The rate at which an operant is produced has often functioned as a fundamental measure of the efficacy of a reinforcer. Previous research has shown that operant behavior is typically organized into bouts implying that rate of responding is a…
The rate at which an operant is produced has often functioned as a fundamental measure of the efficacy of a reinforcer. Previous research has shown that operant behavior is typically organized into bouts implying that rate of responding is a composite of bout-initiation rate, within-bout response rate, and mean bout length. However, it is still unclear whether this organization of behavioral responses into bouts is a product of the motivational processes or a property that arises from the location of an organism in space. To test this proximity hypothesis, two-response sequences were intermittently reinforced: either pressing one lever twice (manipulandum proximal to response termination) or pressing each of two levers, located on either side of an operant chamber, once (manipulandum distal to response termination). In Experiment 1, rats were first trained to lever press for food on a VI schedule before being exposed to the alternation paradigm. Experiment 1 consisted of three phases. In Phase 1, food-deprived rats learned the alternation paradigm under a tandem variable time (VT) 150-s fixed-ratio (FR) 1 schedule of reinforcement. Phase 2 and 3 increased the FR requirement from 1 to 3 or 5 and removed food deprivation, respectively, to examine their effect on response-rate components. In Experiment 2, rats switched between trials consisting of pressing a single lever repeatedly or alternating between two levers for reward. Following stable behavior, lever pressing was extinguished in both trial types to the effect of extinction on response-rate components. Overall, behavioral bouts persisted under the alternation paradigm suggesting that they reflect motivational states and not just location. Additionally, bout-initiation rate decreased with increased response effort and decreased deprivation. Taken together, these results provide support for the use of response-bout analysis to evaluate the value of a reinforcer and its sensitivity to pharmacological manipulations.
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Autism spectrum disorder (ASD) is characterized by deficits in flexible cognition and social behavior. The most common atypical brain structure in ASD, the cerebellum, has multisynaptic connections through the cerebellar nuclei (CN) and thalamus to cognitive- and social-associated brain regions,…
Autism spectrum disorder (ASD) is characterized by deficits in flexible cognition and social behavior. The most common atypical brain structure in ASD, the cerebellum, has multisynaptic connections through the cerebellar nuclei (CN) and thalamus to cognitive- and social-associated brain regions, yet formation and modulation of these pathways are not fully understood. Additionally, a CN output mechanism, perineuronal nets (PNNs), structure and function are undefined. PNNs are specialized extracellular matrix structures whose appearance is associated with the end of the critical period of plasticity and have been implicated in learning and neurodevelopmental disorders, but their role in the CN during development is unknown.To examine the role of CN on cognition, CN activity was increased or decreased in both male and female mice using Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) from postnatal day 21-35. Learning and reversal was analyzed using a pairwise visual discrimination task. Social behavior was assessed using a classic three-chamber assay and analyzed using SLEAP (Social Leap Estimates Animal Poses). A marker of critical periods, perineuronal nets (PNNs), was examined to understand relationships between neural development and behavior.
Interestingly, adolescent CN disruption did not alter task acquisition, yet correct choice reversal performance was dependent on DREADD manipulation and sex. CN inhibition improved reversal learning in males (5 days faster to criteria) and CN excitation improved female reversal learning (10 days faster to criteria) compared to controls. Analysis of social behavior revealed male social preference was abolished in CN manipulated groups, whereas females failed to demonstrate a social preference. Interestingly, CN manipulation in females regardless of direction, reduced PNN intensity, whereas in males only CN inhibition reduced PNN intensity. PNN intensity negatively correlated with reversal performance. CN PNN intensity showed no relation to social behavior. These data suggest chronic adolescent CN manipulation may have compensatory changes in PNN structure and CN output to improve reversal learning and PNN function was unrelated to social behavior. This study provides new evidence for CN in non-motor functions and sex-dependent differences in behavior and CN plasticity.
