, 1988). …”