Neural Plasticity The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . All rights reserved. Brain Connectomics’ Modification to Clarify Motor and Nonmotor Features of Myotonic Dystrophy Type 1 Wed, 25 May 2016 14:20:20 +0000 The adult form of myotonic dystrophy type 1 (DM1) presents with paradoxical inconsistencies between severity of brain damage, relative preservation of cognition, and failure in everyday life. This study, based on the assessment of brain connectivity and mechanisms of plasticity, aimed at reconciling these conflicting issues. Resting-state functional MRI and graph theoretical methods of analysis were used to assess brain topological features in a large cohort of patients with DM1. Patients, compared to controls, revealed reduced connectivity in a large frontoparietal network that correlated with their isolated impairment in visuospatial reasoning. Despite a global preservation of the topological properties, peculiar patterns of frontal disconnection and increased parietal-cerebellar connectivity were also identified in patients’ brains. The balance between loss of connectivity and compensatory mechanisms in different brain networks might explain the paradoxical mismatch between structural brain damage and minimal cognitive deficits observed in these patients. This study provides a comprehensive assessment of brain abnormalities that fit well with both motor and nonmotor clinical features experienced by patients in their everyday life. The current findings suggest that measures of functional connectivity may offer the possibility of characterizing individual patients with the potential to become a clinical tool. Laura Serra, Matteo Mancini, Gabriella Silvestri, Antonio Petrucci, Marcella Masciullo, Barbara Spanò, Mario Torso, Chiara Mastropasqua, Manlio Giacanelli, Carlo Caltagirone, Mara Cercignani, Giovanni Meola, and Marco Bozzali Copyright © 2016 Laura Serra et al. All rights reserved. DNA Damage, Neurodegeneration, and Synaptic Plasticity Wed, 25 May 2016 14:14:13 +0000 Daniela Merlo, Inmaculada Cuchillo-Ibañez, Rosanna Parlato, and Gerhard Rammes Copyright © 2016 Daniela Merlo et al. All rights reserved. Cannabinoids in the Brain: New Vistas on an Old Dilemma Tue, 24 May 2016 12:44:19 +0000 Maurice Ptito, Christian Casanova, and Jean-François Bouchard Copyright © 2016 Maurice Ptito et al. All rights reserved. Repeated Isoflurane Exposures Impair Long-Term Potentiation and Increase Basal GABAergic Activity in the Basolateral Amygdala Mon, 23 May 2016 09:43:25 +0000 After surgery requiring general anesthesia, patients often experience emotional disturbances, but it is unclear if this is due to anesthetic exposure. In the present study, we examined whether isoflurane anesthesia produces long-term pathophysiological alterations in the basolateral amygdala (BLA), a brain region that plays a central role in emotional behavior. Ten-week-old, male rats were administered either a single, 1 h long isoflurane (1.5%) anesthesia or three, 1 h long isoflurane exposures, separated by 48 h. Long-term potentiation (LTP) and spontaneous GABAergic activity in the BLA were studied 1 day, 1 week, and 1 month later. Single isoflurane anesthesia had no significant effect on the magnitude of LTP. In contrast, after repeated isoflurane exposures, LTP was dramatically impaired at both 1 day and 1 week after the last exposure but was restored by 1 month after the exposures. Spontaneous receptor-mediated IPSCs were increased at 1 day and 1 week after repeated exposures but had returned to control levels by 1 month after exposure. Thus, repeated exposures to isoflurane cause a long-lasting—but not permanent—impairment of synaptic plasticity in the BLA, which could be due to increased basal GABAergic activity. These pathophysiological alterations may produce emotional disturbances and impaired fear-related learning. Robert P. Long II, Vassiliki Aroniadou-Anderjaska, Eric M. Prager, Volodymyr I. Pidoplichko, Taiza H. Figueiredo, and Maria F. M. Braga Copyright © 2016 Robert P. Long II et al. All rights reserved. Aromatase Expression in the Hippocampus of AD Patients and 5xFAD Mice Thu, 19 May 2016 17:12:52 +0000 Numerous studies show that 17β-estradiol (E2) protects against Alzheimer’s disease (AD) induced neurodegeneration. The E2-synthesizing enzyme aromatase is expressed in healthy hippocampi, but although the hippocampus is severely affected in AD, little is known about the expression of hippocampal aromatase in AD. To better understand the role of hippocampal aromatase in AD, we studied its expression in postmortem material from patients with AD and in a mouse model for AD (5xFAD mice). In human hippocampi, aromatase-immunoreactivity was observed in the vast majority of principal neurons and signal quantification revealed higher expression of aromatase protein in AD patients compared to age- and sex-matched controls. The tissue-specific first exons of aromatase I.f, PII, I.3, and I.6 were detected in hippocampi of controls and AD patients by RT-PCR. In