Neural Plasticity The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Anxious and Nonanxious Mice Show Similar Hippocampal Sensory Evoked Oscillations under Urethane Anesthesia: Difference in the Effect of Buspirone Thu, 09 Apr 2015 13:47:24 +0000 Hippocampal oscillations recorded under urethane anesthesia are proposed to be modulated by anxiolytics. All classes of clinically effective anxiolytics were reported to decrease the frequency of urethane theta; however, recent findings raise concerns about the direct correlation of anxiolysis and the frequency of hippocampal theta. Here, we took advantage of our two inbred mouse strains displaying extremes of anxiety (anxious (AX) and nonanxious (nAX)) to compare the properties of hippocampal activity and to test the effect of an anxiolytic drugs. No difference was observed in the peak frequency or in the peak power between AX and nAX strains. Buspirone (Bus) applied in 2.5 mg/kg decreased anxiety of AX but did not have any effect on nAX as was tested by elevated plus maze and open field. Interestingly, Bus treatment increased hippocampal oscillatory frequency in the AX but left it unaltered in nAX mice. Saline injection did not have any effect on the oscillation. Paired-pulse facilitation was enhanced by Bus in the nAX, but not in the AX strain. Collectively, these results do not support the hypothesis that hippocampal activity under urethane may serve as a marker for potential anxiolytic drugs. Moreover, we could not confirm the decrease of frequency after anxiolytic treatment. János Horváth, Balázs Barkóczi, Géza Müller, and Viktor Szegedi Copyright © 2015 János Horváth et al. All rights reserved. Neuroplastic Effects of Combined Computerized Physical and Cognitive Training in Elderly Individuals at Risk for Dementia: An eLORETA Controlled Study on Resting States Tue, 07 Apr 2015 09:04:02 +0000 The present study investigates whether a combined cognitive and physical training may induce changes in the cortical activity as measured via electroencephalogram (EEG) and whether this change may index a deceleration of pathological processes of brain aging. Seventy seniors meeting the clinical criteria of mild cognitive impairment (MCI) were equally divided into 5 groups: 3 experimental groups engaged in eight-week cognitive and/or physical training and 2 control groups: active and passive. A 5-minute long resting state EEG was measured before and after the intervention. Cortical EEG sources were modelled by exact low resolution brain electromagnetic tomography (eLORETA). Cognitive function was assessed before and after intervention using a battery of neuropsychological tests including the minimental state examination (MMSE). A significant training effect was identified only after the combined training scheme: a decrease in the post- compared to pre-training activity of precuneus/posterior cingulate cortex in delta, theta, and beta bands. This effect was correlated to improvements in cognitive capacity as evaluated by MMSE scores. Our results indicate that combined physical and cognitive training shows indices of a positive neuroplastic effect in MCI patients and that EEG may serve as a potential index of gains versus cognitive declines and neurodegeneration. This trial is registered with Identifier NCT02313935. Charis Styliadis, Panagiotis Kartsidis, Evangelos Paraskevopoulos, Andreas A. Ioannides, and Panagiotis D. Bamidis Copyright © 2015 Charis Styliadis et al. All rights reserved. Are Visual Peripheries Forever Young? Mon, 06 Apr 2015 09:33:55 +0000 The paper presents a concept of lifelong plasticity of peripheral vision. Central vision processing is accepted as critical and irreplaceable for normal perception in humans. While peripheral processing chiefly carries information about motion stimuli features and redirects foveal attention to new objects, it can also take over functions typical for central vision. Here I review the data showing the plasticity of peripheral vision found in functional, developmental, and comparative studies. Even though it is well established that afferent projections from central and peripheral retinal regions are not established simultaneously during early postnatal life, central vision is commonly used as a general model of development of the visual system. Based on clinical studies and visually deprived animal models, I describe how central and peripheral visual field representations separately rely on early visual experience. Peripheral visual processing (motion) is more affected by binocular visual deprivation than central visual processing (spatial resolution). In addition, our own experimental findings show the possible recruitment of coarse peripheral vision for fine spatial analysis. Accordingly, I hypothesize that the balance between central and peripheral visual processing, established in the course of development, is