Neural Plasticity The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Brain and Behavior Plasticity: From Fundamental Science to Health Outcomes Tue, 01 Sep 2015 07:54:43 +0000 Keh-chung Lin, Steven L. Wolf, Chetwyn Chan, Ching-yi Wu, and Ching-Po Lin Copyright © 2015 Keh-chung Lin et al. All rights reserved. Neural Plastic Effects of Cognitive Training on Aging Brain Mon, 31 Aug 2015 09:39:16 +0000 Increasing research has evidenced that our brain retains a capacity to change in response to experience until late adulthood. This implies that cognitive training can possibly ameliorate age-associated cognitive decline by inducing training-specific neural plastic changes at both neural and behavioral levels. This longitudinal study examined the behavioral effects of a systematic thirteen-week cognitive training program on attention and working memory of older adults who were at risk of cognitive decline. These older adults were randomly assigned to the Cognitive Training Group () and the Active Control Group (). Findings clearly indicated that training induced improvement in auditory and visual-spatial attention and working memory. The training effect was specific to the experience provided because no significant difference in verbal and visual-spatial memory between the two groups was observed. This pattern of findings is consistent with the prediction and the principle of experience-dependent neuroplasticity. Findings of our study provided further support to the notion that the neural plastic potential continues until older age. The baseline cognitive status did not correlate with pre- versus posttraining changes to any cognitive variables studied, suggesting that the initial cognitive status may not limit the neuroplastic potential of the brain at an old age. Natalie T. Y. Leung, Helena M. K. Tam, Leung W. Chu, Timothy C. Y. Kwok, Felix Chan, Linda C. W. Lam, Jean Woo, and Tatia M. C. Lee Copyright © 2015 Natalie T. Y. Leung et al. All rights reserved. Restoration of Central Programmed Movement Pattern by Temporal Electrical Stimulation-Assisted Training in Patients with Spinal Cerebellar Atrophy Mon, 31 Aug 2015 09:28:14 +0000 Disrupted triphasic electromyography (EMG) patterns of agonist and antagonist muscle pairs during fast goal-directed movements have been found in patients with hypermetria. Since peripheral electrical stimulation (ES) and motor training may modulate motor cortical excitability through plasticity mechanisms, we aimed to investigate whether temporal ES-assisted movement training could influence premovement cortical excitability and alleviate hypermetria in patients with spinal cerebellar ataxia (SCA). The EMG of the agonist extensor carpi radialis muscle and antagonist flexor carpi radialis muscle, premovement motor evoked potentials (MEPs) of the flexor carpi radialis muscle, and the constant and variable errors of movements were assessed before and after 4 weeks of ES-assisted fast goal-directed wrist extension training in the training group and of general health education in the control group. After training, the premovement MEPs of the antagonist muscle were facilitated at 50 ms before the onset of movement. In addition, the EMG onset latency of the antagonist muscle shifted earlier and the constant error decreased significantly. In summary, temporal ES-assisted training alleviated hypermetria by restoring antagonist premovement and temporal triphasic EMG patterns in SCA patients. This technique may be applied to treat hypermetria in cerebellar disorders. (This trial is registered with NCT01983670.) Ying-Zu Huang, Yao-Shun Chang, Miao-Ju Hsu, Alice M. K. Wong, and Ya-Ju Chang Copyright © 2015 Ying-Zu Huang et al. All rights reserved. Coincidence Anticipation Timing Performance during an Acute Bout of Brisk Walking in Older Adults: Effect of Stimulus Speed Mon, 31 Aug 2015 09:15:45 +0000 This study examined coincidence anticipation timing (CAT) performance at slow and fast stimulus speeds before, during, and after an acute bout of walking in adults aged 60–76 years. Results from a series of repeated measures ANOVAs indicated significant rest versus exercise × stimulus speed × time interactions for absolute and variable errors (both ) whereby absolute and variable error scores, when stimulus speed was slow, improved as the duration of exercise increased. When stimulus speed was fast there were significantly greater absolute and variable errors at 18 minutes of the walking bout. There was also greater error at 18 minutes during walking compared to rest. These results suggest that, in a task involving walking and CAT, stimulus speeds plays an important role; specifically walking (exercise) enhances CAT performance at slow stimulus speeds but reduces CAT performance at fast stimulus speeds. The implications are that in everyday situations, where events require dual-task responses to be made at different speeds, for example, walking on the pavement whilst avoiding a crowd, compared to crossing a busy road, an understanding of how different stimulus speeds influence dual-task performance is extremely important, particularly in the older adult population. Michael J. Duncan, Michelle Stanley, Mike Smith, Michael J. Price, and Sheila Leddington Wright Copyright © 2015 Michael