Galpha(i2) inhibition of adenylate cyclase regulates presynaptic activity and unmasks cGMP-dependent long-term depression at Schaffer collateral-CA1 hippocampal synapses

Cyclic AMP signaling plays a central role in regulating activity at a number of synapses in the brain. We showed previously that pairing activation of receptors that inhibit adenylate cyclase (AC) and reduce the concentration of cyclic AMP, with elevation of the concentration of cyclic GMP is sufficient to elicit a presynaptically expressed form of LTD at Schaffer collateral-CA1 synapses in the hippocampus. To directly test the role of AC inhibition and G-protein signaling in LTD at these synapses, we utilized transgenic mice that express a mutant, constitutively active inhibitory G protein, Galpha(i2), in principal neurons of the forebrain. Transgene expression of Galpha(i2) markedly enhanced LTD and impaired late-phase LTP at Schaffer collateral synapses, with no associated differences in input/output relations, paired-pulse facilitation, or NMDA receptor-gated conductances. When paired with application of a type V phosphodiesterase inhibitor to elevate the concentration of intracellular cyclic GMP, constitutively active Galpha(i2) expression converted the transient depression normally caused by this treatment to an LTD that persisted after the drug was washed out. Moreover, this effect could be mimicked in control slices by pairing type V phosphodiesterase inhibitor application with application of a PKA inhibitor. Electrophysiological recordings of spontaneous excitatory postsynaptic currents and two-photon visualization of vesicular release using FM1-43 revealed that constitutively active Galpha(i2) tonically reduced basal release probability from the rapidly recycling vesicle pool of Schaffer collateral terminals. Our findings support the hypothesis that inhibitory G-protein signaling acts presynaptically to regulate release, and, when paired with elevations in the concentration of cyclic GMP, converts a transient cyclic GMP-induced depression into a long-lasting decrease in release.     

Activation of CB1 specifically located on GABAergic interneurons inhibits LTD in the lateral amygdala

Previously, we found that in the lateral amygdala (LA) of the mouse, WIN55,212-2 decreases both glutamatergic and GABAergic synaptic transmission via activation of the cannabinoid receptor type 1 (CB1), yet produces an overall reduction of neuronal excitability. This suggests that the effects on excitatory transmission override those on inhibitory transmission. Here we show that CB1 activation by WIN55,212-2 and Delta(9)-THC inhibits long-term depression (LTD) of basal synaptic transmission in the LA, induced by low-frequency stimulation (LFS; 900 pulses/1 Hz). The CB1 agonist WIN55,212-2 blocked LTD via G(i/o) proteins, activation of inwardly rectifying K+ channels (K(ir)s), inhibition of the adenylate cyclase-protein kinase A (PKA) pathway, and PKA-dependent inhibition of voltage-gated N-type Ca2+ channels (N-type VGCCs). Interestingly, WIN55,212-2 effects on LTD were abolished in CB1 knock-out mice (CB1-KO), and in conditional mutants lacking CB1 expression only in GABAergic interneurons, but were still present in mutants lacking CB1 in principal forebrain neurons. LTD induction per se was unaffected by the CB1 antagonist SR141716A and was normally expressed in CB1-KO as well as in both conditional CB1 mutants. Our data demonstrate that activation of CB1 specifically located on GABAergic interneurons inhibits LTD in the LA. These findings suggest that CB1 expressed on either glutamatergic or GABAergic neurons play a differential role in the control of synaptic transmission and plasticity.     

Semiotic Hypercycles Driving the Evolution of Language

The evolution of human symbolic capacity must have been very rapid even in some intermediate stage (e.g. the proto-symbolic behavior of Homo erectus). Such a rapid process requires a runaway model. The type of very selective and hyperbolically growing self-organization called “hypercyle” by Eigen and Schuster could explain the rapidity and depth of the evolutionary process, whereas traditional runaway models of sexual selection seem to be rather implausible in the case of symbolic evolution. We assume two levels: at the first level the species is adapted to ecological demands and accumulates the effects of this process in the genome. At the second level a kind of social/cultural knowledge is accumulated via a set of symbolic forms, one of which is language. Bühler’s model of three basic functions of signs can also be elaborated so that its cyclic structure becomes apparent. We assume that the hypercyclic process of semiosis and functional differentiation was triggered in 2 my BP (with the Homo erectus) and got more and more speed with the species Homo sapiens and later. The consequences for the evolutionary stratification of human languages will be drawn in the last section of the paper. The basic aim of the paper is to provide a semiotic (and not just a linguistic) explanation of the origin of language which can be linked to relevant models in evolutionary biology and which exploits the possibilities contained in self-organizing systems.

Exploring the impact of phonological awareness, visual–spatial working memory, and preschool quantity–number competencies on mathematics achievement in elementary school: Findings from a 3-year longitudinal study

This longitudinal study explored the importance of kindergarten measures of phonological awareness, working memory, and quantity–number competencies (QNC) for predicting mathematical school achievement in third graders (mean age 8 years 8 months). It was found that the impact of phonological awareness and visual–spatial working memory, assessed at 5 years of age, was mediated by early QNC, which predicted math achievement in third grade. Importantly, and confirming our isolated number words hypothesis, phonological awareness had no impact on higher numerical competencies (i.e., when number words needed to be linked with quantities [QNC Level II and above]) but predicted basic numerical competencies (i.e., when number words were isolated from quantities [QNC Level I]), explaining the moderate relationship between early literacy development and the development of mathematical competencies.     

