- Microbiota and Neurodevelopmental Trajectories: Role of Maternal and Early-Life Nutrition. [Journal Article]
- ANAnn Nutr Metab 2019; 74 Suppl 2:16-27
- Pregnancy and early life are characterized by marked changes in body microbial composition. Intriguingly, these changes take place simultaneously with neurodevelopmental plasticity, suggesting a comp…
Pregnancy and early life are characterized by marked changes in body microbial composition. Intriguingly, these changes take place simultaneously with neurodevelopmental plasticity, suggesting a complex dialogue between the microbes that inhabit the gastrointestinal tract and the brain. The purpose of this chapter is to describe the natural trajectory of microbiota during pregnancy and early life, as well as review the literature available on its interaction with neurodevelopment. Several lines of evidence show that the gut microbiota interacts with diet, drugs and stress both prenatally and postnatally. Clinical and preclinical studies are illuminating how these disruptions result in different developmental outcomes. Understanding the role of the microbiota in neurodevelopment may lead to novel approaches to the study of the pathophysiology and treatment of neuropsychiatric disorders.
- Oral L-glutamine pretreatment attenuates skeletal muscle atrophy induced by 24-h fasting in mice. [Journal Article]
- JNJ Nutr Biochem 2019 May 25; 70:202-214
- L-Glutamine (L-Gln) supplementation has been pointed out as an anticatabolic intervention, but its effects on protein synthesis and degradation signaling in skeketal muscle are still poorly known. Th…
L-Glutamine (L-Gln) supplementation has been pointed out as an anticatabolic intervention, but its effects on protein synthesis and degradation signaling in skeketal muscle are still poorly known. The effects of L-Gln pretreatment (1 g kg-1 day-1 body weight for 10 days) on muscle fiber cross-sectional area (CSA), amino acid composition (measured by LC-MS/MS) and protein synthesis (Akt-mTOR) and degradation (ubiquitin ligases) signaling in soleus and extensor digitorum longus (EDL) muscles in 24-h-fasted mice were investigated. The fiber CSA of EDL muscle was not different between the L-Gln-fasted and L-Gln-fed groups. This finding was associated with reduced contents of L-Leu and L-Iso and activation of protein synthesis signaling (p-RPS6Ser240/244 and Akt-mTOR). The spectrum of soleus muscle fiber CSA distribution was larger in L-Gln-fasted as compared with placebo-fasted mice. This effect of L-Gln pretreatment was associated with changes in red fibers L-Gln metabolism as indicated by increased intracellular L-glutamine/L-glutamate ratio, L-aspartate and GABA levels. L-Gln supplementation reduced fasting-induced mass loss in tibialis anterior and gastrocnemius muscles. Evidence is presented that pretreatment with L-glutamine attenuates skeletal muscle atrophy induced by 24-h fasting through mechanisms that vary with the muscle fiber type.
- Prism adaptation enhances decoupling between the default mode network and the attentional networks. [Journal Article]
- NNeuroimage 2019 Jun 21
- Prism adaptation (PA) is a procedure used for studying visuomotor plasticity in healthy individuals, as well as for alleviating spatial neglect in patients. The adaptation is achieved by performing g…
Prism adaptation (PA) is a procedure used for studying visuomotor plasticity in healthy individuals, as well as for alleviating spatial neglect in patients. The adaptation is achieved by performing goal-directed movements while wearing prismatic lenses that induce a lateral displacement of visual information. This results in an initial movement error that is compensated by a recalibration of sensory-motor coordinates; consequently, a lateral bias in both motor and perceptual measurements occurs after prism removal, i.e., after effects. Neuroimaging studies have shown that a brief exposure to rightward prism changes the activations in the inferior parietal lobule (IPL) and modulates interhemispheric balance during attention tasks. However, it is yet unknown how PA changes global interplay between cortical networks as evident from task-free resting state connectivity. Thus we compared resting state functional connectivity patterns before ('Pre') and after ('Post') participants performed session of pointing movements with rightward-shifting prism (N = 14) or with neutral lenses (as a control condition; N = 12). Global connectivity analysis revealed significant decreases in functional connectivity following PA in two nodes of the Default Mode Network (DMN), and the left anterior insula. Further analyses of these regions showed specific connectivity decrease between either of the DMN nodes and areas within the attentional networks, including the inferior frontal gyrus, the anterior insula and the right superior temporal sulcus. On the other hand, the anterior insula decreased its connectivity to a large set of areas, all within the boundaries of the DMN. These results demonstrate that a brief exposure to PA enhances the decoupling between the DMN and the attention networks. The change in interplay between those pre-existing networks might be the basis of the rapid and wide-ranged behavioural changes induce by PA in healthy individuals.
