Neural Plasticity http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Intensity Sensitive Modulation Effect of Theta Burst Form of Median Nerve Stimulation on the Monosynaptic Spinal Reflex Wed, 04 Mar 2015 11:33:16 +0000 http://www.hindawi.com/journals/np/2015/704849/ The effects of electrical stimulation of median nerve with a continuous theta burst pattern (EcTBS) on the spinal H-reflex were studied. Different intensities and durations of EcTBS were given to the median nerve to 11 healthy individuals. The amplitude ratio of the H-reflex to maximum M wave (H/M ratio), corticospinal excitability and inhibition measured using motor evoked potentials (MEPs), short-interval intracortical inhibition and facilitation (SICI/ICF), spinal reciprocal inhibition (RI), and postactivation depression (PAD) were measured before and after EcTBS. In result, the H/M ratio was reduced followed by EcTBS at 90% H-reflex threshold, and the effect lasted longer after 1200 pulses than after 600 pulses of EcTBS. In contrast, EcTBS at 110% threshold facilitated the H/M ratio, while at 80% threshold it had no effect. Maximum M wave, MEPs, SICI/ICF, RI, and PAD all remained unchanged after EcTBS. In conclusion, EcTBS produced lasting effects purely on the H-reflex, probably, through effects on postsynaptic plasticity. The effect of EcTBS depends on the intensity and duration of stimulation. EcTBS is beneficial to research on mechanisms of human plasticity. Moreover, its ability to modulate spinal excitability is expected to have therapeutic benefits on neurological disorders involving spinal cord dysfunction. Kuei-Lin Yeh, Po-Yu Fong, and Ying-Zu Huang Copyright © 2015 Kuei-Lin Yeh et al. All rights reserved. Age-Related Alterations in the Expression of Genes and Synaptic Plasticity Associated with Nitric Oxide Signaling in the Mouse Dorsal Striatum Wed, 04 Mar 2015 11:32:06 +0000 http://www.hindawi.com/journals/np/2015/458123/ Age-related alterations in the expression of genes and corticostriatal synaptic plasticity were studied in the dorsal striatum of mice of four age groups from young (2-3 months old) to old (18–24 months of age) animals. A significant decrease in transcripts encoding neuronal nitric oxide (NO) synthase and receptors involved in its activation (NR1 subunit of the glutamate NMDA receptor and D1 dopamine receptor) was found in the striatum of old mice using gene array and real-time RT-PCR analysis. The old striatum showed also a significantly higher number of GFAP-expressing astrocytes and an increased expression of astroglial, inflammatory, and oxidative stress markers. Field potential recordings from striatal slices revealed age-related alterations in the magnitude and dynamics of electrically induced long-term depression (LTD) and significant enhancement of electrically induced long-term potentiation in the middle-aged striatum (6-7 and 12-13 months of age). Corticostriatal NO-dependent LTD induced by pharmacological activation of group I metabotropic glutamate receptors underwent significant reduction with aging and could be restored by inhibition of cGMP hydrolysis indicating that its age-related deficit is caused by an altered NO-cGMP signaling cascade. It is suggested that age-related alterations in corticostriatal synaptic plasticity may result from functional alterations in receptor-activated signaling cascades associated with increasing neuroinflammation and a prooxidant state. Aisa N. Chepkova, Susanne Schönfeld, and Olga A. Sergeeva Copyright © 2015 Aisa N. Chepkova et al. All rights reserved. Early Maternal Deprivation Enhances Voluntary Alcohol Intake Induced by Exposure to Stressful Events Later in Life Mon, 02 Mar 2015 13:42:41 +0000 http://www.hindawi.com/journals/np/2015/342761/ In the present study, we aimed to assess the impact of early life stress, in the form of early maternal deprivation (MD, 24 h on postnatal day, pnd, 9), on voluntary alcohol intake in adolescent male and female Wistar rats. During adolescence, from pnd 28 to pnd 50, voluntary ethanol intake (20%, v/v) was investigated using the two-bottle free choice paradigm. To better understand the relationship between stress and alcohol consumption, voluntary alcohol intake was also evaluated following additional stressful events later in life, that is, a week of alcohol cessation and a week of alcohol cessation combined with exposure to restraint stress. Female animals consumed more alcohol than males only after a second episode of alcohol cessation combined with restraint stress. MD did not affect baseline voluntary alcohol intake but increased voluntary alcohol intake after stress exposure, indicating that MD may render animals more vulnerable to the effects of stress on alcohol intake. During adolescence, when animals had free access to alcohol, MD animals showed lower body weight gain but a higher growth rate than control animals. Moreover, the higher growth rate was accompanied by a decrease in food intake, suggesting an altered metabolic regulation in MD animals that may interact with alcohol intake. Sara Peñasco, Virginia Mela, Jose Antonio López-Moreno, María-Paz Viveros, and Eva M. Marco Copyright © 2015 Sara Peñasco et al. All rights reserved. Cerebellar Transcranial Direct Current Stimulation Effects on Saccade Adaptation Mon, 02 Mar 2015 09:26:53 +0000 http://www.hindawi.com/journals/np/2015/968970/ Saccade adaptation is a cerebellar-mediated type of motor learning in which the oculomotor system is exposed to repetitive errors. Different types of saccade adaptations are thought to involve distinct underlying cerebellar mechanisms. Transcranial direct current stimulation (tDCS) induces changes in neuronal excitability in a polarity-specific manner and offers a modulatory, noninvasive, functional insight into the learning aspects of different brain regions. We aimed to modulate