susceptible to plastic adaptations during the entire life span, with peripheral vision capable of taking over central processing. Kalina Burnat Copyright © 2015 Kalina Burnat. All rights reserved. Modeling Maintenance of Long-Term Potentiation in Clustered Synapses: Long-Term Memory without Bistability Sun, 05 Apr 2015 13:42:39 +0000 Memories are stored, at least partly, as patterns of strong synapses. Given molecular turnover, how can synapses maintain strong for the years that memories can persist? Some models postulate that biochemical bistability maintains strong synapses. However, bistability should give a bimodal distribution of synaptic strength or weight, whereas current data show unimodal distributions for weights and for a correlated variable, dendritic spine volume. Thus it is important for models to simulate both unimodal distributions and long-term memory persistence. Here a model is developed that connects ongoing, competing processes of synaptic growth and weakening to stochastic processes of receptor insertion and removal in dendritic spines. The model simulates long-term (>1 yr) persistence of groups of strong synapses. A unimodal weight distribution results. For stability of this distribution it proved essential to incorporate resource competition between synapses organized into small clusters. With competition, these clusters are stable for years. These simulations concur with recent data to support the “clustered plasticity hypothesis” which suggests clusters, rather than single synaptic contacts, may be a fundamental unit for storage of long-term memory. The model makes empirical predictions and may provide a framework to investigate mechanisms maintaining the balance between synaptic plasticity and stability of memory. Paul Smolen Copyright © 2015 Paul Smolen. All rights reserved. Altered Theta Oscillations and Aberrant Cortical Excitatory Activity in the 5XFAD Model of Alzheimer’s Disease Thu, 02 Apr 2015 09:54:09 +0000 Alzheimer’s disease (AD) is an age-related neurodegenerative disorder characterized by impairment of memory function. The 5XFAD mouse model was analyzed and compared with wild-type (WT) controls for aberrant cortical excitability and hippocampal theta oscillations by using simultaneous video-electroencephalogram (EEG) monitoring. Seizure staging revealed that 5XFAD mice exhibited cortical hyperexcitability whereas controls did not. In addition, 5XFAD mice displayed a significant increase in hippocampal theta activity from the light to dark phase during nonmotor activity. We also observed a reduction in mean theta frequency in 5XFAD mice compared to controls that was again most prominent during nonmotor activity. Transcriptome analysis of hippocampal probes and subsequent qPCR validation revealed an upregulation of Plcd4 that might be indicative of enhanced muscarinic signalling. Our results suggest that 5XFAD mice exhibit altered cortical excitability, hippocampal dysrhythmicity, and potential changes in muscarinic signaling. Magdalena Elisabeth Siwek, Ralf Müller, Christina Henseler, Astrid Trog, Andreas Lundt, Carola Wormuth, Karl Broich, Dan Ehninger, Marco Weiergräber, and Anna Papazoglou Copyright © 2015 Magdalena Elisabeth Siwek et al. All rights reserved. Neuronal BDNF Signaling Is Necessary for the Effects of Treadmill Exercise on Synaptic Stripping of Axotomized Motoneurons Tue, 31 Mar 2015 09:43:58 +0000 The withdrawal of synaptic inputs from the somata and proximal dendrites of spinal motoneurons following peripheral nerve injury could contribute to poor functional recovery. Decreased availability of neurotrophins to afferent terminals on axotomized motoneurons has been implicated as one cause of the withdrawal. No reduction in contacts made by synaptic inputs immunoreactive to the vesicular glutamate transporter 1 and glutamic acid decarboxylase 67 is noted on axotomized motoneurons if modest treadmill exercise, which stimulates the production of neurotrophins by spinal motoneurons, is applied after nerve injury. In conditional, neuron-specific brain-derived neurotrophic factor (BDNF) knockout mice, a reduction in synaptic contacts onto motoneurons was noted in intact animals which was similar in magnitude to that observed after nerve transection in wild-type controls. No further reduction in coverage was found if nerves were cut in knockout mice. Two weeks of moderate daily treadmill exercise following nerve injury in these BDNF knockout mice did not affect synaptic inputs onto motoneurons. Treadmill exercise has a profound effect on synaptic inputs to motoneurons after peripheral nerve injury which requires BDNF production by those postsynaptic cells. Joey Krakowiak, Caiyue Liu, Chandana Papudesu, P. Jillian Ward, Jennifer C. Wilhelm, and Arthur W. English Copyright © 2015 Joey Krakowiak et al. All rights reserved. Limited Effects of an eIF2αS51A Allele on Neurological