contrast, 3-month-old, female 5xFAD mice showed lower expression of aromatase mRNA and protein (measured by qRT-PCR and semiquantitative immunohistochemistry) than WT controls; no such differences were observed in male mice. Our findings stress the importance of hippocampal aromatase expression in neurodegenerative diseases. Janine Prange-Kiel, Danuta A. Dudzinski, Felicitas Pröls, Markus Glatzel, Jakob Matschke, and Gabriele M. Rune Copyright © 2016 Janine Prange-Kiel et al. All rights reserved. Effects of Transcranial Alternating Current Stimulation on Cognitive Functions in Healthy Young and Older Adults Thu, 19 May 2016 16:31:26 +0000 Recently, transcranial alternating current stimulation (tACS) has emerged as a tool to enhance human cognitive processes. Here, we provide a brief summary of the rationale behind tACS-induced effects on task-relevant brain oscillations and associated cognitive functions and review previous studies in young subjects that have applied tACS in cognitive paradigms. Additionally, we present pilot data where we administered theta-tACS (6 Hz) over the temporoparietal cortex and a supraorbital reference for 20 min during implicit language learning in healthy young (mean/SD age: 22/2) and older (mean/SD age: 66/4) adults, in a sham-controlled crossover design. Linear mixed models revealed significantly increased retrieval accuracy following tACS-accompanied associative learning, after controlling for session order and learning success. These data provide the first implementation of tACS during cognitive performance in older adults and support recent studies suggesting that tACS in the theta frequency range may serve as a tool to enhance cognition, possibly through direct modulation of task-relevant brain oscillations. So far, studies have been heterogeneous in their designs, leaving a number of issues to be addressed in future research, including the setup of electrodes and optimal stimulation frequencies to be employed, as well as the interaction with age and underlying brain pathologies in specific patient populations. Daria Antonenko, Miriam Faxel, Ulrike Grittner, Michal Lavidor, and Agnes Flöel Copyright © 2016 Daria Antonenko et al. All rights reserved. Cortical Reorganization following Injury Early in Life Thu, 19 May 2016 14:22:14 +0000 The brain has a remarkable capacity for reorganization following injury, especially during the first years of life. Knowledge of structural reorganization and its consequences following perinatal injury is sparse. Here we studied changes in brain tissue volume, morphology, perfusion, and integrity in children with hemiplegia compared to typically developing children, using MRI. Children with hemiplegia demonstrated reduced total cerebral volume, with increased cerebrospinal fluid (CSF) and reduced total white matter volumes, with no differences in total gray matter volume, compared to typically developing children. An increase in cortical thickness at the hemisphere contralateral to the lesion (CLH) was detected in motor and language areas, which may reflect compensation for the gray matter loss in the lesion area or retention of ipsilateral pathways. In addition, reduced cortical thickness, perfusion, and surface area were detected in limbic areas. Increased CSF volume and precentral cortical thickness and reduced white matter volume were correlated with worse motor performance. Brain reorganization of the gray matter within the CLH, while not necessarily indicating better outcome, is suggested as a response to neuronal deficits following injury early in life. Moran Artzi, Shelly Irene Shiran, Maya Weinstein, Vicki Myers, Ricardo Tarrasch, Mitchell Schertz, Aviva Fattal-Valevski, Elka Miller, Andrew M. Gordon, Dido Green, and Dafna Ben Bashat Copyright © 2016 Moran Artzi et al. All rights reserved. Circuits in the Ventral Medulla That Phase-Lock Motoneurons for Coordinated Sniffing and Whisking Wed, 18 May 2016 14:13:38 +0000 The exploratory behavior of rodents is characterized by stereotypical movements of the vibrissae, nose, and head, which are phase locked with rapid respiration, that is, sniffing. Here we review the brainstem circuitry that coordinates these actions and propose that respiration may act as a master clock for binding orofacial inputs across different sensory modalities. Martin Deschênes, Anastasia Kurnikova, Michael Elbaz, and David Kleinfeld Copyright © 2016 Martin Deschênes et al. All rights reserved. Glial Cells and Synaptic Plasticity Tue, 17 May 2016 08:17:16 +0000 Fushun Wang, Tifei Yuan, Alfredo Pereira Jr., Alexei Verkhratsky, and Jason H. Huang Copyright © 2016 Fushun Wang et al. All rights reserved. Spindle Activity Orchestrates Plasticity during Development and Sleep Mon, 16 May 2016 12:47:25 +0000 Spindle oscillations have been described during early brain development and in the adult brain. Besides similarities in temporal patterns and involved brain areas, neonatal spindle bursts (NSBs) and adult sleep spindles (ASSs) show differences in their occurrence, spatial