Student Evaluation of a Learning Community Model Adapted to Student and Curriculum Needs.

The Neuroscience Learning Community (LC) that Stonehill introduced to its curriculum grew out of the Great Recession of 2008 and the need for our students to gain hands-on, high-impact learning experiences, despite limited resources. This learning model was first reported in 2013, and since then it has undergone changes that were necessary due to the number of credits and amount of time required for that model. Curriculum changes are common, and Stonehill College changed its credit requirements for LCs to meet students' needs. As a result, the new Neuroscience LC model that we describe here reduced credit hours while leveraging new faculty expertise, collaborations, and new community partnerships. This paper reports student evaluations of an LC model adapted to demand fewer credits and less time, but to retain the community-based learning aspect and to increase faculty collaboration, while maintaining a high standard of learning fundamental neuroscience topics. Evaluations suggest that students valued the updated Neuroscience LC because it helped them understand neuroscience concepts and the impact of neuroscience in our world.

A rodent cage change insomnia model disrupts memory consolidation.

Insomnia involves disruption of sleep initiation, maintenance and/or overall quality, and may interfere with cognition. Here, we evaluated memory impairment produced by rodent mild (acute) insomnia models. Insomnia models consisted of either single or repeated exposure to cages previously occupied (dirtied) by an unfamiliar rat for 5-7 days. Rats were trained in the Morris water maze to remember the platform location (acquisition), and were then exposed to: (a) 6 hr of undisturbed baseline; (b) dirty cage change-induced insomnia (animal placed into a cage dirtied by another rat for 6 hr); or (c) double-dirty cage change-induced insomnia (animal placed into a cage dirtied by another rat for 3 hr, and then another dirty cage 3 hr later). The animal's memory for the platform location was then evaluated in a probe trial. Double-dirty cage change-induced insomnia significantly disrupted sleep, although the effects of dirty cage change-induced insomnia were overall not significant. In the fourth hour of double-dirty cage change-induced insomnia (following the second cage change), sleep episode number and duration alterations indicated sleep fragmentation. Furthermore, power spectral analysis revealed diminished wake and, to a lesser extent, rapid eye movement theta power (indicated by trend difference) in the last 3 hr of exposure. Significant deficits were noted for measures of water maze performance following double-dirty cage change-induced insomnia, indicating impaired memory. In summary, one variant of the rodent insomnia model, double-dirty cage change-induced insomnia, disrupted sleep and attenuated memory consolidation, indicating this paradigm may be useful to evaluate the effects of hypnotics on memory consolidation.

Partnerships in Neuroscience Research Between Small Colleges and Large Institutions: A Case Study.

There are advantages and limitations associated with a science, technology, engineering and math (STEM) education at small, liberal arts colleges relative to larger universities. While there may be increased opportunity for personal attention and access to faculty, students at liberal arts colleges may not always have the opportunity to gain experience with state-of-the-art equipment and technology. Herein, we describe a case study of an inter-institutional partnership between Stonehill College and two neuroscience research laboratories which are part of the Veterans Affairs Boston Healthcare System (VABHS). Both laboratories are affiliated with Harvard Medical School (HMS). We discuss the benefits as well as the challenges associated with the development and maintenance of this partnership. The experience with the use of sophisticated instrumentation and technology available in these laboratories may give students a competitive edge when applying to graduate school programs. However, we contend that the most important advantage of this research experience is the development of a sense of self-esteem and professional competence that will allow students to meet the many challenges that lie ahead in graduate school and beyond.

Handedness and lateralised tympanic membrane temperature in relation to approach-avoidance behaviour in Garnett's bushbaby (Otolemur garnettii).

Studies of handedness suggest a relationship between hemispheric specialisation and emotional processing. Recently measures of lateralised tympanic membrane temperature (TMT) have identified similar relationships (i.e., the left hemisphere is involved in approach behaviour and the right hemisphere avoidance behaviour). In the present study we examined lateralised changes in TMT in response to social interaction in 10 Garnett's bushbabies. Additionally, we examined whether handedness could be used as a predictor of approach-avoidance tendencies. We found a positive association between temperature change and both allogrooming and affiliative approach. Social behaviour did not differ between right- and left-handed bushbabies. These findings are discussed in terms of existing theories of asymmetric emotional processing. Overall, the data suggest that there is a left hemisphere specialisation for processing approach-related behaviours, which is consistent with existing models of lateralised emotional processing. Our data also indicate that TMT is a reliable, cost-effective measure of cerebral activation that is less invasive and more practical than alternative measures such as EEG, PET, and fMRI.