the cerebellar influence on saccade gains during adaptation using tDCS. Subjects performed an inward () or outward () saccade adaptation experiment (25% intrasaccadic target step) while receiving 1.5 mA of anodal cerebellar tDCS delivered by a small contact electrode. Compared to sham stimulation, tDCS increased learning of saccadic inward adaptation but did not affect learning of outward adaptation. This may imply that plasticity mechanisms in the cerebellum are different between inward and outward adaptation. TDCS could have influenced specific cerebellar areas that contribute to inward but not outward adaptation. We conclude that tDCS can be used as a neuromodulatory technique to alter cerebellar oculomotor output, arguably by engaging wider cerebellar areas and increasing the available resources for learning. Eric Avila, Jos N. van der Geest, Sandra Kengne Kamga, M. Claire Verhage, Opher Donchin, and Maarten A. Frens Copyright © 2015 Eric Avila et al. All rights reserved. Neuroplasticity Underlying the Comorbidity of Pain and Depression Wed, 25 Feb 2015 10:17:11 +0000 http://www.hindawi.com/journals/np/2015/504691/ Acute pain induces depressed mood, and chronic pain is known to cause depression. Depression, meanwhile, can also adversely affect pain behaviors ranging from symptomology to treatment response. Pain and depression independently induce long-term plasticity in the central nervous system (CNS). Comorbid conditions, however, have distinct patterns of neural activation. We performed a review of the changes in neural circuitry and molecular signaling pathways that may underlie this complex relationship between pain and depression. We also discussed some of the current and future therapies that are based on this understanding of the CNS plasticity that occurs with pain and depression. Lisa Doan, Toby Manders, and Jing Wang Copyright © 2015 Lisa Doan et al. All rights reserved. Combined Cognitive-Psychological-Physical Intervention Induces Reorganization of Intrinsic Functional Brain Architecture in Older Adults Tue, 24 Feb 2015 12:01:13 +0000 http://www.hindawi.com/journals/np/2015/713104/ Mounting evidence suggests that enriched mental, physical, and socially stimulating activities are beneficial for counteracting age-related decreases in brain function and cognition in older adults. Here, we used functional magnetic resonance imaging (fMRI) to demonstrate the functional plasticity of brain activity in response to a combined cognitive-psychological-physical intervention and investigated the contribution of the intervention-related brain changes to individual performance in healthy older adults. The intervention was composed of a 6-week program of combined activities including cognitive training, Tai Chi exercise, and group counseling. The results showed improved cognitive performance and reorganized regional homogeneity of spontaneous fluctuations in the blood oxygen level-dependent (BOLD) signals in the superior and middle temporal gyri, and the posterior lobe of the cerebellum, in the participants who attended the intervention. Intriguingly, the intervention-induced changes in the coherence of local spontaneous activity correlated with the improvements in individual cognitive performance. Taken together with our previous findings of enhanced resting-state functional connectivity between the medial prefrontal cortex and medial temporal lobe regions following a combined intervention program in older adults, we conclude that the functional plasticity of the aging brain is a rather complex process, and an effective cognitive-psychological-physical intervention is helpful for maintaining a healthy brain and comprehensive cognition during old age. Zhiwei Zheng, Xinyi Zhu, Shufei Yin, Baoxi Wang, Yanan Niu, Xin Huang, Rui Li, and Juan Li Copyright © 2015 Zhiwei Zheng et al. All rights reserved. Effects of Trace Metal Profiles Characteristic for Autism on Synapses in Cultured Neurons Mon, 23 Feb 2015 10:14:02 +0000 http://www.hindawi.com/journals/np/2015/985083/ Various recent studies revealed that biometal dyshomeostasis plays a crucial role in the pathogenesis of neurological disorders such as autism spectrum disorders (ASD). Substantial evidence indicates that disrupted neuronal homeostasis of different metal ions such as Fe, Cu, Pb, Hg, Se, and Zn may mediate synaptic dysfunction and impair synapse formation and maturation. Here, we performed in vitro studies investigating the consequences of an imbalance of transition metals on glutamatergic synapses of hippocampal neurons. We analyzed whether an imbalance of any one metal ion alters cell health and synapse numbers. Moreover, we evaluated whether a biometal profile characteristic for ASD patients influences synapse formation, maturation, and composition regarding NMDA receptor subunits and Shank proteins. Our results show that an ASD like biometal profile leads to a reduction of NMDAR (NR/Grin/GluN) subunit 1 and 2a, as well as Shank gene expression along with a reduction of synapse density. Additionally, synaptic protein levels of GluN2a and Shanks are reduced. Although Zn supplementation is able to rescue the aforementioned alterations, Zn deficiency is not solely responsible as causative factor. Thus, we conclude that balancing Zn levels in ASD might be a prime target to normalize synaptic alterations caused by biometal dyshomeostasis. Simone Hagmeyer, Katharina Mangus, Tobias M. Boeckers, and Andreas M. Grabrucker Copyright © 2015 Simone Hagmeyer et al. All rights reserved. Hunting Increases Phosphorylation of Calcium/Calmodulin-Dependent Protein Kinase Type II in Adult Barn Owls Wed, 18 Feb 2015 10:46:46 +0000 http://www.hindawi.com/journals/np/2015/819257/ Juvenile barn owls readily adapt to prismatic spectacles, whereas adult owls living under standard aviary conditions do not. We previously demonstrated