Changes in CDL Rules and Regulations and What It Means For You

The CDL application process is changing. The DOT’s Federal Motor Carrier Safety Administration (FMCSA) will now have a registry of approved trainers that entry-level truckers must use, Class A and Class B CDL applicants will have separate standards, and there are new requirements for certain endorsements. Potential drivers will have to wait longer to get in a truck and start making money, and for some the training will be cost-prohibitive. Join us for a discussion

Alternate Methods for Preserving Asphalt Pavements

Come hear how the city of Warsaw, Indiana, uses a “mix of fixes” to economically extend the life cycle of its road network while maintaining a safe and politically friendly high pavement condition index (PCI) number. The mixes include rejuvenation, slurry, micro, and crack sealing

Conquering the Fear of Liquids!!

In this session the City of Warsaw’s street superintendent shares his experiences with liquids, including making brine, anti-icing, deicing, and prewetting. Join us to boost your confidence level with regard to adding liquids to your winter maintenance toolbox

Synchronicity:The Role of Midbrain Dopamine in Whole-Brain Coordination

Midbrain dopamine seems to play an outsized role in motivated behavior and learning. Widely associated with mediating reward-related behavior, decision making, and learning, dopamine continues to generate controversies in the field. While many studies and theories focus on what dopamine cells encode, the question of how the midbrain derives the information it encodes is poorly understood and comparatively less addressed. Recent anatomical studies suggest greater diversity and complexity of afferent inputs than previously appreciated, requiring rethinking of prior models. Here, we elaborate a hypothesis that construes midbrain dopamine as implementing a Bayesian selector in which individual dopamine cells sample afferent activity across distributed brain substrates, comprising evidence to be evaluated on the extent to which stimuli in the on-going sensorimotor stream organizes distributed, parallel processing, reflecting implicit value. To effectively generate a temporally resolved phasic signal, a population of dopamine cells must exhibit synchronous activity. We argue that synchronous activity across a population of dopamine cells signals consensus across distributed afferent substrates, invigorating responding to recognized opportunities and facilitating further learning. In framing our hypothesis, we shift from the question of how value is computed to the broader question of how the brain achieves coordination across distributed, parallel processing. We posit the midbrain is part of an “axis of agency” in which the prefrontal cortex (PFC), basal ganglia (BGS), and midbrain form an axis mediating control, coordination, and consensus, respectively

High Fructose Corn Syrup Induces Metabolic Dysregulation and Altered Dopamine Signaling in the Absence of Obesity

The contribution of high fructose corn syrup (HFCS) to metabolic disorder and obesity, independent of high fat, energy-rich diets, is controversial. While high-fat diets are widely accepted as a rodent model of diet-induced obesity (DIO) and metabolic disorder, the value of HFCS alone as a rodent model of DIO is unclear. Impaired dopamine function is associated with obesity and high fat diet, but the effect of HFCS on the dopamine system has not been investigated. The objective of this study was to test the effect of HFCS on weight gain, glucose regulation, and evoked dopamine release using fast-scan cyclic voltammetry. Mice (C57BL/6) received either water or 10% HFCS solution in combination with ad libitum chow for 15 weeks. HFCS consumption with chow diet did not induce weight gain compared to water, chow-only controls but did induce glucose dysregulation and reduced evoked dopamine release in the dorsolateral striatum. These data show that HFCS can contribute to metabolic disorder and altered dopamine function independent of weight gain and high-fat diets

To Do or Not to Do: Dopamine, Affordability and the Economics of Opportunity

Five years ago, we introduced the thrift hypothesis of dopamine (DA), suggesting that the primary role of DA in adaptive behavior is regulating behavioral energy expenditure to match the prevailing economic conditions of the environment. Here we elaborate that hypothesis with several new ideas. First, we introduce the concept of affordability, suggesting that costs must necessarily be evaluated with respect to the availability of resources to the organism, which computes a value not only for the potential reward opportunity, but also the value of resources expended. Placing both costs and benefits within the context of the larger economy in which the animal is functioning requires consideration of the different timescales against which to compute resource availability, or average reward rate. Appropriate windows of computation for tracking resources requires corresponding neural substrates that operate on these different timescales. In discussing temporal patterns of DA signaling, we focus on a neglected form of DA plasticity and adaptation, changes in the physical substrate of the DA system itself, such as up- and down-regulation of receptors or release probability. We argue that changes in the DA substrate itself fundamentally alter its computational function, which we propose mediates adaptations to longer temporal horizons and economic conditions. In developing our hypothesis, we focus on DA D2 receptors (D2R), arguing that D2R implements a form of “cost control” in response to the environmental economy, serving as the “brain’s comptroller”. We propose that the balance between the direct and indirect pathway, regulated by relative expression of D1 and D2 DA receptors, implements affordability. Finally, as we review data, we discuss limitations in current approaches that impede fully investigating the proposed hypothesis and highlight alternative, more semi-naturalistic strategies more conducive to neuroeconomic investigations on the role of DA in adaptive behavior

The Rise and Fall of Dopamine: A Two-Stage Model of the Development and Entrenchment of Anorexia Nervosa

Dopamine has long been implicated as a critical neural substrate mediating anorexia nervosa (AN). Despite nearly 50 years of research, the putative direction of change in dopamine function remains unclear and no consensus on the mechanistic role of dopamine in AN has been achieved. We hypothesize two stages i n AN– corresponding to initial development and entrenchment– characterized by opposite changes in dopamine. First, caloric restriction, particularly when combined with exercise, triggers an escalating spiral of increasing dopamine that facilitates the behavioral plasticity necessary to establish and reinforce weight-loss behaviors. Second, chronic self-starvation reverses this escalation to reduce or impair dopamine which, in turn, confers behavioral inflexibility and entrenchment of now established AN behaviors. This pattern of enhanced, followed by impaired dopamine might be a common path to many behavioral disorders characterized by reinforcement learning and subsequent behavioral inflexibility. If correct, our hypothesis has significant clinical and research implications for AN and other disorders, such as addiction and obesity