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Discovering more about social hierarchies within groups of mice and the underlying brain mechanisms supporting differences in dominance is essential to understanding social roles and individuality. In this study, we aimed to discover if a novel dominance assay is able…
Discovering more about social hierarchies within groups of mice and the underlying brain mechanisms supporting differences in dominance is essential to understanding social roles and individuality. In this study, we aimed to discover if a novel dominance assay is able to determine social hierarchies in groups of three, as well as how this novel assay compares to a classic dominance tube test. SLEAP software, a machine learning tool, was used to analyze the behaviors of the mice in the novel dominance apparatus. In addition, cytokine levels were collected from the mice to assess possible correlations between hierarchical standing and presence of inflammatory agents.
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The cerebellum is recognized for its role in motor movement, balance, and more recently, social behavior. Cerebellar injury at birth and during critical periods reduces social preference in animal models and increases the risk of autism in humans. Social behavior…
The cerebellum is recognized for its role in motor movement, balance, and more recently, social behavior. Cerebellar injury at birth and during critical periods reduces social preference in animal models and increases the risk of autism in humans. Social behavior is commonly assessed with the three-chamber test, where a mouse travels between chambers that contain a conspecific and an object confined under a wire cup. However, this test is unable to quantify interactive behaviors between pairs of mice, which could not be tracked until the recent development of machine learning programs that track animal behavior. In this study, both the three-chamber test and a novel freely-moving social interaction test assessed social behavior in untreated male and female mice, as well as in male mice injected with hM3Dq (excitatory) DREADDs. In the three-chamber test, significant differences were found in the time spent (female: p < 0.05, male: p < 0.001) and distance traveled (female: p < 0.05, male: p < 0.001) in the chamber with the familiar conspecific, compared to the chamber with the object, for untreated male, untreated female, and mice with activated hM3Dq DREADDs. A social memory test was added, where the object was replaced with a novel mouse. Untreated male mice spent significantly more time (p < 0.05) and traveled a greater distance (p < 0.05) in the chamber with the novel mouse, while male mice with activated hM3Dq DREADDs spent more time (p<0.05) in the chamber with the familiar conspecific. Data from the freely-moving social interaction test was used to calculate freely-moving interactive behaviors between pairs of mice and interactions with an object. No sex differences were found, but mice with excited hM3Dq DREADDs engaged in significantly more anogenital sniffing (p < 0.05) and side-side contact (p < 0.05) behaviors. All these results indicate how machine learning allows for nuanced insights into how both sex and chemogenetic excitation impact social behavior in freely-moving mice.
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Memory as whole is impacted by changes associated with aging and menopause. Different memory types are often tested preclinically utilizing rats in different task paradigms. Most studies have focused on understanding social recognition or working memory, however these memory types…
Memory as whole is impacted by changes associated with aging and menopause. Different memory types are often tested preclinically utilizing rats in different task paradigms. Most studies have focused on understanding social recognition or working memory, however these memory types have yet to be studied together. This thesis focuses on the process of creating and testing a new social recognition task that incorporates a working memory load. We tested different types of previously used social recognition paradigms with an increasing load and through qualitative and quantitative observations the task was modified until a final task was developed for a social working memory study. Young female rats were tested in this task in progressive, meaning a chronologically increasing load and nonprogressive, meaning non-chronological increase in load cognitions. It was found that young female rats had the ability to distinguish between the familiar and novel conspecifics before memory load exceeded four familiar and one novel conspecifics. Once validated through future studies, this task may be utilized to understand the impact of different types of menopause on social working memory.
