Biology subjects

Wikenheiser, A. M.

Publications and source records attributed to Wikenheiser, A. M..

10 recordsLinked to original sources

bioRxiv2025

A progressive ratio task with costly resets reveals adaptive effort-delay tradeoffs

The Progressive Ratio (PR) schedule is a popular test for measuring the motivational value of a reinforcer, in which subjects must exert an increasing amount of work to obtain each successive reward. Despite its popularity, the PR task hinges on a low-dimensional behavioral readout--breakpoint, or the maximum work requirement subjects are willing to complete before abandoning the task. Here, we show that with a simple modification, the PR task can be transformed into an optimization problem reminiscent of the patch-leaving foraging scenario, which has been analyzed extensively by behavioral ecologists, psychologists, and neuroscientists. In the Progressive Ratio with Reset (PRR) task, rats perform the PR task on one lever, but can press a second lever to reset the current ratio requirement back to its lowest value at the cost of enduring a reset delay, during which both levers are retracted. Rats used the reset lever adaptively on the PRR task, and their ratio reset decisions were sensitive to the cost of the reset delay. We derived an approach for computing the optimal bout length--the number of rewards to earn before pressing the reset lever that produces the greatest long-term rate of reward--and found that rats flexibly changed their behavior to approximate the optimal strategy. However, rats showed a systematic bias for bout lengths that exceeded the optimal length, an effect reminiscent of "overharvesting" in patch-leaving tasks. The PRR task thus represents a novel means of testing whether and how rats adapt their behavior to the cost-benefit structure of the environment in a way that connects deeply to the broader literature on associative learning and optimal foraging theory.

animal behavior and cognition↗

bioRxiv2025

Risk preferences depend on environmental richness in rats performing a patch-foraging task

Risk, or variance over outcomes, features prominently in many decisions, but the factors that determine when and how risk modulates decision making remain unclear. We tested how risk affected rats strategies for exploiting a diminishing food source as the overall richness of the environment was manipulated. Long-Evans rats earned food by sequentially visiting two foraging patches with different reward schedules--a low-variance standard option and a high-variance risky option--that provided the same average rate of reward. When rats switched between options, they encountered either a long or short delay during which no food was available to simulate the cost of travelling between patches. When the travel delay was short rats allocated more time to the low-variance standard reward schedule than the high-variance risky option. When the travel time was long rats spent the same amount of time in risky and standard patches. Consistent with previous work, rats "overharvested" patches, remaining for longer than the optimal patch residence duration. Overharvesting was prevalent in both risky and standard patches, and the magnitude of overharvesting increased with successive visits to the same patch, suggesting that overharvesting was not driven by uncertainty about the reward statistics of patches.

animal behavior and cognition↗

bioRxiv2025

Striatal cell-type specific stability and reorganization underlying agency and habit

Goal-directed behavior is guided by learned action-outcome associations, allowing actions to adapt when outcomes change. With repetition, behavioral control shifts toward habit, enabling more automatic action execution, but reducing flexibility to outcome changes. Here, we used longitudinal, cellular-resolution calcium imaging, chemogenetics, instrumental conditioning, and the outcome devaluation test to ask how dorsomedial striatum D1+ and D2/A2A+ neurons contribute to the formation of goal-directed behavior and habit. DMS D1+ neurons stably encode instrumental actions, carry information about behavioral engagement and organization, and develop and maintain action-reward representational similarity and conjunctive activation with learning. Correspondingly, these neurons are critical for action-outcome learning and goal-directed decision making. In contrast, one ensemble of DMS A2A+ neurons transiently encodes actions during early action-outcome learning and another slowly starts to encode actions as habits form. Similarly, DMS A2A+ neurons transiently mediate action-outcome learning and become dispensable for goal-directed decision making. Thus, action-outcome associations are learned through DMS D1+ and A2A+ neuronal activity but only DMS D1+ neurons maintain support of adaptive, goal-directed decision making. Habit formation is associated with reorganization of A2A+ neuronal encoding. These data reveal a cell-type-specific dissociation between stable v. reorganizing striatal action representations paralleled by persistent v. transient contributions to goal-directed control.