distribution, and underlying mechanisms. While NSBs have been proposed to coordinate the refinement of the maturating neuronal network, ASSs are associated with the implementation of acquired information within existing networks. Along with these functional differences, separate synaptic plasticity mechanisms seem to be recruited. Here, we review the generation of spindle oscillations in the developing and adult brain and discuss possible implications of their differences for synaptic plasticity. The first part of the review is dedicated to the generation and function of ASSs with a particular focus on their role in healthy and impaired neuronal networks. The second part overviews the present knowledge of spindle activity during development and the ability of NSBs to organize immature circuits. Studies linking abnormal maturation of brain wiring with neurological and neuropsychiatric disorders highlight the importance to better elucidate neonatal plasticity rules in future research. Christoph Lindemann, Joachim Ahlbeck, Sebastian H. Bitzenhofer, and Ileana L. Hanganu-Opatz Copyright © 2016 Christoph Lindemann et al. All rights reserved. Motor Skill Acquisition Promotes Human Brain Myelin Plasticity Mon, 16 May 2016 08:11:35 +0000 Experience-dependent structural changes are widely evident in gray matter. Using diffusion weighted imaging (DWI), the neuroplastic effect of motor training on white matter in the brain has been demonstrated. However, in humans it is not known whether specific features of white matter relate to motor skill acquisition or if these structural changes are associated to functional network connectivity. Myelin can be objectively quantified in vivo and used to index specific experience-dependent change. In the current study, seventeen healthy young adults completed ten sessions of visuomotor skill training (10,000 total movements) using the right arm. Multicomponent relaxation imaging was performed before and after training. Significant increases in myelin water fraction, a quantitative measure of myelin, were observed in task dependent brain regions (left intraparietal sulcus [IPS] and left parieto-occipital sulcus). In addition, the rate of motor skill acquisition and overall change in myelin water fraction in the left IPS were negatively related, suggesting that a slower rate of learning resulted in greater neuroplastic change. This study provides the first evidence for experience-dependent changes in myelin that are associated with changes in skilled movements in healthy young adults. Bimal Lakhani, Michael R. Borich, Jacob N. Jackson, Katie P. Wadden, Sue Peters, Anica Villamayor, Alex L. MacKay, Irene M. Vavasour, Alexander Rauscher, and Lara A. Boyd Copyright © 2016 Bimal Lakhani et al. All rights reserved. Glutamate Receptors in Alzheimer’s Disease: Mechanisms and Therapies Mon, 16 May 2016 07:09:44 +0000 Victor Anggono, Li-Huei Tsai, and Jürgen Götz Copyright © 2016 Victor Anggono et al. All rights reserved. Neuroplastic Mechanisms Underlying Perceptual and Cognitive Enhancement Sun, 15 May 2016 13:57:16 +0000 Etienne de Villers-Sidani, Jyoti Mishra, Xiaoming Zhou, and Patrice Voss Copyright © 2016 Etienne de Villers-Sidani et al. All rights reserved. Neurochemical Plasticity of the Coeliac-Superior Mesenteric Ganglion Complex Neurons Projecting to the Prepyloric Area of the Porcine Stomach following Hyperacidity Sun, 15 May 2016 08:59:41 +0000 This study was designed to determine neurochemical properties of the coeliac-superior mesenteric ganglion (CSMG) neurons supplying the prepyloric area of the porcine stomach in physiological state and following experimentally induced hyperacidity. To localize sympathetic neurons innervating the studied area of stomach, the neuronal retrograde tracer Fast Blue (FB) was applied to control animals and hydrochloric acid infusion (HCl) groups. After 23 days, animals of the HCl group were reintroduced into a state of general anesthesia and intragastrically given 5 mL/kg of body weight of 0.25 M aqueous solution of hydrochloric acid. On the 28th day, all animals were sacrificed. The CSMG complexes were then collected and processed for double-labeling immunofluorescence. In the control animals, FB-positive perikarya displayed immunoreactivity to tyrosine hydroxylase (TH), dopamine β-hydroxylase (DβH), neuropeptide Y (NPY), and galanin (GAL). Experimentally induced gastric hyperacidity changed the neurochemical phenotype of the studied neurons. An upregulated expression of GAL and NPY and the de novo synthesis of neuronal nitric oxide synthase (nNOS) and leu5-enkephalin (LENK) as well as downregulated expression of TH and DβH in the stomach-projecting neurons were observed. These findings enrich existing knowledge about the participation of these active substances in adaptive mechanism(s) of the sympathetic neurons during pathological processes within the gastrointestinal tract. Katarzyna Palus and Jarosław Całka Copyright © 2016 Katarzyna Palus and Jarosław Całka. All rights reserved. A Review on