Community-based, Experiential Learning for Second Year Neuroscience Undergraduates.

Service learning is becoming a keystone of the undergraduate learning experience. At Stonehill College, we implemented a service learning course, called a Learning Community, in Neuroscience. This course was created to complement the basic research available to Stonehill Neuroscience majors with experience in a more applied and "clinical" setting. The Neuroscience Learning Community is designed to promote a deep understanding of Neuroscience by combining traditional classroom instruction with clinical perspectives and real-life experiences. This Neuroscience Learning Community helps students translate abstract concepts within the context of neurodevelopment by providing students with contextual experience in a real-life, unscripted setting. The experiential learning outside of the classroom enabled students to participate in informed discussions in the classroom, especially with regard to neurodevelopmental disorders. We believe that all students taking this course gain an understanding of the importance of basic and applied Neuroscience as it relates to the individual and the community. Students also have used this concrete, learning-by-doing experience to make informed decisions about career paths and choice of major.

Chronic ramelteon treatment in a mouse model of Alzheimer's disease.

Prior research has reported beneficial effects of melatonin in rodent models of Alzheimer's disease (AD). This study evaluated the effect of ramelteon (Rozerem, a melatonin receptor agonist) on spatial learning & memory and neuropathological markers in a transgenic murine model of AD (the B6C3-Tg(APPswe,PSEN1dE9)85Dbo/J transgenic mouse strain; hereafter 'AD mice'). Three months of daily ramelteon treatment (~3mg/kg/day), starting at 3 months of age, did not produce an improvement in the cognitive performance of AD mice (water maze). In contrast to wild-type control mice, AD mice did not show any evidence of having learned the location of the escape platform. The cortex and hippocampus of AD mice contained significant quantities of beta-amyloid plaques and PARP-positive (poly ADP ribose polymerase) cells, indicating apoptosis. Six months of ramelteon treatment, starting at 3 months of age, did not produce any change in these neuropathological markers. The ability of long term melatonin treatment to improve cognition and attenuate neuropathology in AD mice did not generalize to this dosage of ramelteon.

Role of the locus coeruleus and basal forebrain in arousal and attention.

Experimental evidence has implicated multiple neurotransmitter systems in either the direct or indirect modulation of cortical arousal and attention circuitry. In this review, we selectively focus on three such systems: 1) norepinephrine (NE)-containing neurons of the locus coeruleus (LC), 2) acetylcholine (ACh)-containing neurons of the basal forebrain (BF), and 3) parvalbumin (PV)-containing gamma-aminobutyric acid neurons of the BF. Whereas BF-PV neurons serve as a rapid and transient arousal system, LC-NE and BF-ACh neuromodulation are typically activated on slower but longer-lasting timescales. Recent findings suggest that the BF-PV system serves to rapidly respond to even subtle sensory stimuli with a microarousal. We posit that salient sensory stimuli, such as those that are threatening or predict the need for a response, will quickly activate the BF-PV system and subsequently activate both the BF-ACh and LC-NE systems if the circumstances require longer periods of arousal and vigilance. We suggest that NE and ACh have overlapping psychological functions with the main difference being the precise internal/environmental sensory situations/contexts that recruit each neurotransmitter system - a goal for future research to determine. Implications of dysfunction of each of these three attentional systems for our understanding of neuropsychiatric conditions are considered. Finally, the contemporary availability of research tools to selectively manipulate and measure the activity of these distinctive neuronal populations promises to answer longstanding questions, such as how various arousal systems influence downstream decision-making and motor responding.

The cognitive cost of sleep lost.

