Neural Plasticity The latest articles from Hindawi © 2017 , Hindawi Limited . All rights reserved. Constitutive Expression of Adiponectin in Endothelial Progenitor Cells Protects a Rat Model of Cerebral Ischemia Sun, 22 Oct 2017 00:00:00 +0000 Endothelial progenitor cells (EPCs), as precursors to endothelial cells, play a significant part in the process of endogenous blood vessel repair and maintenance of endothelial integrity. Adiponectin (APN) is an adipocyte-specific adipocytokine. In this study, we aim to test whether we transplant a combined graft of EPCs transfected with the adiponectin gene into a rat model of cerebral ischemia could improve functional recovery after middle cerebral artery occlusion (MCAO). Sprague-Dawley (SD) rats were randomly divided into a MCAO control group, a MCAO EPC treatment group, and a MCAO LV-APN-EPC treatment group. A focal cerebral ischemia and reperfusion model was induced by the intraluminal suture method. After 2 h of reperfusion, EPCs were transplanted by injection through the tail vein. A rotarod test was conducted to assess behavioral function before MCAO and on days 1, 7, and 14 after MCAO. After 14 d, TTC staining, CD31 immunofluorescence, and TUNEL staining were used to evaluate infarct volume, microvessel density, and cell apoptosis. Results revealed that behavioral function, infarct area percentage, microvessel density, and cell apoptosis rates were more favorable in the LV-APN-EPC treatment group than in the EPC treatment group. These data suggested that gene-modified cell therapy may be a useful approach for the treatment of ischemic stroke. Renwei Zhang, Xiaorui Xie, Qing Yu, Hongliang Feng, Meiyao Wang, Yan Li, and Yumin Liu Copyright © 2017 Renwei Zhang et al. All rights reserved. Neural Plasticity Is Involved in Physiological Sleep, Depressive Sleep Disturbances, and Antidepressant Treatments Wed, 18 Oct 2017 00:00:00 +0000 Depression, which is characterized by a pervasive and persistent low mood and anhedonia, greatly impacts patients, their families, and society. The associated and recurring sleep disturbances further reduce patient’s quality of life. However, therapeutic sleep deprivation has been regarded as a rapid and robust antidepressant treatment for several decades, which suggests a complicated role of sleep in development of depression. Changes in neural plasticity are observed during physiological sleep, therapeutic sleep deprivation, and depression. This correlation might help us to understand better the mechanism underlying development of depression and the role of sleep. In this review, we first introduce the structure of sleep and the facilitated neural plasticity caused by physiological sleep. Then, we introduce sleep disturbances and changes in plasticity in patients with depression. Finally, the effects and mechanisms of antidepressants and therapeutic sleep deprivation on neural plasticity are discussed. Meng-Qi Zhang, Rui Li, Yi-Qun Wang, and Zhi-Li Huang Copyright © 2017 Meng-Qi Zhang et al. All rights reserved. Spinal Excitability Changes after Transspinal and Transcortical Paired Associative Stimulation in Humans Mon, 16 Oct 2017 10:36:40 +0000 Paired associative stimulation (PAS) produces enduring neuroplasticity based on Hebbian associative plasticity. This study established the changes in spinal motoneuronal excitability by pairing transcortical and transspinal stimulation. Transcortical stimulation was delivered after (transspinal-transcortical PAS) or before (transcortical-transspinal PAS) transspinal stimulation. Before and after 40 minutes of each PAS protocol, spinal neural excitability was assessed based on the amplitude of the transspinal-evoked potentials (TEPs) recorded from ankle muscles of both legs at different stimulation intensities (recruitment input-output curve). Changes in TEPs amplitude in response to low-frequency stimulation and paired transspinal stimuli were also established before and after each PAS protocol. TEP recruitment input-output curves revealed a generalized depression of TEPs in most ankle muscles of both legs after both PAS protocols that coincided with an increased gain only after transcortical-transspinal PAS. Transcortical-transspinal PAS increased and transspinal-transcortical PAS decreased the low-frequency-dependent TEP depression, whereas neither PAS protocol affected the TEP depression observed upon paired transspinal stimuli. These findings support the notion that transspinal and transcortical PAS has the ability to alter concomitantly cortical and spinal synaptic activity. Transspinal and transcortical PAS may contribute to the development of rehabilitation strategies in people with bilateral increased motoneuronal excitability due to cortical or spinal lesions. Maria Knikou Copyright © 2017 Maria Knikou. All rights reserved. Locus Coeruleus and Dopamine-Dependent Memory Consolidation Mon, 16 Oct 2017 09:21:26 +0000 Most everyday memories including many episodic-like memories that we may form automatically in the hippocampus (HPC) are forgotten, while some of them are retained for a long time by a memory stabilization process, called initial memory consolidation. Specifically, the retention of everyday memory is enhanced, in humans and animals, when something novel happens shortly before or after the time of encoding. Converging evidence has indicated that dopamine (DA) signaling via D1/D5 receptors in HPC is required for persistence of synaptic plasticity and memory, thereby playing an important role in the novelty-associated memory enhancement. In this review paper, we aim to provide an overview of the key findings related to D1/D5 receptor-dependent persistence of synaptic plasticity