Impairments in the 5xFAD Mouse Model of Alzheimer’s Disease Thu, 26 Mar 2015 07:30:22 +0000 Alzheimer’s disease (AD) has been associated with increased phosphorylation of the translation initiation factor 2α (eIF2α) at serine 51. Increased phosphorylation of eIF2α alters translational control and may thereby have adverse effects on synaptic plasticity, learning, and memory. To analyze if increased levels of p-eIF2α indeed promote AD-related neurocognitive impairments, we crossed 5xFAD transgenic mice with an knock-in line that expresses the nonphosphorylatable eIF2α variant . Behavioral assessment of the resulting mice revealed motor and cognitive deficits in 5xFAD mice that were, with the possible exception of locomotor hyperactivity, not restored by the allele. Telemetric intracranial EEG recordings revealed no measurable effects of the allele on 5xFAD-associated epileptic activity. Microarray-based transcriptome analyses showed clear transcriptional alterations in 5xFAD hippocampus that were not corrected by the allele. In contrast to prior studies, our immunoblot analyses did not reveal increased levels of p-eIF2α in the hippocampus of 5xFAD mice, suggesting that elevated p-eIF2α levels are not a universal feature of AD models. Collectively, our data indicate that 5xFAD-related pathologies do not necessarily require hyperphosphorylation of eIF2α to emerge; they also show that heterozygosity for the nonphosphorylatable allele has limited effects on 5xFAD-related disease manifestations. Katharina Paesler, Kan Xie, Moritz M. Hettich, Magdalena E. Siwek, Devon P. Ryan, Susanne Schröder, Anna Papazoglou, Karl Broich, Ralf Müller, Astrid Trog, Alexander Garthe, Gerd Kempermann, Marco Weiergräber, and Dan Ehninger Copyright © 2015 Katharina Paesler et al. All rights reserved. The Bipolar Depression Electrical Treatment Trial (BETTER): Design, Rationale, and Objectives of a Randomized, Sham-Controlled Trial and Data from the Pilot Study Phase Tue, 24 Mar 2015 12:59:32 +0000 Background. Bipolar depression (BD) is a prevalent condition, with poor therapeutic options and a high degree of refractoriness. This justifies the development of novel treatment strategies, such as transcranial direct current stimulation (tDCS) that showed promising results in unipolar depression. Methods. We describe a randomized, sham-controlled, double-blinded trial using tDCS for refractory, acutely symptomatic BD (the bipolar depression electrical treatment trial, BETTER). Sixty patients will be enrolled and assessed with clinical and neuropsychological tests. The primary outcome is change (over time and across groups) in the scores of the Hamilton Depression Rating Scale (17 items). Biological markers such as blood neurotrophins and interleukins, genetic polymorphisms, heart rate variability, and motor cortical excitability will be assessed. Twelve anodal-left/cathodal-right 2 mA tDCS sessions over the dorsolateral prefrontal cortex will be performed in 6 weeks. Results. In the pilot phase, five patients received active tDCS and were double-blindly assessed, two presenting clinical response. TDCS was well-tolerated, with no changes in cognitive scores. Conclusion. This upcoming clinical trial will address the efficacy of tDCS for BD on different degrees of refractoriness. The evaluation of biological markers will also help in understanding the pathophysiology of BD and the mechanisms of action of tDCS. Bernardo de Sampaio Pereira Junior, Gabriel Tortella, Beny Lafer, Paula Nunes, Isabela Martins Benseñor, Paulo Andrade Lotufo, Rodrigo Machado-Vieira, and André R. Brunoni Copyright © 2015 Bernardo de Sampaio Pereira Junior et al. All rights reserved. Clinical and Biochemical Manifestations of Depression: Relation to the Neurobiology of Stress Tue, 24 Mar 2015 09:21:17 +0000 Major depressive disorder (MDD) is a chronic, recurrent, and severe psychiatric disorder with high mortality and medical comorbidities. Stress-related pathways have been directly involved in the pathophysiology and treatment of MDD. The present paper provides an overview on the stress system as a model to understand key pathophysiological paradigms in MDD. These mechanisms involve behavioral, cognitive, and systemic manifestations and are also associated with the mechanisms of action of effective antidepressants. Aspects such as depression subtypes, inflammation, insulin resistance, oxidative stress, and prothrombotic states in critical brain circuits and periphery are critically appraised. Finally, new strategies for approaching treatment-resistant major depression and potential adverse effects associated with this complex and intricate network are highlighted. The authors used PubMed as the database for this review. Each author extracted relevant data and assessed the methodological quality of each study. Phillip W. Gold, Rodrigo Machado-Vieira, and Maria G. Pavlatou