A substantial body of literature supports the intuitive notion that a good night's sleep can facilitate human cognitive performance the next day. Deficits in attention, learning & memory, emotional reactivity, and higher-order cognitive processes, such as executive function and decision making, have all been documented following sleep disruption in humans. Thus, whilst numerous clinical and experimental studies link human sleep disturbance to cognitive deficits, attempts to develop valid and reliable rodent models of these phenomena are fewer, and relatively more recent. This review focuses primarily on the cognitive impairments produced by sleep disruption in rodent models of several human patterns of sleep loss/sleep disturbance. Though not an exclusive list, this review will focus on four specific types of sleep disturbance: total sleep deprivation, experimental sleep fragmentation, selective REM sleep deprivation, and chronic sleep restriction. The use of rodent models can provide greater opportunities to understand the neurobiological changes underlying sleep loss induced cognitive impairments. Thus, this review concludes with a description of recent neurobiological findings concerning the neuroplastic changes and putative brain mechanisms that may underlie the cognitive deficits produced by sleep disturbances.

The Dual Orexin Receptor Antagonist DORA-22 Improves Mild Stress-induced Sleep Disruption During the Natural Sleep Phase of Nocturnal Rats.

Dual orexinergic antagonists (DORAs) have been recently developed as a pharmacotherapy alternative to established hypnotics. Hypnotics are largely evaluated in preclinical rodent models in the dark/active period yet should be ideally evaluated in the light/inactive period, analogous to when sleep disruption occurs in humans. We describe here the hypnotic efficacy of DORA-22 in rodent models of sleep disturbance produced by cage changes in the light/inactive period. Rats were administered DORA-22 or the GABA receptor-targeting hypnotic eszopiclone early in the light period, then exposed to six hourly clean cage changes with measurements of NREM sleep onset latency. Both compounds initially promoted sleep (hours 1 and 2), with DORA-22 exhibiting a more rapid hypnotic onset; and exhibited extended efficacy, evident six hours after administration in a sleep latencies test. A common complaint concerning hypnotic use is lingering hypersomnolence, and this is a concern in pharmacotherapy of the elderly. A second study was designed to determine a minimal dose of DORA-22 which would initially promote sleep but exhibit minimal extended hypnotic effect.Animals were administered DORA-22, then exposed for six hours to a single cage previously dirtied by a conspecific, followed by return to home cage. EEG measures indicated that all DORA-22 doses largely promoted sleep in the first hour. The lowest dose (1 mg/kg) did not decrease sleep onset latency at the six-hour timepoint, suggesting no residual hypersomnolence. We described here DORA-22 hypnotic efficacy during the normal sleep period of nocturnal rats, and demonstrate that well-chosen (low) hypnotic doses of DORA-22 may be hypnotically effective yet have minimal lingering effects.

Characterization of basal forebrain glutamate neurons suggests a role in control of arousal and avoidance behavior.

The basal forebrain (BF) is involved in arousal, attention, and reward processing but the role of individual BF neuronal subtypes is still being uncovered. Glutamatergic neurons are the least well-understood of the three main BF neurotransmitter phenotypes. Here we analyzed the distribution, size, calcium-binding protein content and projections of the major group of BF glutamatergic neurons expressing the vesicular glutamate transporter subtype 2 (vGluT2) and tested the functional effect of activating them. Mice expressing Cre recombinase under the control of the vGluT2 promoter were crossed with a reporter strain expressing the red fluorescent protein, tdTomato, to generate vGluT2-cre-tdTomato mice. Immunohistochemical staining for choline acetyltransferase and a cross with mice expressing green fluorescent protein selectively in GABAergic neurons confirmed that cholinergic, GABAergic and vGluT2+ neurons represent distinct BF subpopulations. Subsets of BF vGluT2+ neurons expressed the calcium-binding proteins calbindin or calretinin, suggesting that multiple subtypes of BF vGluT2+ neurons exist. Anterograde tracing using adeno-associated viral vectors expressing channelrhodopsin2-enhanced yellow fluorescent fusion proteins revealed major projections of BF vGluT2+ neurons to neighboring BF cholinergic and parvalbumin neurons, as well as to extra-BF areas involved in the control of arousal or aversive/rewarding behavior such as the lateral habenula and ventral tegmental area. Optogenetic activation of BF vGluT2+ neurons elicited a striking avoidance of the area where stimulation was given, whereas stimulation of BF parvalbumin or cholinergic neurons did not. Together with previous optogenetic findings suggesting an arousal-promoting role, our findings suggest that BF vGluT2 neurons play a dual role in promoting wakefulness and avoidance behavior.

The dual orexinergic receptor antagonist DORA-22 improves the sleep disruption and memory impairment produced by a rodent insomnia model.