and memory in HPC, especially focusing on the emerging evidence for a role of the locus coeruleus (LC) in DA-dependent memory consolidation. We then refer to candidate brain areas and circuits that might be responsible for detection and transmission of the environmental novelty signal and molecular and anatomical evidence for the LC-DA system. We also discuss molecular mechanisms that might mediate the environmental novelty-associated memory enhancement, including plasticity-related proteins that are involved in initial memory consolidation processes in HPC. Miwako Yamasaki and Tomonori Takeuchi Copyright © 2017 Miwako Yamasaki and Tomonori Takeuchi. All rights reserved. Neuroplasticity and Healthy Lifestyle: How Can We Understand This Relationship? Mon, 16 Oct 2017 04:31:16 +0000 Azucena Begega, Luis J. Santín, Pablo Galeano, Debora Cutuli, and Patricia Sampedro Piquero Copyright © 2017 Azucena Begega et al. All rights reserved. Enhancement in Tonically Active Glutamatergic Inputs to the Rostral Ventrolateral Medulla Contributes to Neuropathic Pain-Induced High Blood Pressure Thu, 12 Oct 2017 08:44:30 +0000 Neuropathic pain increases the risk of cardiovascular diseases including hypertension with the characteristic of sympathetic overactivity. The enhanced tonically active glutamatergic input to the rostral ventrolateral medulla (RVLM) contributes to sympathetic overactivity and blood pressure (BP) in cardiovascular diseases. We hypothesize that neuropathic pain enhances tonically active glutamatergic inputs to the RVLM, which contributes to high level of BP and sympathetic outflow. Animal model with the trigeminal neuropathic pain was induced by the infraorbital nerve-chronic constriction injury (ION-CCI). A significant increase in BP and renal sympathetic nerve activity (RSNA) was found in rats with ION-CCI (BP, , RSNA, , ). The concentration of glutamate in the RVLM was significantly increased in the ION-CCI group (, ). Blockade of glutamate receptors by injection of kynurenic acid into the RVLM significantly decreased BP and RSNA in the ION-CCI group (, ). In two major sources (the paraventricular nucleus and periaqueductal gray) for glutamatergic inputs to the RVLM, the ION-CCI group (, ) showed an increase in glutamate content and expression of glutaminase 2, vesicular glutamate transporter 2 proteins, and c-fos. Our results suggest that enhancement in tonically active glutamatergic inputs to the RVLM contributes to neuropathic pain-induced high blood pressure. Wei Wang, Zui Zou, Xing Tan, Ru-Wen Zhang, Chang-Zhen Ren, Xue-Ya Yao, Cheng-Bao Li, Wei-Zhong Wang, and Xue-Yin Shi Copyright © 2017 Wei Wang et al. All rights reserved. Effects of Propofol Treatment in Neural Progenitors Derived from Human-Induced Pluripotent Stem Cells Sun, 08 Oct 2017 00:00:00 +0000 Propofol is an intravenous anesthetic that has been widely used in clinics. Besides its anesthetic effects, propofol has also been reported to influence the regulation of the autonomic system. Controversies exist with regard to whether propofol exposure is safe for pregnant women and young children. In this work, human-induced pluripotent stem cell- (hiPSC-) derived neural progenitor cells (NPCs) were treated with propofol at 20, 50, 100, or 300 μM for 6 h or 24 h, and acute and subacute cell injury, cell proliferation, and apoptosis were evaluated. Comparison of genome-wide gene expression profiles was performed for treated and control iPSC-NPCs. Propofol treatment for 6 h at the clinically relevant concentration (20 or 50 μM) did not affect cell viability, apoptosis, or proliferation, while propofol at higher concentration (100 or 300 μM) decreased NPC viability and induced apoptosis. In addition, 20 μM propofol treatment for 6 h did not alter global gene expression. In summary, propofol treatment at commonly practiced clinical doses for 6 h did not have adverse effects on hiPSC-derived NPCs. In contrast, longer exposure and/or higher concentration could decrease NPC viability and induce apoptosis. Bo Long, Shenglan Li, Haipeng Xue, Li Sun, Dong H. Kim, and Ying Liu Copyright © 2017 Bo Long et al. All rights reserved. Functional Metaplasticity of Hippocampal Schaffer Collateral-CA1 Synapses Is Reversed in Chronically Epileptic Rats Mon, 02 Oct 2017 05:11:50 +0000 Spatial learning and associating spatial information with individual experience are crucial for rodents and higher mammals. Hence, studying the cellular and molecular cascades involved in the key mechanism of information storage in the brain, synaptic plasticity, has led to enormous knowledge in this field. A major open question applies to the interdependence between synaptic plasticity and its behavioral correlates. In this context, it has become clear that behavioral aspects may impact subsequent synaptic plasticity, a phenomenon termed behavioral metaplasticity. Here, we trained control and pilocarpine-treated chronically epileptic rats of two different age groups (adolescent and adult) in a spatial memory task and subsequently tested long-term potentiation (LTP) in vitro at Schaffer collateral—CA1 synapses. As expected, memory acquisition in the behavioral task was significantly impaired both in pilocarpine-treated animals and in adult controls. Accordingly, these groups, without being tested in the behavioral training task, showed reduced CA1-LTP levels compared to untrained young controls. Spatial memory training significantly reduced subsequent CA1-LTP in vitro in the adolescent control group yet enhanced CA1-LTP in the adult pilocarpine-treated group. Such training in the adolescent pilocarpine-treated and adult control groups resulted in intermediate changes. Our study demonstrates