Neural Plasticity The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . All rights reserved. Acute Footshock Stress Induces Time-Dependent Modifications of AMPA/NMDA Protein Expression and AMPA Phosphorylation Thu, 04 Feb 2016 13:05:24 +0000 Clinical studies on patients with stress-related neuropsychiatric disorders reported functional and morphological changes in brain areas where glutamatergic transmission is predominant, including frontal and prefrontal areas. In line with this evidence, several preclinical works suggest that glutamate receptors are targets of both rapid and long-lasting effects of stress. Here we found that acute footshock- (FS-) stress, although inducing no transcriptional and RNA editing alterations of ionotropic AMPA and NMDA glutamate receptor subunits, rapidly and transiently modulates their protein expression, phosphorylation, and localization at postsynaptic spines in prefrontal and frontal cortex. In total extract, FS-stress increased the phosphorylation levels of GluA1 AMPA subunit at Ser845 immediately after stress and of GluA2 Ser880 2 h after start of stress. At postsynaptic spines, stress induced a rapid decrease of GluA2 expression, together with an increase of its phosphorylation at Ser880, suggesting internalization of GluA2 AMPA containing receptors. GluN1 and GluN2A NMDA receptor subunits were found markedly upregulated in postsynaptic spines, 2 h after start of stress. These results suggest selected time-dependent changes in glutamatergic receptor subunits induced by acute stress, which may suggest early and transient enhancement of AMPA-mediated currents, followed by a transient activation of NMDA receptors. Daniela Bonini, Cristina Mora, Paolo Tornese, Nathalie Sala, Alice Filippini, Luca La Via, Marco Milanese, Stefano Calza, Gianbattista Bonanno, Giorgio Racagni, Massimo Gennarelli, Maurizio Popoli, Laura Musazzi, and Alessandro Barbon Copyright © 2016 Daniela Bonini et al. All rights reserved. Natural Product-Derived Treatments for Attention-Deficit/Hyperactivity Disorder: Safety, Efficacy, and Therapeutic Potential of Combination Therapy Thu, 04 Feb 2016 12:50:02 +0000 Typical treatment plans for attention-deficit/hyperactivity disorder (ADHD) utilize nonpharmacological (behavioral/psychosocial) and/or pharmacological interventions. Limited accessibility to behavioral therapies and concerns over adverse effects of pharmacological treatments prompted research for alternative ADHD therapies such as natural product-derived treatments and nutritional supplements. In this study, we reviewed the herbal preparations and nutritional supplements evaluated in clinical studies as potential ADHD treatments and discussed their performance with regard to safety and efficacy in clinical trials. We also discussed some evidence suggesting that adjunct treatment of these agents (with another botanical agent or pharmacological ADHD treatments) may be a promising approach to treat ADHD. The analysis indicated mixed findings with regard to efficacy of natural product-derived ADHD interventions. Nevertheless, these treatments were considered as a “safer” approach than conventional ADHD medications. More comprehensive and appropriately controlled clinical studies are required to fully ascertain efficacy and safety of natural product-derived ADHD treatments. Studies that replicate encouraging findings on the efficacy of combining botanical agents and nutritional supplements with other natural product-derived therapies and widely used ADHD medications are also warranted. In conclusion, the risk-benefit balance of natural product-derived ADHD treatments should be carefully monitored when used as standalone treatment or when combined with other conventional ADHD treatments. James Ahn, Hyung Seok Ahn, Jae Hoon Cheong, and Ike dela Peña Copyright © 2016 James Ahn et al. All rights reserved. The Plastic Glial-Synaptic Dynamics within the Neuropil: A Self-Organizing System Composed of Polyelectrolytes in Phase Transition Mon, 01 Feb 2016 09:12:48 +0000 Several explanations have been proposed to account for the mechanisms of neuroglial interactions involved in neural plasticity. We review experimental results addressing plastic nonlinear interactions between glial membranes and synaptic terminals. These results indicate the necessity of elaborating on a model based on the dynamics