Insomnia-related sleep disruption can contribute to impaired learning and memory. Treatment of insomnia should ideally improve the sleep profile while minimally affecting mnemonic function, yet many hypnotic drugs (e.g. benzodiazepines) are known to impair memory. Here, we used a rat model of insomnia to determine whether the novel hypnotic drug DORA-22, a dual orexin receptor antagonist, improves mild stress-induced insomnia with minimal effect on memory. Animals were first trained to remember the location of a hidden platform (acquisition) in the Morris Water Maze and then administered DORA-22 (10, 30, or 100 mg/kg doses) or vehicle control. Animals were then subjected to a rodent insomnia model involving two exposures to dirty cages over a 6-hr time period (at time points 0 and 3 hr), followed immediately by a probe trial in which memory of the water maze platform location was evaluated. DORA-22 treatment improved the insomnia-related sleep disruption-wake was attenuated and NREM sleep was normalized. REM sleep amounts were enhanced compared with vehicle treatment for one dose (30 mg/kg). In the first hour of insomnia model exposure, DORA-22 promoted the number and average duration of NREM sleep spindles, which have been previously proposed to play a role in memory consolidation (all doses). Water maze measures revealed probe trial performance improvement for select doses of DORA-22, including increased time spent in the platform quadrant (10 and 30 mg/kg) and time spent in platform location and number of platform crossings (10 mg/kg only). In conclusion, DORA-22 treatment improved insomnia-related sleep disruption and memory consolidation deficits.

Assessing sleepiness in the rat: a multiple sleep latencies test compared to polysomnographic measures of sleepiness.

Sleepiness following 6 h of sleep deprivation (SD) was evaluated with a rat multiple sleep latencies test (rMSLT), and the findings were compared to conventional polysomnographic measures of sleepiness. The 6 h of SD was produced by automated activity wheels, and was terminated at either the end of the light period or at the beginning of the dark period. The rMSLT consisted of 5 min wakefulness induced by sensory stimulation followed by 25 min of freedom to sleep. This procedure was repeated every 30 min for 3 h and was designed to minimize the amount of sleep lost due to the testing procedure. In separate rats, 6 h SD was followed by undisturbed recovery, allowing evaluation of conventional polysomnographic measures of sleepiness. Sleep onset latencies were reduced following SD, with recovery in the light (baseline = 8 min, 3 s versus post-SD = 1 min, 17 s) and dark period (baseline = 14 min, 17 s versus 7 min, 7 s). Sleep onset latencies were not altered by varying the duration criterion for the first sleep bout (i.e., sleep bout length criteria of 10, 20, 30, or 60 s were compared). Polysomnographic variables (non-rapid eye movement sleep episode duration, delta power, and number of awakenings) also provided reliable indirect measures of sleepiness, regardless of whether the recovery sleep occurred in the light or dark period. Evaluation of effect size indicated that the rMSLT was a strong measure of sleepiness, and was influenced by homeostatic, circadian, and illumination factors. The rMSLT provided a simple, objective, robust and direct measure of sleepiness that was as effective as conventional polysomnographic measures of sleepiness.

Experimental sleep fragmentation impairs attentional set-shifting in rats.

STUDY OBJECTIVE: To evaluate the effect of experimental sleep fragmentation (sleep interruption; SI) on complex learning in an intradimensional-extradimensional (ID/ED) set-shifting task in rats. DESIGN: A sleep fragmentation paradigm of intermittent forced locomotion was validated in adult rats by examining electrographic effects. Discrimination task performances were assessed in rats following sleep fragmentation or 2 control conditions. PARTICIPANTS: 41 young adult male Fischer-Norway rats. INTERVENTION: A treadmill was used to produce 30 awakenings/h for the 24-h period prior to testing. Exercise control rats received an equivalent amount of treadmill-induced locomotion that permitted 30-minute pauses to allow consolidated sleep. MEASUREMENT AND RESULTS: SI rats were selectively impaired on the extradimensional-shift phase of the task, taking significantly more trials to achieve criterion performance (15.4 +/- 2.0) than either control group (cage control = 10.4 +/- 0.9; exercise control = 6.3 +/- 0.2). The SI schedule reduced the average duration of nonREM sleep (NREMS) episodes to 56 s (baseline = 182 s), while the exercise control group increased average NREMS episode duration to 223 s. Total (24-h) NREMS time declined from 50% during baseline to 33% during SI, whereas rapid eye movement sleep (REMS) was absent in SI animals (7% during baseline and 0% during SI), and time spent awake increased proportionally (from 43% during baseline to 67% during SI). CONCLUSION: 24-hour SI produced impairment in an attentional set-shifting that is comparable to the executive function and cognitive deficits observed in humans with sleep apnea or after a night of experimental sleep fragmentation.