that phosphorylation of the cyclic-AMP response element-binding protein (CREB) provides a readout of the instructive signals that guide plasticity in juveniles. Here we investigated phosphorylation of calcium/calmodulin-dependent protein kinase II (pCaMKII) in both juveniles and adults. In contrast to CREB, we found no differences in pCaMKII expression between prism-wearing and control juveniles within the external nucleus of the inferior colliculus (ICX), the major site of plasticity. For prism-wearing adults that hunted live mice and are capable of adaptation, expression of pCaMKII was increased relative to prism-wearing adults that fed passively on dead mice and are not capable of adaptation. This effect did not bear the hallmarks of instructive information: it was not localized to rostral ICX and did not exhibit a patchy distribution reflecting discrete bimodal stimuli. These data are consistent with a role for CaMKII as a permissive rather than an instructive factor. In addition, the paucity of pCaMKII expression in passively fed adults suggests that the permissive default setting is “off” in adults. Grant S. Nichols and William M. DeBello Copyright © 2015 Grant S. Nichols and William M. DeBello. All rights reserved. Npas4 Expression in Two Experimental Models of the Barrel Cortex Plasticity Mon, 16 Feb 2015 06:44:33 +0000 http://www.hindawi.com/journals/np/2015/175701/ Npas4 has recently been identified as an important factor in brain plasticity, particularly in mechanisms of inhibitory control. Little is known about Npas4 expression in terms of cortical plasticity. In the present study expressions of Npas4 and the archetypal immediate early gene (IEG) c-Fos were investigated in the barrel cortex of mice after sensory deprivation (sparing one row of whiskers for 7 days) or sensory conditioning (pairing stimulation of one row of whiskers with aversive stimulus). Laser microdissection of individual barrel rows allowed for analysis of IEGs expression precisely in deprived and nondeprived barrels (in deprivation study) or stimulated and nonstimulated barrels (in conditioning study). Cortex activation by sensory conditioning was found to upregulate the expression of both Npas4 and c-Fos. Reorganization of cortical circuits triggered by removal of selected rows of whiskers strongly affected c-Fos but not Npas4 expression. We hypothesize that increased inhibitory synaptogenesis observed previously after conditioning may be mediated by Npas4 expression. Aleksandra Kaliszewska and Malgorzata Kossut Copyright © 2015 Aleksandra Kaliszewska and Malgorzata Kossut. All rights reserved. Expression of p53 Target Genes in the Early Phase of Long-Term Potentiation in the Rat Hippocampal CA1 Area Thu, 12 Feb 2015 09:17:40 +0000 http://www.hindawi.com/journals/np/2015/242158/ Gene expression plays an important role in the mechanisms of long-term potentiation (LTP), which is a widely accepted experimental model of synaptic plasticity. We have studied the expression of at least 50 genes that are transcriptionally regulated by p53, as well as other genes that are related to p53-dependent processes, in the early phase of LTP. Within 30 min after Schaffer collaterals (SC) tetanization, increases in the mRNA and protein levels of Bax, which are upregulated by p53, and a decrease in the mRNA and protein levels of Bcl2, which are downregulated by p53, were observed. The inhibition of Mdm2 by nutlin-3 increased the basal p53 protein level and rescued its tetanization-induced depletion, which suggested the involvement of Mdm2 in the control over p53 during LTP. Furthermore, nutlin-3 caused an increase in the basal expression of Bax and a decrease in the basal expression of Bcl2, whereas tetanization-induced changes in their expression were occluded. These results support the hypothesis that p53 may be involved in transcriptional regulation during the early phase of LTP. We hope that the presented data may aid in the understanding of the contribution of p53 and related genes in the processes that are associated with synaptic plasticity. Vladimir O. Pustylnyak, Pavel D. Lisachev, and Mark B. Shtark Copyright © 2015 Vladimir O. Pustylnyak et al. All rights reserved. Physiological Properties of Supragranular Cortical Inhibitory Interneurons Expressing Retrograde Persistent Firing Wed, 11 Feb 2015 09:00:45 +0000 http://www.hindawi.com/journals/np/2015/608141/ Neurons are polarized functional units. The somatodendritic compartment receives and integrates synaptic inputs while the axon relays relevant synaptic information in form of action potentials (APs) across long distance. Despite this well accepted notion, recent research has shown that, under certain circumstances, the axon can also generate APs independent of synaptic inputs at axonal sites distal from the soma. These ectopic APs travel both toward synaptic terminals and antidromically toward the soma. This unusual form of neuronal communication seems to preferentially occur in cortical inhibitory interneurons following a period of intense neuronal activity and might have profound implications for neuronal information processing. Here we show that trains of ectopically generated APs can be induced in a large portion of neocortical layer 2/3 GABAergic interneurons following a somatic depolarization inducing hundreds of APs. Sparsely occurring ectopic spikes were also observed in a large portion of layer 1 interneurons even in absence of prior somatic depolarization. Remarkably, we found that interneurons which produce ectopic APs display specific membrane and morphological properties significantly different from the remaining GABAergic cells and may therefore represent a functionally unique interneuronal subpopulation. Barbara Imbrosci, Angela Neitz, and Thomas Mittmann Copyright © 2015 Barbara Imbrosci et al. All rights reserved. Effects