325 research outputs found

    A Response to: "A Commentary on "Stabilizing Constructs through Collaboration across Different Research Fields as a Way to Foster the Integrative Approach of the Research Domain Criteria (RDoC) Project"

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    This paper is a response to a commentary by Walter Glannon (2016, Frontiers in Human Neuroscience) on my paper "Stabilizing Constructs Across Research Fields as a Way to Foster the Integrative Approach of the Research Domain Criteria Project"

    Regulation of Extracellular Signal-Regulated Kinase During Long-term Potentiation in Area CA1 of the Rat Hippocampus IN VIVO

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    The extracellular signal-regulated kinase (ERK) cascade can transduce cell-surface signals to the nucleus in post-synaptic neurons during hippocampus-dependent learning and hippocampus-dependent synaptic plasticity, yet, whether the cascade can convey information about stimulus frequency or synaptic modification direction to the nucleus during plasticity events has not been addressed. The objective of the current study was to investigate whether ERK regulation differs as a function of stimulus frequency and in accordance with synaptic modification direction by comparing ERK regulation during LTP in area CA1 of the hippocampus in vivo to previous findings for ERK regulation during LTD in area CA1 in vivo (Thiels et al., 2002). The ultimate goal was to determine whether ERK functions as a general or as a specific plasticity kinase during synaptic plasticity events in the hippocampus. Using a combination of in vivo electrophysiology, pharmacology and Western blot analysis, I demonstrate that: (1) LTP induced by high-frequency stimulation applied to commissural fiber inputs to area CA1 pyramidal cells in the adult hippocampus in vivo is accompanied by a rapid yet transient increase in ERK2 activation; (2) blockade of NMDA receptors by MK-801 blocks both LTP induction and the associated increase in ERK2 activation; (3) HFS delivered in the presence of the ERK kinase inhibitor SL327 fails to produce a persistent potentiation; (5) phosphorylation of the transcriptional regulator cAMP response element-binding protein (CREB) is increased after HFS; and (6) inhibition of ERK2 activation by SL327 blocks this observed increase in pCREB. The similarity of the current findings with previous findings for ERK2 activation and regulation during LTD in area CA1 in vivo, suggests that the ERK cascade conveys a general as opposed to a specific plasticity signal during these two forms of synaptic plasticity in area CA1 in vivo. Differences in the coupling of ERK2 activation to CREB phosphorylation between LTP and LTD (Thiels et al., 2002), suggest that other signaling cascades are most likely operative in determining the direction of synaptic modification during bidirectional synaptic plasticity in the hippocampus

    Reliability and Validity of Experiment in the Neurobiology of Learning and Memory

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    The concept of reliability has been definedtraditionally by philosophers of science as a feature that an experiment has when it can be used to arrive at true descriptive or explanatory claims about phenomena. In contrast, philosophers of science typically take the concept of validity to correspond roughly to that of generalizability, which is defined as a featurethat a descriptive or explanatory claim has when it is based on laboratory data but is applicable to phenomena beyond those effectsunder study in the laboratory. Philosophical accounts of experiment typically treat of the reliability of scientific experiment and the validity of descriptive or explanatory claims independently. On my account of experiment, however, these two issues are intimately linked. I show by appeal to case studies from the contemporary neurobiology of learning and memory that measures taken to guarantee the reliability of experiment often result in a decrease in the validity of those scientific claims that are made on thebasis of such experiments and, furthermore, that strategies employed to increase validity often decrease reliability. Yet, since reliability and validity are both desirable goals of scientificexperiments, and, on my account, competing aims, a tension ensues. I focus on two types of neurobiological experiments as case studies toillustrate this tension: (1) organism-level learning experiments and (2) synaptic-level plasticity experiments. I argue that the expresscommitment to the reliability of experimental processes in neurobiology has resulted in the invalidity of mechanistic claims about learning and plasticity made on the basis of data obtainedfrom such experiments. The positive component of the dissertation consists in specific proposals that I offer as guidelines for resolving this tension in the context of experimental design

    Parents' involvement in child care: do parental and work identities matter?