age-dependent functional metaplasticity following a spatial memory training task and its reversal under pathological conditions. Mirko Rehberg, Timo Kirschstein, Xiati Guli, Steffen Müller, Marco Rohde, Denise Franz, Tursonjan Tokay, and Rüdiger Köhling Copyright © 2017 Mirko Rehberg et al. All rights reserved. The Cardiovascular Effect of Systemic Homocysteine Is Associated with Oxidative Stress in the Rostral Ventrolateral Medulla Fri, 29 Sep 2017 08:36:50 +0000 It has been demonstrated that homocysteine (HCY) is a significant risk factor of hypertension, which is characterized by overactivity of sympathetic tone. Excessive oxidative stress in the rostral ventrolateral medulla (RVLM), a key region for control of sympathetic outflow, contributes to sympathetic hyperactivity in hypertension. Therefore, the goal of the present study is to determine the effect of systemic HCY on production of reactive oxygen species (ROS) in the RVLM. In the rat model of the diet-induced hyperhomocysteinemia (L-methionine, 1 g/kg/day, 8 weeks), we found that the HCY resulted in a significant increase (≈3.7-fold, ) in ROS production in the RVLM, which was paralleled with enhanced sympathetic tone and blood pressure (BP). Compared to the vehicle group, levels of BP and basal renal sympathetic nerve activity in the HCY group were significantly (, ) increased by an average of 27 mmHg and 31%, respectively. Furthermore, the rats treated with L-methionine (1 g/kg/day, 8 weeks) showed an upregulation of NADPHase (NOX4) protein expression and a downregulation of superoxide dismutase protein expression in the RVLM. The current data suggest that central oxidative stress induced by systemic HCY plays an important role in hypertension-associated sympathetic overactivity. Mei-Fang Zhong, Yu-Hong Zhao, Hua Xu, Xing Tan, Yang-Kai Wang, and Wei-Zhong Wang Copyright © 2017 Mei-Fang Zhong et al. All rights reserved. Neural Vascular Mechanism for the Cerebral Blood Flow Autoregulation after Hemorrhagic Stroke Tue, 26 Sep 2017 00:00:00 +0000 During the initial stages of hemorrhagic stroke, including intracerebral hemorrhage and subarachnoid hemorrhage, the reflex mechanisms are activated to protect cerebral perfusion, but secondary dysfunction of cerebral flow autoregulation will eventually reduce global cerebral blood flow and the delivery of metabolic substrates, leading to generalized cerebral ischemia, hypoxia, and ultimately, neuronal cell death. Cerebral blood flow is controlled by various regulatory mechanisms, including prevailing arterial pressure, intracranial pressure, arterial blood gases, neural activity, and metabolic demand. Evoked by the concept of vascular neural network, the unveiled neural vascular mechanism gains more and more attentions. Astrocyte, neuron, pericyte, endothelium, and so forth are formed as a communicate network to regulate with each other as well as the cerebral blood flow. However, the signaling molecules responsible for this communication between these new players and blood vessels are yet to be definitively confirmed. Recent evidence suggested the pivotal role of transcriptional mechanism, including but not limited to miRNA, lncRNA, exosome, and so forth, for the cerebral blood flow autoregulation. In the present review, we sought to summarize the hemodynamic changes and underline neural vascular mechanism for cerebral blood flow autoregulation in stroke-prone state and after hemorrhagic stroke and hopefully provide more systematic and innovative research interests for the pathophysiology and therapeutic strategies of hemorrhagic stroke. Ming Xiao, Qiang Li, Hua Feng, Le Zhang, and Yujie Chen Copyright © 2017 Ming Xiao et al. All rights reserved. Acute Exercise and Neurocognitive Development in Preadolescents and Young Adults: An ERP Study Mon, 25 Sep 2017 09:36:21 +0000 The purpose of this study was to examine the effect of a single bout of exercise on neurocognitive function in preadolescent children and young adults by determining the modulatory role of age and the neuroelectrical mechanism(s) underlying the association between acute exercise and executive function. Twenty preadolescents and 20 young adults completed the Stroop test, and neuroelectrical activity was recorded during two treatment sessions performed in a counterbalanced order. Exercise treatments involved moderate intensity aerobic exercise for 20 min as the main exercise and two 5 min periods of warm-up and cool-down. The control treatment participants read for a similar duration of time. Acute exercise improved participant reaction times on the Stroop test, regardless of Stroop congruency, and greater beneficial effects were observed in young adults compared to those in preadolescents. The P3 amplitudes increased after acute exercise in preadolescents and young adults, but acute exercise induced lower conflict sustained potential (conflict SP) amplitudes in preadolescent children. Based on these findings, age influences the beneficial effect of acute exercise on cognitive performance in general. Furthermore, the event-related brain potential differences attributed to acute exercise provide a potential clue to the mechanisms that differentiate the effects of acute exercise on individuals from preadolescence to young adulthood. Chien-Heng Chu, Arthur F. Kramer, Tai-Fen Song, Chih-Han Wu, Tsung-Min Hung, and Yu-Kai Chang Copyright © 2017 Chien-Heng Chu et al. All rights reserved. IL-33 Acts to Express Schaffer Collateral/CA1 LTP and Regulate Learning and Memory by Targeting MyD88 Sun, 24 Sep 2017 00:00:00 +0000 Interleukin-33 (IL-33) is recognized to transmit a signal through a heterodimeric receptor complex ST2/interleukin-1 receptor