of Physical Exercise on Individual Resting State EEG Alpha Peak Frequency Tue, 10 Feb 2015 07:32:19 +0000 http://www.hindawi.com/journals/np/2015/717312/ Previous research has shown that both acute and chronic physical exercises can induce positive effects on brain function and this is associated with improvements in cognitive performance. However, the neurophysiological mechanisms underlying the beneficial effects of exercise on cognitive processing are not well understood. This study examined the effects of an acute bout of physical exercise as well as four weeks of exercise training on the individual resting state electroencephalographic (EEG) alpha peak frequency (iAPF), a neurophysiological marker of the individual’s state of arousal and attention, in healthy young adults. The subjects completed a steady state exercise (SSE) protocol or an exhaustive exercise (EE) protocol, respectively, on two separate days. EEG activity was recorded for 2 min before exercise, immediately after exercise, and after 10 min of rest. All assessments were repeated following four weeks of exercise training to investigate whether an improvement in physical fitness modulates the resting state iAPF and/or the iAPF response to an acute bout of SSE and EE. The iAPF was significantly increased following EE () but not following SSE. It is concluded that the iAPF is increased following intense exercise, indicating a higher level of arousal and preparedness for external input. Boris Gutmann, Andreas Mierau, Thorben Hülsdünker, Carolin Hildebrand, Axel Przyklenk, Wildor Hollmann, and Heiko Klaus Strüder Copyright © 2015 Boris Gutmann et al. All rights reserved. Altered Intra- and Interregional Synchronization in Resting-State Cerebral Networks Associated with Chronic Tinnitus Thu, 05 Feb 2015 06:05:03 +0000 http://www.hindawi.com/journals/np/2015/475382/ Objective. Subjective tinnitus is hypothesized to arise from aberrant neural activity; however, its neural bases are poorly understood. To identify aberrant neural networks involved in chronic tinnitus, we compared the resting-state functional magnetic resonance imaging (fMRI) patterns of tinnitus patients and healthy controls. Materials and Methods. Resting-state fMRI measurements were obtained from a group of chronic tinnitus patients () with normal hearing and well-matched healthy controls (). Regional homogeneity (ReHo) analysis and functional connectivity analysis were used to identify abnormal brain activity; these abnormalities were compared to tinnitus distress. Results. Relative to healthy controls, tinnitus patients had significant greater ReHo values in several brain regions including the bilateral anterior insula (AI), left inferior frontal gyrus, and right supramarginal gyrus. Furthermore, the left AI showed enhanced functional connectivity with the left middle frontal gyrus (MFG), while the right AI had enhanced functional connectivity with the right MFG; these measures were positively correlated with Tinnitus Handicap Questionnaires (, and , , resp.). Conclusions. Chronic tinnitus patients showed abnormal intra- and interregional synchronization in several resting-state cerebral networks; these abnormalities were correlated with clinical tinnitus distress. These results suggest that tinnitus distress is exacerbated by attention networks that focus on internally generated phantom sounds. Yu-Chen Chen, Jian Zhang, Xiao-Wei Li, Wenqing Xia, Xu Feng, Cheng Qian, Xiang-Yu Yang, Chun-Qiang Lu, Jian Wang, Richard Salvi, and Gao-Jun Teng Copyright © 2015 Yu-Chen Chen et al. All rights reserved. Generation of New Neurons in Dorsal Root Ganglia in Adult Rats after Peripheral Nerve Crush Injury Tue, 03 Feb 2015 09:48:03 +0000 http://www.hindawi.com/journals/np/2015/860546/ The evidence of neurons generated ex novo in sensory ganglia of adult animals is still debated. In the present study, we investigated, using high resolution light microscopy and stereological analysis, the changes in the number of neurons in dorsal root ganglia after 30 days from a crush lesion of the rat brachial plexus terminal branches. Results showed, as expected, a relevant hypertrophy of dorsal root ganglion neurons. In addition, we reported, for the first time in the literature, that neuronal hypertrophy was accompanied by massive neuronal hyperplasia leading to a 42% increase of the number of primary sensory neurons. Moreover, ultrastructural analyses on sensory neurons showed that there was not a relevant neuronal loss as a consequence of the nerve injury. The evidence of BrdU-immunopositive neurons and neural progenitors labeled with Ki67, nanog, nestin, and sox-2 confirmed the stereological evidence of posttraumatic neurogenesis in dorsal root ganglia. Analysis of morphological changes following axonal damage in addition to immunofluorescence characterization of cell phenotype suggested that the neuronal precursors which give rise to the newly generated neurons could be represented by satellite glial cells that actively proliferate after the lesion and are able to differentiate toward the neuronal lineage. Luisa Muratori, Giulia Ronchi, Stefania Raimondo, Stefano Geuna, Maria Giuseppina Giacobini-Robecchi, and Michele Fornaro Copyright © 2015 Luisa Muratori et al. All rights reserved. Sleeve Gastrectomy and Roux-en-Y Gastric Bypass Alter the Gut-Brain Communication Tue, 03 Feb 2015 08:04:46 +0000 http://www.hindawi.com/journals/np/2015/601985/ This study investigated the anatomical integrity of vagal innervation of the gastrointestinal tract following vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB) operations. The retrograde tracer fast blue (FB) was injected into the stomach to label vagal neurons originating from nodose ganglion (NG) and dorsal motor nucleus of the vagus (DMV). Microglia activation was determined by quantifying changes in the