J. Duncan et al. All rights reserved. An Influence of Birth Weight, Gestational Age, and Apgar Score on Pattern Visual Evoked Potentials in Children with History of Prematurity Mon, 31 Aug 2015 09:03:18 +0000 Purpose. The objective of our study was to examine a possible influence of gestational age, birth weight, and Apgar score on amplitudes and latencies of P100 wave in preterm born school-age children. Materials and Methods. We examined the following group of school-age children: 28 with history of prematurity (mean age 10.56 ± 1.66 years) and 25 born at term (mean age 11.2 ± 1.94 years). The monocular PVEP was performed in all children. Results. The P100 wave amplitudes and latencies significantly differ between preterm born school-age children and those born at term. There was an essential positive linear correlation of the P100 wave amplitudes with birth weight, gestational age, and Apgar score. There were the negative linear correlations of P100 latencies in 15-minute stimulation from O1 and Oz electrode with Apgar score and O1 and O2 electrode with gestational age. Conclusions. PVEP responses vary in preterm born children in comparison to term. Low birth weight, early gestational age, and poor baseline output seem to be the predicting factors for the developmental rate of a brain function in children with history of prematurity. Further investigations are necessary to determine perinatal factors that can affect the modified visual system function in preterm born children. Marta Michalczuk, Beata Urban, Beata Chrzanowska-Grenda, Monika Oziębło-Kupczyk, and Alina Bakunowicz-Łazarczyk Copyright © 2015 Marta Michalczuk et al. All rights reserved. Age-Related Reduced Somatosensory Gating Is Associated with Altered Alpha Frequency Desynchronization Mon, 31 Aug 2015 09:02:28 +0000 Sensory gating (SG), referring to an attenuated neural response to the second identical stimulus, is considered as preattentive processing in the central nervous system to filter redundant sensory inputs. Insufficient somatosensory SG has been found in the aged adults, particularly in the secondary somatosensory cortex (SII). However, it remains unclear which variables leading to the age-related somatosensory SG decline. There has been evidence showing a relationship between brain oscillations and cortical evoked excitability. Thus, this study used whole-head magnetoencephalography to record responses to paired-pulse electrical stimulation to the left median nerve in healthy young and elderly participants to test whether insufficient stimulus 1- (S1-) induced event-related desynchronization (ERD) contributes to a less-suppressed stimulus 2- (S2-) evoked response. Our analysis revealed that the minimum norm estimates showed age-related reduction of SG in the bilateral SII regions. Spectral power analysis showed that the elderly demonstrated significantly reduced alpha ERD in the contralateral SII (SIIc). Moreover, it was striking to note that lower S1-induced alpha ERD was associated with higher S2-evoked amplitudes in the SIIc among the aged adults. Conclusively, our findings suggest that age-related decline of somatosensory SG is partially attributed to the altered S1-induced oscillatory activity. Chia-Hsiung Cheng, Pei-Ying S. Chan, Sylvain Baillet, and Yung-Yang Lin Copyright © 2015 Chia-Hsiung Cheng et al. All rights reserved. Plasticity of GABAA Receptors during Pregnancy and Postpartum Period: From Gene to Function Sun, 30 Aug 2015 12:45:05 +0000 Pregnancy needs complex pathways that together play a role in proper growth and protection of the fetus preventing its premature loss. Changes during pregnancy and postpartum period include the manifold machinery of neuroactive steroids that plays a crucial role in neuronal excitability by local modulation of specific inhibitory receptors: the GABAA receptors. Marked fluctuations in both blood and brain concentration of neuroactive steroids strongly contribute to GABAA receptor function and plasticity. In this review, we listed several interesting results regarding the regulation and plasticity of GABAA receptor function during pregnancy and postpartum period in rats. The increase in brain levels of neuroactive steroids during pregnancy and their sudden decrease immediately before delivery are causally related to changes in the expression/function of specific GABAA receptor subunits in the hippocampus. These data suggest that alterations in GABAA receptor expression and function may be related to neurological and psychiatric disorders associated with crucial periods in women. These findings could help to provide potential new treatments for these women’s disabling syndromes. Valentina Licheri, Giuseppe Talani, Ashish A. Gorule, Maria Cristina Mostallino, Giovanni Biggio, and Enrico Sanna Copyright © 2015 Valentina Licheri et al. All rights reserved. Molecular Mechanisms of Memory Consolidation, Reconsolidation, and Persistence Wed, 26 Aug 2015 12:12:37 +0000 Emiliano Merlo, Pedro Bekinschtein, Sietse Jonkman, and Jorge H. Medina Copyright © 2015 Emiliano Merlo et al. All rights reserved. Genotype-Dependent Difference in 5-HT2C Receptor-Induced Hypolocomotion: Comparison with 5-HT2A Receptor Functional Activity Wed, 26 Aug 2015 08:37:14 +0000 In the present study behavioral