accessory protein (IL-1RAcP) bearing activation of myeloid differentiation factor 88 (MyD88). High-frequency stimulation to the Schaffer collateral induced long-term potentiation (LTP) in the CA1 region of hippocampal slices from wild-type control mice. Schaffer collateral/CA1 LTP in IL-33-deficient mice was significantly suppressed, which was neutralized by application with IL-33. Similar suppression of the LTP was found with MyD88-deficient mice but not with ST2-deficient mice. In the water maze test, the acquisition latency in IL-33-deficient and MyD88-deficient mice was significantly prolonged as compared with that in wild-type control mice. Moreover, the retention latency in MyD88-deficient mice was markedly prolonged. In contrast, the acquisition and retention latencies in ST2-deficient mice were not affected. Taken together, these results show that IL-33 acts to express Schaffer collateral/CA1 LTP relevant to spatial learning and memory in a MyD88-dependent manner and that the LTP might be expressed through an IL-1R1/IL-1RAcP-MyD88 pathway in the absence of ST2. Tomoyuki Nishizaki Copyright © 2017 Tomoyuki Nishizaki. All rights reserved. Corrigendum to “Short-Term Monocular Deprivation Enhances Physiological Pupillary Oscillations” Sun, 24 Sep 2017 00:00:00 +0000 Paola Binda and Claudia Lunghi Copyright © 2017 Paola Binda and Claudia Lunghi. All rights reserved. Corticospinal Plasticity in Bilateral Primary Motor Cortices Induced by Paired Associative Stimulation to the Dominant Hemisphere Does Not Differ between Young and Older Adults Sun, 24 Sep 2017 00:00:00 +0000 Older adults have been shown to exhibit a reduction in the lateralization of neural activity. Although neuroplasticity induced by noninvasive brain stimulation has been reported to be attenuated in the targeted motor cortex of older adults, it remains possible that the plasticity effects may instead manifest in a more distributed (bilateral) network. Furthermore, attention, which modulates neuroplasticity in young adults, may influence these effects. To address these questions, plasticity was induced in young (19–32 years) and older (65–78 years) adults using transcranial magnetic stimulation (TMS) paired with peripheral nerve stimulation. The plasticity effects induced by this paired associative stimulation (PAS) protocol in the targeted and nontargeted hemispheres were probed using TMS-induced motor-evoked potentials (MEPs) recorded from the abductor pollicis brevis (APB) muscle of each hand. PAS-induced effects were highly variable across individuals, with only half of the participants in each group demonstrating the expected increase in MEP amplitude. Contrary to predictions, however, PAS-induced corticospinal plasticity manifests predominately in the targeted hemisphere for both young and older adults. Attention to the target hand did not enhance corticospinal plasticity. The results suggest that plasticity does not manifest differently across bilateral corticospinal pathways between young and older adults. Daina S. E. Dickins, Marc R. Kamke, and Martin V. Sale Copyright © 2017 Daina S. E. Dickins et al. All rights reserved. The Effect of Aerobic Exercise on Brain-Derived Neurotrophic Factor in People with Neurological Disorders: A Systematic Review and Meta-Analysis Tue, 19 Sep 2017 00:00:00 +0000 Objective. To determine the effect of aerobic exercise on brain-derived neurotrophic factor (BDNF) levels in people with neurological disorders. Data Sources. Six electronic databases (CINAHL, PubMed, Cochrane, PsycINFO, SportDiscus, and Web of Science) were searched until the end of December 2016. Study Selection. Experimental or observational studies of people with neurological disorders who undertook an exercise intervention with BDNF as an outcome measure. The search strategy yielded 984 articles. Data Extraction. Study data were independently extracted from each article. Methodological quality of studies was assessed using the Physiotherapy Evidence Database (PEDro) scale. A meta-analysis was planned based on the assessment of predetermined criteria. Data Synthesis. Eleven articles were included. Studies employed either a program of aerobic exercise, a single bout of aerobic exercise, or both. A meta-analysis of studies comparing a program of aerobic exercise against usual care/nil therapy showed a large effect (SMD: 0.84, 95% CI 0.47–1.20, ) in favour of aerobic exercise to increase levels of BDNF. Findings for a single bout of aerobic exercise were mixed. Quality of studies was low (PEDro average score 4.3/10). Conclusions. A program of aerobic exercise may contribute to increased levels of BDNF in neurological populations. Christopher P. Mackay, Suzanne S. Kuys, and Sandra G. Brauer Copyright © 2017 Christopher P. Mackay et al. All rights reserved. The Effect of Electroacupuncture on PKMzeta in the ACC in Regulating Anxiety-Like Behaviors in Rats Experiencing Chronic Inflammatory Pain Mon, 18 Sep 2017 07:24:06 +0000 Chronic inflammatory pain can induce emotional diseases. Electroacupuncture (EA) has effects on chronic pain and pain-related anxiety. Protein kinase Mzeta (PKMzeta) has been proposed to be essential for the maintenance of pain and may interact with GluR1 to maintain CNS plasticity in the anterior cingulate cortex (ACC). We hypothesized that the PKMzeta-GluR1 pathway in the ACC may be involved in anxiety-like behaviors of chronic inflammatory pain and that the mechanism of EA regulation of pain emotion may involve the PKMzeta pathway in the ACC. Our results showed that chronic inflammatory pain model decreased the paw withdrawal threshold (PWT) and increased anxiety-like behaviors. The protein expression of PKCzeta, p-PKCzeta (T560), PKMzeta, p-PKMzeta (T560), and GluR1 in the ACC of the model group were remarkably enhanced. EA increased PWT and alleviated anxiety-like behaviors. EA significantly inhibited the protein expression of p-PKMzeta (T560) in the ACC, and only a downward trend effect for other substances. Further, the microinjection of ZIP remarkably reversed PWT and anxiety-like behaviors. The present study provides direct evidence that the PKCzeta/PKMzeta-GluR1 pathway is related to pain and pain-induced anxiety-like behaviors. EA treatment both increases pain-related somatosensory behavior and decreases pain-induced anxiety-like behaviors by suppressing PKMzeta activity in the ACC. Junying Du, Junfan Fang, Cun Wen, Xiaomei Shao, Yi Liang, and Jianqiao Fang Copyright © 2017 Junying Du et al. All rights reserved. Neural Plasticity Associated with Hippocampal PKA-CREB and NMDA Signaling Is Involved in the Antidepressant Effect of Repeated Low Dose of Yueju Pill on Chronic Mouse Model of Learned Helplessness Sun, 17 Sep 2017 00:00:00 +0000 Yueju pill is a traditional Chinese medicine formulated to treat syndromes of mood disorders. Here, we investigated the therapeutic effect of repeated low dose of Yueju in the animal model mimicking clinical long-term depression condition and the role of neural plasticity associated with PKA- (protein kinase A-) CREB (cAMP response element binding protein) and NMDA (N-methyl-D-aspartate) signaling. We showed that a single low dose of Yueju demonstrated antidepressant effects in tests of tail suspension, forced swim, and novelty-suppressed feeding. A chronic learned helplessness (LH) protocol resulted in a long-term depressive-like condition. Repeated administration of Yueju following chronic LH remarkably alleviated all of depressive-like symptoms measured, whereas conventional antidepressant fluoxetine only showed a minor improvement. In the hippocampus, Yueju and fluoxetine both normalized brain-derived neurotrophic factor (BDNF) and PKA level. Only Yueju, not fluoxetine, rescued the deficits in CREB signaling. The chronic LH upregulated the expression of NMDA receptor subunits NR1, NR2A, and NR2B, which were all attenuated by Yueju. Furthermore, intracerebraventricular administration of NMDA blunted the antidepressant effect of Yueju. These findings supported the antidepressant efficacy of repeated routine low dose of Yueju in a long-term depression model and the critical role of CREB and NMDA signaling. Zhilu Zou, Yin Chen, Qinqin Shen, Xiaoyan Guo, Yuxuan Zhang, and Gang Chen Copyright © 2017 Zhilu Zou et al. All rights reserved. Does the Somatosensory Temporal Discrimination Threshold Change over Time in Focal Dystonia? Thu, 14 Sep 2017 00:00:00 +0000 Background. The somatosensory temporal discrimination threshold (STDT) is defined as the shortest interval at which an individual recognizes two stimuli as asynchronous. Some evidence suggests that STDT depends on cortical inhibitory interneurons in the basal ganglia and in primary somatosensory cortex. Several studies have reported that the STDT in patients with dystonia is abnormal. No longitudinal studies have yet investigated whether STDT values in different forms of focal dystonia change during the course of the disease. Methods. We designed a follow-up study on 25 patients with dystonia (15 with blepharospasm and 10 with cervical dystonia) who were tested twice: upon enrolment and 8 years later. STDT values from dystonic patients at the baseline were also compared with those from a group of 30 age-matched healthy subjects. Results. Our findings show that the abnormally high STDT values observed in patients with focal dystonia remained unchanged at the 8-year follow-up assessment whereas disease severity worsened. Conclusions. Our observation that STDT abnormalities in dystonia remain unmodified during the course of the disease suggests that the altered activity of inhibitory interneurons—either at cortical or at subcortical level—responsible for the increased STDT does not deteriorate as the disease progresses. Antonella Conte, Gina Ferrazzano, Daniele Belvisi, Nicoletta Manzo, Antonio Suppa, Giovanni Fabbrini, and Alfredo Berardelli Copyright © 2017 Antonella Conte et al. All rights reserved. For Better or Worse: The Effect of Prismatic Adaptation on Auditory Neglect Tue, 12 Sep 2017 08:08:11 +0000 Patients with auditory neglect attend less to auditory stimuli on their left and/or make systematic directional errors when indicating sound positions. Rightward prismatic adaptation (R-PA) was repeatedly shown to alleviate symptoms of visuospatial neglect and once to restore partially spatial bias in dichotic listening. It is currently unknown whether R-PA affects only this ear-related symptom or also other aspects of auditory neglect. We have investigated the effect of R-PA on left ear extinction in dichotic listening, space-related inattention assessed by diotic listening, and directional errors in auditory localization in patients with auditory neglect. The most striking effect of R-PA was the alleviation of left ear extinction in dichotic listening, which occurred in half of the patients with initial deficit. In contrast to nonresponders, their lesions spared the right dorsal attentional system and posterior temporal cortex. The beneficial effect of R-PA on an ear-related performance contrasted with detrimental effects on diotic listening and auditory localization. The former can be parsimoniously explained by the SHD-VAS model (shift in hemispheric dominance within the ventral attentional system; Clarke and Crottaz-Herbette 2016), which is based on the R-PA-induced shift of the right-dominant ventral attentional system to the