fluorescent staining of hindbrain sections against an ionizing calcium adapter binding molecule 1 (Iba1). Reorganization of vagal afferents in the hindbrain was studied by fluorescent staining against isolectin 4 (IB4). The density of Iba1- and IB4-immunoreactivity was analyzed using Nikon Elements software. There was no difference in the number of FB-labeled neurons located in NG and DMV between VSG and VSG-sham rats. RYGB, but not RYGB-sham rats, showed a dramatic reduction in number of FB-labeled neurons located in the NG and DMV. VSG increased, while the RYGB operation decreased, the density of vagal afferents in the nucleus tractus solitarius (NTS). The RYGB operation, but not the VSG procedure, significantly activated microglia in the NTS and DMV. Results of this study show that the RYGB, but not the VSG procedure, triggers microglia activation in vagal structures and remodels gut-brain communication. L. A. Ballsmider, A. C. Vaughn, M. David, A. Hajnal, P. M. Di Lorenzo, and K. Czaja Copyright © 2015 L. A. Ballsmider et al. All rights reserved. Neuraminidase Inhibition Primes Short-Term Depression and Suppresses Long-Term Potentiation of Synaptic Transmission in the Rat Hippocampus Sat, 31 Jan 2015 08:41:40 +0000 http://www.hindawi.com/journals/np/2015/908190/ Neuraminidase (NEU) is a key enzyme that cleaves negatively charged sialic acid residues from membrane proteins and lipids. Clinical and basic science studies have shown that an imbalance in NEU metabolism or changes in NEU activity due to various pathological conditions parallel with behavior and cognitive impairment. It has been suggested that the decreases of NEU activity could cause serious neurological consequences. However, there is a lack of direct evidences that modulation of endogenous NEU activity can impair neuronal function. Using combined rat entorhinal cortex/hippocampal slices and a specific inhibitor of NEU, 2-deoxy-2,3-dehydro-N-acetylneuraminic acid (NADNA), we examined the effect of downregulation of NEU activity on different forms of synaptic plasticity in the hippocampal CA3-to-CA1 network. We show that NEU inhibition results in a significant decrease in long-term potentiation (LTP) and an increase in short-term depression. Synaptic depotentiation restores LTP in NADNA-pretreated slices to the control level. These data suggest that short-term NEU inhibition produces the LTP-like effect on neuronal network, which results in damping of further LTP induction. Our findings demonstrate that downregulation of NEU activity could have a major impact on synaptic plasticity and provide a new insight into the cellular mechanism underlying behavioral and cognitive impairment associated with abnormal metabolism of NEU. Alina Savotchenko, Arthur Romanov, Dmytro Isaev, Oleksandr Maximyuk, Vadym Sydorenko, Gregory L. Holmes, and Elena Isaeva Copyright © 2015 Alina Savotchenko et al. All rights reserved. Sativex in the Management of Multiple Sclerosis-Related Spasticity: Role of the Corticospinal Modulation Thu, 29 Jan 2015 08:51:32 +0000 http://www.hindawi.com/journals/np/2015/656582/ Sativex is an emergent treatment option for spasticity in patients affected by multiple sclerosis (MS). This oromucosal spray, acting as a partial agonist at cannabinoid receptors, may modulate the balance between excitatory and inhibitory neurotransmitters, leading to muscle relaxation that is in turn responsible for spasticity improvement. Nevertheless, since the clinical assessment may not be sensitive enough to detect spasticity changes, other more objective tools should be tested to better define the real drug effect. The aim of our study was to investigate the role of Sativex in improving spasticity and related symptomatology in MS patients by means of an extensive neurophysiological assessment of sensory-motor circuits. To this end, 30 MS patients underwent a complete clinical and neurophysiological examination, including the following electrophysiological parameters: motor threshold, motor evoked potentials amplitude, intracortical excitability, sensory-motor integration, and ratio. The same assessment was applied before and after one month of continuous treatment. Our data showed an increase of intracortical inhibition, a significant reduction of spinal excitability, and an improvement in spasticity and associated symptoms. Thus, we can speculate that Sativex could be effective in reducing spasticity by means of a double effect on intracortical and spinal excitability. Margherita Russo, Rocco Salvatore Calabrò, Antonino Naro, Edoardo Sessa, Carmela Rifici, Giangaetano D’Aleo, Antonino Leo, Rosaria De Luca, Angelo Quartarone, and Placido Bramanti Copyright © 2015 Margherita Russo et al. All rights reserved. Odorant Receptors Signaling Instructs the Development and Plasticity of the Glomerular Map Tue, 20 Jan 2015 13:56:52 +0000 http://www.hindawi.com/journals/np/2015/975367/ The olfactory system provides a great opportunity to explore the mechanisms that underlie the formation and function of neural circuits because of the simplicity of its structure. Olfactory sensory neurons (OSNs) located in the peripheral olfactory epithelium (OE) take part in the initial formation and function of glomeruli in the olfactory bulb (OB) inside the central nervous system. Glomeruli are key in the process of transduction of olfactory information, as they constitute a map in the OB that sorts the different types of odorant inputs. This odorant categorization allows proper olfactory perception, and it is achieved through the anatomical organization and function of the different glomerular circuits. Once formed, glomeruli keep the capacity to undergo diverse plasticity processes, which is unique among the different neural circuits of the central nervous system. In this context, through the expression and function of the odorant