A role for prefrontal calcium-sensitive protein phosphatase and kinase activities in working memory

The prefrontal cortex is involved in the integration and interpretation of information for directing thoughts and planning action. Working memory is defined as the active maintenance of information in mind and is thought to lie at the core of many prefrontal functions. Although dopamine and other neurotransmitters have been implicated, the intracellular events activated by their receptors that influence working memory are poorly understood. We demonstrate that working memory involves transient changes in prefrontal G(q/11)-signaling and in calcium-dependent intracellular protein phosphatase and kinase activity. Interestingly, inhibition of the calcium activated phosphatase calcineurin impaired, while calcium/calmodulin dependent kinase II (CaMKII) and calcium-dependent protein kinase C (PKC) enhanced, working memory. Our findings suggest that the active maintenance of information required for working memory involves transient changes in the balance of these enzymes' activities.     

Distinct prefrontal molecular mechanisms for information storage lasting seconds versus minutes

The prefrontal cortex (PFC) is known to actively hold information "online" for a period of seconds in working memory for guiding goal-directed behavior. It has been proposed that relevant information is stored in other brain regions, which is retrieved and held in working memory for subsequent assimilation by the PFC in order to guide behavior. It is uncertain whether PFC stores information outside the temporal limits of working memory. Here, we demonstrate that although enhanced cAMP-dependent protein kinase A (PKA) activity in the PFC is detrimental to working memory, it is required for performance in tasks involving conflicting representations when memory storage is needed for minutes. This study indicates that distinct molecular mechanisms within the PFC underlie information storage for seconds (working memory) and for minutes (short-term memory). In addition, our results demonstrate that short-term memory storage within the prefrontal cortex is required for guiding behavior in tasks with conflicts and provides a plausible mechanism by which the prefrontal cortex executes cognitive control.     

Intra-medial prefrontal administration of SCH-23390 attenuates ERK phosphorylation and long-term memory for trace fear conditioning in rats

The prefrontal cortex is known to be involved in the acquisition of trace conditioning, a higher-cognitive form of Pavlovian conditioning in which a conditioned stimulus and an unconditioned stimulus are separated by a time gap. We have recently reported that medial prefrontal (mPFC) extracellular-signal regulated kinase (Erk) phosphorylation is involved in the long-term memory storage of trace fear conditioning. Because of the important role dopamine D1 receptors play in prefrontal function, such as working memory, and due to evidence that dopamine D1 receptor activity can modulate plasticity, we investigated their role in prefrontal Erk phosphorylation following trace fear conditioning. We found that inhibition of dopamine D1 receptors through intra-mPFC infusion of SCH-23390 (1 microg/0.5 microL) 15 min prior to trace fear conditioning resulted in a decrease in training-related Erk phosphorylation. Additionally, pre-training intra-mPFC infusion of SCH-23390 also resulted in the impairment of long-term retention of CS-US association. These findings implicate mPFC dopamine D1 receptor activity in the storage of long-term memory for higher-cognitive associative tasks.     

Development of planning and its relation to other cognitive processes

The purpose of this study was to (a) delineate the course of development of children's planning skills during school years, (b) examine whether different levels of planning exist, and (c) explore the role of other cognitive processes as cognitive correlates of planning. The participants were 250 students, 50 from each of the five targeted grades (3, 5, 7, 9, and 11). They each completed a battery of planning, attention, and simultaneous and successive processing tasks. MANOVA indicated that the main effect of grade was significant, whereas gender had no significant effect on planning. Pairwise comparisons of performance means between grades indicated that developmental trajectories were not uniform across planning tasks. Correlation and regression analyses showed that the relationship between planning tasks and attention, and simultaneous and successive processing scores varied as a function of the planning task and the grade level. Furthermore, two planning factors were found and cluster analyses of variables indicated that one of the tasks, Crack-the-Code, may represent a different kind of planning than the other planning tasks used.     

A RELATIONSHIP BETWEEN SIMULTANEOUS-SUCCESSIVE SYNTHESIS AND CONCRETE OPERATIONAL THOUGHT

In two studies, performance in concrete operational tasks was related to individual differences in simultaneous-successive processing. Although the studies were carried out in culturally different populations (in Canada and in India), it was observed that children who prefer simultaneous to successive processing did better in the Piagetian tasks of conservation, transitive inference, and class inclusion. But performance in class inclusion appeared to be helped by both processes in the study in India. On the whole, rational as well as empirical reasons were found to claim that simultaneous processing is utilized in the successful solution of concrete operational tasks.     

Molecular activity underlying working memory

The prefrontal cortex is necessary for directing thought and planning action. Working memory, the active, transient maintenance of information in mind for subsequent monitoring and manipulation, lies at the core of many simple, as well as high-level, cognitive functions. Working memory has been shown to be compromised in a number of neurological and psychiatric conditions and may contribute to the behavioral and cognitive deficits associated with these disorders. It has been theorized that working memory depends upon reverberating circuits within the prefrontal cortex and other cortical areas. However, recent work indicates that intracellular signals and protein dephosphorylation are critical for working memory. The present article will review recent research into the involvement of the modulatory neurotransmitters and their receptors in working memory. The intracellular signaling pathways activated by these receptors and evidence that indicates a role for G(q)-initiated PI-PLC and calcium-dependent protein phosphatase calcineurin activity in working memory will be discussed. Additionally, the negative influence of calcium- and cAMP-dependent protein kinase (i.e., calcium/calmodulin-dependent protein kinase II (CaMKII), calcium/diacylglycerol-activated protein kinase C (PKC), and cAMP-dependent protein kinase A (PKA)) activities on working memory will be reviewed. The implications of these experimental findings on the observed inverted-U relationship between D(1) receptor stimulation and working memory, as well as age-associated working memory dysfunction, will be presented. Finally, we will discuss considerations for the development of clinical treatments for working memory disorders.     

An Evaluation of the Ability to Voluntarily Reduce the Heart Rate after a Month of Yoga Practice

The study aimed at determining whether novices to yoga would be able to reduce their heart rate voluntarily and whether the magnitude of reduction would be more after 30 days of yoga training. Two groups (yoga and control, n = 12 each) were assessed on Day 1 and on Day 30. During the intervening 30 days, the yoga group received training in yoga techniques while the control group carried on with their routine. At each assessment the baseline heart rate was recorded for one minute, this was followed by a six-minute period during which participants were asked to attempt to voluntarily reduce their heart rate, using any strategy. Both the baseline heart rate and the lowest heart rate achieved voluntarily during the six-minute period were significantly lower in the yoga group on Day 30 compared to Day 1 by a group average of 10.7 beats per minute (i.e., bpm) and 6.8 bpm, respectively (p < .05, Wilcoxon paired signed ranks test). In contrast, there was no significant change in either the baseline heart rate or the lowest heart rate achieved voluntarily in the control group on Day 30 compared to Day 1. The results suggest that yoga training can enable practitioners to use their own strategies to reduce the heart rate, which has possible therapeutic applications.