Attachment--and loss.

LTP and LTD: an embarrassment of riches.

The principles of classification and a classification of mammals. Bulletin of the AMNH ; v. 85

Synaptic plasticity: multiple forms, functions, and mechanisms.

Tasken, Kjetil, and Einar Martin Aandahl. Localized Effects of cAMP Mediated by Distinct Routes of Protein Kinase A. Physiol Rev 84: 137–167, 2004; 10.1152/physrev.00021.2003.—More than 20% of the ...

https://www.physiology.org/doi/pdf/10.1152/physrev.00021.2003

Localized Effects of cAMP Mediated by Distinct Routes of Protein Kinase A

At the postsynaptic membrane of glutamatergic synapses, the cAMP-dependent protein kinase (PKA), protein kinase C (PKC), and calcineurin (CaN) anchoring protein AKAP79/150 is recruited to NMDA and AMPA glutamate receptors by postsynaptic density (PSD)-95 family membrane-associated guanylate kinase (MAGUK) scaffold proteins. These signaling scaffold complexes may function to regulate receptor phosphorylation in synaptic plasticity. Thus, it is important to understand regulation of AKAP79/150 targeting to synapses and recruitment to PSD-MAGUK complexes. AKAP79 is targeted to the plasma membrane by an N-terminal basic domain that binds phosphatidylinositol-4,5-bisphosphate (PI-4,5-P(2)) and is regulated by PKC phosphorylation and calmodulin binding. Here we demonstrate that this same domain also binds F-actin in a calmodulin- and PKC-regulated manner, targets to membrane ruffles enriched in F-actin and PI-4,5-P(2) in COS7 cells, and localizes to dendritic spines with F-actin and PSD-MAGUKs in hippocampal neurons. Inhibition of actin polymerization disrupted AKAP79 targeting of PKA and CaN to ruffles in COS7 cells and endogenous AKAP79/150 dendritic spine localization with PKA, CaN, and PSD-MAGUKs in neurons. AKAP79/150 postsynaptic localization was rapidly regulated by NMDA receptors through CaN activation and F-actin remodeling, further suggesting that AKAP79/150 signaling scaffold targeting depends on actin dynamics. NMDA receptor activation also regulated dendritic spine localization of PKA and CaN and association of the AKAP79/150-PKA complex with PSD-MAGUKs. Because AMPA receptor PKA phosphorylation and synaptic localization are regulated by similar NMDA receptor-CaN signaling pathways linked to hippocampal long-term depression, this regulation of AKAP79/150 postsynaptic targeting might be important for synaptic plasticity.

https://www.jneurosci.org/content/jneuro/22/16/7027.full.pdf

Regulation of A-Kinase Anchoring Protein 79/150–cAMP-Dependent Protein Kinase Postsynaptic Targeting by NMDA Receptor Activation of Calcineurin and Remodeling of Dendritic Actin

Discovering the processes through which early adverse experiences affect children's nervous-system development, health, and behavior is critically important for developing effective interventions. However, advances in our understanding of these processes have been constrained by conceptualizations that rely on categories of adversity that are overlapping, have vague boundaries, and lack consistent biological evidence. Here, we discuss central problems in understanding the link between early-life adversity and children's brain development. We conclude by suggesting alternative formulations that hold promise for advancing knowledge about the neurobiological mechanisms through which adversity affects human development.

https://journals.sagepub.com/doi/pdf/10.1177/1745691620920725

Rethinking Concepts and Categories for Understanding the Neurodevelopmental Effects of Childhood Adversity

Recent research indicates that the neuropeptide oxytocin and the gene for the oxytocin receptor (OXTR) have been implicated in the modulation of various social behaviors, including those related to empathy and sensitivity to others. In this study, we examine the hypothesis that genetic variation in OXTR is associated with autonomic reactions when perceiving others in distress. We also explore the possibility that individual disposition in empathic concern would differ by OXTR genotype. To address these questions, fifty-one male participants (18–35 years of age), genotyped for OXTR rs53576, viewed a social interaction containing high levels of individual distress and apparent physical pain. Electrodermal activity, a measure of sympathetic nervous system activity, was collected during the presentation of the stimuli. Participants also completed a self-report dispositional measure of empathy prior to starting the study and provided ratings of arousal while viewing the stimuli. OXTR variant rs53576 GG individuals showed increased levels of sympathetic and subjective arousal in response to the stimuli compared to A allele carriers. GG homozygotes also expressed greater levels of empathic concern. These findings support the importance of the oxytocin receptor variation in emotional and physiological reactions to the experiences of other conspecifics.

