Neural Plasticity The latest articles from Hindawi © 2018 , Hindawi Limited . All rights reserved. Bilateral Transcranial Direct Current Stimulation Reshapes Resting-State Brain Networks: A Magnetoencephalography Assessment Thu, 11 Jan 2018 09:22:20 +0000 Transcranial direct current stimulation (tDCS) can noninvasively induce brain plasticity, and it is potentially useful to treat patients affected by neurological conditions. However, little is known about tDCS effects on resting-state brain networks, which are largely involved in brain physiological functions and in diseases. In this randomized, sham-controlled, double-blind study on healthy subjects, we have assessed the effect of bilateral tDCS applied over the sensorimotor cortices on brain and network activity using a whole-head magnetoencephalography system. Bilateral tDCS, with the cathode (−) centered over C4 and the anode (+) centered over C3, reshapes brain networks in a nonfocal fashion. Compared to sham stimulation, tDCS reduces left frontal alpha, beta, and gamma power and increases global connectivity, especially in delta, alpha, beta, and gamma frequencies. The increase of connectivity is consistent across bands and widespread. These results shed new light on the effects of tDCS and may be of help in personalizing treatments in neurological disorders. Giovanni Pellegrino, Matteo Maran, Cristina Turco, Luca Weis, Giovanni Di Pino, Francesco Piccione, and Giorgio Arcara Copyright © 2018 Giovanni Pellegrino et al. All rights reserved. Precision Light for the Treatment of Psychiatric Disorders Thu, 11 Jan 2018 00:00:00 +0000 Circadian timekeeping can be reset by brief flashes of light using stimulation protocols thousands of times shorter than those previously assumed to be necessary for traditional phototherapy. These observations point to a future where flexible architectures of nanosecond-, microsecond-, and millisecond-scale light pulses are compiled to reprogram the brain’s internal clock when it has been altered by psychiatric illness or advanced age. In the current review, we present a chronology of seminal experiments that established the synchronizing influence of light on the human circadian system and the efficacy of prolonged bright-light exposure for reducing symptoms associated with seasonal affective disorder. We conclude with a discussion of the different ways that precision flashes could be parlayed during sleep to effect neuroadaptive changes in brain function. This article is a contribution to a special issue on Circadian Rhythms in Regulation of Brain Processes and Role in Psychiatric Disorders curated by editors Shimon Amir, Karen Gamble, Oliver Stork, and Harry Pantazopoulos. Sevag Kaladchibachi and Fabian Fernandez Copyright © 2018 Sevag Kaladchibachi and Fabian Fernandez. All rights reserved. Photoperiodic Programming of the SCN and Its Role in Photoperiodic Output Tue, 09 Jan 2018 00:00:00 +0000 Though the seasonal response of organisms to changing day lengths is a phenomenon that has been scientifically reported for nearly a century, significant questions remain about how photoperiod is encoded and effected neurobiologically. In mammals, early work identified the master circadian clock, the suprachiasmatic nuclei (SCN), as a tentative encoder of photoperiodic information. Here, we provide an overview of research on the SCN as a coordinator of photoperiodic responses, the intercellular coupling changes that accompany that coordination, as well as the SCN’s role in a putative brain network controlling photoperiodic input and output. Lastly, we discuss the importance of photoperiodic research in the context of tangible benefits to human health that have been realized through this research as well as challenges that remain. Michael C. Tackenberg and Douglas G. McMahon Copyright © 2018 Michael C. Tackenberg and Douglas G. McMahon. All rights reserved. Botanicals as Modulators of Neuroplasticity: Focus on BDNF Sun, 31 Dec 2017 00:00:00 +0000 The involvement of brain-derived neurotrophic factor (BDNF) in different central nervous system (CNS) diseases suggests that this neurotrophin may represent an interesting and reliable therapeutic target. Accordingly, the search for new compounds, also from natural sources, able to modulate BDNF has been increasingly explored. The present review considers the literature on the effects of botanicals on BDNF. Botanicals considered were Bacopa monnieri (L.) Pennell, Coffea arabica L., Crocus sativus L., Eleutherococcus senticosus Maxim., Camellia sinensis (L.) Kuntze (green tea), Ginkgo biloba L., Hypericum perforatum L., Olea europaea L. (olive oil), Panax ginseng C.A. Meyer, Rhodiola rosea L., Salvia miltiorrhiza Bunge, Vitis vinifera L., Withania somnifera (L.) Dunal, and Perilla frutescens (L.) Britton. The effect of the active principles responsible for the efficacy of the extracts is reviewed and discussed as well. The high number of articles published (more than one hundred manuscripts for 14 botanicals) supports the growing interest in the use of natural products as BDNF modulators. The studies reported strengthen the hypothesis that botanicals may be considered useful modulators of BDNF in CNS diseases, without high side effects. Further clinical studies are mandatory to confirm botanicals as preventive agents or as useful adjuvant to the pharmacological treatment. Enrico Sangiovanni, Paola