Locomotor Training after Spinal Cord Injury: Reorganization of Spinal Neuronal Circuits and Recovery of Motor Function Wed, 11 May 2016 12:10:11 +0000 Locomotor training is a classic rehabilitation approach utilized with the aim of improving sensorimotor function and walking ability in people with spinal cord injury (SCI). Recent studies have provided strong evidence that locomotor training of persons with clinically complete, motor complete, or motor incomplete SCI induces functional reorganization of spinal neuronal networks at multisegmental levels at rest and during assisted stepping. This neuronal reorganization coincides with improvements in motor function and decreased muscle cocontractions. In this review, we will discuss the manner in which spinal neuronal circuits are impaired and the evidence surrounding plasticity of neuronal activity after locomotor training in people with SCI. We conclude that we need to better understand the physiological changes underlying locomotor training, use physiological signals to probe recovery over the course of training, and utilize established and contemporary interventions simultaneously in larger scale research studies. Furthermore, the focus of our research questions needs to change from feasibility and efficacy to the following: what are the physiological mechanisms that make it work and for whom? The aforementioned will enable the scientific and clinical community to develop more effective rehabilitation protocols maximizing sensorimotor function recovery in people with SCI. Andrew C. Smith and Maria Knikou Copyright © 2016 Andrew C. Smith and Maria Knikou. All rights reserved. Age-Dependent Switch of the Role of Serotonergic 5-HT1A Receptors in Gating Long-Term Potentiation in Rat Visual Cortex In Vivo Tue, 10 May 2016 13:39:47 +0000 The rodent primary visual cortex (V1) is densely innervated by serotonergic axons and previous in vitro work has shown that serotonin (5-HT) can modulate plasticity (e.g., long-term potentiation (LTP)) at V1 synapses. However, little work has examined the effects of 5-HT on LTP under in vivo conditions. We examined the role of 5-HT on LTP in V1 elicited by theta burst stimulation (TBS) of the lateral geniculate nucleus in urethane-anesthetized (adult and juvenile) rats. Thalamic TBS consistently induced potentiation of field postsynaptic potentials (fPSPs) recorded in V1. While 5-HT application (0.1–10 mM) itself did not alter LTP levels, the broad-acting 5-HT receptor antagonists methiothepin (1 mM) resulted in a clear facilitation of LTP in adult animals, an effect that was mimicked by the selective 5- receptor antagonist WAY 100635 (1 mM). Interestingly, in juvenile rats, WAY 100635 application inhibited LTP, indicative of an age-dependent switch in the role of 5- receptors in gating V1 plasticity. Analyses of spontaneous electrocorticographic (ECoG) activity in V1 indicated that the antagonist-induced LTP enhancement was not related to systematic changes in oscillatory activity in V1. Together, these data suggest a facilitating role of 5- receptor activation on LTP in the juvenile V1, which switches to a tonic, inhibitory influence in adulthood. Peter J. Gagolewicz and Hans C. Dringenberg Copyright © 2016 Peter J. Gagolewicz and Hans C. Dringenberg. All rights reserved. Olfactory Bulb Field Potentials and Respiration in Sleep-Wake States of Mice Tue, 10 May 2016 13:24:08 +0000 It is well established that local field potentials (LFP) in the rodent olfactory bulb (OB) follow respiration. This respiration-related rhythm (RR) in OB depends on nasal air flow, indicating that it is conveyed by sensory inputs from the nasal epithelium. Recently RR was found outside the olfactory system, suggesting that it plays a role in organizing distributed network activity. It is therefore important to measure RR and to delineate it from endogenous electrical rhythms like theta which cover similar frequency bands in small rodents. In order to validate such measurements in freely behaving mice, we compared rhythmic LFP in the OB with two respiration-related biophysical parameters: whole-body plethysmography (PG) and nasal temperature (thermocouple; TC). During waking, all three signals reflected respiration with similar reliability. Peak power of RR in OB decreased with increasing respiration rate whereas power of PG increased. During NREM sleep, respiration-related TC signals disappeared and large amplitude slow waves frequently concealed RR in OB. In this situation, PG provided a reliable signal while breathing-related rhythms in TC and OB returned only during microarousals. In summary, local field potentials in the olfactory bulb do reliably reflect respiratory rhythm during wakefulness and REM sleep but not during NREM sleep. Jakob Jessberger, Weiwei Zhong, Jurij Brankačk, and Andreas Draguhn Copyright © 2016 Jakob Jessberger et al. All rights reserved. Assessment of the Central Effects of Natural Uranium via Behavioural Performances and the Cerebrospinal Fluid Metabolome Tue, 10 May 2016 11:32:33 +0000 Natural uranium (NU), a component of the earth’s crust, is not only a heavy metal but also an alpha particle emitter, with chemical and radiological toxicity. Populations may therefore be chronically exposed to NU through drinking water and food. Since the central nervous system is known to be sensitive to pollutants during its development, we assessed the effects on the behaviour and the cerebrospinal fluid (CSF) metabolome of rats exposed for 9 months from birth to NU via lactation and drinking water (1.5, 10, or 40 mg·L−1 for male rats and 40 mg·L−1 for female rats). Medium-term memory decreased in comparison to controls in male rats exposed to 1.5, 10, or 40 mg·L−1 NU. In male rats, spatial working memory and anxiety- and depressive-like behaviour were only altered by exposure to 40 mg·L−1 NU and any significant effect was observed on locomotor activity. In female rats exposed to NU, only locomotor activity was significantly increased in comparison with controls. LC-MS metabolomics of CSF discriminated the fingerprints of the male and/or female NU-exposed and control groups. This study suggests that exposure to environmental doses of NU from development to adulthood can have an impact on rat brain function. P. Lestaevel, S. Grison, G. Favé, C. Elie, B. Dhieux, J. C. Martin, K. Tack, and M. Souidi Copyright © 2016 P. Lestaevel et al. All rights reserved. Cellular Zinc Homeostasis Contributes to Neuronal Differentiation in Human Induced Pluripotent Stem Cells Mon, 09 May 2016 14:23:10 +0000 Disturbances in neuronal differentiation and function are an underlying factor of many brain disorders. Zinc homeostasis and signaling are important mediators for a normal brain development and function, given that zinc deficiency was shown to result in cognitive and emotional deficits in animal models that might be associated with neurodevelopmental disorders. One underlying mechanism of the observed detrimental effects of zinc deficiency on the brain might be impaired proliferation and differentiation of stem cells participating in neurogenesis. Thus, to examine the molecular mechanisms regulating zinc metabolism and signaling in differentiating neurons, using a protocol for motor neuron differentiation, we characterized the expression of zinc homeostasis genes during neurogenesis using human induced pluripotent stem cells (hiPSCs) and evaluated the influence of altered zinc levels on the expression of zinc homeostasis genes, cell survival, cell fate, and neuronal function. Our results show that zinc transporters are highly regulated genes during neuronal differentiation and that low zinc levels are associated with decreased cell survival, altered neuronal differentiation, and, in particular, synaptic function. We conclude that zinc deficiency in a critical time window during brain development might influence brain function by modulating neuronal differentiation. Stefanie Pfaender, Karl Föhr, Anne-Kathrin Lutz, Stefan Putz, Kevin Achberger, Leonhard Linta, Stefan Liebau, Tobias M. Boeckers, and Andreas M. Grabrucker Copyright © 2016 Stefanie Pfaender et al. All rights reserved. Differences in Cortical Representation and Structural Connectivity of Hands and Feet between Professional Handball Players and Ballet Dancers Mon, 09 May 2016 08:08:12 +0000 It is known that intensive training and expertise are associated with functional and structural neuroadaptations. Most studies, however, compared experts with nonexperts; hence it is, specifically for sports, unclear whether the neuroplastic adaptations reported are sport-specific or sport-general. Here we aimed at investigating sport-specific adaptations in professional handball players and ballet dancers by focusing on the primary motor and somatosensory grey matter (GM) representation of hands and feet using voxel-based morphometry as well as on fractional anisotropy (FA) of the corticospinal tract by means of diffusion tensor imaging-based fibre tractography. As predicted, GM volume was increased in hand areas of handball players, whereas ballet dancers showed increased GM volume in foot areas. Compared to handball players, ballet dancers showed decreased FA in both fibres connecting the foot and hand areas, but they showed lower FA in fibres connecting the foot compared to their hand areas, whereas handball players showed lower FA in fibres connecting the hand compared to their foot areas. Our results suggest that structural adaptations are sport-specific and are manifested in brain regions associated with the neural processing of sport-specific skills. We believe this enriches the plasticity research in general and extends our knowledge of sport expertise in particular. Jessica Meier, Marlene Sofie Topka, and Jürgen Hänggi Copyright © 2016 Jessica Meier et al. All rights reserved. Radiation-Induced Growth Retardation and Microstructural and Metabolite Abnormalities in the Hippocampus Sun, 08 May 2016 07:00:00 +0000 Cranial radiotherapy (CRT) increases survival in pediatric brain-tumor patients but can cause deleterious