- Automagic: Standardized preprocessing of big EEG data. [Journal Article]
- NNeuroimage 2019 Jun 21
- Electroencephalography (EEG) recordings have been rarely included in large-scale studies. This is arguably not due to a lack of information that lies in EEG recordings but mainly on account of method…
Electroencephalography (EEG) recordings have been rarely included in large-scale studies. This is arguably not due to a lack of information that lies in EEG recordings but mainly on account of methodological issues. In many cases, particularly in clinical, pediatric and aging populations, the EEG has a high degree of artifact contamination and the quality of EEG recordings often substantially differs between subjects. Although there exists a variety of standardized preprocessing methods to clean EEG from artifacts, currently there is no method to objectively quantify the quality of preprocessed EEG. This makes the commonly accepted procedure of excluding subjects from analyses due to exceeding contamination of artifacts highly subjective. As a consequence, P-hacking is fostered, the replicability of results is decreased, and it is difficult to pool data from different study sites. In addition, in large-scale studies, data are collected over years or even decades, requiring software that controls and manages the preprocessing of ongoing and dynamically growing studies. To address these challenges, we developed Automagic, an open-source MATLAB toolbox that acts as a wrapper to run currently available preprocessing methods and offers objective standardized quality assessment for growing studies. The software is compatible with the Brain Imaging Data Structure (BIDS) standard and hence facilitates data sharing. In the present paper we outline the functionality of Automagic and examine the effect of applying combinations of methods on a sample of resting EEG data. This examination suggests that applying a pipeline of algorithms to detect artifactual channels in combination with Multiple Artifact Rejection Algorithm (MARA), an independent component analysis (ICA)-based artifact correction method, is sufficient to reduce a large extent of artifacts.
- Inconclusive efficacy of intervention on upper-limb function after tetraplegia: a systematic review and meta-analysis. [Review]
- APAnn Phys Rehabil Med 2019 Jun 21
- CONCLUSIONS: We can provide no recommendations for using intensive versus less intensive interventions or neuromodulation versus sham during tetraplegia rehabilitation. Further multicentre studies of high methodological quality are required to reduce uncertainty about the efficacy of these interventions.
- Glutamate receptor interacting protein acts within the prefrontal cortex to blunt cocaine seeking. [Journal Article]
- NNeuropharmacology 2019 Jun 21; :107672
- Glutamate receptor interacting protein (GRIP) is a neuronal scaffolding protein that anchors GluA2-containing AMPA receptors to the cell membrane. GRIP plays a critical role in activity-dependent syn…
Glutamate receptor interacting protein (GRIP) is a neuronal scaffolding protein that anchors GluA2-containing AMPA receptors to the cell membrane. GRIP plays a critical role in activity-dependent synaptic plasticity, including that which occurs after drug exposure. Given that cocaine administration alters glutamate receptor trafficking within the prefrontal cortex (PFC), a better understanding of the role of receptor trafficking proteins could lead to a more complete understanding of addictive phenotypes. AMPA receptor trafficking in general, and GRIP specifically, is known to play a role in cocaine seeking and conditioned reward in the nucleus accumbens, but its role in the PFC has not been characterized. The current study demonstrates that conditional deletion of GRIP1 in the medial prefrontal cortex increases the motivation for cocaine and potentiates cue-induced reinstatement of cocaine seeking in male and female mice. As no effects of PFC GRIP1 deletion were seen in reinstatement of food seeking, strategy set-shifting, or reversal learning the effects on cocaine seeking are not related to generalized alterations in cognitive function. While disrupting GRIP1 might be expected to lead to decreased AMPA transmission, our electrophysiological data indicate an increase in sEPSC amplitude in the prefrontal cortex and a corresponding decrease in paired pulse facilitation in the nucleus accumbens. Taken together this suggests a strengthening of the PFC to NAc input following prefrontal GRIP1 deletion that may mediate the enhanced drug seeking behavior.
- Age-dependent impairment of metabotropic glutamate receptor 2-dependent long-term depression in the mouse striatum by chronic ethanol exposure. [Journal Article]
- AAlcohol 2019 Jun 21
- Chronic alcohol exposure is associated with increased reliance on behavioral strategies involving the dorsolateral striatum (DLS), including habitual or stimulus-response behaviors. Presynaptic G pro…
Chronic alcohol exposure is associated with increased reliance on behavioral strategies involving the dorsolateral striatum (DLS), including habitual or stimulus-response behaviors. Presynaptic G protein-coupled receptors (GPCRs) on cortical and thalamic inputs to the DLS inhibit glutamate release, and alcohol-induced disruption of presynaptic GPCR function represents a mechanism by which alcohol could disinhibit DLS neurons and thus bias towards use of DLS-dependent behaviors. Metabotropic glutamate receptor 2 (mGlu2) is a Gi/o-coupled GPCR that robustly modulates glutamate transmission in the DLS, inducing long-term depression (LTD) at both cortical and thalamic synapses. Loss of mGlu2 function has recently been associated with increased ethanol seeking and consumption, but the ability of alcohol to produce adaptations in mGlu2 function in the DLS has not been investigated. We exposed male C57Bl/6J mice to a two-week chronic intermittent ethanol (CIE) paradigm followed by a brief withdrawal period, then used whole-cell patch clamp recordings of glutamatergic transmission in the striatum to assess CIE effects on mGlu2-mediated synaptic plasticity. We report that CIE differentially disrupts mGlu2-mediated long-term depression in the DLS vs. dorsomedial striatum (DMS). Interestingly, CIE-induced impairment of mGlu2-LTD in the dorsolateral striatum is only observed when alcohol exposure occurs during adolescence. Incubation of striatal slices from CIE-exposed adolescent mice with a positive allosteric modulator of mGlu2 fully rescues mGlu2-LTD. In contrast to the two-week CIE paradigm, acute exposure of striatal slices to ethanol concentrations that mimic ethanol levels during CIE fails to disrupt mGlu2-LTD. We did not observe a reduction of mGlu2 mRNA or protein levels following CIE, suggesting that alcohol effects on mGlu2 occur at the functional level. Our findings contribute to growing evidence that adolescents are uniquely vulnerable to certain alcohol-induced neuroadaptations, and identify enhancement of mGlu2 activity as a strategy to reverse the effects of adolescent alcohol exposure on DLS physiology.