Brivio, Mario Dell’Agli, and Francesca Calabrese Copyright © 2017 Enrico Sangiovanni et al. All rights reserved. Relationship between Insulin Levels and Nonpsychotic Dementia: A Systematic Review and Meta-Analysis Wed, 27 Dec 2017 00:00:00 +0000 Objectives. To explore the relationship between insulin levels and nonpsychotic dementia. Methods. Six electronic databases (PubMed, Cochrane, SCI, CNKI, VIP, and Wanfang) were searched from January 1, 2007, to March 1, 2017. Experimental or observational studies that enrolled people with nonpsychotic dementia or abnormal insulin levels in which insulin levels or MMSE scores (events in nonpsychotic dementia) were the outcome measures. Random-effects models were chosen for this meta-analysis. Sample size, mean, s.d., and events were primarily used to generate effect sizes (with the PRIMA registration number CRD42017069860). Results. 50 articles met the final inclusion criteria. Insulin levels in cerebrospinal fluid were lower (Hedges’ g = 1.196, 95% CI = 0.238 to 2.514, and ), while the levels in peripheral blood were higher in nonpsychotic dementia patients (Hedges’ g = 0.853 and 95% CI = 0.579 to 1.127), and MMSE scores were significantly lower in the high insulin group than in the healthy control group (Hedges’ g = 0.334, 95% CI = 0.249 to 0.419, and ). Conclusions. Our comprehensive results indicate that blood insulin levels may increase in patients with nonpsychotic dementia. Qiu-xia Pan, Xiao-juan Li, Yue-yun Liu, Fang-fang Wang, Ya-jing Hou, Qing-lai Bian, Wen-qi Qiu, Zhi-yi Yan, You-ming Jiang, and Jia-xu Chen Copyright © 2017 Qiu-xia Pan et al. All rights reserved. Neural Mechanisms of Autonomic Dysfunction in Neurological Diseases Wed, 27 Dec 2017 00:00:00 +0000 De-Pei Li, Yu-Long Li, Jianhua Li, and Sheng Wang Copyright © 2017 De-Pei Li et al. All rights reserved. Effects of Various Extents of High-Frequency Hearing Loss on Speech Recognition and Gap Detection at Low Frequencies in Patients with Sensorineural Hearing Loss Wed, 27 Dec 2017 00:00:00 +0000 This study explored whether the time-compressed speech perception varied with the degree of hearing loss in high-frequency sensorineural hearing loss (HF SNHL) individuals. 65 HF SNHL individuals with different cutoff frequencies were recruited and further divided into mildly, moderately, and/or severely affected subgroups in terms of the averaged thresholds of all frequencies exhibiting hearing loss. Time-compressed speech recognition scores under both quiet and noisy conditions and gap detection thresholds within low frequencies that had normal thresholds were obtained from all patients and compared with data from 11 age-matched individuals with normal hearing threshold at all frequencies. Correlations of the time-compressed speech recognition scores with the extents of HF SNHL and with the 1 kHz gap detection thresholds were studied across all participants. We found that the time-compressed speech recognition scores were significantly affected by and correlated with the extents of HF SNHL. The time-compressed speech recognition scores also correlated with the 1 kHz gap detection thresholds except when the compression ratio of speech was 0.8 under quiet condition. Above all, the extents of HF SNHL were significantly correlated with the 1 kHz gap thresholds. Bei Li, Yang Guo, Guang Yang, Yanmei Feng, and Shankai Yin Copyright © 2017 Bei Li et al. All rights reserved. The Role of Mammalian Glial Cells in Circadian Rhythm Regulation Mon, 25 Dec 2017 00:00:00 +0000 Circadian rhythms are biological oscillations with a period of about 24 hours. These rhythms are maintained by an innate genetically determined time-keeping system called the circadian clock. A large number of the proteins involved in the regulation of this clock are transcription factors controlling rhythmic transcription of so-called clock-controlled genes, which participate in a plethora of physiological functions in the organism. In the brain, several areas, besides the suprachiasmatic nucleus, harbor functional clocks characterized by a well-defined time pattern of clock gene expression. This expression rhythm is not restricted to neurons but is also present in glia, suggesting that these cells are involved in circadian rhythmicity. However, only certain glial cells fulfill the criteria to be called glial clocks, namely, to display molecular oscillators based on the canonical clock protein PERIOD, which depends on the suprachiasmatic nucleus for their synchronization. In this contribution, we summarize the current information about activity of the clock genes in glial cells, their potential role as oscillators as well as clinical implications. Donají Chi-Castañeda and Arturo Ortega Copyright © 2017 Donají Chi-Castañeda and Arturo Ortega. All rights reserved. Trans-Synaptic Spread of Amyloid-β in Alzheimer’s Disease: Paths to β-Amyloidosis Sun, 24 Dec 2017 00:00:00 +0000 Neuronal activity has a strong causal role in the production and release of the neurotoxic β-amyloid peptide (Aβ). Because of this close link, gradual accumulation of Aβ into amyloid plaques has been reported in brain areas with intense neuronal activity, including cortical regions that display elevated activation at resting state. However, the link between Aβ and activity is not always linear and recent studies report exceptions to the view of “more activity, more plaques.” Here, we