Copyright © 2015 Phillip W. Gold et al. All rights reserved. Zinc in Gut-Brain Interaction in Autism and Neurological Disorders Mon, 23 Mar 2015 11:31:55 +0000 A growing amount of research indicates that abnormalities in the gastrointestinal (GI) system during development might be a common factor in multiple neurological disorders and might be responsible for some of the shared comorbidities seen among these diseases. For example, many patients with Autism Spectrum Disorder (ASD) have symptoms associated with GI disorders. Maternal zinc status may be an important factor given the multifaceted effect of zinc on gut development and morphology in the offspring. Zinc status influences and is influenced by multiple factors and an interdependence of prenatal and early life stress, immune system abnormalities, impaired GI functions, and zinc deficiency can be hypothesized. In line with this, systemic inflammatory events and prenatal stress have been reported to increase the risk for ASD. Thus, here, we will review the current literature on the role of zinc in gut formation, a possible link between gut and brain development in ASD and other neurological disorders with shared comorbidities, and tie in possible effects on the immune system. Based on these data, we present a novel model outlining how alterations in the maternal zinc status might pathologically impact the offspring leading to impairments in brain functions later in life. Guillermo Vela, Peter Stark, Michael Socha, Ann Katrin Sauer, Simone Hagmeyer, and Andreas M. Grabrucker Copyright © 2015 Guillermo Vela et al. All rights reserved. Enhanced Chemosensory Detection of Negative Emotions in Congenital Blindness Mon, 23 Mar 2015 11:27:33 +0000 It is generally acknowledged that congenitally blind individuals develop superior sensory abilities in order to compensate for their lack of vision. Substantial research has been done on somatosensory and auditory sensory information processing of the blind. However, relatively little information is available about compensatory plasticity in the olfactory domain. Although previous studies indicate that blind individuals have superior olfactory abilities, no studies so far have investigated their sense of smell in relation to social and affective communication. The current study compares congenitally blind and normal sighted individuals in their ability to discriminate and identify emotions from body odours. A group of 14 congenitally blind and 14 age- and sex-matched sighted control subjects participated in the study. We compared participants’ abilities to detect and identify by smelling sweat from donors who had been watching excerpts from emotional movies showing amusement, fear, disgust, or sexual arousal. Our results show that congenitally blind subjects outperformed sighted controls in identifying fear from male donors. In addition, there was a strong tendency that blind individuals were also better in detecting disgust. Our findings reveal that congenitally blind individuals are better at identifying ecologically important emotions and provide new insights into the mechanisms of social and affective communication in blindness. Katrine D. Iversen, Maurice Ptito, Per Møller, and Ron Kupers Copyright © 2015 Katrine D. Iversen et al. All rights reserved. Reconciling Homeostatic and Use-Dependent Plasticity in the Context of Somatosensory Deprivation Wed, 18 Mar 2015 14:07:35 +0000 The concept of homeostatic plasticity postulates that neurons maintain relatively stable rates of firing despite changing inputs. Homeostatic and use-dependent plasticity mechanisms operate concurrently, although they have different requirements for induction. Depriving central somatosensory neurons of their primary activating inputs reduces activity and results in compensatory changes that favor excitation. Both a reduction of GABAergic inhibition and increase in glutamatergic excitatory transmission are observed in input-deprived cortex. Topographic reorganization of the adult somatosensory cortex is likely driven by both homeostatic and use-dependent mechanisms. Plasticity is induced by changes in the strengths of synaptic inputs, as well as changes in temporal correlation of neuronal activity. However, there is less certainty regarding the in vivo contribution of homeostatic mechanisms as in vitro experiments rely on manipulations that create states that do not normally occur in the living nervous system. Homeostatic plasticity seems to occur, but more in vivo research is needed to determine mechanisms. In vitro research is also needed but should better conform to conditions that might occur naturally in vivo. John J. Orczyk and Preston E. Garraghty Copyright © 2015 John J. Orczyk and Preston E. Garraghty. All rights reserved. Efficacy and Interindividual Variability in Motor-Cortex Plasticity following Anodal tDCS and Paired-Associative