effects of the 5-HT2C serotonin receptor were investigated in different mouse strains. The 5-HT2C receptor agonist MK-212 applied intraperitoneally induced significant dose-dependent reduction of distance traveled in the open field test in CBA/Lac mice. This effect was receptor-specific because it was inhibited by the 5-HT2C receptor antagonist RS102221. To study the role of genotype in 5-HT2C receptor-induced hypolocomotion, locomotor activity of seven inbred mouse strains was measured after MK-212 acute treatment. We found that the 5-HT2C receptor stimulation by MK-212 decreased distance traveled in the open field test in CBA/Lac, C57Bl/6, C3H/He, and ICR mice, whereas it failed to affect locomotor activity in DBA/2J, Asn, and Balb/c mice. We also compared the interstrain differences in functional response to 5-HT2C and 5-HT2A receptors activation measured by the quantification of receptor-mediated head-twitches. These experiments revealed significant positive correlation between 5-HT2C and 5-HT2A receptors functional responses for all investigated mouse strains. Moreover, we found that 5-HT2A receptor activation with DOI did not change locomotor activity in CBA/Lac mice. Taken together, our data indicate the implication of 5-HT2C receptors in regulation of locomotor activity and suggest the shared mechanism for functional responses mediated by 5-HT2C and 5-HT2A receptors. Darya V. Bazovkina, Elena M. Kondaurova, Vladimir S. Naumenko, and Evgeni Ponimaskin Copyright © 2015 Darya V. Bazovkina et al. All rights reserved. Behavioral Tagging: A Translation of the Synaptic Tagging and Capture Hypothesis Tue, 25 Aug 2015 14:01:03 +0000 Similar molecular machinery is activated in neurons following an electrical stimulus that induces synaptic changes and after learning sessions that trigger memory formation. Then, to achieve perdurability of these processes protein synthesis is required for the reinforcement of the changes induced in the network. The synaptic tagging and capture theory provided a strong framework to explain synaptic specificity and persistence of electrophysiological induced plastic changes. Ten years later, the behavioral tagging hypothesis (BT) made use of the same argument, applying it to learning and memory models. The hypothesis postulates that the formation of lasting memories relies on at least two processes: the setting of a learning tag and the synthesis of plasticity related proteins, which once captured at tagged sites allow memory consolidation. BT explains how weak events, only capable of inducing transient forms of memories, can result in lasting memories when occurring close in time with other behaviorally relevant experiences that provide proteins. In this review, we detail the findings supporting the existence of BT process in rodents, leading to the consolidation, persistence, and interference of a memory. We focus on the molecular machinery taking place in these processes and describe the experimental data supporting the BT in humans. Diego Moncada, Fabricio Ballarini, and Haydée Viola Copyright © 2015 Diego Moncada et al. All rights reserved. Retrosplenial Cortex and Long-Term Memory: Molecules to Behavior Tue, 25 Aug 2015 08:41:19 +0000 The retrosplenial cortex (RSC) is reciprocally connected with the hippocampus and various parahippocampal cortical regions, suggesting that RSC is well-positioned to contribute to hippocampal-dependent memory. Consistent with this, substantial behavioral evidence indicates that RSC is essential for consolidating and/or retrieving contextual and spatial memories. In addition, there is growing evidence that RSC neurons undergo activity-dependent plastic changes during memory formation and retrieval. In this paper we review both the behavioral and cellular/molecular data and posit that the RSC has a particularly important role in the storage and retrieval of spatial and contextual memories perhaps due its involvement in binding together multiple cues in the environment. We identify remaining questions and avenues for future research that take advantage of emerging methods to selectively manipulate RSC neurons both spatially and temporally and to image the RSC in awake, behaving animals. Travis P. Todd and David J. Bucci Copyright © 2015 Travis P. Todd and David J. Bucci. All rights reserved. Involvement of Adult Hippocampal Neurogenesis in Learning and Forgetting Tue, 25 Aug 2015 06:50:18 +0000 Adult hippocampal neurogenesis is a process involving the continuous generation of newborn neurons in the hippocampus of adult animals. Mounting evidence has suggested that hippocampal neurogenesis contributes to some forms of hippocampus-dependent learning and memory; however, the detailed mechanism concerning how this small number of newborn neurons could affect learning and memory remains unclear. In this review, we discuss the relationship between adult-born neurons and learning and memory, with a highlight on recently discovered potential roles of neurogenesis in pattern separation and forgetting. Suk-yu Yau, Ang Li, and Kwok-Fai So Copyright © 2015 Suk-yu Yau et al. All rights reserved. Muscarinic ACh Receptors Contribute to Aversive Olfactory Learning in Drosophila Tue, 25 Aug 2015 06:48:04 +0000 The most studied form of associative learning