receptors (ORs), OSNs perform two of the most important roles in the olfactory system: transducing odorant information to the nervous system and initiating the development of the glomerular map to organize olfactory information. This review addresses essential information that has emerged in recent years about the molecular basis of these processes. Pablo Valle-Leija Copyright © 2015 Pablo Valle-Leija. All rights reserved. Auditory Cortex tACS and tRNS for Tinnitus: Single versus Multiple Sessions Mon, 22 Dec 2014 00:10:14 +0000 http://www.hindawi.com/journals/np/2014/436713/ Tinnitus is the perception of a sound in the absence of an external acoustic source, which often exerts a significant impact on the quality of life. Currently there is evidence that neuroplastic changes in both neural pathways are involved in the generation and maintaining of tinnitus. Neuromodulation has been suggested to interfere with these neuroplastic alterations. In this study we aimed to compare the effect of two upcoming forms of transcranial electrical neuromodulation: alternating current stimulation (tACS) and random noise stimulation (tRNS), both applied on the auditory cortex. A database with 228 patients with chronic tinnitus who underwent noninvasive neuromodulation was retrospectively analyzed. The results of this study show that a single session of tRNS induces a significant suppressive effect on tinnitus loudness and distress, in contrast to tACS. Multiple sessions of tRNS augment the suppressive effect on tinnitus loudness but have no effect on tinnitus distress. In conclusion this preliminary study shows a possibly beneficial effect of tRNS on tinnitus and can be a motivation for future randomized placebo-controlled clinical studies with auditory tRNS for tinnitus. Auditory alpha-modulated tACS does not seem to be contributing to the treatment of tinnitus. Laura Claes, Hannah Stamberger, Paul Van de Heyning, Dirk De Ridder, and Sven Vanneste Copyright © 2014 Laura Claes et al. All rights reserved. Environmental Control of Adult Neurogenesis: From Hippocampal Homeostasis to Behavior and Disease Thu, 18 Dec 2014 09:56:21 +0000 http://www.hindawi.com/journals/np/2014/808643/ Sjoukje D. Kuipers, Clive R. Bramham, Heather A. Cameron, Carlos P. Fitzsimons, Aniko Korosi, and Paul J. Lucassen Copyright © 2014 Sjoukje D. Kuipers et al. All rights reserved. Recovery of Olfactory Function Induces Neuroplasticity Effects in Patients with Smell Loss Wed, 03 Dec 2014 00:10:14 +0000 http://www.hindawi.com/journals/np/2014/140419/ The plasticity of brain function, especially reorganization after stroke or sensory loss, has been investigated extensively. Based upon its special characteristics, the olfactory system allows the investigation of functional networks in patients with smell loss, as it holds the unique ability to be activated by the sensorimotor act of sniffing, without the presentation of an odor. In the present study, subjects with chronic peripheral smell loss and healthy controls were investigated using functional magnetic resonance imaging (fMRI) to compare functional networks in one of the major olfactory areas before and after an olfactory training program. Data analysis revealed that olfactory training induced alterations in functional connectivity networks. Thus, olfactory training is capable of inducing neural reorganization processes. Furthermore, these findings provide evidence for the underlying neural mechanisms of olfactory training. Kathrin Kollndorfer, Ksenia Kowalczyk, Elisabeth Hoche, Christian A. Mueller, Michael Pollak, Siegfried Trattnig, and Veronika Schöpf Copyright © 2014 Kathrin Kollndorfer et al. All rights reserved. Glucagon-Like Peptide-1 as Predictor of Body Mass Index and Dentate Gyrus Neurogenesis: Neuroplasticity and the Metabolic Milieu Sun, 23 Nov 2014 12:00:38 +0000 http://www.hindawi.com/journals/np/2014/917981/ Glucagon-like peptide-1 (GLP-1) regulates carbohydrate metabolism and promotes neurogenesis. We reported an inverse correlation between adult body mass and neurogenesis in nonhuman primates. Here we examine relationships between physiological levels of the neurotrophic incretin, plasma GLP-1 (pGLP-1), and body mass index (BMI) in adolescence to adult neurogenesis and associations with a diabesity diathesis and infant stress. Morphometry, fasting pGLP-1, insulin resistance, and lipid profiles were measured in early adolescence in 10 stressed and 4 unstressed male bonnet macaques. As adults, dentate gyrus neurogenesis was assessed by doublecortin staining. High pGLP-1, low body weight, and low central adiposity, yet peripheral insulin resistance and high plasma lipids, during adolescence were associated with relatively high adult neurogenesis rates. High pGLP-1 also predicted low body weight with, paradoxically, insulin resistance and high plasma lipids. No rearing effects for neurogenesis rates were observed. We replicated an inverse relationship between BMI and neurogenesis. Adolescent pGLP-1 directly predicted adult neurogenesis. Two divergent processes relevant to human diabesity emerge—high BMI, low pGLP-1, and low neurogenesis and low BMI, high pGLP-1, high neurogenesis, insulin resistance, and lipid elevations. Diabesity markers putatively reflect high nutrient levels necessary for neurogenesis at the expense of peripheral tissues. Jeremy D. Coplan, Shariful Syed, Tarique D. Perera, Sasha L. Fulton, Mary Ann Banerji, Andrew J. Dwork, and John G. Kral Copyright © 2014 Jeremy D. Coplan et al. All rights reserved. Functional Near-Infrared Spectroscopy to Probe State- and Trait-Like Conditions in Chronic Tinnitus: A Proof-of-Principle Study Sun, 16 Nov 2014 00:00:00 +0000 http://www.hindawi.com/journals/np/2014/894203/ Objective. Several neuroscience tools showed the involvement of auditory cortex in chronic tinnitus. In this proof-of-principle