effects. This study evaluates the acute and long-term impact of CRT delivered during childhood/adolescence on the brain and body using a rodent model. Rats received CRT, either 4 Gy fractions × 5 d (fractionated) or a cumulative dose of 20 Gy (single dose) at 28 d of age. Animals were euthanized 1 d, 5 d, or 3.5 mo after CRT. The 3.5 mo group was imaged prior to euthanasia. At 3.5 mo, we observed significant growth retardation in irradiated animals, versus controls, and the effects of single dose on brain and body weights were more severe than fractionated. Acutely single dose significantly reduced body weight but increased brain weight, whereas fractionation significantly reduced brain but not body weights, versus controls. CRT suppressed cell proliferation in the hippocampal subgranular zone acutely. Fractional anisotropy (FA) in the fimbria was significantly lower in the single dose versus controls. Hippocampal metabolite levels were significantly altered in the single dose animals, reflecting a heightened state of inflammation that was absent in the fractionated. Our findings indicate that despite the differences in severity between the doses they both demonstrated an effect on cell proliferation and growth retardation, important factors in pediatric CRT. Shaefali P. Rodgers, Janice A. Zawaski, Iman Sahnoune, J. Leigh Leasure, and M. Waleed Gaber Copyright © 2016 Shaefali P. Rodgers et al. All rights reserved. Early Social Enrichment Improves Social Motivation and Skills in a Monogenic Mouse Model of Autism, the Oprm1−/− Mouse Wed, 04 May 2016 16:30:28 +0000 Environmental enrichment has been proven to have positive effects on both behavioral and physiological phenotypes in rodent models of mental and neurodevelopmental disorders. In this study, we used mice lacking the µ-opioid receptor gene (Oprm1−/−), which has been shown to have deficits in social competence and communication, to assess the hypothesis that early enrichment can ameliorate sociability during development and adulthood. Due to the immaturity of sensory-motor capabilities of young pups, we chose as environmental stimulation a second lactating female, who provided extra maternal care and stimulation from birth. The results show that double mothering normalized the abnormal response to maternal separation in Oprm1−/− pups and increased social motivation in juveniles and adult knockout mice. Additionally, we observed that Oprm1−/− mice act as less attractive social partners than wild types, which suggests that social motivation can be modulated by the stimulus employed. This experiment supports previous findings suggesting that early social environmental stimulation has profound and long-term beneficial effects, encouraging the use of nonpharmacological interventions for the treatment of social defects in neurodevelopmental diseases. Luciana Garbugino, Eleonora Centofante, and Francesca R. D’Amato Copyright © 2016 Luciana Garbugino et al. All rights reserved. Astrocyte Hypertrophy Contributes to Aberrant Neurogenesis after Traumatic Brain Injury Wed, 04 May 2016 11:44:52 +0000 Traumatic brain injury (TBI) is a widespread epidemic with severe cognitive, affective, and behavioral consequences. TBIs typically result in a relatively rapid inflammatory and neuroinflammatory response. A major component of the neuroinflammatory response is astrocytes, a type of glial cell in the brain. Astrocytes are important in maintaining the integrity of neuronal functioning, and it is possible that astrocyte hypertrophy after TBIs might contribute to pathogenesis. The hippocampus is a unique brain region, because neurogenesis persists in adults. Accumulating evidence supports the functional importance of these newborn neurons and their associated astrocytes. Alterations to either of these cell types can influence neuronal functioning. To determine if hypertrophied astrocytes might negatively influence immature neurons in the dentate gyrus, astrocyte and newborn neurons were analyzed at 30 days following a TBI in mice. The results demonstrate a loss of radial glial-like processes extending through the granule cell layer after TBI, as well as ectopic growth and migration of immature dentate neurons. The results further show newborn neurons in close association with hypertrophied astrocytes, suggesting a role for the astrocytes in aberrant neurogenesis. Future studies are needed to determine the functional significance of these alterations to the astrocyte/immature neurons after TBI. Clark Robinson, Christopher Apgar, and Lee A. Shapiro Copyright © 2016 Clark Robinson et al. All rights reserved. Increase in Growth Cone Size Correlates with Decrease in Neurite Growth Rate Wed, 04 May 2016 07:14:08 +0000 Several important discoveries in growth cone cell biology were made possible by the use of growth cones derived from cultured Aplysia bag cell neurons, including the characterization of the organization and dynamics of the cytoskeleton. The majority of these Aplysia studies focused on large growth cones induced by