review the literature about the activity-dependent production of Aβ in both human cases and AD models and focus on the evidences that brain regions with elevated convergence of synaptic connections (herein referred to as brain nodes) are particularly vulnerable to Aβ accumulation. Next, we will examine data supporting the hypothesis that, since Aβ is released from synaptic terminals, β-amyloidosis can spread in AD brain by advancing through synaptically connected regions, which makes brain nodes vulnerable to Aβ accumulation. Finally, we consider possible mechanisms that account for β-amyloidosis progression through synaptically linked regions. Annabella Pignataro and Silvia Middei Copyright © 2017 Annabella Pignataro and Silvia Middei. All rights reserved. Low-Frequency Repetitive Transcranial Magnetic Stimulation for Stroke-Induced Upper Limb Motor Deficit: A Meta-Analysis Thu, 21 Dec 2017 10:02:13 +0000 Background and Purpose. This meta-analysis aimed to evaluate the therapeutic potential of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) over the contralesional hemisphere on upper limb motor recovery and cortex plasticity after stroke. Methods. Databases of PubMed, Medline, ScienceDirect, Cochrane, and Embase were searched for randomized controlled trials published before Jun 31, 2017. The effect size was evaluated by using the standardized mean difference (SMD) and a 95% confidence interval (CI). Resting motor threshold (rMT) and motor-evoked potential (MEP) were also examined. Results. Twenty-two studies of 1 Hz LF-rTMS over the contralesional hemisphere were included. Significant efficacy was found on finger flexibility (SMD = 0.75), hand strength (SMD = 0.49), and activity dexterity (SMD = 0.32), but not on body function (SMD = 0.29). The positive changes of rMT (SMD = 0.38 for the affected hemisphere and SMD = −0.83 for the unaffected hemisphere) and MEP (SMD = −1.00 for the affected hemisphere and SMD = 0.57 for the unaffected hemisphere) were also significant. Conclusions. LF-rTMS as an add-on therapy significantly improved upper limb functional recovery especially the hand after stroke, probably through rebalanced cortical excitability of both hemispheres. Future studies should determine if LF-rTMS alone or in conjunction with practice/training would be more effective. Clinical Trial Registration Information. This trial is registered with unique identifier CRD42016042181. Lan Zhang, Guoqiang Xing, Shiquan Shuai, Zhiwei Guo, Huaping Chen, Morgan A. McClure, Xiaojuan Chen, and Qiwen Mu Copyright © 2017 Lan Zhang et al. All rights reserved. Enhancing Plasticity of the Central Nervous System: Drugs, Stem Cell Therapy, and Neuro-Implants Sun, 17 Dec 2017 00:00:00 +0000 Stroke represents the first cause of adult acquired disability. Spontaneous recovery, dependent on endogenous neurogenesis, allows for limited recovery in 50% of patients who remain functionally dependent despite physiotherapy. Here, we propose a review of novel drug therapies with strong potential in the clinic. We will also discuss new avenues of stem cell therapy in patients with a cerebral lesion. A promising future for the development of efficient drugs to enhance functional recovery after stroke seems evident. These drugs will have to prove their efficacy also in severely affected patients. The efficacy of stem cell engraftment has been demonstrated but will have to prove its potential in restoring tissue function for the massive brain lesions that are most debilitating. New answers may lay in biomaterials, a steadily growing field. Biomaterials should ideally resemble lesioned brain structures in architecture and must be proven to increase functional reconnections within host tissue before clinical testing. Alice Le Friec, Anne-Sophie Salabert, Carole Davoust, Boris Demain, Christophe Vieu, Laurence Vaysse, Pierre Payoux, and Isabelle Loubinoux Copyright © 2017 Alice Le Friec et al. All rights reserved. Activation State-Dependent Substrate Gating in Ca2+/Calmodulin-Dependent Protein Kinase II Sun, 17 Dec 2017 00:00:00 +0000 Calcium/calmodulin-dependent protein kinase II (CaMKII) is highly concentrated in the brain where its activation by the Ca2+ sensor CaM, multivalent structure, and complex autoregulatory features make it an ideal translator of Ca2+ signals created by different patterns of neuronal activity. We provide direct evidence that graded levels of kinase activity and extent of T287 (T286 α isoform) autophosphorylation drive changes in catalytic output and substrate selectivity. The catalytic domains of CaMKII phosphorylate purified PSDs much more effectively when tethered together in the holoenzyme versus individual subunits. Using multisubstrate SPOT arrays, high-affinity substrates are preferentially phosphorylated with limited subunit activity per holoenzyme, whereas multiple subunits or maximal subunit activation is required for intermediate- and low-affinity, weak substrates, respectively. Using a monomeric form of CaMKII to control T287 autophosphorylation, we demonstrate that increased Ca2+/CaM-dependent activity for all substrates tested, with the extent of weak, low-affinity substrate phosphorylation governed by the extent of T287 autophosphorylation. Our data suggest T287 autophosphorylation regulates substrate gating, an intrinsic property of the catalytic domain, which is amplified within the multivalent