study we probed the capability of functional near-infrared spectroscopy (fNIRS) for the measurement of brain oxygenation in auditory cortex in dependence from chronic tinnitus and from intervention with transcranial magnetic stimulation. Methods. Twenty-three patients received continuous theta burst stimulation over the left primary auditory cortex in a randomized sham-controlled neuronavigated trial (verum = 12; placebo = 11). Before and after treatment, sound-evoked brain oxygenation in temporal areas was measured with fNIRS. Brain oxygenation was measured once in healthy controls . Results. Sound-evoked activity in right temporal areas was increased in the patients in contrast to healthy controls. Left-sided temporal activity under the stimulated area changed over the course of the trial; high baseline oxygenation was reduced and vice versa. Conclusions. By demonstrating that rTMS interacts with auditory evoked brain activity, our results confirm earlier electrophysiological findings and indicate the sensitivity of fNIRS for detecting rTMS induced changes in brain activity. Moreover, our findings of trait- and state-related oxygenation changes indicate the potential of fNIRS for the investigation of tinnitus pathophysiology and treatment response. Martin Schecklmann, Anette Giani, Sara Tupak, Berthold Langguth, Vincent Raab, Thomas Polak, Csanád Várallyay, Wilma Harnisch, Martin J. Herrmann, and Andreas J. Fallgatter Copyright © 2014 Martin Schecklmann et al. All rights reserved. Long-Term Effects of Musical Training and Functional Plasticity in Salience System Thu, 13 Nov 2014 00:00:00 +0000 http://www.hindawi.com/journals/np/2014/180138/ Musicians undergoing long-term musical training show improved emotional and cognitive function, which suggests the presence of neuroplasticity. The structural and functional impacts of the human brain have been observed in musicians. In this study, we used data-driven functional connectivity analysis to map local and distant functional connectivity in resting-state functional magnetic resonance imaging data from 28 professional musicians and 28 nonmusicians. Compared with nonmusicians, musicians exhibited significantly greater local functional connectivity density in 10 regions, including the bilateral dorsal anterior cingulate cortex, anterior insula, and anterior temporoparietal junction. A distant functional connectivity analysis demonstrated that most of these regions were included in salience system, which is associated with high-level cognitive control and fundamental attentional process. Additionally, musicians had significantly greater functional integration in this system, especially for connections to the left insula. Increased functional connectivity between the left insula and right temporoparietal junction may be a response to long-term musical training. Our findings indicate that the improvement of salience network is involved in musical training. The salience system may represent a new avenue for exploration regarding the underlying foundations of enhanced higher-level cognitive processes in musicians. Cheng Luo, Shipeng Tu, Yueheng Peng, Shan Gao, Jianfu Li, Li Dong, Gujing Li, Yongxiu Lai, Hong Li, and Dezhong Yao Copyright © 2014 Cheng Luo et al. All rights reserved. Activation of the Prefrontal Cortex While Performing a Task at Preferred Slow Pace and Metronome Slow Pace: A Functional Near-Infrared Spectroscopy Study Mon, 10 Nov 2014 06:52:25 +0000 http://www.hindawi.com/journals/np/2014/269120/ Individuals have a preferred pace at which they perform voluntary repetitive movements. Previous studies have reported that greater activation of the prefrontal cortex was observed during self-initiated movements than during externally triggered movements. The purpose of the present study is to compare the activation of the prefrontal cortex induced when the subjects performed a peg-board task at their preferred slow pace (PSP, the self-initiated condition) with that induced when they performed the same task at metronome slow pace (MSP, the externally triggered condition) using functional near-infrared spectroscopy. Healthy subjects performed the task while sitting in a chair. By assessing the activated channels individually, we confirmed that all of the prefrontal regions of interest were activated by both tasks. In the second-level analyses, we found that the activation detected in the frontopolar cortex (FPPFC; Brodmann area 10) was higher during the PSP task than during the MSP task. The FPPFC is known to be at the top of prefrontal hierarchy, and specifically involved in evaluating self-generated information. In addition, the FPPFC plays a role in coordinating lateral prefrontal cortex. In the present study, the subjects evaluated and managed the internally generated PSP by coordinating the activity of other lower level prefrontal regions. Kaori Shimoda, Yoshiya Moriguchi, Kenji Tsuchiya, Shiori Katsuyama, and Fusae Tozato Copyright © 2014 Kaori Shimoda et al. All rights reserved. Gastrodin Suppresses the Amyloid β-Induced Increase of Spontaneous Discharge in the Entorhinal Cortex of Rats Thu, 30 Oct 2014 07:32:38 +0000 http://www.hindawi.com/journals/np/2014/320937/ Accumulated soluble amyloid beta- (Aβ-) induced aberrant neuronal network activity may directly contribute to cognitive deficits, which are the most outstanding characteristics of Alzheimer’s disease (AD). The entorhinal cortex (EC) is one of the earliest affected brain regions in AD. Impairments of EC neurons are responsible for the cognitive deficits in AD. However, little effort has been made to investigate the effects of soluble Aβ on the discharge properties of EC neurons in vivo. The present study was designed to examine the effects of soluble Aβ1−42 on the discharge properties of EC neurons, using in vivo extracellular single unit recordings. The