poly-L-lysine substrates at early stages in cell culture. Under these conditions, the growth cones are in a steady state with very little net advancement. Here, we offer a comprehensive cellular analysis of the motile behavior of Aplysia growth cones in culture beyond this pausing state. We found that average growth cone size decreased with cell culture time whereas average growth rate increased. This inverse correlation of growth rate and growth cone size was due to the occurrence of large growth cones with a peripheral domain larger than 100 μm2. The large pausing growth cones had central domains that were less consistently aligned with the direction of growth and could be converted into smaller, faster-growing growth cones by addition of a three-dimensional collagen gel. We conclude that the significant lateral expansion of lamellipodia and filopodia as observed during these culture conditions has a negative effect on neurite growth. Yuan Ren and Daniel M. Suter Copyright © 2016 Yuan Ren and Daniel M. Suter. All rights reserved. Transcranial Alternating Current and Random Noise Stimulation: Possible Mechanisms Tue, 03 May 2016 13:50:17 +0000 Background. Transcranial alternating current stimulation (tACS) is a relatively recent method suited to noninvasively modulate brain oscillations. Technically the method is similar but not identical to transcranial direct current stimulation (tDCS). While decades of research in animals and humans has revealed the main physiological mechanisms of tDCS, less is known about the physiological mechanisms of tACS. Method. Here, we review recent interdisciplinary research that has furthered our understanding of how tACS affects brain oscillations and by what means transcranial random noise stimulation (tRNS) that is a special form of tACS can modulate cortical functions. Results. Animal experiments have demonstrated in what way neurons react to invasively and transcranially applied alternating currents. Such findings are further supported by neural network simulations and knowledge from physics on entraining physical oscillators in the human brain. As a result, fine-grained models of the human skull and brain allow the prediction of the exact pattern of current flow during tDCS and tACS. Finally, recent studies on human physiology and behavior complete the picture of noninvasive modulation of brain oscillations. Conclusion. In future, the methods may be applicable in therapy of neurological and psychiatric disorders that are due to malfunctioning brain oscillations. Andrea Antal and Christoph S. Herrmann Copyright © 2016 Andrea Antal and Christoph S. Herrmann. All rights reserved. Synaptic Cell Adhesion Molecules in Alzheimer’s Disease Tue, 03 May 2016 13:09:55 +0000 Alzheimer’s disease (AD) is a neurodegenerative brain disorder associated with the loss of synapses between neurons in the brain. Synaptic cell adhesion molecules are cell surface glycoproteins which are expressed at the synaptic plasma membranes of neurons. These proteins play key roles in formation and maintenance of synapses and regulation of synaptic plasticity. Genetic studies and biochemical analysis of the human brain tissue, cerebrospinal fluid, and sera from AD patients indicate that levels and function of synaptic cell adhesion molecules are affected in AD. Synaptic cell adhesion molecules interact with Aβ, a peptide accumulating in AD brains, which affects their expression and synaptic localization. Synaptic cell adhesion molecules also regulate the production of Aβ via interaction with the key enzymes involved in Aβ formation. Aβ-dependent changes in synaptic adhesion affect the function and integrity of synapses suggesting that alterations in synaptic adhesion play key roles in the disruption of neuronal networks in AD. Iryna Leshchyns’ka and Vladimir Sytnyk Copyright © 2016 Iryna Leshchyns’ka and Vladimir Sytnyk. All rights reserved. Synaptic Plasticity, a Prominent Contributor to the Anxiety in Fragile X Syndrome Thu, 28 Apr 2016 17:12:27 +0000 Fragile X syndrome (FXS) is an inheritable neuropsychological disease caused by expansion of the CGG trinucleotide repeat affecting the fmr1 gene on X chromosome, resulting in silence of the fmr1 gene and failed expression of FMRP. Patients with FXS suffer from cognitive impairment, sensory integration deficits, learning disability, anxiety, autistic traits, and so forth. Specifically, the morbidity of anxiety in FXS individuals remains high from childhood to adulthood. By and large, it is common that the change of brain plasticity plays a key role in the progression of disease. But for now, most studies excessively emphasized the one-sided factor on the change of synaptic plasticity participating in the generation of anxiety during the development of FXS. Here we proposed an integrated concept to acquire better recognition about the details of this process. Tao Yang, Huan Zhao, Changbo Lu, Xiaoyu Li, Yingli Xie, Hao Fu, and Hui Xu Copyright © 2016 Tao Yang et al. All rights reserved. Mechanisms Underlying