in Drosophila consists in pairing an odorant, the conditioned stimulus (CS), with an unconditioned stimulus (US). The timely arrival of the CS and US information to a specific Drosophila brain association region, the mushroom bodies (MB), can induce new olfactory memories. Thus, the MB is considered a coincidence detector. It has been shown that olfactory information is conveyed to the MB through cholinergic inputs that activate acetylcholine (ACh) receptors, while the US is encoded by biogenic amine (BA) systems. In recent years, we have advanced our understanding on the specific neural BA pathways and receptors involved in olfactory learning and memory. However, little information exists on the contribution of cholinergic receptors to this process. Here we evaluate for the first time the proposition that, as in mammals, muscarinic ACh receptors (mAChRs) contribute to memory formation in Drosophila. Our results show that pharmacological and genetic blockade of mAChRs in MB disrupts olfactory aversive memory in larvae. This effect is not explained by an alteration in the ability of animals to respond to odorants or to execute motor programs. These results show that mAChRs in MB contribute to generating olfactory memories in Drosophila. Bryon Silva, Claudia Molina-Fernández, María Beatriz Ugalde, Eduardo I. Tognarelli, Cristian Angel, and Jorge M. Campusano Copyright © 2015 Bryon Silva et al. All rights reserved. Autobiographical Memory Disturbances in Depression: A Novel Therapeutic Target? Tue, 25 Aug 2015 06:01:35 +0000 Major depressive disorder (MDD) is characterized by a dysfunctional processing of autobiographical memories. We review the following core domains of deficit: systematic biases favoring materials of negative emotional valence; diminished access and response to positive memories; a recollection of overgeneral memories in detriment of specific autobiographical memories; and the role of ruminative processes and avoidance when dealing with autobiographical memories. Furthermore, we review evidence from functional neuroimaging studies of neural circuits activated by the recollection of autobiographical memories in both healthy and depressive individuals. Disruptions in autobiographical memories predispose and portend onset and maintenance of depression. Thus, we discuss emerging therapeutics that target memory difficulties in those with depression. We review strategies for this clinical domain, including memory specificity training, method-of-loci, memory rescripting, and real-time fMRI neurofeedback training of amygdala activity in depression. We propose that the manipulation of the reconsolidation of autobiographical memories in depression might represent a novel yet largely unexplored, domain-specific, therapeutic opportunity for depression treatment. Cristiano A. Köhler, André F. Carvalho, Gilberto S. Alves, Roger S. McIntyre, Thomas N. Hyphantis, and Martín Cammarota Copyright © 2015 Cristiano A. Köhler et al. All rights reserved. Evidence of Maintenance Tagging in the Hippocampus for the Persistence of Long-Lasting Memory Storage Tue, 25 Aug 2015 06:00:07 +0000 The synaptic tagging and capture (STC) hypothesis provides a compelling explanation for synaptic specificity and facilitation of long-term potentiation. Its implication on long-term memory (LTM) formation led to postulate the behavioral tagging mechanism. Here we show that a maintenance tagging process may operate in the hippocampus late after acquisition for the persistence of long-lasting memory storage. The proposed maintenance tagging has several characteristics: (1) the tag is transient and time-dependent; (2) it sets in a late critical time window after an aversive training which induces a short-lasting LTM; (3) exposing rats to a novel environment specifically within this tag time window enables the consolidation to a long-lasting LTM; (4) a familiar environment exploration was not effective; (5) the effect of novelty on the promotion of memory persistence requires dopamine D1/D5 receptors and Arc expression in the dorsal hippocampus. The present results can be explained by a broader version of the behavioral tagging hypothesis and highlight the idea that the durability of a memory trace depends either on late tag mechanisms induced by a training session or on events experienced close in time to this tag. Micol Tomaiuolo, Cynthia Katche, Haydee Viola, and Jorge H. Medina Copyright © 2015 Micol Tomaiuolo et al. All rights reserved. New Insights on Retrieval-Induced and Ongoing Memory Consolidation: Lessons from Arc Mon, 24 Aug 2015 14:30:25 +0000 The mainstream view on the neurobiological mechanisms underlying memory formation states that memory traces reside on the network of cells activated during initial acquisition that becomes active again upon retrieval (reactivation). These activation and reactivation processes have been called “conjunctive trace.” This process implies that singular molecular events must occur during acquisition, strengthening the connection between the implicated cells whose synchronous activity must underlie subsequent reactivations. The strongest experimental support for the conjunctive trace model comes from the study of immediate early genes such as c-fos, zif268, and activity-regulated