- White matter plasticity and maturation in human cognition. [Review]
- GLIAGlia 2019 Jun 24
- White matter plasticity likely plays a critical role in supporting cognitive development. However, few studies have used the imaging methods specific to white matter tissue structure or experimental …
White matter plasticity likely plays a critical role in supporting cognitive development. However, few studies have used the imaging methods specific to white matter tissue structure or experimental designs sensitive to change in white matter necessary to elucidate these relations. Here we briefly review novel imaging approaches that provide more specific information regarding white matter microstructure. Furthermore, we highlight recent studies that provide greater clarity regarding the relations between changes in white matter and cognition maturation in both healthy children and adolescents and those with white matter insult. Finally, we examine the hypothesis that white matter is linked to cognitive function via its impact on neural synchronization. We test this hypothesis in a population of children and adolescents with recurrent demyelinating syndromes. Specifically, we evaluate group differences in white matter microstructure within the optic radiation; and neural phase synchrony in visual cortex during a visual task between 25 patients and 28 typically developing age-matched controls. Children and adolescents with demyelinating syndromes show evidence of myelin and axonal compromise and this compromise predicts reduced phase synchrony during a visual task compared to typically developing controls. We investigate one plausible mechanism at play in this relationship using a computational model of gamma generation in early visual cortical areas. Overall, our findings show a fundamental connection between white matter microstructure and neural synchronization that may be critical for cognitive processing. In the future, longitudinal or interventional studies can build upon our knowledge of these exciting relations between white matter, neural communication, and cognition.
- Myelinated axon physiology and regulation of neural circuit function. [Review]
- GLIAGlia 2019 Jun 24
- The study of structural and functional plasticity in the central nervous system (CNS) to date has focused primarily on that of neurons and synapses. However, more recent studies implicate glial cells…
The study of structural and functional plasticity in the central nervous system (CNS) to date has focused primarily on that of neurons and synapses. However, more recent studies implicate glial cells as key regulators of neural circuit function. Among these, the myelinating glia of the CNS, oligodendrocytes, have been shown to be responsive to extrinsic signals including neuronal activity, and in turn, tune neurophysiological function. Due to the fact that myelin fundamentally alters the conduction properties of axons, much attention has focused on how dynamic regulation of myelination might represent a form of functional plasticity. Here, we highlight recent research that indicates that it is not only myelin, but essentially all the function-regulating components of the myelinated axon that are responsive to neuronal activity. For example, the axon initial segment, nodes of Ranvier, heminodes, axonal termini, and the morphology of the axon itself all exhibit the potential to respond to neuronal activity, and in so doing might underpin specific functional outputs. We also highlight emerging evidence that the myelin sheath itself has a rich physiology capable of influencing axonal physiology. We suggest that to fully understand nervous system plasticity we need to consider the fact that myelinated axon is an integrated functional unit and adaptations that influence the entire functional unit are likely to underpin modifications to neural circuit function.
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- Exercise-induced enhancement of synaptic function triggered by the inverse BAR protein, Mtss1L. [Journal Article]
- EElife 2019 Jun 24; 8
- Exercise is a potent enhancer of learning and memory, yet we know little of the underlying mechanisms that likely include alterations in synaptic efficacy in the hippocampus. To address this issue, w…
Exercise is a potent enhancer of learning and memory, yet we know little of the underlying mechanisms that likely include alterations in synaptic efficacy in the hippocampus. To address this issue, we exposed mice to a single episode of voluntary exercise, and permanently marked activated mature hippocampal dentate granule cells using conditional Fos-TRAP mice. Exercise-activated neurons (Fos-TRAPed) showed an input-selective increase in dendritic spines and excitatory postsynaptic currents at 3 days post-exercise, indicative of exercise-induced structural plasticity. Laser-capture microdissection and RNASeq of activated neurons revealed that the most highly induced transcript was Mtss1L, a little-studied I-BAR domain-containing gene, which we hypothesized could be involved in membrane curvature and dendritic spine formation. shRNA-mediated Mtss1L knockdown in vivo prevented the exercise-induced increases in spines and excitatory postsynaptic currents. Our results link short-term effects of exercise to activity-dependent expression of Mtss1L, which we propose as a novel effector of activity-dependent rearrangement of synapses.