Endogenous dopamine regulates the rhythm of expression of the clock protein PER2 in the rat dorsal striatum via daily activation of D2 dopamine receptors.

A role for dopamine (DA) in the regulation of clock genes in the mammalian brain is suggested by evidence that manipulations of DA receptors can alter the expression of some clock genes outside the suprachiasmatic nucleus (SCN), the master circadian clock. The role of endogenous DA in the regulation of clock gene expression is unknown. Here, we demonstrate a direct relationship between extracellular DA levels and the rhythm of expression of the clock protein PERIOD2 (PER2) in the dorsal striatum of the male Wistar rat. Specifically, we show that the peak of the daily rhythm of extracellular DA in the dorsal striatum precedes the peak of PER2 by ∼6 h and that depletion of striatal DA by 6-hydroxydopamine or α-methyl-para-tyrosine or blockade of D(2) DA receptors by raclopride blunts the rhythm of striatal PER2. Furthermore, timed daily activation of D(2) DA receptors, but not D(1) DA receptors, restores and entrains the PER2 rhythm in the DA-depleted striatum. None of these manipulations had any effect on the PER2 rhythm in the SCN. Our findings are consistent with the idea that the rhythm of expression of PER2 in the dorsal striatum depends on daily dopaminergic activation of D(2) DA receptors. These observations may have implications for circadian abnormalities seen in Parkinson's disease.

Professional Development, Shifting Perspectives, and Instructional Change among Community College Anatomy and Physiology Instructors.

This paper presents community college (CC) instructors' responses to the Community College Anatomy and Physiology Educational Research (CAPER) project, a professional development program focused on active learning and educational research. We engage with conceptual change theory to better understand why and how CC instructors shifted their perspectives toward active learning. Qualitative data indicate that the participating CC instructors experienced pedagogical discontentment, leading to increased positive beliefs about active learning and educational research. In addition, we find that CC instructors have continued their pursuit of pedagogical change and educational research through communities of practice, which provide positive learning environments.

Some Believe, Not All Achieve: The Role of Active Learning Practices in Anxiety and Academic Self-Efficacy in First-Generation College Students.

First-generation college students face a variety of barriers in higher education compared with their continuing-generation peers. Active learning practices in STEM classrooms can potentially narrow the achievement gap by increasing academic self-efficacy, or confidence in academic abilities. However, these practices can also provoke anxiety in students. Given that anxiety can impair cognitive performance, we sought to understand how first-generation students perceive active learning practices and whether these perceptions affect the anticipated benefits of active learning. As part of a larger study on pedagogical practices in anatomy and physiology courses at the community college level, we asked students to rate various active learning techniques on how much each provoked anxiety and how much each contributed to their learning. All students (N = 186) rated some techniques as more anxiety-provoking than others (e.g., cold calling); however, compared to continuing-generation students, first-generation students' ratings tended to be higher. First-generation students anticipated doing more poorly in a course and attained lower final grades. Notably, the use of active learning practices did not improve first-generation students' academic self-efficacy: by the end of term, academic self-efficacy decreased in non-white first-generation students whereas other students showed little change. When introducing active learning strategies, instructors may need to proactively address underrepresented minority students' emotional reactions and ensure that all students experience success with these practices early in a course as a way to bolster academic self-efficacy.

Biological Clocks and Rhythms of Anger and Aggression.

The body's internal timekeeping system is an under-recognized but highly influential force in behaviors and emotions including anger and reactive aggression. Predictable cycles or rhythms in behavior are expressed on several different time scales such as circadian (circa diem, or approximately 24-h rhythms) and infradian (exceeding 24 h, such as monthly or seasonal cycles). The circadian timekeeping system underlying rhythmic behaviors in mammals is constituted by a network of clocks distributed throughout the brain and body, the activity of which synchronizes to a central pacemaker, or master clock. Our daily experiences with the external environment including social activity strongly influence the exact timing of this network. In the present review, we examine evidence from a number of species and propose that anger and reactive aggression interact in multiple ways with circadian clocks. Specifically, we argue that: (i) there are predictable rhythms in the expression of aggression and anger; (ii) disruptions of the normal functioning of the circadian system increase the likelihood of aggressive behaviors; and (iii) conversely, chronic expression of anger can disrupt normal rhythmic cycles of physiological activities and create conditions for pathologies such as cardiovascular disease to develop. Taken together, these observations suggest that a comprehensive perspective on anger and reactive aggression must incorporate an understanding of the role of the circadian timing system in these intense affective states.