protective effects of gastrodin (GAS) were also investigated against Aβ1−42-induced alterations in EC neuronal activities. The results showed that the spontaneous discharge of EC neurons was increased by local application of soluble Aβ1−42 and that GAS can effectively reverse Aβ1−42-induced facilitation of spontaneous discharge in a concentration-dependent manner. Moreover, whole-cell patch clamp results indicated that the protective function of GAS on abnormal hyperexcitability may be partially mediated by its inhibitory action on Aβ1−42-elicited inward currents in EC neurons. Our study suggested that GAS may provide neuroprotective effects on Aβ1−42-induced hyperactivity in EC neurons of rats. Peng-zhi Chen, Hui-hui Jiang, Bo Wen, Shuan-cheng Ren, Yang Chen, Wei-gang Ji, Bo Hu, Jun Zhang, Fenglian Xu, and Zhi-ru Zhu Copyright © 2014 Peng-zhi Chen et al. All rights reserved. NMDA Receptor-Dependent Metaplasticity by High-Frequency Magnetic Stimulation Tue, 28 Oct 2014 00:00:00 +0000 http://www.hindawi.com/journals/np/2014/684238/ High-frequency magnetic stimulation (HFMS) can elicit N-methyl-D-aspartate (NMDA) receptor-dependent long-term potentiation (LTP) at Schaffer collateral-CA1 pyramidal cell synapses. Here, we investigated the priming effect of HFMS on the subsequent magnitude of electrically induced LTP in the CA1 region of rat hippocampal slices using field excitatory postsynaptic potential (fEPSP) recordings. In control slices, electrical high-frequency conditioning stimulation (CS) could reliably induce LTP. In contrast, the same CS protocol resulted in long-term depression when HFMS was delivered to the slice 30 min prior to the electrical stimulation. HFMS-priming was diminished when applied in the presence of the metabotropic glutamate receptor antagonists (RS)-α-methylserine-O-phosphate (MSOP) and (RS)-α-methyl-4-carboxyphenylglycine (MCPG). Moreover, when HFMS was delivered in the presence of the NMDA receptor-antagonist D-2-amino-5-phosphonovalerate (50 µM), CS-induced electrical LTP was again as high as under control conditions in slices without priming. These results demonstrate that HFMS significantly reduced the propensity of subsequent electrical LTP and show that both metabotropic glutamate and NMDA receptor activation were involved in this form of HFMS-induced metaplasticity. Tursonjan Tokay, Timo Kirschstein, Marco Rohde, Volker Zschorlich, and Rüdiger Köhling Copyright © 2014 Tursonjan Tokay et al. All rights reserved. Cytokines in Bipolar Disorder: Paving the Way for Neuroprogression Tue, 09 Sep 2014 00:00:00 +0000 http://www.hindawi.com/journals/np/2014/360481/ Bipolar disorder (BD) is a severe, chronic, and recurrent psychiatric illness. It has been associated with high prevalence of medical comorbidities and cognitive impairment. Its neurobiology is not completely understood, but recent evidence has shown a wide range of immune changes. Cytokines are proteins involved in the regulation and the orchestration of the immune response. We performed a review on the involvement of cytokines in BD. We also discuss the cytokines involvement in the neuroprogression of BD. It has been demonstrated that increased expression of cytokines in the central nervous system in postmortem studies is in line with the elevated circulating levels of proinflammatory cytokines in BD patients. The proinflammatory profile and the immune imbalance in BD might be regarded as potential targets to the development of new therapeutic strategies. Izabela Guimarães Barbosa, Moisés Evandro Bauer, Rodrigo Machado-Vieira, and Antonio Lucio Teixeira Copyright © 2014 Izabela Guimarães Barbosa et al. All rights reserved. Plasticity of Neural Systems in Tinnitus Mon, 08 Sep 2014 09:07:31 +0000 http://www.hindawi.com/journals/np/2014/968029/ Martin Meyer, Berthold Langguth, Tobias Kleinjung, and Aage R. Møller Copyright © 2014 Martin Meyer et al. All rights reserved. Blockade of Lysosomal Acid Ceramidase Induces GluN2B-Dependent Tau Phosphorylation in Rat Hippocampal Slices Mon, 08 Sep 2014 05:23:30 +0000 http://www.hindawi.com/journals/np/2014/196812/ The lysosomal acid ceramidase, an enzyme known to limit intracellular ceramide accumulation, has been reported to be defective in neurodegenerative disorders. We show here that rat hippocampal slices, preincubated with the acid ceramidase inhibitor (ACI) d-NMAPPD, exhibit increased N-methyl-D-aspartate (NMDA) receptor-mediated field excitatory postsynaptic potentials (fEPSPs) in CA1 synapses. The ACI by itself did not interfere with either paired pulse facilitation or alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor-mediated fEPSPs, indicating that its influence on synaptic transmission is postsynaptic in origin and specific to the NMDA subtype of glutamate receptors. From a biochemical perspective, we observed that Tau phosphorylation at the Ser262 epitope was highly increased in hippocampal slices preincubated with the ACI, an effect totally prevented by the global NMDA receptor antagonist D/L(−)-2-amino-5-phosphonovaleric acid (AP-5), the calcium chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA), and the GluN2B (but not the GluN2A) receptor antagonist RO25-6981. On the other hand, preincubation of hippocampal slices with the compound KN-62, an inhibitor known to interfere with calcium/calmodulin-dependent protein kinase II (CaMKII), totally abolished the effect of ACI on Tau phosphorylation at Ser262 epitopes. Collectively, these results provide experimental evidence that ceramides play an important role in regulating Tau phosphorylation in the hippocampus via a mechanism dependent on GluN2B receptor subunits and CaMKII activation. Marie-Elaine Laurier-Laurin, Audrée De Montigny, Suzanne Attiori Essis, Michel Cyr, and Guy Massicotte Copyright © 2014 Marie-Elaine Laurier-Laurin et al. All rights reserved.