Acting while perceiving: assimilation precedes contrast

To explore the nature of specific interactions between concurrent perception and action, participants were asked to move one of their hands in a certain direction while simultaneously observing an independent stimulus motion of a (dis)similar direction. The kinematics of the hand trajectories revealed a form of contrast effect (CE) in that the produced directions were biased away from the perceived directions ("Experiment 1"). Specifically, the endpoints of horizontal movements were lower when having watched an upward as opposed to a downward motion. However, when participants moved under higher speed constraints and were not presented with the stimulus motion prior to initiating their movements, the CE was preceded by an assimilation effect, i.e., movements were biased toward the stimulus motion directions ("Experiment 2"). These findings extend those of related studies by showing that CEs of this type actually correspond to the second phase of a bi-phasic pattern of specific perception-action interference.     

The easily learned,easily remembered heuristic in children

A previous study with adults [Koriat, A. (2008a). Easy comes, easy goes? The link between learning and remembering and its exploitation in metacognition. Memory & Cognition, 36, 416–428] established a correlation between learning and remembering: items requiring more trials to acquisition (TTA) were less likely to be recalled than those requiring fewer trials. Furthermore, learners’ judgments of learning (JOLs) seemed to rely on the easily learned, easily remembered (ELER) heuristic, that items requiring fewer TTAs are more likely to be recalled. This study extended investigation of these effects to 2nd- and 4th-grade children. When the list included hard and easy paired-associates (Experiment 1, N = 40, 7–10 years), recall and JOL decreased with increasing TTAs for both grades, supporting the validity of the ELER heuristic and its utilization in monitoring one's own learning. When presented only with hard pairs (Experiment 2, N = 60, 7–10 years), however, 4th graders’ but not 2nd graders’ JOLs evidenced reliance on this heuristic. The results suggest an early development of metacognitive heuristics that incorporate information about the links between characteristics of the encoding process and subsequent remembering.     

Die therapeutische Beziehung

The therapeutic relationship is deserving of special consideration. Both knowledge of the widely varying aspects of proposals in terms of possible relationship regulation and acquisition of the different forms of therapeutic relationship management are crucial for therapeutic success. Impact factors are used in the psychotherapeutic process (resource activation, problem activation, problem identification and problem solving), which are predominantly used in rapid succession or even simultaneously. This is also true of the relationship proposals intended and deployed by the therapist, which can also be conceptualised on the basis of impact factors. It has been shown that a single relationship quality can have very different mechanisms of action (e.g. on problem updating and identification). Successful therapeutic relationship regulation is characterized by high flexibility on the part of the therapist, who is able to move between the poles of understanding/confirmation, guidance/support and leadership/control. A good therapeutic relationship in terms of effecting an improvement in the patient is characterized according to the therapist’s flexibility as regards what he/she can offer in the relationship, a flexibility which can no longer be squarely attributed to one therapy discipline alone. In order to take the significance of the therapeutic relationship into account, the training and specific skills required for this need to be taught during training and supervision. A prerequisite to this, in addition to a sound theoretical training in the relevant aspects of relationship regulation, is relationship regulation skills in terms of both concept and own practical experience.     

Psychodynamische Diagnostik

The paper describes the development and objectives of psychoanalytic diagnostics. It shows that one of the key tasks of psychoanalytic/psychodynamic interviews is to initiate the doctor-patient relationship and that the patient’s motivation for treatment is to be examined and promoted in the interview. Different sources of information for the interview are then described; following a presentation of various systematic approaches of psychodynamic diagnostics, the principles of biographic history-taking are also explained. Modern psychodynamic diagnostics provides complex access to the patient, covering both elements of open interviewing and more exploratory approaches. Options for integrating these various methodological approaches are highlighted. Finally, more recent approaches in psychodynamic diagnostics that have a stronger relation to treatment planning are presented. These include the Structural Interview developed by Kernberg and Operationalised Psychodynamic Diagnostics (OPD).     

Career transitions and their causes: A country‐comparative perspective

This empirical paper investigates how individuals conceptualize causes of career transitions, focusing on the three European countries of Austria, Serbia, and Spain in comparison to the USA and China. Collectively, these countries represent four separate cultural regions according to Schwartz. Semi‐structured interviews were conducted with members of three occupational groups: business people, nurses, and blue‐collar workers. Analysis of the data generates greater insight about the existence of both region‐specific patterns as well as potentially universalistic tendencies regarding perceived causes of career transitions. Perceptions of internal (to the person) drivers of career transitions as activating forces are evident in all five countries. The overall results support contemporary notions of occupational careers that are highly individualized, a characterization strongly emphasized in the current career literature. In the European culture clusters, causes of career transitions are attributed internally and externally. China, representing the Confucian cultural region, stresses external causes for career transitions. By contrast, in the USA only internal attributions of causes are reported.