Chronic buprenorphine reduces the response to sucrose-associated cues in non food-deprived rats.

The mechanisms through which buprenorphine (BUP), a mixed opioid agonist-antagonist, reduces both heroin and cocaine taking remain unclear. Evidence suggests that chronic exposure to BUP blunts drug seeking by attenuating the salience of drug-associated cues. Here, we examined the effect of chronic BUP treatment (osmotic minipumps, 3.0 mg/kg/day) in rats on responding for sucrose pellets and associated cues on FR1, FR5, and PR schedules and on extinction and reinstatement of sucrose seeking by sucrose priming. The effect of chronic BUP treatment on the dopamine (DA) response in the nucleus accumbens (NAc) to sucrose pellets and to lab chow was also measured using in vivo microdialysis. Whereas chronic BUP treatment had only a modest effect on pellet intake on the FR1 schedule, it significantly reduced responding at the outset of sessions and reduced lever pressing during sucrose-associated cue presentations. No effect was observed in the FR5 or PR schedules. BUP slightly reduced responding during extinction and significantly reduced reinstatement. Chronic BUP did not alter the NAc DA response to either sucrose pellets or lab chow, although it did significantly increase basal DA. Consistent with previous studies with heroin and cocaine, chronic BUP reduced responding in the presence of reward-related cues.

The aging clock: circadian rhythms and later life.

Circadian rhythms play an influential role in nearly all aspects of physiology and behavior in the vast majority of species on Earth. The biological clockwork that regulates these rhythms is dynamic over the lifespan: rhythmic activities such as sleep/wake patterns change markedly as we age, and in many cases they become increasingly fragmented. Given that prolonged disruptions of normal rhythms are highly detrimental to health, deeper knowledge of how our biological clocks change with age may create valuable opportunities to improve health and longevity for an aging global population. In this Review, we synthesize key findings from the study of circadian rhythms in later life, identify patterns of change documented to date, and review potential physiological mechanisms that may underlie these changes.

Neurodegeneration and the Circadian Clock.

Despite varied etiologies and symptoms, several neurodegenerative diseases-specifically, Alzheimer's (AD), Parkinson's (PD), and Huntington's diseases (HDs)-share the common feature of abnormal circadian rhythms, such as those in behavior (e.g., disrupted sleep/wake cycles), physiological processes (e.g., diminished hormone release) and biochemical activities (e.g., antioxidant production). Circadian disturbances are among the earliest symptoms of these diseases, and the molecular mechanisms of the circadian system are suspected to play a pivotal, and possibly causal, role in their natural histories. Here, we review the common circadian abnormalities observed in ADs, PDs and HDs, and summarize the evidence that the molecular circadian clockwork directly influences the course of these disease states. On the basis of this research, we explore several circadian-oriented interventions proposed as treatments for these neurological disorders.

Effects of bilateral anterior agranular insula lesions on food anticipatory activity in rats.