Cortisol response to relocation stress in Garnett's bushbaby (Otolemur garnettii).

Relocation of research animals, either within a facility or from one facility to another, is assumed to be stressful. Development of appropriate research methodologies may be facilitated by understanding the extent and duration of the physiological response to relocation stress and whether the stress can be buffered by environmental or social factors, such as the presence of a cagemate. To characterize the response to relocation stress in Garnett's bushbaby, we assessed cortisol concentrations in nine female and six male bushbabies during relocation to a different facility; six of the animals were pair-housed at the time of the move and were moved with their respective cagemates. Fecal cortisol was assessed at three time points: 1) baseline (1 day prior to moving); 2) relocation (the day the animals were relocated); and 3) post-relocation (7 days after relocation). Cortisol concentrations were higher at the relocation time point than at baseline and post-relocation, which did not differ. Cortisol concentration did not differ as a function of having a cagemate during relocation. Although relocation resulted in a significant (P < 0.05) increase in cortisol excretion concentration, the levels returned to baseline within 7 days after the stressor.

A re-evaluation of the role of tetrahydropapaveroline in ethanol consumption in rats.

The role of tetrahydropapaveroline (THP), a condensation product of a dopaldehyde with dopamine, in the regulation of alcohol consumption was investigated. In the first experiment, rats received intraventricular injections of either racemic THP hydrobromide (0.65 or 1.3 microg/microl), R-(+)-THP (0.66 or 1.4 microg/microl), or an equal volume of vehicle. The lower doses of both (+/-)-THP and (+)-THP significantly increased volitional alcohol intake. For the racemic compound, the increase was significant at 7-13% concentrations. The R-(+)-enantiomer increased consumption at 4-11 and 15-20% concentrations of ethanol. The higher doses of both compounds did not significantly alter alcohol preference. A second experiment evaluated the chronic effect of THP delivered subcutaneously via osmotic minipump. Animals receiving THP (0.1, 0.5, 1.0, 2.0, and 4.0 mg/ml) did not differ in their alcohol intake, compared to vehicle-treated controls. Whether or not endogenously formed THP participates in the etiology of alcohol addiction remains unclear. Nonetheless, there are few known compounds that induce a preference for unsweetened alcohol solutions over water in laboratory animals.

Modafinil facilitates performance on a delayed nonmatching to position swim task in rats.

Modafinil is a wake-promoting drug approved by the FDA for the treatment of narcolepsy. Recent evidence suggests that modafinil may improve learning and memory processes. To further evaluate possible cognitive properties associated with modafinil, male Sprague-Dawley rats were tested in a delayed nonmatching to position (DNMTP) task. A modified water maze allowed animals to make one of two choices for the location of the escape platform. Each trial consisted of two swims. On the information swim (IS), only one choice was open to the animal for escape. One minute later, a choice swim (CS) presented the animal with two choices with the escape platform in the opposite position. There were 10 trials per day for 10 days. Rats received 0, 30, 55, or 100 mg/kg ip of modafinil 30 min prior to testing. Locomotor activity was also assessed. Animals that received 55 and 100 mg/kg made significantly more correct choices, indicating that higher doses of modafinil learned the task faster than did controls. While animals that received 100 mg/kg did exhibit an enhancement of locomotor activity, this effect did not result in more efficient goal-directed behavior. The evidence is consistent with previous research showing that modafinil facilitates cognitive processes.

Ginkgo biloba extract: cognitive enhancer or antistress buffer.

