Hoffforbes7959

Recording neuronal activity with penetrating extracellular multi-channel electrode arrays, more commonly known as neural probes, is one of the most widespread approaches to probe neuronal activity. Despite a plethora of available extracellular probe designs, the time-consuming process of mapping of electrode channel order and relative geometries, as required by spike-sorting software is invariably left to the end-user. Consequently, this manual process is prone to mis-mapping mistakes, which in turn lead to undesirable spike-sorting errors and inefficiencies. Here, we introduce ProbeInterface, an open-source project that aims to unify neural probe metadata descriptions by removing the manual step of probe mapping prior to spike-sorting for the analysis of extracellular neural recordings. ProbeInterface is first of all a Python API, which enables users to create and visualize probes and probe groups at any required complexity level. Second, ProbeInterface facilitates the generation of comprehensive wiring description in a reproducible fashion for any specific data-acquisition setup, which usually involves the use of a recording probe, a headstage, adapters, and an acquisition system. Third, we collaborate with probe manufacturers to compile an open library of available probes, which can be downloaded at run time using our Python API. Finally, with ProbeInterface we define a file format for probe handling which includes all necessary information for a FAIR probe description and is compatible with and complementary to other open standards in neuroscience.[This corrects the article DOI 10.3389/fnhum.2021.746081.].According to the shared signal hypothesis (SSH) the impact of facial expressions on emotion processing partially depends on whether the gaze is directed toward or away from the observer. In autism spectrum disorder (ASD) several aspects of face processing have been found to be atypical, including attention to eye gaze and the identification of emotional expressions. However, there is little research on how gaze direction affects emotional expression processing in typically developing (TD) individuals and in those with ASD. This question is investigated here in two multimodal experiments. Experiment 1 required processing eye gaze direction while faces differed in emotional expression. Forty-seven children (aged 9-12 years) participated. Their Autism Diagnostic Observation Schedule (ADOS) scores ranged from 0 to 6 in the experiment. Event-related potentials (ERPs) were sensitive to gaze direction and emotion, but emotion processing did not depend on gaze direction. However, for angry faces the gaze direction effrom ERPs and eye tracking confirm the hypothesis of an impaired sensitivity to gaze direction in children with ASD or elevated autistic traits, at least for specific emotions. Therefore, we conclude that multimodal investigations of the interaction between emotional processing and stimulus gaze direction are promising to understand the characteristics of individuals differing along the autism trait dimension.In drug discovery and development, traditional assessment of human patients and preclinical subjects occurs at limited time points in potentially stressful surroundings (i.e., the clinic or a test arena), which can impact data quality and welfare. However, recent advances in remote digital monitoring technologies enable the assessment of human patients and preclinical subjects across multiple time points in familiar surroundings. The ability to monitor a patient throughout disease progression provides an opportunity for more relevant and efficient diagnosis as well as improved assessment of drug efficacy and safety. In preclinical in vivo animal models, these digital technologies allow for continuous, longitudinal, and non-invasive monitoring in the home environment. This manuscript provides an overview of digital monitoring technologies for use in preclinical studies including their history and evolution, current engagement through use cases, and impact of digital biomarkers (DBs) on drug discovery and the 3Rs. We also discuss barriers to implementation and strategies to overcome them. Finally, we address data consistency and technology standards from the perspective of technology providers, end-users, and subject matter experts. Overall, this review establishes an improved understanding of the value and implementation of digital biomarker (DB) technologies in preclinical research.Temporal recalibration (TR) may arise to realign asynchronous stimuli after exposure to a short, constant delay between voluntary movement and sensory stimulus. The objective of this study was to determine if awareness of the temporal lag between a motor response (i.e., a keypress) and a sensory event (i.e., a visual flash) is necessary for TR to occur. We further investigated whether manipulating the required motor and perceptual judgment tasks modified the influence of awareness on TR. Participants (n = 48) were randomly divided between two groups (Group 1 Aware and Group 2 Unaware). The Aware group was told of the temporal lag between their keypress and visual flash at the beginning of the experiment, whereas the Unaware group was not. All participants completed eight blocks of trials, in which the motor task (single or repetitive tap), perceptual judgment task (judging the temporal order of the keypress in relation to the visual flash or judging whether the two stimuli were simultaneous or not), and fixed temporal lag between keypress and visual flash (0 or 100 ms) varied. TR was determined by comparing judgments between corresponding blocks of trials in which the temporal lag was 0 or 100 ms. Results revealed that both the Aware and Unaware groups demonstrated a similar magnitude of TR across all motor and perceptual judgment tasks, such that the magnitude of TR did not vary between Aware and Unaware participants. These results suggest that awareness of a temporal lag does not influence the magnitude of TR achieved and that motor and perceptual judgment task demands do not modulate the influence of awareness on TR.Environmental