1 2 3 4 5 6 7 8 MEDIAL FRONTAL CORTEX AND PROGRESSIVE RATIO PERFORMANCE 2 AbstractThe medial frontal cortex (MFC) is crucial for selecting actions and evaluating their outcomes.Outcome monitoring may be triggered by rostral parts of the MFC, which contain neurons that are modulated by reward consumption and are necessary for the expression of relative reward value. Here, we examined if the MFC further has a role in the control of instrumental licking.We used a progressive ratio licking task in which rats had to make increasing numbers of licks to receive liquid sucrose rewards. We determined what measures of progressive ratio performance are sensitive to value by testing rats with rewards containing 0-16% sucrose. We found some measures (breakpoint, number of licking bouts) were sensitive to sucrose concentration and others (response rate, duration of licking bouts) were not. Then, we examined the effects of reversibly inactivating rostral (medial orbital) and caudal (prelimbic) parts of the MFC. We were surprised to find that inactivation had no effects on measures associated with value (e.g. breakpoint). Instead, inactivation altered behavioral measures associated with the pace of task performance (response rate and time to break). These effects depended on where inactivations were made. Response rates increased and time to break decreased when the caudal prelimbic area was inactivated. By contrast, response rates decreased and the time to break increased when the rostral medial orbital cortex was inactivated. Our findings suggest that the medial frontal cortex has a role in maintaining task engagement, but not in the motivational control of action, in the progressive ratio licking task.Inhibition is a classic interpretation of orbitofrontal function (Dias et al., 1996).However, more recent studies have emphasized a role for the medial orbital areas in predictions and evaluations of behavioral outcomes (Rudebeck & Murray, 2014;Rudebeck et al., 2017) and inferences based on learned associations between actions and outcomes (Bradfield et al., 2015).As such, disruptions of medial orbital control should reduce, not increase, breakpoints, as is also 441 442 443 444 445 446 447 448 449 450 451 452 453 454 455 456 457 458 459 460 461 462 cues signaling reward delivery, and the method, spatial extent, and cell type affected by the brain perturbations (lesion, muscimol, chemogenetics, optogenetics). Our findings on breakpoint are similar to three published studies. Kheramin et al. (2005), Schweimer & Hauber (2005), and Gourley et al. (2010) found no effects of lesions in three different cortical areas, two different actions, two different species, and very different levels of training. The Kheramin study used rats, required lever pressing, and lesioned the ventral orbital area after 60 training sessions. The Schweimer study also used rats, required lever pressing, and lesioned the perigenual prelimbic and cingulate after 6 training sessions. The Gourley study used

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.

Operant behavior procedures often rely on visual stimuli to cue the initiation or secession of a response, and to provide a means for discriminating between two or more simultaneously available responses. While primate and human studies typically use LCD or OLED monitors and touch screens, rodent studies use a variety of methods to present visual cues ranging from traditional incandescent light bulbs, single LEDs, and, more recently, touch screen monitors. Commercially available systems for visual stimulus presentation are costly, challenging to customize, and are typically closed source. We developed an open-source, highly-modifiable visual stimulus presentation platform that can be combined with a 3D-printed operant response device. The device uses an eight by eight matrix of LEDs, and can be expanded to control much larger LED matrices. Implementing the platform is low-cost (<$70 USD per device in the year 2020). Using the platform, we trained rats to make nosepoke responses and discriminate between two distinct visual cues in a location-independent manner. This visual stimulus presentation platform is a costeffective way to implement complex visually-guided operant behavior, including the use of moving or dynamically changing visual stimuli. Significance StatementThe design of an open source and low cost device for presenting visual stimuli is described. It is capable of presenting complex visual patterns and dynamically changing stimuli. A practical demonstration of the device is also reported, from an experiment in which rats performed a luminance based visual discrimination. The device has utility for studying visual processing, psychophysics, and decision making in a variety of species.

The purpose of this study was to measure the availability of the estrogen receptor in submandibular and parotid salivary glands in female rats. The presence of a specific, competitive, and saturable estrogen binder in rat salivary gland tissue was determined by saturation analysis and steroid competition in cell-free homogenates of salivary gland tissue from adult ovariectomized females. Scatchard analysis of the data indicated an estrogen receptor content of 1971.1 +/- 651.4 femtomoles/gm of tissue in submandibular salivary gland. This was significantly (p less than 0.01) greater than the number of estrogen binding sites in the parotid gland (457.1 +/- 123.4 femtomoles/gm tissue). Thus, there is a differential distribution in estrogen receptor content between parotid and submandibular salivary glands. The presence of an estrogen receptor in salivary gland tissue may serve to promote gender differences in submandibular salivary gland EGF content, to mediate changes in saliva composition during the female reproductive cycle and to regulate EGF release for cyclic uterine growth.

Reversal learning depends on cognitive flexibility. Many reversal learning studies assess cognitive flexibility based on the number of reversals that occur over a test session. Reversals occur when an option is repeatedly chosen, e.g., eight times in a row. This design feature encourages win-stay behavior and thus makes it difficult to understand how win-stay decisions influence reversal performance. We used an alternative design, reversals over blocks of trials independent of performance, to study how perturbations of the medial orbital cortex and the noradrenergic system influence reversal learning. We found that choice accuracy varies independently of win-stay behavior and the noradrenergic system controls sensitivity to positive feedback during reversal learning.