Biology subjects

Seib, D. R.

Publications and source records attributed to Seib, D. R..

8 recordsLinked to original sources

bioRxiv2026

A Novel Operant Conditioning Task to Assess Motivation to Exercise in Rats

Voluntary physical activity is a highly motivated behavior with important implications for physical and mental health, yet the neural and endocrine mechanisms underlying motivation to exercise remain poorly understood. In contrast, motivation for sugar/palatable foods, drugs, and sex has been extensively characterized using operant paradigms. Here, we describe a novel progressive ratio operant task to measure motivation to run, independent of running ability. Using female Long Evans rats, which exhibit robust voluntary running behavior, we validated this paradigm by applying a manipulation well known to enhance the motivation to run: calorie restriction. Calorie-restricted animals exhibited increased operant responding to gain access to a running wheel, thus demonstrating heightened motivation for exercise. More specifically, calorie-restricted rats completed more ratios, reached a higher breakpoint in the progressive ratio task, ran more, and spent more time in the operant chamber. We did not observe any effects of calorie restriction on the estrous cycle or steroids (e.g. corticosterone, testosterone) in the blood or brain. Importantly, our task dissociates the motivational drive for physical activity from the ability to perform the physical activity itself, providing a new paradigm for studying the neural and endocrine mechanisms that regulate exercise motivation.

animal behavior and cognition↗

bioRxiv2025

Maternal sucrose intake during pregnancy alone disrupts testosterone and allopregnanolone levels in the fetal brain of rats

BackgroundIntake of added sugars, such as sucrose, is high globally. In rats, a maternal high-sucrose diet (HSD) from 10 wk before pregnancy to embryonic day (E)19.5 has widespread impacts on maternal, placental, and fetal blood and brain steroid levels, including glucocorticoids, androgens, and aldosterone. ObjectiveThis study examined whether maternal HSD during pregnancy alone is sufficient to alter maternal, placental, and fetal steroids. MethodsPregnant rats received either a control diet (1% kcal sucrose) or an isocaloric, nutrient-matched HSD (26% kcal sucrose) between E0.5-19.5. On E19.5, we collected maternal serum, placenta, fetal blood and brain, and amniotic fluid. We microdissected the placenta and fetal brain and measured 14 steroids using highly sensitive and specific liquid chromatography-tandem mass spectrometry (n=12-15/diet/sex). ResultsMaternal HSD during pregnancy alone did not alter maternal food intake, maternal body mass, and litter size (all p values [≥] 0.29, Students t-test) but increased the percentage of males in a litter (p = 0.03, Students t-test). Maternal HSD did not alter steroids in the maternal serum (all p values [≥] 0.21, Students t-test), placenta (all p values [≥] 0.07, 2-way analysis of variance (ANOVA)), and fetal blood (all p values [≥] 0.13, 2-way ANOVA). Nonetheless, maternal HSD increased testosterone in the fetal nucleus accumbens (p = 0.04, 2-way ANOVA), decreased allopregnanolone in the fetal amygdala (p = 0.01, 2-way ANOVA), and decreased 11-dehydrocorticosterone in the amniotic fluid (p = 0.05, 2-way ANOVA). ConclusionsMaternal HSD during pregnancy alone does not affect steroid levels in the maternal serum, placenta, or fetal blood, but disrupts testosterone and allopregnanolone levels in critical regions of the fetal brain that regulate reward-seeking and emotion. Thus, while a long-term maternal HSD is necessary for widespread endocrine effects, the fetal brain is sensitive to short-term increases in maternal sucrose consumption during pregnancy.

neuroscience↗

bioRxiv2023

Maternal high-sucrose consumption increases maternal and fetal glucocorticoids and decreases fetal androgens in the rat