of hydroionic waves within the neuropil. These waves have been detected in a small scale experimental model of the central nervous system, the in vitro retina. We suggest that the brain, as the heart and kidney, is a system for which the state of water is functional. The use of nonlinear thermodynamics supports experiments at convenient biological spatiotemporal scales, while an understanding of the properties of ions and their interactions with water requires explanations based on quantum theories. In our approach, neural plasticity is seen as part of a larger process that encompasses higher brain functions; in this regard, hydroionic waves within the neuropil are considered to carry both physiological and cognitive functions. Vera Maura Fernandes de Lima and Alfredo Pereira Jr. Copyright © 2016 Vera Maura Fernandes de Lima and Alfredo Pereira Jr. All rights reserved. Developmental Dynamics of Rett Syndrome Sun, 31 Jan 2016 16:54:11 +0000 Rett Syndrome was long considered to be simply a disorder of postnatal development, with phenotypes that manifest only late in development and into adulthood. A variety of recent evidence demonstrates that the phenotypes of Rett Syndrome are present at the earliest stages of brain development, including developmental stages that define neurogenesis, migration, and patterning in addition to stages of synaptic and circuit development and plasticity. These phenotypes arise from the pleotropic effects of MeCP2, which is expressed very early in neuronal progenitors and continues to be expressed into adulthood. The effects of MeCP2 are mediated by diverse signaling, transcriptional, and epigenetic mechanisms. Attempts to reverse the effects of Rett Syndrome need to take into account the developmental dynamics and temporal impact of MeCP2 loss. Danielle Feldman, Abhishek Banerjee, and Mriganka Sur Copyright © 2016 Danielle Feldman et al. All rights reserved. The Response to Oxidative DNA Damage in Neurons: Mechanisms and Disease Sun, 31 Jan 2016 09:36:41 +0000 There is a growing body of evidence indicating that the mechanisms that control genome stability are of key importance in the development and function of the nervous system. The major threat for neurons is oxidative DNA damage, which is repaired by the base excision repair (BER) pathway. Functional mutations of enzymes that are involved in the processing of single-strand breaks (SSB) that are generated during BER have been causally associated with syndromes that present important neurological alterations and cognitive decline. In this review, the plasticity of BER during neurogenesis and the importance of an efficient BER for correct brain function will be specifically addressed paying particular attention to the brain region and neuron-selectivity in SSB repair-associated neurological syndromes and age-related neurodegenerative diseases. Laura Narciso, Eleonora Parlanti, Mauro Racaniello, Valeria Simonelli, Alessio Cardinale, Daniela Merlo, and Eugenia Dogliotti Copyright © 2016 Laura Narciso et al. All rights reserved. Glia and TRPM2 Channels in Plasticity of Central Nervous System and Alzheimer’s Diseases Thu, 28 Jan 2016 10:11:09 +0000 Synaptic plasticity refers to the ability of neurons to strengthen or weaken synaptic efficacy in response to activity and is the basis for learning and memory. Glial cells communicate with neurons and in this way contribute in part to plasticity in the CNS and to the pathology of Alzheimer’s disease (AD), a neurodegenerative disease in which impaired synaptic plasticity is causally implicated. The transient receptor potential melastatin member 2 (TRPM2) channel is a nonselective Ca2+-permeable channel expressed in both glial cells (microglia and astrocytes) and neurons. Recent studies indicated that TRPM2 regulates synaptic plasticity as well as the activation of glial cells. TRPM2 also modulates oxidative stress and inflammation through interaction with glial cells. As both oxidative stress and inflammation have been implicated in AD pathology, this suggests a possible contribution of TRPM2 to disease processes. Through modulating the homeostasis of glutathione, TRPM2 is involved in the process of aging which is a risk factor of AD. These results potentially point TRPM2 channel to be involved in AD through glial cells. This review summarizes recent advances in studying the