Cholinergic and ghrelinergic receptors and KCNQ channels in the medial PFC regulate the expression of palatability

Abstract

The medial prefrontal cortex (mPFC) is a key brain region for the control of consummatory behavior. Neuronal activity in this area is modulated when rats initiate consummatory licking and reversible inactivations eliminate reward contrast effects and reduce a measure of palatability, the duration of licking bouts. Together, these data suggest the hypothesis that rhythmic neuronal activity in the mPFC is crucial for the control of consummatory behavior. The muscarinic cholinergic system is known to regulate membrane excitability and control low-frequency rhythmic activity in the mPFC. Muscarinic receptors (mAChRs) act through KCNQ (Kv7) potassium channels, which have recently been linked to the orexigenic peptide ghrelin. To understand if drugs that act on KCNQ channels within the mPFC have effects on consummatory behavior, we made infusions of several muscarinic drugs (scopolamine, oxotremorine, physostigmine), the KCNQ channel blocker XE-991, and ghrelin into the mPFC and evaluated their effects on consummatory behavior. A consistent finding across all drugs was an effect on the duration of licking bouts when animals consume solutions with a relatively high concentration of sucrose. The muscarinic antagonist scopolamine reduced bout durations, both systemically and intra-cortically. By contrast, the muscarinic agonist oxotremorine, the cholinesterase inhibitor physostigmine, the KCNQ channel blocker XE-991, and ghrelin all increased the durations of licking bouts when infused into the mPFC. Our findings suggest that cholinergic and ghrelinergic signaling in the mPFC, acting through KCNQ channels, regulates the expression of palatability.

The rat medial frontal cortex controls pace, but not breakpoint, in a progressive ratio licking task.

“…For the inactivations in the medial orbital cortex, we had expected to find reductions in breakpoint, similar to Gardner et al (2018). This outcome was expected based on our previous studies on the medial orbital region in the control of consummatory licking (Amarante et al, 2017;Parent et al, 2015a;Parent et al, 2015b), which demonstrate that the medial orbital cortex has an enabling or excitatory role in maintaining licking behavior. The alternative, that breakpoints would elevate, has been reported in two studies (mice lesioned before training in Gourley et al, 2010;Münster & Hauber, 2017), and would indicate that the medial orbital cortex has an inhibitory role in the control of progressive ratio performance.…”

The rat medial frontal cortex controls pace, but not breakpoint, in a progressive ratio licking task

“…For the inactivations in the medial orbital cortex, we had expected to find reductions in breakpoint, similar to Gardner et al (2018). This outcome was expected based on our previous studies on the medial orbital region in the control of consummatory licking (Amarante et al, 2017;Parent et al, 2015a;Parent et al, 2015b), which demonstrate that the medial orbital cortex has an enabling or excitatory role in maintaining licking behavior. The alternative, that breakpoints would elevate, has been reported in two studies (mice lesioned before training in Gourley et al, 2010;Münster & Hauber, 2017), and would indicate that the medial orbital cortex has an inhibitory role in the control of progressive ratio performance.…”

Pharmacological modulation of the voltage-gated neuronal Kv7/KCNQ/M-channel alters the intrinsic excitability and synaptic responses of pyramidal neurons in rat prefrontal cortex slices

“…Male Sprague-Dawley rats (postnatal day [21][22][23][24][25] were deeply anesthetized with pentobarbital (150 mg/kg), and after decapitation, the brains were rapidly placed in ice-cold, oxygenated artificial cerebrospinal fluid (ACSF) containing (in mmol/L) NaCl 125, KCl 2.5, NaH 2 PO 4 1.25, NaHCO 3 25, MgSO 4 1, CaCl 2 1.2 and glucose 16 (pH 7.2-7.4), which was bubbled with carbogen gas (95% O 2 and 5% CO 2 ). Coronal slices of the medial prefrontal cortex (mPFC) (350 μm) were cut using a vibratome (VT 1200S, Leica), and brain slices were maintained at room temperature (22-25 °C) in a submerged-style holding chamber with oxygenated ACSF for at least 60 min before being transferred to the recording chamber perfused with oxygenated ACSF.…”

“…The pre-synaptic localization of M-channels plays an important role in regulating glutamate release in the hippocampus [22][23][24] . All these investigations suggest a critical role for the Kv7/KCNQ/M-channel in regulating the excitability of PFC neurons [12] and animal behaviors [25] . However, whether the function of the PFC is pharmacologically regulated by Kv7/KCNQ/M-current modulators still remains elusive.…”