architecture of the CaMKII holoenzyme. D. E. Johnson and A. Hudmon Copyright © 2017 D. E. Johnson and A. Hudmon. All rights reserved. Drosophila: An Emergent Model for Delineating Interactions between the Circadian Clock and Drugs of Abuse Sun, 17 Dec 2017 00:00:00 +0000 Endogenous circadian oscillators orchestrate rhythms at the cellular, physiological, and behavioral levels across species to coordinate activity, for example, sleep/wake cycles, metabolism, and learning and memory, with predictable environmental cycles. The 21st century has seen a dramatic rise in the incidence of circadian and sleep disorders with globalization, technological advances, and the use of personal electronics. The circadian clock modulates alcohol- and drug-induced behaviors with circadian misalignment contributing to increased substance use and abuse. Invertebrate models, such as Drosophila melanogaster, have proven invaluable for the identification of genetic and molecular mechanisms underlying highly conserved processes including the circadian clock, drug tolerance, and reward systems. In this review, we highlight the contributions of Drosophila as a model system for understanding the bidirectional interactions between the circadian system and the drugs of abuse, alcohol and cocaine, and illustrate the highly conserved nature of these interactions between Drosophila and mammalian systems. Research in Drosophila provides mechanistic insights into the corresponding behaviors in higher organisms and can be used as a guide for targeted inquiries in mammals. Aliza K. De Nobrega and Lisa C. Lyons Copyright © 2017 Aliza K. De Nobrega and Lisa C. Lyons. All rights reserved. Comparison of Adult Hippocampal Neurogenesis and Susceptibility to Treadmill Exercise in Nine Mouse Strains Sun, 17 Dec 2017 00:00:00 +0000 The genetic background of mice has various influences on the efficacy of physical exercise, as well as adult neurogenesis in the hippocampus. In this study, we investigated the basal level of hippocampal neurogenesis, as well as the effects of treadmill exercise on adult hippocampal neurogenesis in 9 mouse strains: 8 very commonly used laboratory inbred mouse strains (C57BL/6, BALB/c, A/J, C3H/HeJ, DBA/1, DBA/2, 129/SvJ, and FVB) and 1 outbred mouse strain (ICR). All 9 strains showed diverse basal levels of cell proliferation, neuroblast differentiation, and integration into granule cells in the sedentary group. C57BL/6 mice showed the highest levels of cell proliferation, neuroblast differentiation, and integration into granule cells at basal levels, and the DBA/2 mice showed the lowest levels. The efficacy of integration into granule cells was maximal in ICR mice. Treadmill exercise increased adult hippocampal neurogenesis in all 9 mouse strains. These results suggest that the genetic background of mice affects hippocampal neurogenesis and C57BL/6 mice are the most useful strain to assess basal levels of cell proliferation and neuroblast differentiation, but not maturation into granule cells. In addition, the DBA/2 strain is not suitable for studying hippocampal neurogenesis. Jong Whi Kim, Sung Min Nam, Dae Young Yoo, Hyo Young Jung, Il Yong Kim, In Koo Hwang, Je Kyung Seong, and Yeo Sung Yoon Copyright © 2017 Jong Whi Kim et al. All rights reserved. Longitudinal Brain Functional Connectivity Changes of the Cortical Motor-Related Network in Subcortical Stroke Patients with Acupuncture Treatment Mon, 11 Dec 2017 07:12:29 +0000 In clinical practice, the effectiveness of the rehabilitation therapy such as acupuncture combining conventional Western medicine (AG) on stroke people’s motor-related brain network and their behaviors has not been systematically studied. In the present study, seventeen adult ischemic patients were collected and divided into two groups: the conventional Western medicine treatment group (CG) and the AG. The neurological deficit scores (NDS) and resting-state functional MRI data were collected before and after treatment. Compared with the CG patients, AG patients exhibited a significant enhancement of the percent changes of NDS from pre- to posttreatment intervention. All patients showed significant changes of functional connectivity (FC) between the pair of cortical motor-related regions. After treatment, both patient groups showed a recovery of brain connectivity to the nearly normal level compared with the controls in these pairs. Moreover, a significant correlation between the percent changes of NDS and the pretreatment FC values of bilateral primary motor cortex (M1) in all patients was found. In conclusion, our results showed that AG therapy can be an effective means for ischemic stroke patients to recover their motor function ability. The FC strengths between bilateral M1 of stroke patients can predict stroke patients’ treatment outcome after rehabilitation therapy. Yongxin Li, Ya Wang, Chenxi Liao, Wenhua Huang, and Ping Wu Copyright © 2017 Yongxin Li et al. All rights reserved. Transcutaneous Vagus Nerve Stimulation Combined with Robotic Rehabilitation Improves Upper Limb Function after Stroke Sun, 10 Dec 2017 00:00:00 +0000 The efficacy of standard rehabilitative therapy for improving upper limb functions after stroke is limited; thus, alternative strategies are needed. Vagus nerve stimulation (VNS) paired with rehabilitation is a promising approach, but the invasiveness of this technique limits its clinical