Biology subjects

Sweis, B. M.

Publications and source records attributed to Sweis, B. M..

8 recordsLinked to original sources

bioRxiv2024

Simultaneous dual-color calcium imaging in freely-behaving mice

Miniaturized fluorescence microscopes (miniscopes) enable imaging of calcium events from a large population of neurons in freely behaving animals. Traditionally, miniscopes have only been able to record from a single fluorescence wavelength. Here, we present a new open-source dual-channel Miniscope that simultaneously records two wavelengths in freely behaving animals. To enable simultaneous acquisition of two fluorescent wavelengths, we incorporated two CMOS sensors into a single Miniscope. To validate our dual-channel Miniscope, we imaged hippocampal CA1 region that co-expressed a dynamic calcium indicator (GCaMP) and a static nuclear signal (tdTomato) while mice ran on a linear track. Our results suggest that, even when neurons were registered across days using tdTomato signals, hippocampal spatial coding changes over time. In conclusion, our novel dual-channel Miniscope enables imaging of two fluorescence wavelengths with minimal crosstalk between the two channels, opening the doors to a multitude of new experimental possibilities. TeaserNovel open-source dual-channel Miniscope that simultaneously records two wavelengths with minimal crosstalk in freely behaving animals.

neuroscience↗

bioRxiv2024

Ketamine reverses stress-induced hypersensitivity to sunk costs

How mood interacts with information processing in the brain is thought to mediate the maladaptive behaviors observed in depressed individuals. However, the neural mechanisms underlying impairments in emotion-cognition interactions are poorly understood. This includes influencing the balance between how past-sensitive vs. future-looking one is during decision-making. Recent insights from the field of neuroeconomics offer novel approaches to study changes in such valuation processes in a manner that is biologically tractable and readily translatable across species. We recently discovered that rodents are sensitive to "sunk costs" - a feature of higher cognition previously thought to be unique to humans. The sunk costs bias describes the phenomenon in which an individual overvalues and escalates commitment to continuing an ongoing endeavor, even if suboptimal, as a function of irrecoverable past (sunk) losses - information that, according to classic economic theory, should be ignored. In the present study, mice were exposed to chronic social defeat stress paradigm, a well-established animal model used for the study of depression. Mice were then tested on our longitudinal neuroeconomic foraging task, Restaurant Row. We found mice exposed to this severe stressor displayed an increased sensitivity to sunk costs, without altering overall willingness to wait. Mice were then randomly assigned to receive a single intraperitoneal injection of either saline or ketamine (20 mg/kg). We discovered that stress-induced hypersensitivity to sunk costs was renormalized following a single dose of ketamine. Interestingly, in non-defeated mice, ketamine treatment completely abolished sunk cost sensitivity, causing mice to no longer value irrecoverable losses during re-evaluation decisions who instead based choices solely on the future investment required to obtain a goal. These findings suggest that the antidepressant effects of ketamine may be mediated in part through changes in the processing of past-sensitive information during on-going decision-making, reducing its weight as a potential source of cognitive dissonance that could modulate behavior and instead promoting more future-thinking behavior.

neuroscience↗

bioRxiv2024

Sex differences in change-of-mind neuroeconomic decision-making is modulated by LINC00473 in medial prefrontal cortex

Changing ones mind involves re-appraisals between past-costs versus future-value and may be altered in psychopathology. Long intergenic non-coding RNA LINC00473 in medial prefrontal cortex (mPFC) can induce stress-resilience in a sex-dependent manner, but its role in cognition is unknown. We characterized decision-making behavior in male and female mice in the neuroeconomic paradigm Restaurant Row following virus-mediated expression of LINC00473 in mPFC. Mice foraged for food among varying temporal-costs and subjective-value while on a limited time-budget. Without affecting primary deliberative decisions, LINC00473 selectively influenced re-evaluative choices in a sex-dependent manner. This included changing how mice (i) cached value with the passage of time and (ii) weighed prior mistakes, which underlie the computational bases of sensitivity to sunk costs and regret. These findings suggest a common value function is shared between these neuroeconomic processes and reveal a bridge between molecular drivers of stress-resilience and psychological mechanisms underlying sex-specific proclivities in negative rumination.

neuroscience↗

bioRxiv2024

Diabetes alters neuroeconomically dissociable forms of mental accounting

Those with diabetes mellitus are at high-risk of developing psychiatric disorders, yet the link between hyperglycemia and alterations in motivated behavior has not been explored in detail. We characterized value-based decision-making behavior of a streptozocin-induced diabetic mouse model on a naturalistic neuroeconomic foraging paradigm called Restaurant Row. Mice made self-paced choices while on a limited time-budget accepting or rejecting reward offers as a function of cost (delays cued by tone-pitch) and subjective value (flavors), tested daily in a closed-economy system across months. We found streptozocin-treated mice disproportionately undervalued less-preferred flavors and inverted their meal-consumption patterns shifted toward a more costly strategy that overprioritized high-value rewards. We discovered these foraging behaviors were driven by impairments in multiple decision-making systems, including the ability to deliberate when engaged in conflict and cache the value of the passage of time in the form of sunk costs. Surprisingly, diabetes-induced changes in behavior depended not only on the type of choice being made but also the salience of reward-scarcity in the environment. These findings suggest complex relationships between glycemic regulation and dissociable valuation algorithms underlying unique cognitive heuristics and sensitivity to opportunity costs can disrupt fundamentally distinct computational processes and could give rise to psychiatric vulnerabilities.

