The role of rat prelimbic cortex in decision making.

The frontal cortex plays a critical role in decision-making. One specific frontal area, the anterior cingulate cortex, has been identified as crucial for setting a threshold for how much evidence is needed before a choice is made (Domenech & Dreher, 2010). Threshold is a key concept in drift diffusion models, a popular framework used to understand decision-making processes. Here, we investigated the role of the prelimbic cortex, part of the rodent cingulate cortex, in decision making. Male and female rats learned to choose between stimuli associated with high and low value rewards. Females learned faster, were more selective in their responses, and integrated information about the stimuli more quickly. By contrast, males learned more slowly and showed a decrease in their decision thresholds during choice learning. Inactivating the prelimbic cortex in female and male rats sped up decision making without affecting choice accuracy. Drift diffusion modeling found selective effects of prelimbic cortex inactivation on the decision threshold, which was reduced with increasing doses of the GABA-A agonist muscimol. Stimulating the prelimbic cortex through mu opioid receptors slowed the animals' choice latencies and increased the decision threshold. These findings provide the first causal evidence that the prelimbic cortex directly influences decision processes. Additionally, they suggest possible sex-based differences in early choice learning.

Learning to Choose: Behavioral Dynamics Underlying the Initial Acquisition of Decision Making.

Current theories of decision making propose that decisions arise through competition between choice options. Computational models of the decision process estimate how quickly information about choice options is integrated and how much information is needed to trigger a choice. Experiments using this approach typically report data from well-trained participants. As such, we do not know how the decision process evolves as a decision-making task is learned for the first time. To address this gap, we used a behavioral design separating learning the value of choice options from learning to make choices. We trained male rats to respond to single visual stimuli with different reward values. Then, we trained them to make choices between pairs of stimuli. Initially, the rats responded more slowly when presented with choices. However, as they gained experience in making choices, this slowing reduced. Response slowing on choice trials persisted throughout the testing period. We found that it was specifically associated with increased exponential variability when the rats chose the higher value stimulus. Additionally, our analysis using drift diffusion modeling revealed that the rats required less information to make choices over time. Surprisingly, we observed reductions in the decision threshold after just a single session of choice learning. These findings provide new insights into the learning process of decision-making tasks. They suggest that the value of choice options and the ability to make choices are learned separately, and that experience plays a crucial role in improving decision-making performance.

The rostral medial frontal cortex is crucial for engagement in consummatory behavior.

The medial frontal cortex (MFC) in rodents emits rhythmic activity that is entrained to the animal's licking cycle during consumption and encodes the value of consumed fluids. These signals are especially prominent in the rostral half of the MFC. This region is located above an orbitofrontal region where mu-opioid receptors regulate intake and reversible inactivation reduces behavioral measures associated with the incentive value and palatability of liquid sucrose. Here, we examined the effects of reversible inactivation and stimulation of mu-opioid receptors in rostral MFC on behavior in an incentive contrast licking task. Adult male rats licked to receive access to liquid sucrose, which alternated between high (16%) and low (4%) values over 30 s periods. Bilateral infusion of muscimol reduced the total number of licks over the 30 min test sessions, the time spent actively consuming sucrose, and the ratio of licks for the higher and lower value fluids. Inactivation did not alter licking frequency or variability or microstructural measures such as the duration of licking bouts that are classically associated with the palatability of a liquid reward. Infusions of [d-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO; 1 µg/µL) at the same sites had inconsistent behavioral effects across different subjects. Our findings suggest that the rostral MFC has a distinct role in the control of consummatory behavior and contributes to persistent consumption and not to the expression of palatability. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Immunotherapy for non-muscle-invasive bladder cancer: from the origins of BCG to novel therapies.

Supplies of intravesical Bacillus Calmette-Guérin (BCG), the first-line treatment for most intermediate- and high-risk non-muscle-invasive bladder cancers (NMIBC), have proven unreliable over the past decade. This review considers the evolution of BCG immunotherapy for NMIBC: from the discovery of the antitumour side effects of tuberculosis and subsequently the BCG vaccine, to recent advances in novel immunotherapeutic agents. We summarize the evidence for alternative options to standard intravesical BCG therapy regimens and describe the potential for immune response manipulating drugs in the treatment of NMIBC. These new agents, including immune checkpoint inhibitors, toll-like receptor agonists and recombinant viral vectors, may provide better options in the management of NMIBC in the future.

Lay abstract Many patients with non-invasive bladder cancers may need treatments into the bladder, including one called Bacillus Calmette-Guérin (BCG). Unfortunately, the supplies of BCG have been interrupted and somewhat unreliable since 2012. Because of this, we have been forced to look at other means of treating our patients using drugs similar to BCG. This has made us think about how BCG treatment was first developed more than 40 years ago and how it has evolved as a treatment for bladder cancer. In this article, we review the current uses of BCG and other treatments for bladder cancer and explore what the future may hold for bladder cancer treatment.

An Open Source Platform for Presenting Dynamic Visual Stimuli.

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 Liquid-Crystal Display (LCD) or Organic Light-Emitting Diode (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 8 × 8 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 cost-effective way to implement complex visually-guided operant behavior, including the use of moving or dynamically changing visual stimuli.

What, If Anything, Is Rodent Prefrontal Cortex?

Prefrontal cortex (PFC) means different things to different people. In recent years, there has been a major increase in publications on the PFC, especially using mice. However, inconsistencies in the nomenclature and anatomical boundaries of PFC areas has made it difficult for researchers to compare data and interpret findings across species. We conducted a meta-analysis of publications on the PFC of humans and rodents and found dramatic differences in the focus of research on these species. In addition, we compared anatomical terms and criteria across several common rodent brain atlases and found inconsistencies among, and even within, leading atlases. To assess the impact of these issues on the research community, we conducted a survey of established PFC researchers on their use of anatomical terms and found little consensus. We report on the results of the survey and propose an alternative scheme for interpreting data from rodent studies, based on structural analysis of the corpus callosum and nomenclature used in research on the anterior cingulate cortex (ACC) of primates.