Adaptation of Respiratory Network Activity to Modulatory Stimuli in the Mouse Embryo Thu, 28 Apr 2016 13:32:41 +0000 Breathing is a rhythmic behavior that requires organized contractions of respiratory effector muscles. This behavior must adapt to constantly changing conditions in order to ensure homeostasis, proper body oxygenation, and CO2/pH regulation. Respiratory rhythmogenesis is controlled by neural networks located in the brainstem. One area considered to be essential for generating the inspiratory phase of the respiratory rhythm is the preBötzinger complex (preBötC). Rhythmogenesis emerges from this network through the interplay between the activation of intrinsic cellular properties (pacemaker properties) and intercellular synaptic connections. Respiratory activity continuously changes under the impact of numerous modulatory substances depending on organismal needs and environmental conditions. The preBötC network has been shown to become active during the last third of gestation. But only little is known regarding the modulation of inspiratory rhythmicity at embryonic stages and even less on a possible role of pacemaker neurons in this functional flexibility during the prenatal period. By combining electrophysiology and calcium imaging performed on embryonic brainstem slice preparations, we provide evidence showing that embryonic inspiratory pacemaker neurons are already intrinsically sensitive to neuromodulation and external conditions (i.e., temperature) affecting respiratory network activity, suggesting a potential role of pacemaker neurons in mediating rhythm adaptation to modulatory stimuli in the embryo. Marc Chevalier, Rafaël De Sa, Laura Cardoit, and Muriel Thoby-Brisson Copyright © 2016 Marc Chevalier et al. All rights reserved. Fractalkine Attenuates Microglial Cell Activation Induced by Prenatal Stress Wed, 27 Apr 2016 16:15:03 +0000 The potential contribution of inflammation to the development of neuropsychiatric diseases has recently received substantial attention. In the brain, the main immune cells are the microglia. As they are the main source of inflammatory factors, it is plausible that the regulation of their activation may be a potential therapeutic target. Fractalkine (CX3CL1) and its receptor CX3CR1 play a crucial role in the control of the biological activity of the microglia. In the present study, using microglial cultures we investigated whether fractalkine is able to reverse changes in microglia caused by a prenatal stress procedure. Our study found that the microglia do not express fractalkine. Prenatal stress decreases the expression of the fractalkine receptor, which in turn is enhanced by the administration of exogenous fractalkine. Moreover, treatment with fractalkine diminishes the prenatal stress-induced overproduction of proinflammatory factors such as IL-1β, IL-18, IL-6, TNF-α, CCL2, or NO in the microglial cells derived from prenatally stressed newborns. In conclusion, the present results revealed that the pathological activation of microglia in prenatally stressed newborns may be attenuated by fractalkine administration. Therefore, understanding of the role of the CX3CL1-CX3CR1 system may help to elucidate the mechanisms underlying the neuron-microglia interaction and its role in pathological conditions in the brain. Joanna Ślusarczyk, Ewa Trojan, Katarzyna Głombik, Katarzyna Chamera, Adam Roman, Bogusława Budziszewska, and Agnieszka Basta-Kaim Copyright © 2016 Joanna Ślusarczyk et al. All rights reserved. Differential DNA Methylation of MicroRNA Genes in Temporal Cortex from Alzheimer’s Disease Individuals Tue, 26 Apr 2016 10:24:04 +0000 This study investigated for the first time the genomewide DNA methylation changes of noncoding RNA genes in the temporal cortex samples from individuals with Alzheimer’s disease (AD). The methylome of 10 AD individuals and 10 age-matched controls were obtained using Illumina 450 K methylation array. A total of 2,095 among the 15,258 interrogated noncoding RNA CpG sites presented differential methylation, 161 of which were associated with miRNA genes. In particular, 10 miRNA CpG sites that were found to be hypermethylated in AD compared to control brains represent transcripts that have been previously associated with the disease. This miRNA set is predicted to target 33 coding genes from the neuregulin receptor complex (ErbB) signaling pathway, which is required for the neurons myelination process. For 6 of these miRNA genes (MIR9-1, MIR9-3, MIR181C, MIR124-1, MIR146B, and MIR451), the hypermethylation pattern is in agreement with previous results from literature that shows downregulation of miR-9, miR-181c, miR-124, miR-146b, and miR-451 in the AD brain. Our data implicate dysregulation of miRNA methylation as contributor to the pathogenesis of AD. Darine Villela, Rodrigo F. Ramalho, Aderbal R. T. Silva, Helena Brentani, Claudia K. Suemoto, Carlos Augusto Pasqualucci, Lea T. Grinberg, Ana C. V. Krepischi, and Carla Rosenberg Copyright © 2016 Darine Villela et al. All rights reserved.