left hemisphere. The negative effects in space-related tasks may be due to the complex nature of auditory space encoding at a cortical level. Isabel Tissieres, Mona Elamly, Stephanie Clarke, and Sonia Crottaz-Herbette Copyright © 2017 Isabel Tissieres et al. All rights reserved. Following Spinal Cord Injury Transected Reticulospinal Tract Axons Develop New Collateral Inputs to Spinal Interneurons in Parallel with Locomotor Recovery Tue, 12 Sep 2017 00:00:00 +0000 The reticulospinal tract (RtST) descends from the reticular formation and terminates in the spinal cord. The RtST drives the initiation of locomotion and postural control. RtST axons form new contacts with propriospinal interneurons (PrINs) after incomplete spinal cord injury (SCI); however, it is unclear if injured or uninjured axons make these connections. We completely transected all traced RtST axons in rats using a staggered model, where a hemisection SCI at vertebra T10 is followed by a contralateral hemisection at vertebra T7. In one group of the animals, the T7 SCI was performed 2 weeks after the T10 SCI (delayed; dSTAG), and in another group, the T10 and T7 SCIs were concomitant (cSTAG). dSTAG animals had significantly more RtST-PrIN contacts in the grey matter compared to cSTAG animals (). These results were accompanied by enhanced locomotor recovery with dSTAG animals significantly outperforming cSTAG animals (BBB test; ). This difference suggests that activity in neuronal networks below the first SCI may contribute to enhanced recovery, because dSTAG rats recovered locomotor ability before the second hemisection. In conclusion, our findings support the hypothesis that the injured RtST forms new connections and is a key player in the recovery of locomotion post-SCI. Zacnicte May, Keith K. Fenrich, Julia Dahlby, Nicholas J. Batty, Abel Torres-Espín, and Karim Fouad Copyright © 2017 Zacnicte May et al. All rights reserved. Down but Not Out: The Consequences of Pretangle Tau in the Locus Coeruleus Tue, 05 Sep 2017 00:00:00 +0000 Degeneration of locus coeruleus (LC) is an underappreciated hallmark of Alzheimer’s disease (AD). The LC is the main source of norepinephrine (NE) in the forebrain, and its degeneration is highly correlated with cognitive impairment and amyloid-beta (Aβ) and tangle pathology. Hyperphosphorylated tau in the LC is among the first detectable AD-like neuropathology in the brain, and while the LC/NE system impacts multiple aspects of AD (e.g., cognition, neuropathology, and neuroinflammation), the functional consequences of hyperphosphorylated tau accrual on LC neurons are not known. Recent evidence suggests that LC neurons accumulate aberrant tau species for decades before frank LC cell body degeneration occurs in AD, suggesting that a therapeutic window exists. In this review, we combine the literature on how pathogenic tau affects forebrain neurons with the known properties and degeneration patterns of LC neurons to synthesize hypotheses on hyperphosphorylated tau-induced dysfunction of LC neurons and the prion-like spread of pretangle tau from the LC to the forebrain. We also propose novel experiments using both in vitro and in vivo models to address the many questions surrounding the impact of hyperphosphorylated tau on LC neurons in AD and its role in disease progression. Termpanit Chalermpalanupap, David Weinshenker, and Jacki M. Rorabaugh Copyright © 2017 Termpanit Chalermpalanupap et al. All rights reserved. Vagotomy Reduces Insulin Clearance in Obese Mice Programmed by Low-Protein Diet in the Adolescence Wed, 30 Aug 2017 04:12:59 +0000 The aim of this study was to investigate the effect of subdiaphragmatic vagotomy on insulin sensitivity, secretion, and degradation in metabolic programmed mice, induced by a low-protein diet early in life, followed by exposure to a high-fat diet in adulthood. Weaned 30-day-old C57Bl/6 mice were submitted to a low-protein diet (6% protein). After 4 weeks, the mice were distributed into three groups: LP group, which continued receiving a low-protein diet; LP + HF group, which started to receive a high-fat diet; and LP + HFvag group, which underwent vagotomy and also was kept at a high-fat diet. Glucose-stimulated insulin secretion (GSIS) in isolated islets, ipGTT, ipITT, in vivo insulin clearance, and liver expression of the insulin-degrading enzyme (IDE) was accessed. Vagotomy improved glucose tolerance and reduced insulin secretion but did not alter adiposity and insulin sensitivity in the LP + HFvag, compared with the LP + HF group. Improvement in glucose tolerance was accompanied by increased insulinemia, probably due to a diminished insulin clearance, as judged by the lower C-peptide : insulin ratio, during the ipGTT. Finally, vagotomy also reduced liver IDE expression in this group. In conclusion, when submitted to vagotomy, the metabolic programmed mice showed improved glucose tolerance, associated with an increase of plasma insulin concentration as a result of insulin clearance reduction, a phenomenon probably due to diminished liver IDE expression. Camila Lubaczeuski, Luciana Mateus Gonçalves, Jean Franciesco Vettorazzi, Mirian Ayumi Kurauti, Junia Carolina Santos-Silva, Maria Lúcia Bonfleur, Antonio Carlos Boschero, José Maria Costa-Júnior, and Everardo Magalhães Carneiro Copyright © 2017 Camila Lubaczeuski et al. All rights reserved. Neuronal-Glial Interactions Maintain Chronic Neuropathic Pain after Spinal Cord Injury Tue, 29 Aug 2017 06:52:47 +0000 The hyperactive state of sensory neurons in the spinal cord enhances pain transmission. Spinal glial cells have also been implicated in enhanced excitability of spinal dorsal horn neurons, resulting in pain amplification and