Constituents extracted from the leaves of the Ginkgo biloba tree possess beneficial properties that may buffer the aging nervous system from deterioration due to oxidative stress. In the present investigation, a standardized extract of G. biloba (EGb 761) or an equal volume of the vehicle was administered (100 mg/kg/day) to senescent (20-month) C57BL/6 male mice for up to 82 consecutive days. Animals were tested twice in the Morris water maze (MWM) after 28 and 70 days of treatment. No differences were observed in acquisition or retention of performance on the water maze. Elevated-plus maze (EPM) trials were conducted prior to and subsequent to the chronic treatment regimen. Marked baseline differences in plus-maze performance were present in the first experiment. A second experiment used a matched-pairs design to minimize preexisting differences. Results supported the hypothesis that EGb 761 may serve as an antistress buffer, attenuating the increase in anxiety typically observed in animals after cold water exposure. Tissue samples from the hippocampus and cortex were analyzed by Western blot for the transcription factor cyclic-AMP response element binding (CREB) protein. EGb 761 had no significant effect on immunoreactivity to CREB from either the hippocampus or the cerebral cortex.

Chronic sleep restriction impairs spatial memory in rats.

Although numerous experimental investigations have evaluated the neurobehavioral effects of either short periods of total sleep deprivation or selective rapid eye movement sleep deprivation, few studies have examined the effects of chronic sleep restriction (CSR). Long-Evans rats were deprived of sleep by the automated movement of activity wheels for 18 h/day for 5 consecutive days from 16:00 to 10:00 h, and were allowed 6 h/day of sleep opportunity (10:00-16:00 h; lights on from 10:00 to 22:00 h). Activity wheels were intermittently activated on a 3 s on : 12 s off schedule for the CSR condition, whereas a schedule of 36 min of continuous wheel movement in every 3 h was used for a cage movement control condition. A cross-over design was used with rats serving in both the CSR and the movement control conditions with 2 days of rest between conditions. Water maze acquisition training occurred at 16:00 h immediately after the 6-h sleep opportunity on each of the first 4 days, followed by a probe trial on day 5 to assess spatial memory recall. Although the rate of learning/acquisition was not affected by the daily 18 h of CSR, the day 5 recall of the platform location was impaired on three different probe trial measures. Thus, CSR impaired spatial memory, but did not affect the rate of learning/acquisition in the water maze.

Risk of obstructive sleep apnea lower in double reed wind musicians.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is caused by a collapse of the upper airway. Respiratory muscle training with a wind instrument (didgeridoo) in patients with moderate OSA has been previously shown to improve OSA symptomology. However, a survey of orchestra members did not indicate a difference in OSA risk between wind and non-wind instrumentalist. The present study examines whether playing of different wind instrument types may affect the risk of OSA. METHODS: A national sample of active musicians (n = 906) was surveyed through the internet. Participants' risk for OSA was determined by the Berlin Questionnaire. Additional survey items included questions about general health and musical experience. RESULTS: A binary logistic regression was conducted to determine if OSA risk was predicted by gender, age, number of years playing instrument, number of hours per week playing instrument, and instrument type. Musicians who played a double reed instrument had a lower risk of OSA (p = 0.047) than non-wind instrumentalists. Additionally, in double reed instrumentalists, the number of hours spent playing the instrument predicted lower OSA risk (p = 0.020). The risk for OSA in other wind instruments (i.e., single reed, high brass, and low brass) was not significantly different from non-wind musicians. CONCLUSIONS: Playing a double reed musical instrument was associated with a lower risk of OSA.

Sex differences on the judgment of line orientation task: a function of landmark presence and hormonal status.

It has been well-established that men outperform women on some spatial tasks. The tools commonly used to demonstrate this difference (e.g. The Mental Rotations Task) typically involve problems and solutions that are presented in a context devoid of referents. The study presented here assessed whether the addition of referents (or "landmarks") would attenuate the well-established sex difference on the judgment of line orientation task (JLOT). Three versions of the JLOT were presented in a within design. The first iteration contained the original JLOT (JLOT 1). JLOT 2 contained three "landmarks" or referents and JLOT 3 contained only one landmark. The sex difference on JLOT 1 was completely negated by the addition of three landmarks on JLOT 2 or the addition of one landmark on JLOT3. In addition, salivary testosterone was measured. In men, gains in performance on the JLOT due to the addition of landmarks were positively correlated with testosterone levels. This suggests that men with the highest testosterone levels benefited the most from the addition of landmarks. These data help to highlight different strategies used by men and women to solve spatial tasks.