neuroscience↗

bioRxiv2023

A double-hit of social and economic stress in mice precipitates changes in decision-making strategies

Economic stress can serve as a "second-hit" for those who already accumulated a history of adverse life experiences. How one recovers from a setback is a core feature of resilience but is seldom captured in animal studies. We challenged mice in a novel two-hit stress model by exposing animals to chronic social defeat stress (first-hit) and then testing how mice adapt to reward scarcity on a neuroeconomic task (second-hit). Mice were tested longitudinally across months on the Restaurant Row task during which mice foraged daily for their sole source of food while on a limited time budget. An abrupt transition into a reward-scarce environment on this task elicits an economic crisis, precipitating a massive drop in food intake and body weight to which mice must respond in order to survive. We found that mice with a history of social defeat mounted a robust behavioral response to this economic challenge. This recovery was achieved through a complex redistribution of how time was allocated among competing opportunities via multiple valuation algorithms. Interestingly, we found that mice with a history of social defeat displayed changes in the development of decision-making policies during the recovery process important for not only ensuring food security necessary for survival but also prioritizing subjective value. These findings indicate that an individuals capacity to "bounce back" from economic stress depends on ones prior history of stress and can affect multiple aspects of subjective well-being, highlighting a motivational balance that may be altered in stress-related disorders such as depression. In BriefDurand-de Cuttoli et al. found that after chronic social defeat stress, when mice were subsequently challenged on a neuroeconomic foraging task, an economic stressor can serve as a "second hit" and reveal changes in the development of complex decision-making strategies important for maintaining the balance between food security and subjective well-being.

animal behavior and cognition↗

bioRxiv2022

Chronic social stress induces isolated deficits in reward anticipation on a neuroeconomic foraging task

Measuring reward anticipation distinct from other aspects of reward value, including costs required to obtain a reward or the intrinsic hedonic value of consuming the reward itself, can be difficult to disentangle. Here, we show that mice trained on a self-paced neuroeconomic foraging task convey reward anticipation via differentially invigorated travel times between uniquely flavored feeding sites separate from willingness to wait, consummatory behaviors, or place preferences measured within the same trial. Following exposure to chronic social defeat stress, we found that only stress-susceptible but not stress-resilient mice revealed deficits in this metric after consuming but not after rejecting a reward on the previous trial, indicating that blunted anticipation in these animals is state-dependent, or punctuated by recent reward receipt. After increasing economic pressure and task demands, locomotion was globally invigorated and, in turn, masked stress-related deficits in reward anticipation. These findings suggest that the ability to detect changes in specific aspects of motivational deficits associated with depression and other stress-related disorders depends on an interaction between the state of an individual and environmental circumstances.

animal behavior and cognition↗

bioRxiv2022

Region-specific CREB function regulates distinct forms of regret associated with resilience versus susceptibility to chronic stress

Regret describes recognizing that alternative actions could have led to better outcomes. This can transform into behavioral consequences, altering subsequent valuations, but remains unclear if regret derives from a generalized computation for mistake appraisal or instead is made up of dissociable action-specific processes. Using a novel neuroeconomic decision-making paradigm, we found mice were differentially sensitive to fundamentally distinct types of missed opportunities following exposure to chronic social defeat stress or manipulations of CREB, a key transcription factor implicated in chronic stress action. Bias to make compensatory decisions after rejecting high-value offers (regret type I) was unique to stress-susceptible mice. Bias following the converse operation, accepting low-value offers (regret type II), was enhanced in stress-resilient and absent in stress-susceptible mice. CREB function in either the medial prefrontal cortex or nucleus accumbens was required to suppress regret type I but differentially affected regret type II. We provide insight into how adaptive versus maladaptive stress-response traits may be related to fundamentally distinct forms of counterfactual thinking and could steer psychotherapy for mood disorders such as depression toward unveiling circuit-specific computations through a careful description of decision narrative.

neuroscience↗

bioRxiv2021

Sunk cost sensitivity in mice, rats, and humans on the Restaurant Row and WebSurf tasks cannot be explained by attrition biases alone

In a recent bioRxiv preprint, Ott et al. argue that sensitivities to sunk costs that have been reported in two serial foraging tasks (the Restaurant Row task in mice and rats, and the Web-Surf task in humans) may be due to simple consequences of the way that subjects perform these tasks and not due to an actual sensitivity to sunk costs. However, several variants of these tasks have been studied, in which the sensitivity to sunk costs changes. In order to test the Ott et al. model against these experimental observations, we simulated the model under these additional experimental conditions. We find that it is incompatible with the actual data. While we applaud the simplicity of the Ott et al. model, we must reject it as an explanation for the observed sensitivity to sunk costs seen in these tasks. We thus conclude that the alternative explanation - that mice, rats, and humans are sensitive to actual sunk costs in these tasks - is a better explanation for the data.

neuroscience↗