distortions. Traumatic injuries of the neural system such as spinal cord injury (SCI) induce neuronal hyperactivity and glial activation, causing maladaptive synaptic plasticity in the spinal cord. Recent studies demonstrate that SCI causes persistent glial activation with concomitant neuronal hyperactivity, thus providing the substrate for central neuropathic pain. Hyperactive sensory neurons and activated glial cells increase intracellular and extracellular glutamate, neuropeptides, adenosine triphosphates, proinflammatory cytokines, and reactive oxygen species concentrations, all of which enhance pain transmission. In addition, hyperactive sensory neurons and glial cells overexpress receptors and ion channels that maintain this enhanced pain transmission. Therefore, post-SCI neuronal-glial interactions create maladaptive synaptic circuits and activate intracellular signaling events that permanently contribute to enhanced neuropathic pain. In this review, we describe how hyperactivity of sensory neurons contributes to the maintenance of chronic neuropathic pain via neuronal-glial interactions following SCI. Young S. Gwak, Claire E. Hulsebosch, and Joong Woo Leem Copyright © 2017 Young S. Gwak et al. All rights reserved. Cholinergic Potentiation of Restoration of Visual Function after Optic Nerve Damage in Rats Sun, 27 Aug 2017 00:00:00 +0000 Enhancing cortical plasticity and brain connectivity may improve residual vision following a visual impairment. Since acetylcholine plays an important role in attention and neuronal plasticity, we explored whether potentiation of the cholinergic transmission has an effect on the visual function restoration. To this end, we evaluated for 4 weeks the effect of the acetylcholinesterase inhibitor donepezil on brightness discrimination, visually evoked potentials, and visual cortex reactivity after a bilateral and partial optic nerve crush in adult rats. Donepezil administration enhanced brightness discrimination capacity after optic nerve crush compared to nontreated animals. The visually evoked activation of the primary visual cortex was not restored, as measured by evoked potentials, but the cortical neuronal activity measured by thallium autometallography was not significantly affected four weeks after the optic nerve crush. Altogether, the results suggest a role of the cholinergic system in postlesion cortical plasticity. This finding agrees with the view that restoration of visual function may involve mechanisms beyond the area of primary damage and opens a new perspective for improving visual rehabilitation in humans. Mira Chamoun, Elena G. Sergeeva, Petra Henrich-Noack, Shaobo Jia, Lisa Grigartzik, Jing Ma, Qing You, Frédéric Huppé-Gourgues, Bernhard A. Sabel, and Elvire Vaucher Copyright © 2017 Mira Chamoun et al. All rights reserved. Soluble Epoxide Hydrolase Inhibitor and 14,15-Epoxyeicosatrienoic Acid-Facilitated Long-Term Potentiation through cAMP and CaMKII in the Hippocampus Thu, 24 Aug 2017 00:00:00 +0000 Epoxyeicosatrienoic acids (EETs) are derived from arachidonic acid and metabolized by soluble epoxide hydrolase (sEH). The role of EETs in synaptic function in the central nervous system is still largely unknown. We found that pharmacological inhibition of sEH to stabilize endogenous EETs and exogenous 14,15-EET significantly increased the field excitatory postsynaptic potential (fEPSP) response in the CA1 area of the hippocampus, while additionally enhancing high-frequency stimulation- (HFS-) induced long-term potentiation (LTP) and forskolin- (FSK-) induced LTP. sEH inhibitor (sEHI) N-[1-(oxopropyl)-4-piperidinyl]-N’-[4-(trifluoromethoxy) phenyl)-urea (TPPU) and exogenous 14,15-EET increased HFS-LTP, which could be blocked by an N-methyl-D-aspartate (NMDA) receptor subunit NR2B antagonist. TPPU- or 14,15-EET-facilitated FSK-mediated LTP can be potentiated by an A1 adenosine receptor antagonist and a phosphodiesterase inhibitor, but is prevented by a cAMP-dependent protein kinase (PKA) inhibitor. sEHI and 14,15-EET upregulated the activation of extracellular signal-regulated kinases (ERKs) and Ca2+/calmodulin- (CaM-) dependent protein kinase II (CaMKII). Phosphorylation of synaptic receptors NR2B and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluR1 was increased by TPPU and 14,15-EET administration. These results indicated that EETs increased NMDAR- and FSK-mediated synaptic potentiation via the AC-cAMP-PKA signaling cascade and upregulated the ERKs and CaMKII, resulting in increased phosphorylation of NR2B and GluR1 in the hippocampus. Han-Fang Wu, Yi-Ju Chen, Su-Zhen Wu, Chi-Wei Lee, I-Tuan Chen, Yi-Chao Lee, Chi-Chen Huang, Chung-Hsi Hsing, Chih-Wei Tang, and Hui-Ching Lin Copyright © 2017 Han-Fang Wu et al. All rights reserved. Maturation, Refinement, and Serotonergic Modulation of Cerebellar Cortical Circuits in Normal Development and in Murine Models of Autism Tue, 15 Aug 2017 00:00:00 +0000 The formation of the complex cerebellar cortical circuits follows different phases, with initial synaptogenesis and subsequent processes of refinement guided by a variety of mechanisms. The regularity of the cellular and synaptic organization of the cerebellar cortex allowed detailed studies of the structural plasticity mechanisms underlying the formation of new synapses and retraction of redundant ones. For the attainment of the monoinnervation of the Purkinje cell by a single climbing fiber, several signals are involved, including electrical activity, contact signals, homosynaptic and heterosynaptic interaction, calcium transients, postsynaptic receptors, and transduction pathways. An important role in this developmental program is played by serotonergic