/pdf/oxytocin-receptor-gene-variation-predicts-empathic-concern-idoc98wmop.pdf

Oxytocin receptor gene variation predicts empathic concern and autonomic arousal while perceiving harm to others.

Chronic and/or extreme stress in early life, often referred to as early adversity, childhood trauma, or early life stress, has been associated with a wide range of adverse effects on development. However, while early life stress has been linked to negative effects on a number of neural systems, the specific mechanisms through which early life stress influences development and individual differences in children’s outcomes are still not well understood. The current paper reviews the existing literature on the neurobiological effects of early life stress and their ties to children’s psychological and behavioral development. Early life stress has persistent and pervasive effects on prefrontal–hypothalamic–amygdala and dopaminergic circuits that are at least partially mediated by alterations in hypothalamic–pituitary–adrenal axis function. However, to date, this research has primarily utilized methods of assessment that focus solely on children’s event exposures. Incorporating assessment of factors that influence children’s interpretation of stressors, along with stressful events, has the potential to provide further insight into the mechanisms contributing to individual differences in neurodevelopmental effects of early life stress. This can aid in further elucidating specific mechanisms through which these neurobiological changes influence development and contribute to risk for psychopathology and health disorders.

/pdf/early-life-stress-and-development-potential-mechanisms-for-3zwn6rxpjo.pdf

Early life stress and development: potential mechanisms for adverse outcomes.

Context
Empathy is an essential aspect of clinical care, associated with improved patient satisfaction, increased adherence to treatment, and fewer malpractice complaints. Previous studies suggest that empathy declines during medical training. However, past research relied on a single narrowly operationalised, self-report measure of empathy. As empathy is a complex socio-emotional construct, it is critical to assess changes across its distinct components using multiple measures in order to better understand how it is influenced by medical training.

Methods
In a longitudinal study, medical students completed a series of self-report and behavioural measures twice per year during the first 3 years of their study (2012–2015). These included the previously used Jefferson Scale of Physician Empathy (JSPE), designed to assess empathy in the clinical context, the Questionnaire of Cognitive and Affective Empathy (QCAE), designed to assess overall empathy and its main components, and behavioural measures of sensitivity to others’ pain and understanding of others’ emotions, both of which are important aspects of empathy. The employment of multiple measures allowed for a more complete assessment of medical students’ empathy and related processes.

Results
In reflection of findings in previous work, students’ empathy assessed by the JSPE decreased over training. However, on the QCAE, aspects of students’ empathy, specifically overall cognitive empathy and its subcomponent perspective taking, and the emotion contagion subcomponent of affective empathy improved, whereas the remaining subcomponents remained stable. During medical school, students also exhibited comparable growth in their understanding of others’ emotions and increased sensitivity to others’ pain.

Conclusions
Changes in empathy during medical school cannot be simply characterised as representing an overall decline. Indeed, aspects of empathy thought to be valuable in positive physician–patient interactions improve during training. Overall, this study points to the importance of assessing the distinct components of empathy using multiple forms of measurement in order to better understand the mechanisms involved in empathy changes in medical practice.

Karen E. Smith

Papers

Regulation of A-Kinase Anchoring Protein 79/150–cAMP-Dependent Protein Kinase Postsynaptic Targeting by NMDA Receptor Activation of Calcineurin and Remodeling of Dendritic Actin

Rethinking Concepts and Categories for Understanding the Neurodevelopmental Effects of Childhood Adversity

Oxytocin receptor gene variation predicts empathic concern and autonomic arousal while perceiving harm to others.

Early life stress and development: potential mechanisms for adverse outcomes.

The complexity of empathy during medical school training: evidence for positive changes