application. Recently, a noninvasive method to stimulate vagus nerve has been developed. The aim of the present study was to explore whether noninvasive VNS combined with robotic rehabilitation can enhance upper limb functionality in chronic stroke. Safety and efficacy of this combination have been assessed within a proof-of-principle, double-blind, semirandomized, sham-controlled trial. Fourteen patients with either ischemic or haemorrhagic chronic stroke were randomized to robot-assisted therapy associated with real or sham VNS, delivered for 10 working days. Efficacy was evaluated by change in upper extremity Fugl–Meyer score. After intervention, there were no adverse events and Fugl–Meyer scores were significantly better in the real group compared to the sham group. Our pilot study confirms that VNS is feasible in stroke patients and can produce a slight clinical improvement in association to robotic rehabilitation. Compared to traditional stimulation, noninvasive VNS seems to be safer and more tolerable. Further studies are needed to confirm the efficacy of this innovative approach. Fioravante Capone, Sandra Miccinilli, Giovanni Pellegrino, Loredana Zollo, Davide Simonetti, Federica Bressi, Lucia Florio, Federico Ranieri, Emma Falato, Alessandro Di Santo, Alessio Pepe, Eugenio Guglielmelli, Silvia Sterzi, and Vincenzo Di Lazzaro Copyright © 2017 Fioravante Capone et al. All rights reserved. Long-Term High Salt Intake Involves Reduced SK Currents and Increased Excitability of PVN Neurons with Projections to the Rostral Ventrolateral Medulla in Rats Wed, 06 Dec 2017 00:00:00 +0000 Evidence indicates that high salt (HS) intake activates presympathetic paraventricular nucleus (PVN) neurons, which contributes to sympathoexcitation of salt-sensitive hypertension. The present study determined whether 5 weeks of HS (2% NaCl) intake alters the small conductance Ca2+-activated potassium channel (SK) current in presympathetic PVN neurons and whether this change affects the neuronal excitability. In whole-cell voltage-clamp recordings, HS-treated rats had significantly decreased SK currents compared to rats with normal salt (NS, 0.4% NaCl) intake in PVN neurons. The sensitivity of PVN neuronal excitability in response to current injections was greater in HS group compared to NS controls. The SK channel blocker apamin augmented the neuronal excitability in both groups but had less effect on the sensitivity of the neuronal excitability in HS group compared to NS controls. In the HS group, the interspike interval (ISI) was significantly shorter than that in NS controls. Apamin significantly shortened the ISI in NS controls but had less effect in the HS group. This data suggests that HS intake reduces SK currents, which contributes to increased PVN neuronal excitability at least in part through a decrease in spike frequency adaptation and may be a precursor to the development of salt-sensitive hypertension. Andrew D. Chapp, Renjun Wang, Zixi (Jack) Cheng, Zhiying Shan, and Qing-Hui Chen Copyright © 2017 Andrew D. Chapp et al. All rights reserved. Brain-Specific SNAP-25 Deletion Leads to Elevated Extracellular Glutamate Level and Schizophrenia-Like Behavior in Mice Tue, 28 Nov 2017 00:00:00 +0000 Several studies have associated reduced expression of synaptosomal-associated protein of 25 kDa (SNAP-25) with schizophrenia, yet little is known about its role in the illness. In this paper, a forebrain glutamatergic neuron-specific SNAP-25 knockout mouse model was constructed and studied to explore the possible pathogenetic role of SNAP-25 in schizophrenia. We showed that SNAP-25 conditional knockout (cKO) mice exhibited typical schizophrenia-like phenotype. A significantly elevated extracellular glutamate level was detected in the cerebral cortex of the mouse model. Compared with Ctrls, SNAP-25 was dramatically reduced by about 60% both in cytoplasm and in membrane fractions of cerebral cortex of cKOs, while the other two core members of SNARE complex: Syntaxin-1 (increased ~80%) and Vamp2 (increased ~96%) were significantly increased in cell membrane part. Riluzole, a glutamate release inhibitor, significantly attenuated the locomotor hyperactivity deficits in cKO mice. Our findings provide in vivo functional evidence showing a critical role of SNAP-25 dysfunction on synaptic transmission, which contributes to the developmental of schizophrenia. It is suggested that a SNAP-25 cKO mouse, a valuable model for schizophrenia, could address questions regarding presynaptic alterations that contribute to the etiopathophysiology of SZ and help to consummate the pre- and postsynaptic glutamatergic pathogenesis of the illness. Hua Yang, Mengjie Zhang, Jiahao Shi, Yunhe Zhou, Zhipeng Wan, Yicheng Wang, Yinghan Wan, Jun Li, Zhugang Wang, and Jian Fei Copyright © 2017 Hua Yang et al. All rights reserved. Neural Mechanisms of Circadian Regulation of Natural and Drug Reward Tue, 21 Nov 2017 00:00:00 +0000 Circadian rhythms are endogenously generated near 24-hour variations of physiological and behavioral functions. In humans, disruptions to the circadian system are associated with negative health outcomes, including metabolic, immune, and psychiatric diseases, such as addiction. Animal models suggest bidirectional relationships between the circadian system and drugs of abuse, whereby desynchrony, misalignment, or disruption may promote