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Research demonstrates that chronic stress produces a depressive-like profile in rodents, affecting several domains including, cognition, depressive-like behavior, and anxiety-like behavior. However, chronic stress leads to these outcomes in a sex-dependent manner, as young adult female rodents fail to exhibit…
Research demonstrates that chronic stress produces a depressive-like profile in rodents, affecting several domains including, cognition, depressive-like behavior, and anxiety-like behavior. However, chronic stress leads to these outcomes in a sex-dependent manner, as young adult female rodents fail to exhibit impaired cognition and increased depressive and anxiety-like behavior following chronic stress. The primary goal of this dissertation was to reveal novel elements contributing to female susceptibility to stress-induced depressive-like presentations and possible factors that may counteract such outcomes. In chapter 2, novel stress paradigms were investigated to determine whether more robust stressors would lead to spatial memory deficits and elevated anxiety in young adult female and male rats. Results demonstrated that chronic stress impaired spatial memory in males, while the robust stressors failed to impair spatial memory in females. Chapter 3 revealed that both females and males in chapter 2 showed BLA dendritic hypertrophy days following the stressor without hippocampal alterations, with the latter likely due to the passage of time allowing for restructuring. Consequently, chapters 4 through 6 were conducted to investigate whether females would show chronic stress effects at middle-age in ovariectomized (OVX) females because menopause is a period of high vulnerability to cognitive and depressive-like effects. Chapter 4 investigated whether the stress hormone, corticosterone, would impair spatial working memory and increase the depressive-like profile of OVX, middle-aged female rats, which was confirmed using the radial arm water maze (RAWM), sucrose preference (SP), forced swim test (FST), and elevated plus maze (EPM). Chapter 5 investigated if estradiol (E2) may prevent the negative valence outcomes induced by OVX in middle-aged female rats. However, E2 showed antidepressant properties during FST, but failed to do so in other behavioral tasks. Chapter 6 further explored E2’s role in mitigating corticosterone-induced effects on cognition and mood in middle-aged female and male rats, with more pronounced antidepressant effects in females. Notably, this chapter unveiled a novel correlation between spatial memory and anxiety-like behavior in corticosterone-treated female rats. Collectively, these studies delineate a corticosterone-based model of depression in female rodents and introduce a novel approach for analyzing variables across multiple behavioral domains.
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Many organisms associate environmental events that occur together and can predict the outcome of the event. This ability is termed associative learning. Through associative learning, organisms are able to change their behavior to increase their fitness and survival. However, little…
Many organisms associate environmental events that occur together and can predict the outcome of the event. This ability is termed associative learning. Through associative learning, organisms are able to change their behavior to increase their fitness and survival. However, little is known about how these same learning processes proceed when subjects are not alone, but in a group. The behavior of conspecifics could serve as a cue for learning, similar to stimuli during individual learning. This study was designed to compare learning across rats exposed to a simple simultaneous discrimination task, either in an individual or a social learning setting. Sixteen rats were trained to choose between two corridors differentiated by visual stimuli (flashing or steady light). One of the two cues signaled that food was available in the feeders at the end of the corridor. Half of the rats were trained individually and the other half were trained in groups of four. To compare the effect of the social training setting, all rats were tested independently and in a group. Next, contingencies were reversed and the previously non-reinforced cue now signaled the availability of food, and rats were again tested individually and in a group. The results suggest that the social setting interferes with the rats’ ability to make associations but makes the performance of the rats less sensitive to changes in their learning environment.
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Social isolation in early childhood can have life-long effects on social behaviors and development. Cerebellar crus I has additionally been linked to social behaviors through forebrain pathways. In this study, we hypothesized that social isolation of mice from postnatal day…
Social isolation in early childhood can have life-long effects on social behaviors and development. Cerebellar crus I has additionally been linked to social behaviors through forebrain pathways. In this study, we hypothesized that social isolation of mice from postnatal day 21 (P21) until p35 would result in impaired social behaviors. Additionally, we hypothesized that gq DREADD injections into crus I, to increase levels of cerebellar stimulation, at the start of the isolation period would counteract the effects of isolation, leading to mice who displayed normal social behaviors. Social behavior at P35 was tested using the 3-Chamber Task, a well-established model, and SLEAP deep-learning software was used to obtain quantifiable data. We found no difference in social behaviors between socially raised and isolated mice. However, gq DREADD mice displayed greater levels of social interaction and exploration than either socially raised mice or isolated mice. This research carries implications for possible therapeutic interventions for groups prone to social isolation, such as those with developmental disabilities, minority groups, the elderly, and prison populations.
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