projections that, acting on temporally and spatially regulated postsynaptic receptors, induce and modulate the phases of synaptic formation and maturation. In the adult cerebellar cortex, many developmental mechanisms persist but play different roles, such as supporting synaptic plasticity during learning and formation of cerebellar memory traces. A dysfunction at any stage of this process can lead to disorders of cerebellar origin, which include autism spectrum disorders but are not limited to motor deficits. Recent evidence in animal models links impairment of Purkinje cell function with autism-like symptoms including sociability deficits, stereotyped movements, and interspecific communication by vocalization. Eriola Hoxha, Pellegrino Lippiello, Bibiana Scelfo, Filippo Tempia, Mirella Ghirardi, and Maria Concetta Miniaci Copyright © 2017 Eriola Hoxha et al. All rights reserved. AAV-KLF7 Promotes Descending Propriospinal Neuron Axonal Plasticity after Spinal Cord Injury Sun, 13 Aug 2017 00:00:00 +0000 DPSN axons mediate and maintain a variety of normal spinal functions. Unsurprisingly, DPSN tracts have been shown to mediate functional recovery following SCI. KLF7 could contribute to CST axon plasticity after spinal cord injury. In the present study, we assessed whether KLF7 could effectively promote DPSN axon regeneration and synapse formation following SCI. An AAV-KLF7 construct was used to overexpress KLF7. In vitro, KLF7 and target proteins were successfully elevated and axonal outgrowth was enhanced. In vivo, young adult C57BL/6 mice received a T10 contusion followed by an AAV-KLF7 injection at the T7–9 levels above the lesion. Five weeks later, overexpression of KLF7 was expressed in DPSN. KLF7 and KLF7 target genes (NGF, TrkA, GAP43, and P0) were detectably increased in the injured spinal cord. Myelin sparring at the lesion site, DPSN axonal regeneration and synapse formation, muscle weight, motor endplate morphology, and functional parameters were all additionally improved by KLF7 treatment. Our findings suggest that KLF7 promotes DPSN axonal plasticity and the formation of synapses with motor neurons at the caudal spinal cord, leading to improved functional recovery and further supporting the potential of AAV-KLF7 as a therapeutic agent for spinal cord injury. Wen-Yuan Li, Ying Wang, Feng-Guo Zhai, Ping Sun, Yong-Xia Cheng, Ling-Xiao Deng, and Zhen-Yu Wang Copyright © 2017 Wen-Yuan Li et al. All rights reserved. Brain-Derived Neurotrophic Factor, Depression, and Physical Activity: Making the Neuroplastic Connection Tue, 08 Aug 2017 07:51:32 +0000 Brain-derived neurotrophic factor (BDNF) is a neurotrophin that is vital to the survival, growth, and maintenance of neurons in key brain circuits involved in emotional and cognitive function. Convergent evidence indicates that neuroplastic mechanisms involving BDNF are deleteriously altered in major depressive disorder (MDD) and animal models of stress. Herein, clinical and preclinical evidence provided that stress-induced depressive pathology contributes to altered BDNF level and function in persons with MDD and, thereby, disruptions in neuroplasticity at the regional and circuit level. Conversely, effective therapeutics that mitigate depressive-related symptoms (e.g., antidepressants and physical activity) optimize BDNF in key brain regions, promote neuronal health and recovery of function in MDD-related circuits, and enhance pharmacotherapeutic response. A greater knowledge of the interrelationship between BDNF, depression, therapeutic mechanisms of action, and neuroplasticity is important as it necessarily precedes the derivation and deployment of more efficacious treatments. Cristy Phillips Copyright © 2017 Cristy Phillips. All rights reserved. The Effect of Glucocorticoid and Glucocorticoid Receptor Interactions on Brain, Spinal Cord, and Glial Cell Plasticity Tue, 08 Aug 2017 00:00:00 +0000 Stress, injury, and disease trigger glucocorticoid (GC) elevation. Elevated GCs bind to the ubiquitously expressed glucocorticoid receptor (GR). While GRs are in every cell in the nervous system, the expression level varies, suggesting that diverse cell types react differently to GR activation. Stress/GCs induce structural plasticity in neurons, Schwann cells, microglia, oligodendrocytes, and astrocytes as well as affect neurotransmission by changing the release and reuptake of glutamate. While general nervous system plasticity is essential for adaptation and learning and memory, stress-induced plasticity is often maladaptive and contributes to neuropsychiatric disorders and neuropathic pain. In this brief review, we describe the evidence that stress/GCs activate GR to promote cell type-specific changes in cellular plasticity throughout the nervous system. Kathryn M. Madalena and Jessica K. Lerch Copyright © 2017 Kathryn M. Madalena and Jessica K. Lerch. All rights reserved. Modulation of Central Synapses by Astrocyte-Released ATP and Postsynaptic P2X Receptors Sun, 06 Aug 2017 00:00:00 +0000 Communication between neuronal and glial cells is important for neural plasticity. P2X receptors are ATP-gated cation channels widely expressed in the brain where they mediate action of extracellular ATP released by neurons and/or glia. Recent data show that postsynaptic P2X receptors underlie slow neuromodulatory actions rather than fast synaptic transmission at brain synapses. Here, we review these findings with a particular focus on the release of ATP by astrocytes and the diversity of postsynaptic P2X-mediated modulation of synaptic strength and plasticity in the CNS. Eric Boué-Grabot and Yuriy Pankratov Copyright © 2017 Eric Boué-Grabot and Yuriy Pankratov. All rights reserved.