vulnerability to drug use and the transition to addiction, while exposure to drugs of abuse may entrain, disrupt, or perturb the circadian timing system. Recent evidence suggests natural (i.e., food) and drug rewards may influence overlapping neural circuitry, and the circadian system may modulate the physiological and behavioral responses to these stimuli. Environmental disruptions, such as shifting schedules or shorter/longer days, influence food and drug intake, and certain mutations of circadian genes that control cellular rhythms are associated with altered behavioral reward. We highlight the more recent findings associating circadian rhythms to reward function, linking environmental and genetic evidence to natural and drug reward and related neural circuitry. Lauren M. DePoy, Colleen A. McClung, and Ryan W. Logan Copyright © 2017 Lauren M. DePoy et al. All rights reserved. Sustained Activity of Metabotropic Glutamate Receptor: Homer, Arrestin, and Beyond Tue, 21 Nov 2017 00:00:00 +0000 When activated, metabotropic glutamate receptors (mGlus) exert long-lasting changes within the glutamatergic synapses. One mechanism is a tonic effect of downstream signal transduction pathways via sustained activation of mGlu itself. Like many other G protein-coupled receptors (GPCRs), mGlu can exist in a constitutively active state, which persists agonist independently. In this paper, we review the current knowledge of the mechanisms underlying the constitutive activity of group I mGlus. The issues concerning Homer1a mechanism in the constitutive activity of group I mGlus and recent findings regarding the significant role of β-arrestin in sustained GPCR activity are also discussed. We propose that once in a state of sustained activation, the mGlu persistently activates downstream signaling pathways, including various adaptor proteins and kinases, such as β-arrestin and mitogen-activated protein kinases. In turn, these effector molecules bind to or phosphorylate the mGlu C-terminal binding domains and consequently regulate the activation state of the mGlu. Geehoon Chung and Sang Jeong Kim Copyright © 2017 Geehoon Chung and Sang Jeong Kim. All rights reserved. Interhemispheric Pathways Are Important for Motor Outcome in Individuals with Chronic and Severe Upper Limb Impairment Post Stroke Thu, 16 Nov 2017 10:10:18 +0000 Background. Severity of arm impairment alone does not explain motor outcomes in people with severe impairment post stroke. Objective. Define the contribution of brain biomarkers to upper limb motor outcomes in people with severe arm impairment post stroke. Methods. Paretic arm impairment (Fugl-Meyer upper limb, FM-UL) and function (Wolf Motor Function Test rate, WMFT-rate) were measured in 15 individuals with severe (FM-UL ≤ 30/66) and 14 with mild–moderate (FM-UL > 40/66) impairment. Transcranial magnetic stimulation and diffusion weight imaging indexed structure and function of the corticospinal tract and corpus callosum. Separate models of the relationship between possible biomarkers and motor outcomes at a single chronic (≥6 months) time point post stroke were performed. Results. Age (ΔR20.365, ) and ipsilesional-transcallosal inhibition (ΔR20.182, ) explained a 54.7% () variance in paretic WMFT-rate. Prefrontal corpus callous fractional anisotropy (PF-CC FA) alone explained 49.3% () variance in FM-UL outcome. The same models did not explain significant variance in mild–moderate stroke. In the severe group, k-means cluster analysis of PF-CC FA distinguished two subgroups, separated by a clinically meaningful and significant difference in motor impairment () and function () outcomes. Conclusion. Corpus callosum function and structure were identified as possible biomarkers of motor outcome in people with chronic and severe arm impairment. Kathryn S. Hayward, Jason L. Neva, Cameron S. Mang, Sue Peters, Katie P. Wadden, Jennifer K. Ferris, and Lara A. Boyd Copyright © 2017 Kathryn S. Hayward et al. All rights reserved. A Longitudinal fMRI Research on Neural Plasticity and Sensory Outcome of Carpal Tunnel Syndrome Thu, 16 Nov 2017 00:00:00 +0000 Peripheral nerve compression is reported to induce cortical plasticity, which was well pictured by former researches. However, the longitudinal changes brought by surgical treatment are not clear. In this research, 18 subjects who suffered from bilateral carpal tunnel syndrome were evaluated using task-dependent fMRI and electromyography assessment before and after surgery. The third digit was tactually simulated by von Frey filaments. The results demonstrated that the pattern of activation was similar but a decreased extent of activation in the postcentral gyrus, inferior frontal lobe, superior frontal lobe, and parahippocampal gyrus after surgery was found. The correlation analysis showed a significant correlation between the decreased number of activated voxels and the improvement of EMG performance. This result implied a potential connection between fMRI measurement and clinical improvement. Hao Ma, Yechen Lu, Xuyun Hua, Yundong Shen, Mouxiong Zheng, and Wendong Xu Copyright © 2017 Hao Ma et al. All rights reserved. New Insights into the Role of the Locus Coeruleus-Noradrenergic System in Memory and Perception Dysfunction Thu, 09 Nov 2017 00:00:00 +0000 O. Eschenko, P. B. Mello-Carpes, and N. Hansen Copyright © 2017 O. Eschenko et al. All rights reserved. Glucose Intake