cytoskeletal-associated protein. The expressions of these genes are reliably induced by behaviorally relevant neuronal activity and their products often play a central role in long-term memory formation. In this review, we propose that the peculiar characteristics of Arc protein, such as its optimal expression after ongoing experience or familiar behavior, together with its versatile and central functions in synaptic plasticity could explain how familiarization and recognition memories are stored and preserved in the mammalian brain. Jean-Pascal Morin, Kioko Guzmán-Ramos, and Federico Bermudez-Rattoni Copyright © 2015 Jean-Pascal Morin et al. All rights reserved. Hippocampal Infusion of Zeta Inhibitory Peptide Impairs Recent, but Not Remote, Recognition Memory in Rats Mon, 24 Aug 2015 14:16:45 +0000 Spatial memory in rodents can be erased following the infusion of zeta inhibitory peptide (ZIP) into the dorsal hippocampus via indwelling guide cannulas. It is believed that ZIP impairs spatial memory by reversing established late-phase long-term potentiation (LTP). However, it is unclear whether other forms of hippocampus-dependent memory, such as recognition memory, are also supported by hippocampal LTP. In the current study, we tested recognition memory in rats following hippocampal ZIP infusion. In order to combat the limited targeting of infusions via cannula, we implemented a stereotaxic approach for infusing ZIP throughout the dorsal, intermediate, and ventral hippocampus. Rats infused with ZIP 3–7 days after training on the novel object recognition task exhibited impaired object recognition memory compared to control rats (those infused with aCSF). In contrast, rats infused with ZIP 1 month after training performed similar to control rats. The ability to form new memories after ZIP infusions remained intact. We suggest that enhanced recognition memory for recent events is supported by hippocampal LTP, which can be reversed by hippocampal ZIP infusion. Jena B. Hales, Amber C. Ocampo, Nicola J. Broadbent, and Robert E. Clark Copyright © 2015 Jena B. Hales et al. All rights reserved. Effects of Exercise in Immersive Virtual Environments on Cortical Neural Oscillations and Mental State Thu, 20 Aug 2015 14:51:17 +0000 Virtual reality environments are increasingly being used to encourage individuals to exercise more regularly, including as part of treatment those with mental health or neurological disorders. The success of virtual environments likely depends on whether a sense of presence can be established, where participants become fully immersed in the virtual environment. Exposure to virtual environments is associated with physiological responses, including cortical activation changes. Whether the addition of a real exercise within a virtual environment alters sense of presence perception, or the accompanying physiological changes, is not known. In a randomized and controlled study design, moderate-intensity Exercise (i.e., self-paced cycling) and No-Exercise (i.e., automatic propulsion) trials were performed within three levels of virtual environment exposure. Each trial was 5 minutes in duration and was followed by posttrial assessments of heart rate, perceived sense of presence, EEG, and mental state. Changes in psychological strain and physical state were generally mirrored by neural activation patterns. Furthermore, these changes indicated that exercise augments the demands of virtual environment exposures and this likely contributed to an enhanced sense of presence. Tobias Vogt, Rainer Herpers, Christopher D. Askew, David Scherfgen, Heiko K. Strüder, and Stefan Schneider Copyright © 2015 Tobias Vogt et al. All rights reserved. Neural Plasticity in Common Forms of Chronic Headaches Thu, 20 Aug 2015 12:21:51 +0000 Headaches are universal experiences and among the most common disorders. While headache may be physiological in the acute setting, it can become a pathological and persistent condition. The mechanisms underlying the transition from episodic to chronic pain have been the subject of intense study. Using physiological and imaging methods, researchers have identified a number of different forms of neural plasticity associated with migraine and other headaches, including peripheral and central sensitization, and alterations in the endogenous mechanisms of pain modulation. While these changes have been proposed to contribute to headache and pain chronification, some findings are likely the results of repetitive noxious stimulation, such as atrophy of brain areas involved in pain perception and modulation. In this review, we provide a narrative overview of recent advances on the neuroimaging, electrophysiological and genetic aspects of neural plasticity associated with the most common forms of chronic headaches, including migraine, cluster headache, tension-type headache, and medication overuse headache. Tzu-Hsien Lai, Ekaterina Protsenko, Yu-Chen Cheng, Marco L. Loggia, Gianluca Coppola, and Wei-Ta Chen Copyright © 2015 Tzu-Hsien Lai et al. All rights reserved. Prophylactic Subacute Administration of Zinc Increases CCL2, CCR2, FGF2, and IGF-1 Expression and Prevents the Long-Term Memory Loss in a Rat Model of Cerebral Hypoxia-Ischemia Tue, 18 Aug 2015 08:45:00 +0000 Prophylactic subacute