contribution of TRPM2 in health and in AD pathology, with a focus on contributions via glia cells. Jing Wang, Michael F. Jackson, and Yu-Feng Xie Copyright © 2016 Jing Wang et al. All rights reserved. Value of Functionalized Superparamagnetic Iron Oxide Nanoparticles in the Diagnosis and Treatment of Acute Temporal Lobe Epilepsy on MRI Wed, 27 Jan 2016 07:39:37 +0000 Purpose. Although active targeting of drugs using a magnetic-targeted drug delivery system (MTDS) with superparamagnetic iron oxide nanoparticles (SPIONs) is a very effective treatment approach for tumors and other illnesses, successful results of drug-resistant temporal lobe epilepsy (TLE) are unprecedented. A hallmark in the neuropathology of TLE is brain inflammation, in particular the activation of interleukin-1β (IL-1β) induced by activated glial cells, which has been considered a new mechanistic target for treatment. The purpose of this study was to determine the feasibility of the functionalized SPIONs with anti-IL-1β monoclonal antibody (mAb) attached to render MRI diagnoses and simultaneously provide targeted therapy with the neutralization of IL-1β overexpressed in epileptogenic zone of an acute rat model of TLE. Experimental Design. The anti-IL-1β mAb-SPIONs were studied in vivo versus plain SPIONs and saline. Lithium-chloride pilocarpine-induced TLE models () were followed by Western blot, Perl’s iron staining, Nissl staining, and immunofluorescent double-label staining after MRI examination. Results. The magnetic anti-IL-1β mAb-SPION administered intravenously, which crossed the BBB and was concentrated in the astrocytes and neurons in epileptogenic tissues, rendered these tissues visible on MRI and simultaneously delivered anti-IL-1β mAb to the epileptogenic focus. Conclusions. Our study provides the first evidence that the novel approach enhanced accumulation and the therapeutic effect of anti-IL-1β mAb by MTDS using SPIONs. Tingting Fu, Qingxia Kong, Huaqiang Sheng, and Lingyun Gao Copyright © 2016 Tingting Fu et al. All rights reserved. Maladaptive Plasticity and Neuropathic Pain Wed, 27 Jan 2016 06:57:11 +0000 Xiang-Yao Li, You Wan, Shao-Jun Tang, Yun Guan, Feng Wei, and Daqing Ma Copyright © 2016 Xiang-Yao Li et al. All rights reserved. Dynamic Alterations of miR-34c Expression in the Hypothalamus of Male Rats after Early Adolescent Traumatic Stress Tue, 26 Jan 2016 16:47:11 +0000 Several types of microRNA (miRNA) overexpression in the brain are associated with stress. One of the targets of miR-34c is the stress-related corticotrophin releasing factor receptor 1 mRNA (CRFR1 mRNA). Here we will probe into the short-term effect and long-term effect of early adolescent traumatic stress on the expression of miR-34c and CRFR1 mRNA. Traumatic stress was established by electric foot shock for six consecutive days using 28-day rats. The anxiety-like behaviors, memory damage, CRFR1 protein, CRFR1 mRNA, and miR-34c expression were detected in our study. The results of our study proved that exposure to acute traumatic stress in early adolescent can cause permanent changes in neural network, resulting in dysregulation of CRFR1 expression and CRFR1 mRNA and miR-34c expression in hypothalamus, anxiety-like behavior, and memory impairment, suggesting that the miR-34c expression in hypothalamus may be an important factor involved in susceptibility to PTSD. Chuting Li, Yuan Liu, Dexiang Liu, Hong Jiang, and Fang Pan Copyright © 2016 Chuting Li et al. All rights reserved. Carbachol-Induced Reduction in the Activity of Adult Male Zebra Finch RA Projection Neurons Wed, 20 Jan 2016 09:44:04 +0000 Cholinergic mechanism is involved in motor behavior. In songbirds, the robust nucleus of the arcopallium (RA) is a song premotor nucleus in the pallium and receives cholinergic inputs from the basal forebrain. The activity of projection neurons in RA determines song motor behavior. Although many evidences suggest that cholinergic system is implicated in song production, the cholinergic modulation of RA is not clear until now. In the present study, the electrophysiological effects of carbachol, a nonselective cholinergic receptor agonist, were investigated on the RA projection neurons of adult male zebra finches through whole-cell patch-clamp techniques in vitro. Our results show that carbachol produced a significant decrease in the spontaneous