Patterns of hippocampal ensemble activity that occur during a spatial experience are reactivated during subsequent rest periods and slow wave sleep. Connections between active cells are thought to be strengthened, via long term potentiation (LTP), by repeated co-activation during experience, which suggests that the level of memory trace reactivation would increase proportionately with repetition. Alternatively, plasticity associated with memory formation, such as LTP-dependent place field expansion and the induction of activity-dependent immediate early gene, ARC, saturates after only a few laps, indicating that reactivation would plateau after a few repetitions. The length of the repeated sequence may also affect reactivation, since activation of a very short sequence can be repeated more frequently than a long sequence in a given time period. We studied how memory trace reactivation was affected by repetition and the length of the repeated sequence by observing the reactivated patterns of cell-pair correlations after a rat ran laps around a long circular track versus running more laps around a short track. On the shorter track, fewer cells had place fields, but they covered more of the track, resulting in generally stronger correlations among active cells. In addition, neuronal activity was recorded from dorsal and mid-ventral CA1. In mid-ventral CA1, there were fewer place fields in the environment but they were larger, with generally stronger correlations among active cells. The comparison between dorsal and mid-ventral regions is thus analogous to the comparison between the sequence of place fields on a long versus short track, respectively. Although there were more cells active in the dorsal region, but more potent correlations in the middle region, no differences in memory trace reactivation were found with respect to repetitions, track length or hippocampal region. This suggests that although spatial scaling increased along the dorsoventral axis of the hippocampus, reactivation is balanced, and possibly coherent across the hippocampal axis and it is relatively independent of sequence length or number of repetitions, at least when that number exceeds about 20.

No description available.

An acute increase in hypothalamic glucose and its downstream metabolite lactate lower glucose production (GP) and plasma glucose (PG) levels in normal rodents. However, the effectiveness of this nutrient-sensing mechanism in metabolic disease is unknown. We assessed the effects of intracerebroventricular (i.c.v.) or intra-hypothalamic glucose and lactate on in vivo glucose kinetics in conscious rats. Study I revealed that i.c.v. lactate lowered PG via a suppression of GP in rodents with uncontrolled diabetes and diet-induced insulin resistance. Study II demonstrated that i.c.v. glucose was ineffective at suppressing GP in uncontrolled diabetic rodents or rodents with a prior 24 h whole-body or hypothalamic hyperglycemic insult. When PG levels per se were normalized in diabetic rodents hypothalamic glucose sensing to lower GP was rescued. As such, sustained hyperglycemia per se impairs hypothalamic glucose effectiveness in diabetes. Further studies are necessary to determine defective mechanisms upstream of lactate metabolism hindering CNS glucose sensing.

An acute increase in hypothalamic glucose and its downstream metabolite lactate lower glucose production (GP) and plasma glucose (PG) levels in normal rodents. However, the effectiveness of this nutrient-sensing mechanism in metabolic disease is unknown. We assessed the effects of intracerebroventricular (i.c.v.) or intra-hypothalamic glucose and lactate on in vivo glucose kinetics in conscious rats. Study I revealed that i.c.v. lactate lowered PG via a suppression of GP in rodents with uncontrolled diabetes and diet-induced insulin resistance. Study II demonstrated that i.c.v. glucose was ineffective at suppressing GP in uncontrolled diabetic rodents or rodents with a prior 24 h whole-body or hypothalamic hyperglycemic insult. When PG levels per se were normalized in diabetic rodents hypothalamic glucose sensing to lower GP was rescued. As such, sustained hyperglycemia per se impairs hypothalamic glucose effectiveness in diabetes. Further studies are necessary to determine defective mechanisms upstream of lactate metabolism hindering CNS glucose sensing.

Thesis (M.S.) in Wildlife Ecology--University of Maine, 2009. / Includes vita. Includes bibliographical references (leaves 124-152).

Population structure and phylogenetic relationships were studied in coccidia parasitizing the rodent families Muridae and Arvicolidae, in 40 localities in 14 European countries. Sequences of mitochondrial gene for cytochrome c oxidase subunit I (COI) and nuclear 18S rRNA gene (SSU) were used for phylogenetic analyses and for reconstruction of evolutionary relationships among coccidian species.

abstract: Approximately 2.8 million Americans seek medical care for traumatic brain injury (TBI) each year. Of this population, the majority are sufferers of diffuse TBI, or concussion. It is unknown how many more individuals decline to seek medical care following mild TBI. This likely sizeable population of un- or self-treated individuals combined with a lack of definitive biomarkers or objective post-injury diagnostics creates a unique need for practical therapies among diffuse TBI sufferers. Practical therapies stand to decrease the burden of TBI among those who would otherwise not seek treatment or do not meet clinical diagnostic criteria upon examination. For this unique treatment niche, practical therapies for TBI are defined as having one or more of the following qualities: common availability, easy administration, excellent safety profile, and cost-effectiveness. This dissertation identifies and critically examines the efficacy of four classes of practical treatments in improving rodent outcome from experimental diffuse traumatic brain injury. Over-the-counter (OTC) analgesics, omega-3 fatty acids, specialized pro-resolving mediators (SPMs), and remote ischemic conditioning (RIC) were administered before or following midline fluid percussion injury. Behavioral, histological, and molecular analyses were used to assess treatment effects on functional outcome and secondary injury progression. Acute administration of common OTC analgesics had little effect on post-injury outcome in mice. Dietary supplementation with omega-3 fatty acid docosahexaenoic acid (DHA) prior to or following diffuse TBI significantly reduced injury-induced sensory sensitivity and markers of neuroinflammation with no effect on spatial learning. Intraperitoneal administration of omega-3 fatty acid-derived SPM resolvin E1 significantly increased post-injury sleep and suppressed microglial activation. Aspirin-triggered (AT) resolvin D1 administration improved both motor and cognitive outcome following diffuse TBI. RIC treatment in mice demonstrated little effect on functional outcome from diffuse TBI. Untargeted proteomic analysis of plasma samples from RIC-treated mice was used to identify candidate molecular correlates of RIC. Identification of these candidates represents a vital first step in elucidating the neuroprotective mechanisms underlying RIC. The overall findings suggest that omega-3 fatty acid supplementation, SPM administration, and RIC may serve as effective practical therapies to reduce the somatic, cognitive, and neurological burden of diffuse TBI felt by millions of Americans. / Dissertation/Thesis / Doctoral Dissertation Neuroscience 2017