administration of zinc decreases lipoperoxidation and cell death following a transient cerebral hypoxia-ischemia, thus suggesting neuroprotective and preconditioning effects. Chemokines and growth factors are also involved in the neuroprotective effect in hypoxia-ischemia. We explored whether zinc prevents the cerebral cortex-hippocampus injury through regulation of CCL2, CCR2, FGF2, and IGF-1 expression following a 10 min of common carotid artery occlusion (CCAO). Male rats were grouped as follows: (1) Zn96h, rats injected with ZnCl2 (one dose every 24 h during four days); (2) Zn96h + CCAO, rats treated with ZnCl2 before CCAO; (3) CCAO, rats with CCAO only; (4) Sham group, rats with mock CCAO; and (5) untreated rats. The cerebral cortex-hippocampus was dissected at different times before and after CCAO. CCL2/CCR2, FGF2, and IGF-1 expression was assessed by RT-PCR and ELISA. Learning in Morris Water Maze was achieved by daily training during 5 days. Long-term memory was evaluated on day 7 after learning. Subacute administration of zinc increased expression of CCL2, CCR2, FGF2, and IGF-1 in the early and late phases of postreperfusion and prevented the CCAO-induced memory loss in the rat. These results might be explained by the induction of neural plasticity because of the expression of CCL2 and growth factors. Victor Manuel Blanco-Alvarez, Guadalupe Soto-Rodriguez, Juan Antonio Gonzalez-Barrios, Daniel Martinez-Fong, Eduardo Brambila, Maricela Torres-Soto, Ana Karina Aguilar-Peralta, Alejandro Gonzalez-Vazquez, Constantino Tomás-Sanchez, I. Daniel Limón, Jose R. Eguibar, Araceli Ugarte, Jeanett Hernandez-Castillo, and Bertha Alicia Leon-Chavez Copyright © 2015 Victor Manuel Blanco-Alvarez et al. All rights reserved. Poststroke Cell Therapy of the Aged Brain Tue, 11 Aug 2015 11:25:42 +0000 During aging, many neurodegenerative disorders are associated with reduced neurogenesis and a decline in the proliferation of stem/progenitor cells. The development of the stem cell (SC), the regenerative therapy field, gained tremendous expectations in the diseases that suffer from the lack of treatment options. Stem cell based therapy is a promising approach to promote neuroregeneration after brain injury and can be potentiated when combined with supportive pharmacological drug treatment, especially in the aged. However, the mechanism of action for a particular grafted cell type, the optimal delivery route, doses, or time window of administration after lesion is still under debate. Today, it is proved that these protections are most likely due to modulatory mechanisms rather than the expected cell replacement. Our group proved that important differences appear in the aged brain compared with young one, that is, the accelerated progression of ischemic area, or the delayed initiation of neurological recovery. In this light, these age-related aspects should be carefully evaluated in the clinical translation of neurorestorative therapies. This review is focused on the current perspectives and suitable sources of stem cells (SCs), mechanisms of action, and the most efficient delivery routes in neurorestoration therapies in the poststroke aged environment. Aurel Popa-Wagner, Madalina Filfan, Adriana Uzoni, Pouya Pourgolafshan, and Ana-Maria Buga Copyright © 2015 Aurel Popa-Wagner et al. All rights reserved. Glial Plasticity Wed, 05 Aug 2015 06:19:47 +0000 Tomas C. Bellamy, Anna Dunaevsky, and H. Rheinallt Parri Copyright © 2015 Tomas C. Bellamy et al. All rights reserved. Fractalkine Signaling and Microglia Functions in the Developing Brain Tue, 04 Aug 2015 11:29:29 +0000 Microglial cells are the resident macrophages of the central nervous system (CNS). Besides their classical roles in pathological conditions, these immune cells also dynamically interact with neurons and influence their structure and function in physiological conditions. The neuronal chemokine fractalkine and its microglial receptor CX3CR1 are one important signaling pathway involved in these reciprocal interactions. In the present review, we will discuss recent evidence indicating that fractalkine signaling also determines several functions of microglial cells during normal CNS development. It has been known for a decade that microglial cells influence the neuronal death that normally occurs during CNS development. Surprisingly, recent evidence indicates that they can also support survival of developing neurons, control axon outgrowth, and laminar positioning of subsets of interneurons in the forebrain. Moreover, microglial cells influence the maturation of synaptic circuits at early postnatal stages: their phagocytic activity allows them to eliminate inappropriate synapses and they can also influence the functional expression of synaptic proteins by releasing mediators. Fractalkine signaling controls these functions of microglial cells in part by regulating their timely recruitment at sites of developing synapses. Finally, on-going research suggests that this signaling pathway is also a key player in neurodevelopmental disorders. Isabelle Arnoux and Etienne Audinat Copyright © 2015 Isabelle Arnoux and Etienne Audinat. All rights reserved. Activity-Dependent Plasticity of Astroglial Potassium and Glutamate Clearance Tue, 04 Aug 2015 11:27:13 +0000 