Maternal diet has long-term effects on offspring brain development and behavior. Sucrose (table sugar) intakes are high in modern diets, but it is not clear how a maternal high-sucrose diet (HSD) affects the offspring. In rats, a maternal HSD (26% of calories from sucrose, which is human-relevant) alters maternal metabolism and brain and also alters adult offspring endocrinology and behavior in a sex-specific manner. Maternal sucrose intake increases corticosterone levels in adult female offspring and increases motivation for a sugar reward in adult male offspring. Here, to identify possible underlying mechanisms, we examined how a maternal HSD affects steroids in the dam, placenta, and fetus at embryonic day 19.5 using liquid chromatography tandem mass spectrometry. Maternal sucrose intake increased glucocorticoids (11-deoxycorticosterone and 11-dehydrocorticosterone) and tended to increase the mineralocorticoid aldosterone in maternal serum. In the placenta, maternal sucrose intake decreased androstenedione and testosterone. Maternal HSD increased aldosterone in the fetal blood. Similarly, in the fetal brain, maternal high-sucrose intake increased aldosterone in the medial prefrontal cortex and nucleus accumbens, decreased testosterone in the nucleus accumbens, and decreased corticosterone in the orbital cortex. In addition, the 11-dehydrocorticosterone/corticosterone and aldosterone/corticosterone ratios were increased in most examined brain regions. Lastly, maternal HSD increased 11-dehydrocorticosterone and aldosterone in the amniotic fluid. In summary, we found dramatic and widespread changes in maternal, placental, and fetal steroids that might mediate the long-term effects of maternal sucrose consumption on adult offspring neuroendocrinology and behavior.

neuroscience↗

bioRxiv2021

Inhibiting adult neurogenesis differentially affects spatial learning in females and males

Adult hippocampal neurogenesis has been implicated in the spatial processing functions of the hippocampus but ablating neurogenesis does not consistently lead to behavioral deficits in spatial tasks. Parallel studies have shown that adult-born neurons also regulate behavioral responses to stressful and aversive stimuli. We therefore hypothesized that spatial functions of adult-born neurons may be more prominent under conditions of stress, and may differ between males and females given established sex differences in stress responding. To test this we trained intact and neurogenesis-deficient rats in the spatial water maze at temperatures that vary in their degree of aversiveness. At standard temperatures (25{degrees}C) ablating neurogenesis did not alter learning and memory in either sex, consistent with prior work. However, in cold water (16{degrees}C), ablating neurogenesis had divergent sex-dependent effects: relative to intact rats, male neurogenesis-deficient rats were slower to escape and female neurogenesis-deficient rats were faster. Neurogenesis promoted temperature-related changes in search strategy in females, but it promoted search strategy stability in males. Females displayed greater recruitment of the dorsal hippocampus than males, particularly at 16{degrees}C. However, blocking neurogenesis did not alter activity-dependent immediate-early gene expression in either sex. Finally, morphological analyses of retrovirally-labelled neurons revealed greater experience-dependent plasticity in new neurons in males. Neurons had comparable morphology in untrained rats but 16{degrees}C training increased spine density, and 25{degrees}C training caused shrinkage of mossy fiber presynaptic terminals, specifically in males. Collectively, these findings indicate that neurogenesis functions in memory are prominent under conditions of stress, they provide the first evidence for sex differences in the behavioral function of newborn neurons, and they suggest possibly distinct roles for neurogenesis in cognition and mental health in males and females.

neuroscience↗

bioRxiv2021

Androgen synthesis inhibition but not gonadectomy reduces persistence during strategy set-shifting and reversal learning in male rats

Androgens regulate behavioural flexibility, which is essential to adapt to a changing environment and depends on the medial prefrontal cortex (mPFC). Testosterone (T) administration decreases behavioural flexibility. It is well known that T is produced in the gonads, but T is also produced in the mesocorticolimbic system, which modulates behavioural flexibility. It is unclear how T produced in the brain versus the gonads influences behavioural flexibility. Here, we assess the effects of the androgen synthesis inhibitor abiraterone acetate (ABI) and long-term gonadectomy (GDX) on behavioural flexibility in two paradigms. In Experiment 1, ABI independent of GDX reduced the number of trials to criterion and perseverative errors in a strategy set-shifting task. Similarly, in Experiment 2, ABI but not GDX reduced perseverative errors in a reversal learning task. In subjects from Experiment 1, we also examined tyrosine hydroxylase immunoreactivity (TH-ir), and ABI but not GDX increased TH-ir in the mPFC. Our findings suggest that neurally-produced androgens modulate behavioural flexibility via modification of dopamine signalling in the mesocorticolimbic system. These results suggest novel roles for neurosteroids and possible side effects of ABI treatment for prostate cancer.