Food anticipatory activity (FAA) refers to a daily rhythm of locomotor activity that emerges under conditions of food restriction, whereby animals develop an intense, predictable period of activity in the few hours leading up to a predictable, daily delivery of food. The neural mechanisms by which FAA is regulated are not yet fully understood. Although a number of brain regions appear to be involved in regulating the development and expression of FAA, there is little evidence to date concerning the role of the anterior agranular insular cortex (AICa). The AICa plays a critical role in integrating the perception of visceral states with motivational behaviour such as feeding. We assessed the effect of bilateral electrolytic or ibotenic acid lesions of the AICa on FAA in male Wistar rats receiving food for varying lengths of time (2 h, 3 h, or 5 h) during the middle of the light phase (starting at either ZT4 or ZT6). Contrary to our initial expectations, we found that both electrolytic and ibotenic acid lesions significantly increased, rather than decreased, the amount of FAA expressed in lesioned rats. Despite increased FAA, lesioned rats did not eat significantly more during restricted feeding (RF) periods than control rats. Similar to controls, AlCa-lesioned rats showed negligible anticipatory activity to a restricted treat suggesting that the increased anticipatory activity in lesioned rats is associated with food restriction, rather than the appetitive value of the meal. Monitoring behaviour in an open field indicated that increased FAA in AlCa-lesioned rats was not explained by a general increase in locomotor activity. Together, these findings suggest that the AICa contributes to the network of brain regions involved in FAA.

Reward and aversive stimuli produce similar nonphotic phase shifts.

Circadian rhythms in rodents respond to arousing, nonphotic stimuli that contribute to daily patterns of entrainment. To examine whether the motivational significance of a stimulus is important for eliciting nonphotic circadian phase shirts in Syrian hamsters (Mesocricetus auratus), the authors compared responses to a highly rewarding stimulus (lateral hypothalamic brain stimulation reward [BSR]) and a highly aversive stimulus (footshock). Animals were housed on a 14:10-hr light-dark cycle until test day, when they were given a 1-hr BSR session (trained animals) or a 1-mA electric footshock at 1 of 8 circadian times, and were maintained in constant dark thereafter. Both BSR pulses and footshock produced nonphotic phase response curves. These results support the hypothesis that arousal resulting from the motivational significance of a stimulus is a major factor in nonphotic phase shifts.

Global depletion of dopamine using intracerebroventricular 6-hydroxydopamine injection disrupts normal circadian wheel-running patterns and PERIOD2 expression in the rat forebrain.

Normal circadian rhythms of behavior are disrupted in disorders involving the dopamine (DA) system, such as Parkinson's disease. We have reported previously using unilateral injections of the catecholamine toxin, 6-hydroxydopamine (6-OHDA), into the medial forebrain bundle that DA signaling regulates daily expression of the clock protein, PERIOD2 (PER2), in the dorsal striatum of the rat. In the present study, we made widespread lesions of DA fibers using large injections of 6-OHDA into the third ventricle to determine the involvement of DA in normal daily rhythms of wheel-running activity and PER2 patterns in the suprachiasmatic nucleus (SCN) and several regions of the limbic forebrain. Rats injected with 6-OHDA and housed in constant darkness were less active in the wheel and showed a disorganized pattern of activity in which wheel running was not confined to a specific phase over 24 h. The 6-OHDA injection had no effect on the daily PER2 pattern in the SCN, but blunted the normal rise in PER2 in the dorsal striatum. 6-OHDA also blunted PER2 expression in the periventricular nucleus of the hypothalamus, a region in which a daily PER2 pattern has not been previously reported in male rats, and in the oval nucleus of the bed nucleus of the stria terminalis, but not in the central nucleus of the amygdala. These results indicate that DA plays a prominent role in regulating circadian activity at both behavioral and molecular levels.

Interference control in a new rule use task: age-related changes, labeling, and attention.

Three experiments examined 3- to 6-year-olds' interference control using a task in which children saw 2 corresponding sets of colored cards, a large set in front of them and a small set behind them. A colored candy (Smartie) was placed on a large card with mismatching color, and children could win the Smartie by selecting the small card that matched the color of the large card. Three-year-olds performed poorly whereas older children performed well. Having children label the correct color before responding improved 3-year-olds' performance (Experiment 2), as did pointing to the large card (Experiment 3); decreasing the affective salience of the stimuli (colored beads vs. Smarties) did not (Experiment 3). Results reveal the role of selective attention in action control.