Recent evidence has shown that astrocytes play essential roles in synaptic transmission and plasticity. Nevertheless, how neuronal activity alters astroglial functional properties and whether such properties also display specific forms of plasticity still remain elusive. Here, we review research findings supporting this aspect of astrocytes, focusing on their roles in the clearance of extracellular potassium and glutamate, two neuroactive substances promptly released during excitatory synaptic transmission. Their subsequent removal, which is primarily carried out by glial potassium channels and glutamate transporters, is essential for proper functioning of the brain. Similar to neurons, different forms of short- and long-term plasticity in astroglial uptake have been reported. In addition, we also present novel findings showing robust potentiation of astrocytic inward currents in response to repetitive stimulations at mild frequencies, as low as 0.75 Hz, in acute hippocampal slices. Interestingly, neurotransmission was hardly affected at this frequency range, suggesting that astrocytes may be more sensitive to low frequency stimulation and may exhibit stronger plasticity than neurons to prevent hyperexcitability. Taken together, these important findings strongly indicate that astrocytes display both short- and long-term plasticity in their clearance of excess neuroactive substances from the extracellular space, thereby regulating neuronal activity and brain homeostasis. Giselle Cheung, Jérémie Sibille, Jonathan Zapata, and Nathalie Rouach Copyright © 2015 Giselle Cheung et al. All rights reserved. Astroglial Plasticity Is Implicated in Hippocampal Remodelling in Adult Rats Exposed to Antenatal Dexamethasone Tue, 04 Aug 2015 11:15:22 +0000 The long-term effects of antenatal dexamethasone treatment on brain remodelling in 3-month-old male Sprague Dawley rats whose mothers had been treated with dexamethasone were investigated in the present study. Dorsal hippocampus, basolateral amygdala and nucleus accumbens volume, cell numbers, and GFAP-immunoreactive astroglial cell morphology were analysed using stereology. Total brain volume as assessed by micro-CT was not affected by the treatment. The relative volume of the dorsal hippocampus (% of total brain volume) showed a moderate, by 8%, but significant reduction in dexamethasone-treated versus control animals. Dexamethasone had no effect on the total and GFAP-positive cell numbers in the hippocampal subregions, basolateral amygdala, and nucleus accumbens. Morphological analysis indicated that numbers of astroglial primary processes were not affected in any of the hippocampal subregions analysed but significant reductions in the total primary process length were observed in CA1 by 32%, CA3 by 50%, and DG by 25%. Mean primary process length values were also significantly decreased in CA1 by 25%, CA3 by 45%, and DG by 25%. No significant astroglial morphological changes were found in basolateral amygdala and nucleus accumbens. We propose that the dexamethasone-dependent impoverishment of hippocampal astroglial morphology is the case of maladaptive glial plasticity induced prenatally. Vishvesh H. Shende, Simon McArthur, Glenda E. Gillies, and Jolanta Opacka-Juffry Copyright © 2015 Vishvesh H. Shende et al. All rights reserved. Glutamatergic Transmission: A Matter of Three Tue, 04 Aug 2015 11:13:19 +0000 Glutamatergic transmission in the vertebrate brain requires the involvement of glia cells, in a continuous molecular dialogue. Glial glutamate receptors and transporters are key molecules that sense synaptic activity and by these means modify their physiology in the short and long term. Posttranslational modifications that regulate protein-protein interactions and modulate transmitter removal are triggered in glial cells by neuronal released glutamate. Moreover, glutamate signaling cascades in these cells are linked to transcriptional and translational control and are critically involved in the control of the so-called glutamate/glutamine shuttle and by these means in glutamatergic neurotransmission. In this contribution, we summarize our current understanding of the biochemical consequences of glutamate synaptic activity in their surrounding partners and dissect the molecular mechanisms that allow neurons to take control of glia physiology to ensure proper glutamate-mediated neuronal communication. Zila Martínez-Lozada and Arturo Ortega Copyright © 2015 Zila Martínez-Lozada and Arturo Ortega. All rights reserved. Static and Dynamic Factors Promoting Resilience following Traumatic Brain Injury: A Brief Review Tue, 04 Aug 2015 10:40:23 +0000 Traumatic brain injury (TBI) is the greatest contributing cause of death and disability among children and young adults in the United States. The current paper briefly summarizes contemporary literature on factors that can improve outcomes (i.e., promote resilience) for children and adults following TBI. For the purpose of this paper, the authors divided these factors into static or unmodifiable factors (i.e., age, sex, intellectual abilities/education, and preinjury psychiatric history) and dynamic or modifiable factors (i.e., socioeconomic status, family functioning/social support, nutrition, and exercise). Drawing on