neuroscience↗

bioRxiv2019

Adult-born hippocampal neurons undergo extended development and are morphologically distinct from neonatally-born neurons

During immature stages, adult-born neurons pass through critical periods for survival and plasticity. It is generally assumed that by 2 months of age adult-born neurons are mature and equivalent to the broader neuronal population, raising questions of how they might contribute to hippocampal function in old age when neurogenesis has declined. However, few have examined adult-born neurons beyond the critical period, or directly compared them to neurons born in infancy. Here, we used a retrovirus to visualize functionally-relevant morphological features of 2- to 24-week-old adult-born neurons in male rats. From 2-7 weeks neurons grew and attained a relatively mature phenotype. However, several features of 7-week-old neurons suggested a later wave of growth: these neurons had larger nuclei, thicker dendrites and more dendritic filopodia than all other groups. Indeed, between 7-24 weeks, adult-born neurons gained additional dendritic branches, grew a 2nd primary dendrite, acquired more mushroom spines and had enlarged mossy fiber presynaptic terminals. Compared to neonatally-born neurons, old adult-born neurons had greater spine density, larger presynaptic terminals, and more putative efferent filopodial contacts onto inhibitory neurons. By integrating rates of cell birth and growth across the lifespan, we estimate that adult neurogenesis ultimately produces half of the cells and the majority of spines in the dentate gyrus. Critically, protracted development contributes to the plasticity of the hippocampus through to the end of life, even after cell production declines. Persistent differences from neonatally-born neurons may additionally endow adult-born neurons with unique functions even after they have matured. SIGNIFICANCE STATEMENTNeurogenesis occurs in the hippocampus throughout adult life and contributes to memory and emotion. It is generally assumed that new neurons have the greatest impact on behavior when they are immature and plastic. However, since neurogenesis declines dramatically with age, it is unclear how they might contribute to behavior later in life when cell proliferation has slowed. Here we find that newborn neurons mature over many months in rats, and end up with distinct morphological features compared to neurons born in infancy. Using a mathematical model, we estimate that a large fraction of neurons is added in adulthood. Moreover, their extended growth produces a reserve of plasticity that persists even after neurogenesis has declined to low rates.

neuroscience↗

bioRxiv2018

Hippocampal neurogenesis promotes preference for future rewards

Adult hippocampal neurogenesis is implicated in a number of disorders where reward processes are disrupted but whether new neurons regulate specific reward behaviors remains unknown. We find that blocking neurogenesis in rats reduces activation of the ventral dentate gyrus and causes a profound aversion for delayed rewards. Delay-based decision-making restructured dendrites and spines in adult-born neurons, consistent with activity-dependent neuronal recruitment. These findings identify a novel role for neurogenesis in decisions about future rewards, which is compromised in disorders where short-sighted gains are preferred at the expense of long-term health.

neuroscience↗

bioRxiv2018

Intact memory for local and distal cues in male and female rats that lack adult neurogenesis

The dentate gyrus is essential for remembering the fine details of experiences that comprise episodic memory. Dentate gyrus granule cells receive highly-processed sensory information and are hypothesized to perform a pattern separation function, whereby similar sensory inputs are transformed into orthogonal neural representations. Behaviorally, this is believed to enable distinct memory for highly interfering stimuli. Since the dentate gyrus is comprised of a large number of adult-born neurons, which have unique synaptic wiring and neurophysiological firing patterns, it has been proposed that neurogenesis may contribute to this process in unique ways. Some behavioral evidence exists to support this role, whereby neurogenesis-deficient rodents are impaired at discriminating the fine visuospatial details of experiences. However, the extent to which newborn neurons contribute to dentate gyrus-dependent learning tasks is unclear. Furthermore, since most studies of dentate gyrus function are conducted in male rats, little is known about how females perform in similar situations, and whether there might be sex differences in the function of adult neurogenesis. To address these issues, we examined spatial discrimination memory in transgenic male and female rats that lacked adult neurogenesis. The first task probed memory for the position of local objects in an open field, assessed by behavioral responses to novel object locations. The second task examined memory for distal environmental cues. All rats were able to successfully discriminate local and distal cue changes. Males and females also performed comparably, although females displayed higher levels of rearing and locomotion. Collectively, our results indicate that rats are capable of learning about local and distal cues in the absence of adult neurogenesis.

neuroscience↗