neuroscience↗

bioRxiv2024

Rats pursue food and leisure following the same rational principles

Animals in the wild must balance multiple, potentially mutually-exclusive goals simultaneously in order to survive. Yet laboratory tests of decision making often investigate how animals optimize their behavior to achieve a single, well-defined goal, which is often a nutritive reward. Thus, how animals solve multi-objective optimization problems is not well understood. Here, we devised an ethologically-inspired decision making task to examine how rats balance the pursuit of food and non-food reinforcement. Rats performed a free-choice patch-foraging task, in which they could earn food in one location (food patch) or interact with a rodent play structure in a different location (toy patch). The cost of switching between patches was manipulated by requiring rats to endure a long or short "travel time" penalty during which they were not able to access either patch. Rats devoted a considerable amount of their limited foraging time to patches of both types, showing a small but significant preference for food patches. In accordance with theoretical models of foraging, when the cost of switching patches was high rats chose longer stay durations in both types of patches, suggesting that similar rational principles guided their pursuit of food and non-food rewards. Examining the within-session dynamics of time allocation revealed that rats showed an early preference for spending time in toy patches that reversed over the course of the session. Satiety manipulations demonstrated that patch residence time decisions were under goal-directed control, and responsive to current needs and recent consumption. These results validate a naturalistic approach to testing decision making in rats over a range of food and non-food goods. Key words: Patch foraging, decision making, multi-objective optimization, play, leisure Significance StatementThe mechanisms by which animals trade off competing goals remain poorly understood. Here, we investigated whether rats use rational decision-making strategies to balance essential needs with non-essential pursuits like leisure by letting rats choose between earning food and engaging with a play structure. Rats performing a free-choice patch-foraging task adjusted their behavior based on opportunity costs, staying longer in patches when switching costs were high, in accordance with models of optimal foraging. Rats allocated significant time to toy patches, even at the expense of food rewards, underscoring the intrinsic value of non-food reinforcers. These results validate a naturalistic approach for studying tradeoffs between qualitatively-different rewards, and advance our understanding of multi-goal optimization in the context of a naturalistic decision problem.

animal behavior and cognition↗

bioRxiv2024

Neural coding of choice and outcome are modulated by uncertainty in orbitofrontal but not secondary motor cortex

Orbitofrontal cortex (OFC) and secondary motor cortex (M2) are both implicated in flexible reward learning but the conditions that differentially recruit these regions are not fully understood. We imaged calcium activity from single neurons in OFC or M2 during de novo learning of increasingly uncertain reward probability schedules. Predictions of choice were decoded from M2 neurons with high accuracy under all certainty conditions, but were more accurately decoded from OFC neurons under greater uncertainty. The number of choice- and reward-selective neurons was significantly higher in M2 than in OFC across schedules, but these proportions increased across levels of uncertainty only in OFC. Decoding accuracy of choice and outcome was predicted by behavioral strategies Win-Stay and Lose-Shift in OFC, but not M2. We also tested causal involvement of these regions with chemogenetic perturbation as rats learned increasing and then decreasing uncertainty schedules. Whereas inhibition of OFC neurons attenuated learning across all schedules, M2 neurons were found to support learning in the most certain reward schedule. Thus, OFC neurons preferentially encode choices and outcomes that foster a greater reliance on adaptive strategies under uncertainty. This reveals a novel functional heterogeneity within frontal cortex in support of flexible learning.

neuroscience↗

bioRxiv2024

Prior cocaine use diminishes encoding of latent information by orbitofrontal, but not medial, prefrontal ensembles

Maladaptive decision-making is a hallmark of substance use disorders, though how drugs of abuse alter neural representations supporting adaptive behavior remains poorly understood. Past studies show the orbitofrontal (OFC) and prelimbic (PL) cortices are important for decision making, tracking both task-relevant and latent information. However, previous studies have focused on how drugs of abuse impact the firing rates of individual units. More work at the ensemble level is necessary to accurately characterize potential drug-induced changes. Using single-unit recordings in rats during a multidimensional decision-making task and then applying population and ensemble level analyses, we show that prior use of cocaine altered the strength and structure of task-relevant and latent representations in the OFC, changes relatable to suboptimal decision making in this and perhaps other settings. These data expand our understanding of the neuropathological underpinnings of maladaptive decision-making in SUDs, potentially enabling enhanced future treatment strategies.

neuroscience↗

bioRxiv2023

Sex differences in patch-leaving foraging decisions in rats

The ubiquity, importance, and sophistication of foraging behavior makes it an ideal platform for studying naturalistic decision making in animals. We developed a spatial patch-foraging task for rats, in which subjects chose how long to remain in one foraging patch as the rate of food earnings steadily decreased. The cost of seeking out a new location was varied across sessions. The behavioral task was designed to mimic the structure of natural foraging problems, where distinct spatial locations are associated with different reward statistics, and decisions require navigation and movement through space. Male and female Long-Evans rats generally followed the predictions of theoretical models of foraging, albeit with a consistent tendency to persist with patches for too long compared to behavioral strategies that maximize food intake rate. The tendency to choose overly-long patch residence times was stronger in male rats. We also observed sex differences in locomotion as rats performed the task, but these differences in movement only partially accounted for the differences in patch residence durations observed between male and female rats. Together, these results suggest a nuanced relationship between movement, sex, and foraging decisions. Significance statementForaging behavior offers a naturalistic way of studying temporal investment amongst different choice options, a translationally-important form of decision making. Previous laboratory investigations have relied on foraging tasks that require little movement from subjects, which could affect the strategies that animals use and the neural mechanisms that support them. We developed a spatial foraging task for rats. Behavior generally matched the predictions of theoretical models, although rats remained in patches for longer than prescribed. Male rats exhibited a stronger tendency to overharvest patches than female rats. Sex differences in movement did not account for sex differences in foraging. These data highlight the interplay between movement and decision making, and demonstrate the utility of spatial tasks for studies of foraging.