No description available.

BACKGROUND: As space programs such as NASA prepare for interplanetary missions to Mars, the potential hazards of long-term space travel are being increasingly considered. Of these hazards, astronaut exposure to galactic cosmic radiation (GCR) is of specific concern. Despite increased efforts to study the consequences of deep space radiation exposure, studies have been inconsistent in their dosage and types of radiation used. This study marks the first to use a simulated form of GCR, accurately representing the dosage and full spectrum of ions astronauts would encounter on an extended journey to Mars. The disruption of cognition and behavior by radiation has been a hallmark of previous investigations, however, it is unknown whether accurate full-spectrum GCR causes similar impairment. Additionally, reports exploring the efficacy of radioprotectant drugs are lacking despite their potential utility in deep space travel. Nicotinamide Mononucleate, an NAD+ precursor, shows promise for radioprotection, as its roles in promoting DNA repair and longevity pathways in mice are well established. OBJECTIVE: To define behavioral responses to accurate full-spectrum Galactic Cosmic Radiation (GCR) in mice and test the neuroprotective potential of an NAD+ booster, nicotinamide mononucleotide (NMN). METHODS: Male C57BL/6 mice (n=48) began NMN treatment (600 mg/kg daily) and GCR radiation exposure at six months of age. Mice (n=24) were exposed to GCR for 24 total days for a total dose of ~49.92 cGy before being shipped to Harvard Medical School for analysis. Between nine and 11.5 months of age, all mice underwent a series of behavioral assays. Learning and memory behaviors were assessed using the Barnes Maze test and measured by comparing time spent at the target hole and target quadrant. Anxiety and motility were assessed using the Open Field test and measured by comparing the % time spent in the center of the maze and total distances traveled. Dominance and aggression were assessed using the Tube Dominance test and measured in total number of bouts won by each mouse. RESULTS: Mice from all four groups showed no difference in percentage of time spent at the target hole or in percentage of time spent within the target quadrant, indicating that mouse learning and memory were unaffected by chronic GCR and NMN treatment. Mice from all four groups showed no difference in percentage of time spent in the center of the maze, or in total distance traveled, suggesting that mouse anxiety and motility were unaffected by chronic GCR and NMN treatment. Irradiated mice were found to be significantly more dominant than non-irradiated mice as determined by the Tube Dominance test. When comparing irradiated mice +/- NMN, it was found that NMN treated mice scored 90.9% lower in dominance. CONCLUSIONS: Behavioral results indicate very limited potential for neurological impairment by accurate, full-spectrum GCR in mice, however, further research is needed to confirm this. Mouse dominance behavior was found to be affected by GCR, suggesting future behavioral studies should include dominance and aggression analyses. NMN shows potential as a novel radioprotective agent that should be further investigated. / 2022-06-08T00:00:00Z

Social defeat is an ethologically relevant stressor that utilizes the natural establishment of social rank in male rodents and has been shown to be relevant to major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). In the present study, we wished to establish a social defeat stress model in combination with the chronic unpredictable stress model, which is considered a mild stressor to the rodent. In this way, we create a “double hit” model that may more accurately mimic severe stress that is common in both MDD and PTSD. In the present study, residents established dominance over the intruder for 10 consecutive days. In addition, social defeat stress was followed by another stressor given at random times during each day, i.e. chronic unpredictable stress. These unpredictable stressors included 30 min restraint, 1 h shaking/crowding, a cold water swim, a warm water swim or a tipped cage for 24 h. In one cohort of animals, brain tissue was taken 24 h after the last stressor for DNA. In a second cohort, animals were tested on a sucrose preference test in which two bottles containing 0.8% sucrose was placed on their cages for 3 consecutive days (days 8-10 of social defeat stress), and the total amount of sucrose was calculated relative to total volume consumed. Brain tissue analyses revealed significantly elevated DNA oxidation in white matter comparing stressed animals to non-stressed controls, consistent with what has been found in post-mortem white matter from MDD subjects. Further, animals given the social defeat + chronic unpredictable stress demonstrated a deficit in sucrose preference, a natural reward, revealing that these animals were anhedonic as compared to controls. Stressed animals also demonstrated fear of the intruder in a social interaction test performed one day after the social defeat/chronic unpredictable stress was complete. Therefore, it appears that social defeat plus chronic unpredictable stress produces a phenotype relevant to clinical data in humans.