Neural Plasticity The latest articles from Hindawi © 2017 , Hindawi Limited . 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. HINT1 in Neuropsychiatric Diseases: A Potential Neuroplastic Mediator Mon, 30 Oct 2017 00:00:00 +0000 Although many studies have investigated the functions of histidine triad nucleotide-binding protein 1 (HINT1), its roles in neurobiological processes remain to be fully elucidated. As a member of the histidine triad (HIT) enzyme superfamily, HINT1 is distributed in almost every organ and has both enzymatic and nonenzymatic activity. Accumulating clinical and preclinical evidence suggests that HINT1 may play an important role as a neuroplastic mediator in neuropsychiatric diseases, such as schizophrenia, inherited peripheral neuropathies, mood disorders, and drug addiction. Though our knowledge of HINT1 is limited, it is believed that further research on the neuropathological functions of HINT1 would eventually benefit patients with neuropsychiatric and even psychosomatic diseases. Peng Liu, Zhongwei Liu, Jiabei Wang, Xiancang Ma, and Yonghui Dang Copyright © 2017 Peng Liu et al. All rights reserved. Treadmill Exercise Improves Motor Dysfunction and Hyperactivity of the Corticostriatal Glutamatergic Pathway in Rats with 6-OHDA-Induced Parkinson’s Disease Tue, 24 Oct 2017 09:26:57 +0000 Hyperactivity in the corticostriatal glutamatergic pathway (CGP) induces basal ganglia dysfunction, contributing to parkinsonian syndrome (PS). Physical exercise can improve PS. However, the effect of exercise on the CGP, and whether this pathway is involved in the improvement of PS, remains unclear. Parkinson’s disease (PD) was induced in rats by 6-hydroxydopamine injection into the right medial forebrain bundle. Motor function was assessed using the cylinder test. Striatal neuron (SN) spontaneous and evoked firing activity was recorded, and the expression levels of Cav1.3 and CaMKII in the striatum were measured after 4 weeks of treadmill exercise. The motor function in PD rats was improved by treadmill exercise. SN showed significantly enhanced excitability, and treadmill exercise reduced SN excitability in PD rats. In addition, firing activity was evoked in SNs by stimulation of the primary motor cortex, and SNs exhibited significantly decreased stimulus threshold, increased firing rates, and reduced latency. The expression of Cav1.3 and p-CaMKII (Thr286) in the striatum were enhanced in PD rats. However, these effects were reversed by treadmill exercise. These findings suggest that treadmill exercise inhibits CGP hyperactivity in PD rats, which may be related to improvement of PS. Wei Chen, Decai Qiao, Xiaoli Liu, and Kaixuan Shi Copyright © 2017 Wei Chen et al. 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.