animal behavior and cognition↗

bioRxiv2021

Theta oscillations in frontal cortex differentially modulate accuracy and speed in flexible stimulus- and action-based learning

Flexible reward learning relies on frontal cortex, with substantial evidence indicating that anterior cingulate cortex (ACC) and orbitofrontal cortex (OFC) subregions play important roles. Recent studies in both rat and macaque suggest theta oscillations (5-10 Hz) may be a spectral signature that coordinates this learning. However, network-level interactions between ACC and OFC in flexible learning remain unclear. We investigated the learning of stimulus-reward associations using a combination of simultaneous in-vivo electrophysiology in dorsal ACC and ventral OFC, partnered with bilateral inhibitory DREADDs in ACC. In freely-behaving male and female rats and using a within-subject design, we examined accuracy and speed of response across distinct and precisely-defined trial epochs during initial visual discrimination learning and subsequent reversal of stimulus-reward contingencies. Following ACC inhibition there was a propensity for random responding in early reversal learning, with correct vs. incorrect trials distinguished only from OFC, not ACC, theta power differences in the reversal phase. ACC inhibition also hastened incorrect choices during reversal. This same pattern of change in accuracy and speed was not observed in viral control animals. Thus, characteristics of impaired reversal learning following ACC inhibition are poor deliberation and weak theta signaling of accuracy in this region. The present results also point to OFC theta oscillations as a prominent feature of reversal learning, unperturbed by ACC inhibition.

neuroscience↗

bioRxiv2021

A bidirectional corticoamygdala circuit for the encoding and retrieval of detailed reward memories

Adaptive reward-related decision making often requires accurate and detailed representation of potential available rewards. Environmental reward-predictive stimuli can facilitate these representations, allowing one to infer which specific rewards might be available and choose accordingly. This process relies on encoded relationships between the cues and the sensory-specific details of the reward they predict. Here we interrogated the function of the basolateral amygdala (BLA) and its interaction with the lateral orbitofrontal cortex (lOFC) in the ability to learn such stimulus-outcome associations and use these memories to guide decision making. Using optical recording and inhibition approaches, Pavlovian cue-reward conditioning, and the outcome-selective Pavlovian-to-instrumental transfer (PIT) test in male rats, we found that the BLA is robustly activated at the time of stimulus-outcome learning and that this activity is necessary for sensory-specific stimulus-outcome memories to be encoded, so they can subsequently influence reward choices. Direct input from the lOFC was found to support the BLA in this function. Based on prior work, activity in BLA projections back to the lOFC was known to support the use of stimulus-outcome memories to influence decision making. By multiplexing optogenetic and chemogenetic inhibition we performed a serial circuit disconnection and found that the lOFC[->]BLA and BLA[->]lOFC pathways form a functional circuit regulating the encoding (lOFC[->]BLA) and subsequent use (BLA[->]lOFC) of the stimulus-dependent, sensory-specific reward memories that are critical for adaptive, appetitive decision making.

neuroscience↗

bioRxiv2018

Rat orbitofrontal ensemble activity contains a multiplexed but value-invariant representation of task structure in an odor sequence task

The orbitofrontal cortex (OFC) has long been implicated in signaling information about expected outcomes to facilitate adaptive or flexible behavior. Current proposals focus on signaling of expected reward values versus the representation of a value-agnostic cognitive map of the task. While often suggested as mutually exclusive, these alternatives may represent two extreme ends of a continuum determined by the complexity of the environment and the subjects experience in it. As learning proceeds, an initial, detailed cognitive map might be acquired, based largely on external information. With more experience, this hypothesized map can then be tailored to include relevant abstract hidden cognitive constructs. This might default to expected values in situations where other attributes are minimized or largely irrelevant, whereas in richer tasks, a more detailed structure might continue to be represented, at least where relevant to behavior, and possibly alongside value. Here we sought to arbitrate between these options by recording single unit activity from the OFC in rats navigating an odor sequence task analogous to a spatial maze. The odor sequences provided a clearly mappable state space, with 24 unique \"positions\" defined by sensory information, likelihood of reward, or both. Consistent with the hypothesis that the OFC represents a cognitive map tailored to the subjects intentions or plans, we found a close correspondence between how subjects behavior suggested they were using the sequences, and the neural representations of the sequences in OFC ensembles. Multiplexed with this value-invariant representation of the task, we also found a representation of the expected value at each location. Thus value and task structure are co-existing and potentially dissociable components of the neural code in OFC.

neuroscience↗