Alters Expression of Neuropeptides Derived from Proopiomelanocortin in the Lateral Hypothalamus and the Nucleus Accumbens in Fructose Preference Rats Wed, 08 Nov 2017 00:00:00 +0000 To study the neuroendocrine mechanism of sugar preference, we investigated the role of glucose feeding in the regulation of expression levels of neuropeptides derived from proopiomelanocortin (POMC) in the lateral hypothalamus (LH) and nucleus accumbens (NAc) in fructose preference rats. Fructose preference rats were induced by using the lithium chloride backward conditioning procedure. The fructose preference was confirmed by the two-bottle test. The drinking behavior of rats was assessed by the fructose concentration gradient test. The preference of 10% glucose or 0.1% saccharine was assessed, and the expression levels of neuropeptides derived from POMC in the LH and the NAc in fructose preference rats were measured by Western blot analysis. Fructose preference rats displayed a greater fructose preference than control rats. Furthermore, fructose preference rats preferred glucose solution rather than saccharine solution, while control rats preferred saccharine solution rather than glucose solution. The expression levels of neuropeptides derived from POMC in the LH and the NAc were changed by glucose but not saccharine intake. In summary, the data suggests that glucose intake increases the expression of neuropeptides derived from POMC in the LH and the NAc in fructose preference rats. Guangfa Jiao, Guozhong Zhang, Haiying Wang, Weilin Zhao, Yanwei Cui, Yongjing Liu, Feng Gao, Fang Yuan, and Yi Zhang Copyright © 2017 Guangfa Jiao et al. All rights reserved. Hippocampal Regulation of Postsynaptic Density Homer1 by Associative Learning Tue, 07 Nov 2017 00:00:00 +0000 Genes involved in synaptic plasticity, particularly genes encoding postsynaptic density proteins, have been recurrently linked to psychiatric disorders including schizophrenia and autism. Postsynaptic density Homer1 proteins contribute to synaptic plasticity through the competing actions of short and long isoforms. The activity-induced expression of short Homer1 isoforms, Homer1a and Ania-3, is thought to be related to processes of learning and memory. However, the precise regulation of Homer1a and Ania-3 with different components of learning has not been investigated. Here, we used in situ hybridization to quantify short and long Homer1 expression in the hippocampus following consolidation, retrieval, and extinction of associative fear memory, using contextual fear conditioning in rats. Homer1a and Ania-3, but not long Homer1, were regulated by contextual fear learning or novelty detection, although their precise patterns of expression in hippocampal subregions were dependent on the isoform. We also show for the first time that the two short Homer1 isoforms are regulated after the retrieval and extinction of contextual fear memory, albeit with distinct temporal and spatial profiles. These findings support a role of activity-induced Homer1 isoforms in learning and memory processes in discrete hippocampal subregions and suggest that Homer1a and Ania-3 may play separable roles in synaptic plasticity. Nicholas E. Clifton, Darren Cameron, Simon Trent, Lucy H. Sykes, Kerrie L. Thomas, and Jeremy Hall Copyright © 2017 Nicholas E. Clifton et al. All rights reserved. Sphingosine 1-Phosphate Receptor 1 Modulates CNTF-Induced Axonal Growth and Neuroprotection in the Mouse Visual System Mon, 06 Nov 2017 03:42:21 +0000 The lack of axonal regeneration and neuronal cell death causes permanent neurological deficits in the injured CNS. Using the classical CNS injury model of optic nerve crush in mice, ciliary neurotrophic factor (CNTF) was found to stimulate retinal ganglion cell (RGC) survival and axonal growth, but in an incomplete fashion. The elucidation of molecular mechanisms impairing CNTF-induced axonal regeneration is paramount to promote visual recovery. In the present study, we sought to evaluate the contribution of sphingosine 1-phosphate receptor 1 (S1PR1) to the neuroprotective and regenerative effects of CNTF. The transduction of retinal cells with adeno-associated viruses (AAV) allowed to activate CNTF/signal transducer and activator of transcription 3 (Stat3) signaling and to modulate S1PR1 expression in RGCs. Our results showed that CNTF/Stat3 prevented injury-induced S1PR1 downregulation. Silencing S1PR1 in RGCs significantly enhanced CNTF-induced axonal growth in the injured optic nerve. In contrast, RGC survival was markedly decreased when S1PR1 was repressed with viral vectors. The level of phosphorylated Stat3 (P-Stat3), an intracellular mediator of CNTF, did not fluctuate after S1PR1 inhibition and CNTF stimulation. Collectively, these results suggest that S1PR1 acts as a major regulator of retinal neuron survival and restricts the RGC growth response induced by CNTF. Sandrine Joly, Deniz Dalkara, and Vincent Pernet Copyright © 2017 Sandrine Joly et al. All rights reserved. Circadian Rhythm Disturbances in Mood Disorders: Insights into the Role of the Suprachiasmatic Nucleus Sun, 05 Nov 2017 00:00:00 +0000 Circadian rhythm disturbances are a common symptom among individuals with mood disorders. The suprachiasmatic nucleus (SCN), in the ventral part of the anterior hypothalamus, orchestrates physiological and behavioral circadian rhythms. The SCN consists of self-sustaining