enrichment is known to induce neuronal changes; however, the underlying structural and functional factors involved are not fully known and remain an active area of study. To investigate these factors, we assessed enriched environment (EE) and standard environment (SE) control mice over 30 days using structural and functional MRI methods. Naïve adult male mice (n = 30, ≈20 g, C57BL/B6J, postnatal day 60 initial scan) were divided into SE and EE groups and scanned before and after 30 days. Structural analyses included volumetry based on manual segmentation as well as diffusion tensor imaging (DTI). Functional analyses included seed-based analysis (SBA), independent component analysis (ICA), the amplitude of low-frequency fluctuation (ALFF), and fractional ALFF (fALFF). Structural results indicated that environmental enrichment led to an increase in the volumes of cornu ammonis 1 (CA1) and dentate gyrus. Structural results indicated changes in radial diffusivity and mean diffusivity in the visual cortex and secondary somatosensory cortex after EE. Furthermore, SBA and ICA indicated an increase in resting-state functional MRI (rsfMRI) functional connectivity in the hippocampus. Using parallel structural and functional analyses, we have demonstrated coexistent structural and functional changes in the hippocampal subdivision CA1. Future research should map alterations temporally during environmental enrichment to investigate the initiation of these structural and functional changes.Although lithium has long been one of the most widely used pharmacological agents in psychiatry, its mechanisms of action at the cellular and molecular levels remain poorly understood. One of the targets of Li+ is the phosphoinositide pathway, but whereas the impact of Li+ on inositol lipid metabolism is well documented, information on physiological effects at the cellular level is lacking. We examined in two mammalian cell lines the effect of acute Li+ exposure on the mobilization of internal Ca2+ and phospholipase C (PLC)-dependent membrane conductances. We first corroborated by Western blots and immunofluorescence in HEK293 cells the presence of key signaling elements of a muscarinic PLC pathway (M1AchR, Gq, PLC-β1, and IP3Rs). Stimulation with carbachol evoked a dose-dependent mobilization of Ca, as determined with fluorescent indicators. This was due to release from internal stores and proved susceptible to the PLC antagonist U73122. Li+ exposure reproducibly potentiated the Ca response in a concentration-dependent manner extending to the low millimolar range. To broaden those observations to a neuronal context and probe potential Li modulation of electrical signaling, we next examined the cell line SHsy5y. We replicated the potentiating effects of Li on the mobilization of internal Ca, and, after characterizing the basic properties of the electrical response to cholinergic stimulation, we also demonstrated an equally robust upregulation of muscarinic membrane currents. Finally, by directly stimulating the signaling pathway at different links downstream of the receptor, the site of action of the observed Li effects could be narrowed down to the G protein and its interaction with PLC-β. These observations document a modulation of Gq/PLC/IP3-mediated signaling by acute exposure to lithium, reflected in distinct physiological changes in cellular responses.Hair cells are mechanosensitive cells in the inner ear, characterized by dozens to hundreds of actin-based stereocilia and one tubulin-based kinocilium on the apical surface of each cell. Two types of hair cells, namely cochlear hair cells and vestibular hair cells (VHCs), are responsible for the sensation of sound and balancing information, respectively. In each hair cell, the stereocilia are organized into rows of increasing heights with the mechano-electrical transduction (MET) channels localized at the tips of shorter-row stereocilia. A so-called "row 2 protein complex" also localizes at the tips of shorter-row mechanotransducing stereocilia, which plays important roles in the maintenance of mechanotransducing stereocilia. Recently, we and others identified BAIAP2L2 as a new component of row 2 complex. Baiap2l2 inactivation causes degeneration of the mechanotransducing stereocilia in cochlear hair cells, and leads to profound hearing loss in mice. In the present work, we examined the role of BAIAP2L2 in the VHC stereocilia. Confocal microscopy reveals that BAIAP2L2 immunoreactivity is localized at the tips of shorter-row stereocilia in VHCs. However, stereocilia development and maintenance are unaffected in Baiap2l2-/- VHCs. Meanwhile, MET function of VHCs as well as vestibular functions are also unaffected in Baiap2l2-/- mice. Further investigations show that the stereociliary tip localization of CAPZB2, another known row 2 complex component, is not affected in Baiap2l2-/- VHCs, consistent with the unaltered stereocilia morphology. Taken together, our present data show that BAIAP2L2 inactivation does not affect vestibular hair cell stereocilia.Depression and obesity are major public health concerns, and there is mounting evidence that they share etiopathophysiological mechanisms. The neurobiological pathways involved in both mood and energy balance regulation are complex, multifactorial and still incompletely understood. As a coactivator of the pleiotropic transcription factor cAMP response element-binding protein (CREB), CREB-regulated transcription coactivator 1 (CRTC1) has recently emerged as a novel regulator of neuronal plasticity and brain functions, while CRTC1 dysfunction has been associated with neurodegenerative and psychiatric diseases. click here This review focuses on recent evidence emphasizing the critical role of CRTC1 in the neurobiology of depression and comorbid obesity. We discuss the role of CRTC1 downregulation in mediating chronic stress-induced depressive-like behaviors, and antidepressant response in the light of the previously characterized Crtc1 knockout mouse model of depression. The putative role of CRTC1 in the alteration of brain energy homeostasis observed in depression is also discussed.