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    The current study draws on identity theory to explore mothers' and fathers' involvement in childcare. It examined the relationships between the salience and centrality of individuals’ parental and work-related identities and the extent to which they are involved in various forms of childcare. A sample of 148 couples with at least one child aged 6 years or younger completed extensive questionnaires. As hypothesized, the salience and centrality of parental identities were positively related to mothers' and fathers' involvement in childcare. Moreover, maternal identity salience was negatively related to fathers' hours of childcare and share of childcare tasks. Finally, work hours mediated the negative relationships between the centrality of work identities and time invested in childcare, and gender moderated this mediation effect. That is, the more central a mother's work identity, the more hours she worked for pay and the fewer hours she invested in childcare. These findings shed light on the role of parental identities in guiding behavioral choices, and attest to the importance of distinguishing between identity salience and centrality as two components of self-structure

    Exploring Regulatory Flexibility to Create Novel Incentives to Optimize Drug Discovery

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    Efforts by governments, firms, and patients to deliver pioneering drugs for critical health needs face a challenge of diminishing efficiency in developing those medicines. While multi-sectoral collaborations involving firms, researchers, patients, and policymakers are widely recognized as crucial for countering this decline, existing incentives to engage in drug development predominantly target drug manufacturers and thereby do little to stimulate collaborative innovation. In this mini review, we consider the unexplored potential within pharmaceutical regulations to create novel incentives to encourage a diverse set of actors from the public and private spheres to engage in the kind of collaborative knowledge exchange requisite for fostering enhanced innovation in early drug development

    Acute inhibition of estradiol synthesis impacts vestibulo-ocular reflex adaptation and cerebellar long-term potentiation in male rats

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    The vestibulo-ocular reflex (VOR) adaptation is an ideal model for investigating how the neurosteroid 17 beta-estradiol (E2) contributes to the modification of behavior by regulating synaptic activities. We hypothesized that E2 impacts VOR adaptation by affecting cerebellar synaptic plasticity at the parallel fiber–Purkinje cell (PF) synapse. To verify this hypothesis, we investigated the acute effect of blocking E2 synthesis on gain increases and decreases in adaptation of the VOR in male rats using an oral dose (2.5 mg/kg) of the aromatase inhibitor letrozole. We also assessed the effect of letrozole on synaptic plasticity at the PF synapse in vitro, using cerebellar slices from male rats. We found that letrozole acutely impaired both gain increases and decreases adaptation of the VOR without altering basal ocular-motor performance. Moreover, letrozole prevented long-term potentiation at the PF synapse (PF-LTP) without affecting long-term depression (PF-LTD). Thus, in male rats neurosteroid E2 has a relevant impact on VOR adaptation and affects exclusively PF-LTP. These findings suggest that E2 might regulate changes in VOR adaptation by acting locally on cerebellar and extra-cerebellar synaptic plasticity sites

    Sensory inflow manipulation induces learning-like phenomena in motor behavior

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    © 2020, Springer-Verlag GmbH Germany, part of Springer Nature. Purpose: Perceptual and goal-directed behaviors may be improved by repetitive sensory stimulations without practice-based training. Focal muscle vibration (f-MV) modulating the spatiotemporal properties of proprioceptive inflow is well-suited to investigate the effectiveness of sensory stimulation in influencing motor outcomes. Thus, in this study, we verified whether optimized f-MV stimulation patterns might affect motor control of upper limb movements. Methods: To answer this question, we vibrated the slightly tonically contracted anterior deltoid (AD), posterior deltoid (PD), and pectoralis major muscles in different combinations in forty healthy subjects at a frequency of 100 Hz for 10 min in single or repetitive administrations. We evaluated the vibration effect immediately after f-MV application on upper limb targeted movements tasks, and one week later. We assessed target accuracy, movement mean and peak speed, and normalized Jerk using a 3D optoelectronic motion capture system. Besides, we evaluated AD and PD activity during the tasks using wireless electromyography. Results: We found that f-MV may induce increases (p \u3c 0.05) in movement accuracy, mean speed and smoothness, and changes (p \u3c 0.05) in the electromyographic activity. The main effects of f-MV occurred overtime after repetitive vibration of the AD and PD muscles. Conclusion: Thus, in healthy subjects, optimized f-MV stimulation patterns might over time affect the motor control of the upper limb movement. This finding implies that f-MV may improve the individual’s ability to produce expected motor outcomes and suggests that it may be used to boost motor skills and learning during training and to support functional recovery in rehabilitation
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