oscillators and receives photic and nonphotic cues, which entrain the SCN to the external environment. In turn, through synaptic and hormonal mechanisms, the SCN can drive and synchronize circadian rhythms in extra-SCN brain regions and peripheral tissues. Thus, genetic or environmental perturbations of SCN rhythms could disrupt brain regions more closely related to mood regulation and cause mood disturbances. Here, we review clinical and preclinical studies that provide evidence both for and against a causal role for the SCN in mood disorders. Chelsea A. Vadnie and Colleen A. McClung Copyright © 2017 Chelsea A. Vadnie and Colleen A. McClung. All rights reserved. Regionally Specific Regulation of Sensorimotor Network Connectivity Following Tactile Improvement Thu, 02 Nov 2017 05:56:51 +0000 Correlations between inherent, task-free low-frequency fluctuations in the blood oxygenation level-dependent (BOLD) signals of the brain provide a potent tool to delineate its functional architecture in terms of intrinsic functional connectivity (iFC). Still, it remains unclear how iFC is modulated during learning. We employed whole-brain resting-state magnetic resonance imaging prior to and after training-independent repetitive sensory stimulation (rSS), which is known to induce somatosensory cortical reorganization. We investigated which areas in the sensorimotor network are susceptible to neural plasticity (i.e., where changes in functional connectivity occurred) and where iFC might be indicative of enhanced tactile performance. We hypothesized iFC to increase in those brain regions primarily receiving the afferent tactile input. Strengthened intrinsic connectivity within the sensorimotor network after rSS was found not only in the postcentral gyrus contralateral to the stimulated hand, but also in associative brain regions, where iFC correlated positively with tactile performance or learning. We also observed that rSS led to attenuation of the network at higher cortical levels, which possibly promotes facilitation of tactile discrimination. We found that resting-state BOLD fluctuations are linked to behavioral performance and sensory learning, indicating that network fluctuations at rest are predictive of behavioral changes and neuroplasticity. Stefanie Heba, Melanie Lenz, Tobias Kalisch, Oliver Höffken, Lauren M. Schweizer, Benjamin Glaubitz, Nicolaas A. J. Puts, Martin Tegenthoff, Hubert R. Dinse, and Tobias Schmidt-Wilcke Copyright © 2017 Stefanie Heba et al. All rights reserved. Modulation Effects of Cordycepin on Voltage-Gated Sodium Channels in Rat Hippocampal CA1 Pyramidal Neurons in the Presence/Absence of Oxygen Tue, 31 Oct 2017 00:00:00 +0000 Our previous study revealed that cordycepin features important neuroprotective effects against hypoxic insult by improvement of neuronal electrophysiological function. Modulation on voltage-gated sodium channel (VGSC) in CA1 neurons is the initial event during hypoxia/ischemia. However, no study comprehensively investigated cordycepin on VGSC. Hence, this study investigated modulation effects of cordycepin on VGSC not only in oxygen physiological conditions but also in acute oxygen deprivation injury conditions. Results revealed that cordycepin (80 μM) reduced the amplitude of VGSC currents (INa) (77.6% of control, ) within 1 min of drug exposure coupled with a negative shift in steady-state inactivation and prolonged recovery time course from inactivation. Additionally, this mild reduction on the peak of INa induced by the pretreatment with cordycepin can attenuate and delay the following hypoxia causing rapid dramatic decrease in INa with no additive change in the voltage dependence of inactivation. As modulation on VGSC in CA1 neurons represents the initial event during ischemia, we propose that suppression effect of cordycepin on VGSC is an important neuronal protective mechanism that may enhance neuronal tolerance to acute oxygen deprivation and delay hypoxia-induced neuronal injuries. Zhi-Bin Liu, Chao Liu, Bin Zeng, Li-Ping Huang, and Li-Hua Yao Copyright © 2017 Zhi-Bin Liu et al. All rights reserved. Correlation between Traits of Emotion-Based Impulsivity and Intrinsic Default-Mode Network Activity Tue, 31 Oct 2017 00:00:00 +0000 Negative urgency (NU) and positive urgency (PU) are implicated in several high-risk behaviors, such as eating disorders, substance use disorders, and nonsuicidal self-injury behavior. The current study aimed to explore the possible link between trait of urgency and brain activity at rest. We assessed the amplitude of low-frequency fluctuations (ALFF) of the resting-state functional magnetic resonance imaging (fMRI) signal in 85 healthy volunteers. Trait urgency measures were related to ALFF in the lateral orbitofrontal cortex, dorsolateral prefrontal cortex, ventral and dorsal medial frontal cortex, anterior cingulate, and posterior cingulate cortex/precuneus. In addition, trait urgency measures showed significant correlations with the functional connectivity of the posterior cingulate cortex/precuneus seed with the thalamus and midbrain region. These findings suggest an association between intrinsic brain activity and impulsive behaviors in healthy humans. Jizheng Zhao, Dardo Tomasi, Corinde E. Wiers, Ehsan Shokri-Kojori, Şükrü B. Demiral, Yi Zhang, Nora D. Volkow, and Gene-Jack Wang Copyright © 2017 Jizheng Zhao et al. All rights reserved.