human and animal studies, the research reviewed indicated that these various factors can improve outcomes in multiple domains of functioning (e.g., cognition, emotion regulation, health and wellness, behavior, etc.) following a TBI. However, many of these factors have not been studied across populations, have been limited to preclinical investigations, have been limited in their scope or follow-up, or have not involved a thorough evaluation of outcomes. Thus, although promising, continued research is vital in the area of factors promoting resilience following TBI in children and adults. Jessica N. Holland and Adam T. Schmidt Copyright © 2015 Jessica N. Holland and Adam T. Schmidt. All rights reserved. Multiscale Modeling Indicates That Temperature Dependent [Ca2+]i Spiking in Astrocytes Is Quantitatively Consistent with Modulated SERCA Activity Tue, 04 Aug 2015 10:36:54 +0000 Changes in the cytosolic Ca2+ concentration () are the most predominant active signaling mechanism in astrocytes that can modulate neuronal activity and is assumed to influence neuronal plasticity. Although Ca2+ signaling in astrocytes has been intensively studied in the past, our understanding of the signaling mechanism and its impact on tissue level is still incomplete. Here we revisit our previously published data on the strong temperature dependence of Ca2+ signals in both cultured primary astrocytes and astrocytes in acute brain slices of mice. We apply multiscale modeling to test the hypothesis that the temperature dependent spiking is mainly caused by the increased activity of the sarcoendoplasmic reticulum ATPases (SERCAs) that remove Ca2+ from the cytosol into the endoplasmic reticulum. Quantitative comparison of experimental data with multiscale simulations supports the SERCA activity hypothesis. Further analysis of multiscale modeling and traditional rate equations indicates that the experimental observations are a spatial phenomenon where increasing pump strength leads to a decoupling of Ca2+ release sites and subsequently to vanishing spikes. Niko Komin, Mahsa Moein, Mark H. Ellisman, and Alexander Skupin Copyright © 2015 Niko Komin et al. All rights reserved. Motor-Skill Learning Is Dependent on Astrocytic Activity Tue, 04 Aug 2015 10:34:49 +0000 Motor-skill learning induces changes in synaptic structure and function in the primary motor cortex through the involvement of a long-term potentiation- (LTP-) like mechanism. Although there is evidence that calcium-dependent release of gliotransmitters by astrocytes plays an important role in synaptic transmission and plasticity, the role of astrocytes in motor-skill learning is not known. To test the hypothesis that astrocytic activity is necessary for motor-skill learning, we perturbed astrocytic function using pharmacological and genetic approaches. We find that perturbation of astrocytes either by selectively attenuating IP3R2 mediated astrocyte Ca2+ signaling or using an astrocyte specific metabolic inhibitor fluorocitrate (FC) results in impaired motor-skill learning of a forelimb reaching-task in mice. Moreover, the learning impairment caused by blocking astrocytic activity using FC was rescued by administration of the gliotransmitter D-serine. The learning impairments are likely caused by impaired LTP as FC blocked LTP in slices and prevented motor-skill training-induced increases in synaptic AMPA-type glutamate receptor in vivo. These results support the conclusion that normal astrocytic Ca2+ signaling during a reaching task is necessary for motor-skill learning. Ragunathan Padmashri, Anand Suresh, Michael D. Boska, and Anna Dunaevsky Copyright © 2015 Ragunathan Padmashri et al. All rights reserved. Astrocyte and Neuronal Plasticity in the Somatosensory System Tue, 04 Aug 2015 06:55:14 +0000 Changing the whisker complement on a rodent’s snout can lead to two forms of experience-dependent plasticity (EDP) in the neurons of the barrel cortex, where whiskers are somatotopically represented. One form, termed coding plasticity, concerns changes in synaptic transmission and connectivity between neurons. This is thought to underlie learning and memory processes and so adaptation to a changing environment. The second, called homeostatic plasticity, serves to maintain a restricted dynamic range of neuronal activity thus preventing its saturation or total downregulation. Current explanatory models of cortical EDP are almost exclusively neurocentric. However, in recent years, increasing evidence has emerged on the role of astrocytes in brain function, including plasticity. Indeed, astrocytes appear as necessary partners of neurons at the core of the mechanisms of coding and homeostatic plasticity recorded in neurons. In addition to neuronal plasticity, several different forms of astrocytic plasticity have recently been discovered. They extend from changes in receptor expression and dynamic changes in morphology to alteration in gliotransmitter release. It is however unclear how astrocytic plasticity contributes to the neuronal EDP. Here, we review the known and possible roles for astrocytes in the barrel cortex, including its plasticity. Robert E. Sims, John B. Butcher, H. Rheinallt Parri, and Stanislaw Glazewski Copyright © 2015 Robert E. Sims et al. All rights reserved.