Stimulation Tue, 17 Mar 2015 13:52:25 +0000 Interindividual response variability to various motor-cortex stimulation protocols has been recently reported. Comparative data of stimulation protocols with different modes of action is lacking. We aimed to compare the efficacy and response variability of two LTP-inducing stimulation protocols in the human motor cortex: anodal transcranial direct current stimulation (a-tDCS) and paired-associative stimulation (PAS25). In two experiments 30 subjects received 1mA a-tDCS and PAS25. Data analysis focused on motor-cortex excitability change and response defined as increase in MEP applying different cut-offs. Furthermore, the predictive pattern of baseline characteristics was explored. Both protocols induced a significant increase in motor-cortical excitability. In the PAS25 experiments the likelihood to develop a MEP response was higher compared to a-tDCS, whereas for intracortical facilitation (ICF) the likelihood for a response was higher in the a-tDCS experiments. Baseline ICF (12 ms) correlated positively with an increase in MEPs only following a-tDCS and responders had significantly higher ICF baseline values. Contrary to recent studies, we showed significant group-level efficacy following both stimulation protocols confirming older studies. However, we also observed a remarkable amount of nonresponders. Our findings highlight the need to define sufficient physiological read-outs for a given plasticity protocol and to develop predictive markers for targeted stimulation. Wolfgang Strube, Tilmann Bunse, Berend Malchow, and Alkomiet Hasan Copyright © 2015 Wolfgang Strube et al. All rights reserved. In Vitro Studies of Neuronal Networks and Synaptic Plasticity in Invertebrates and in Mammals Using Multielectrode Arrays Tue, 17 Mar 2015 09:28:55 +0000 Brain functions are strictly dependent on neural connections formed during development and modified during life. The cellular and molecular mechanisms underlying synaptogenesis and plastic changes involved in learning and memory have been analyzed in detail in simple animals such as invertebrates and in circuits of mammalian brains mainly by intracellular recordings of neuronal activity. In the last decades, the evolution of techniques such as microelectrode arrays (MEAs) that allow simultaneous, long-lasting, noninvasive, extracellular recordings from a large number of neurons has proven very useful to study long-term processes in neuronal networks in vivo and in vitro. In this work, we start off by briefly reviewing the microelectrode array technology and the optimization of the coupling between neurons and microtransducers to detect subthreshold synaptic signals. Then, we report MEA studies of circuit formation and activity in invertebrate models such as Lymnaea, Aplysia, and Helix. In the following sections, we analyze plasticity and connectivity in cultures of mammalian dissociated neurons, focusing on spontaneous activity and electrical stimulation. We conclude by discussing plasticity in closed-loop experiments. Paolo Massobrio, Jacopo Tessadori, Michela Chiappalone, and Mirella Ghirardi Copyright © 2015 Paolo Massobrio et al. All rights reserved. Full Anatomical Recovery of the Dopaminergic System after a Complete Spinal Cord Injury in Lampreys Mon, 16 Mar 2015 13:58:08 +0000 Following a spinal injury, lampreys at first are paralyzed below the level of transection. However, they recover locomotion after several weeks, and this is accompanied by the regeneration of descending axons from the brain and the production of new neurons in the spinal cord. Here, we aimed to analyse the changes in the dopaminergic system of the sea lamprey after a complete spinal transection by studying the changes in dopaminergic cell numbers and dopaminergic innervation in the spinal cord. Changes in the expression of the D2 receptor were also studied. We report the full anatomical regeneration of the dopaminergic system after an initial decrease in the number of dopaminergic cells and fibres. Numbers of dopaminergic cells were recovered rostrally and caudally to the site of injury. Quantification of dopaminergic profiles revealed the full recovery of the dopaminergic innervation of the spinal cord rostral and caudal to the site of injury. Interestingly, no changes in the expression of the D2 receptor were observed at time points in which a reduced dopaminergic innervation of the spinal cord was observed. Our observations reveal that in lampreys a spinal cord injury is followed by the full anatomical recovery of the dopaminergic system. Blanca Fernández-López, Daniel Romaus-Sanjurjo, María Eugenia Cornide-Petronio, Sonia Gómez-Fernández, Antón Barreiro-Iglesias, and María Celina Rodicio Copyright © 2015 Blanca Fernández-López et al. 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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.