Tonic Dopamine Modulates Exploitation of Reward Learning

The impact of dopamine on adaptive behavior in a naturalistic environment is largely unexamined. Experimental work suggests that phasic dopamine is central to reinforcement learning whereas tonic dopamine may modulate performance without altering learning per se; however, this idea has not been developed formally or integrated with computational models of dopamine function. We quantitatively evaluate the role of tonic dopamine in these functions by studying the behavior of hyperdopaminergic DAT knockdown mice in an instrumental task in a semi-naturalistic homecage environment. In this “closed economy” paradigm, subjects earn all of their food by pressing either of two levers, but the relative cost for food on each lever shifts frequently. Compared to wild-type mice, hyperdopaminergic mice allocate more lever presses on high-cost levers, thus working harder to earn a given amount of food and maintain their body weight. However, both groups show a similarly quick reaction to shifts in lever cost, suggesting that the hyperdominergic mice are not slower at detecting changes, as with a learning deficit. We fit the lever choice data using reinforcement learning models to assess the distinction between acquisition and expression the models formalize. In these analyses, hyperdopaminergic mice displayed normal learning from recent reward history but diminished capacity to exploit this learning: a reduced coupling between choice and reward history. These data suggest that dopamine modulates the degree to which prior learning biases action selection and consequently alters the expression of learned, motivated behavior

A Soluble C1b Protein and Its Regulation of Soluble Type 7 Adenylyl Cyclase†

Adenylyl cyclase (AC) is a prototypical cell-signaling molecule expressed in virtually all organisms from bacteria to man. While C1b, a poorly conserved region within mammalian AC, has been implicated in numerous isoform-specific regulatory properties, no one has purified the C1b region as a functional protein to homogeneity in order to study its role in enzyme function. We hypothesize that C1b is an internal regulatory subunit. To pursue this hypothesis, we constructed several soluble C1b proteins from type VII AC, arriving at one, 7C1b-S, which can be expressed and purified from Escherichia coli. 7C1b-S is relatively stable, as demonstrated by limited proteolytic analysis, circular dichroism, and UV Raman spectroscopy. Using size-exclusion chromatography and co-immunoprecipitation we demonstrate that 7C1b-S interacts with a cardinal activator of AC (Gsα) and with the conserved first catalytic domain (C1a) of type VII AC. We show that 7C1b-S inhibits Gsα-stimulated and Gsα-forskolin stimulated activity in our soluble ACVII model system. On the basis of these results, we suggest that 7C1b-S meets basic criteria to serve as a model protein for the C1b region and may be used as a prototype to develop other isoform C1b soluble model proteins to further investigate the role of this domain in isoform-specific regulation of adenylyl cyclase

Resistance Training and Milk-Substitution Enhance Body Composition and Bone Health in Adolescent Girls

Background: Increased soft-drink consumption has contributed to poor calcium intake with 90% of adolescent girls consuming less than the RDA for calcium. Purpose/objectives: The purpose of this investigation was to determine the independent and additive effects of two interventions (milk and resistance training) on nutrient adequacy, body composition, and bone health in adolescent girls. Methods: The experimental design consisted of four experimental groups of adolescent girls 14–17 years of age: (1) Milk + resistance training [MRT]; n = 15; (2) Resistance training only [RT]; n = 15; (3) Milk only [M] n = 20; (4) Control [C] n = 16. A few significant differences were observed at baseline between the groups for subject characteristics. Testing was performed pre and post-12 week training period for all groups. Milk was provided (3, 8 oz servings) for both the MRT and the M groups. The MRT group and the RT groups performed a supervised periodized resistance training program consisting of supervised one-hour exercise sessions 3 d/wk (M, W, F) for 12 wk. Baseline dietary data was collected utilizing the NUT-P-FFQ and/or a 120 item FFQ developed by the Fred Hutchinson Cancer Research Center (Seattle, Washington). Body composition was measured in the morning after an overnight fast using dual-energy X-ray absorptiometry (DXA) with a total body scanner (ProdigyTM, Lunar Corporation, Madison, WI). A whole body scan for bone density and lumbar spine scans were performed on all subjects. Maximal strength of the upper and lower body was assessed via a one-repetition maximum (1-RM) squat and bench press exercise protocols. Significance was set at P ≤ 0.05. Results: Significant differences in nutrient intakes between groups generally reflected the nutrient composition of milk with greater intakes of protein and improved nutrient adequacy for several B vitamins, vitamin A, vitamin D, calcium, magnesium, phosphorus, potassium, and zinc. Mean calcium intake was 758 and 1581 mg/d, in the non-milk and milk groups, respectively, with 100% of girls in the milk groups consuming \u3e RDA of 1300 mg/d. There were no effects of milk on body composition or muscle performance, but resistance training had a main effect and significantly increased body mass, lean body mass, muscle strength, and muscle endurance. There was a main effect of milk and resistance training on several measures of bone mineral density (BMD). Changes in whole body BMD in the M, RT, MRT, and CON were 0.45, 0.52, 1.32, and −0.19%, respectively (P \u3c 0.01). Conclusions: Over the course of 12 weeks the effects of 1300 mg/d of calcium in the form of fluid milk combined with a heavy resistance training program resulted in the additive effects of greater nutrient adequacy and BMD in adolescent girls. While further studies are needed, combining increased milk consumption with resistance training appears to optimize bone health in adolescent girls