and evoked action potential (AP) firing frequency of RA projection neurons, accompanying a hyperpolarization of the membrane potential, an increase in the evoked AP latency, afterhyperpolarization (AHP) peak amplitude, and AHP time to peak, and a decrease in the membrane input resistance, membrane time constant, and membrane capacitance. These results indicate that carbachol reduces the activity of RA projection neurons by hyperpolarizing the resting membrane potential and increasing the AHP and the membrane conductance, suggesting that the cholinergic modulation of RA may play an important role in song production. Wei Meng, Song-Hua Wang, and Dong-Feng Li Copyright © 2016 Wei Meng et al. All rights reserved. Impaired Functional Connectivity in the Prefrontal Cortex: A Mechanism for Chronic Stress-Induced Neuropsychiatric Disorders Tue, 19 Jan 2016 18:13:10 +0000 Chronic stress-related psychiatric diseases, such as major depression, posttraumatic stress disorder, and schizophrenia, are characterized by a maladaptive organization of behavioral responses that strongly affect the well-being of patients. Current evidence suggests that a functional impairment of the prefrontal cortex (PFC) is implicated in the pathophysiology of these diseases. Therefore, chronic stress may impair PFC functions required for the adaptive orchestration of behavioral responses. In the present review, we integrate evidence obtained from cognitive neuroscience with neurophysiological research with animal models, to put forward a hypothesis that addresses stress-induced behavioral dysfunctions observed in stress-related neuropsychiatric disorders. We propose that chronic stress impairs mechanisms involved in neuronal functional connectivity in the PFC that are required for the formation of adaptive representations for the execution of adaptive behavioral responses. These considerations could be particularly relevant for understanding the pathophysiology of chronic stress-related neuropsychiatric disorders. Ignacio Negrón-Oyarzo, Francisco Aboitiz, and Pablo Fuentealba Copyright © 2016 Ignacio Negrón-Oyarzo et al. All rights reserved. Inducing LTD-Like Effect in the Human Motor Cortex with Low Frequency and Very Short Duration Paired Associative Stimulation: An Exploratory Study Tue, 19 Jan 2016 18:08:12 +0000 Introduction. Paired associative stimulation (PAS) is an established technique to investigate synaptic plasticity in the human motor cortex (M1). Classically, to induce long-term depression- (LTD-) or long-term potentiation-like effects in the human M1, studies have used low frequency and long duration trains of PAS. In the present study, we explored an LTD-like effect using very short duration and low frequency of protocols in human M1. Methods. Six protocols of low frequency (ranging from 0.2 Hz to 1 Hz) were investigated with very short durations of 1 and 2 minutes stimulation. Six healthy volunteers were included in each protocol. We obtained motor-evoked potentials from right abductor pollicis brevis muscle before and after applying up to 30 minutes. After we found protocol which induced an LTD-like effect, we tested that protocol on additional 5 subjects. Results. One-way repeated-measures ANOVA showed that only the group of 1-minute stimulation of 0.25 Hz induced an LTD-like effect. When adding the additional subjects, the effect remained and lasted for 30 minutes. Conclusion. Low frequency and very short duration of potentially induced an LTD-like effect in human M1. With further verification, this method might be useful for research relating to synaptic plasticity by reducing the duration of study and minimizing subject discomfort. Prachaya Srivanitchapoom, Jung E. Park, Nivethida Thirugnanasambandam, Pattamon Panyakaew, Vesper Fe Marie Ramos, Sanjay Pandey, Tianxia Wu, and Mark Hallett Copyright © 2016 Prachaya Srivanitchapoom et al. All rights reserved. Caught in the Net: Perineuronal Nets and Addiction Tue, 19 Jan 2016 14:06:22 +0000 Exposure to drugs of abuse induces plasticity in the brain and creates persistent drug-related memories. These changes in plasticity and persistent drug memories are believed to produce aberrant motivation and reinforcement contributing to addiction. Most studies have explored the effect drugs of abuse have on pre- and postsynaptic cells and astrocytes; however, more recently, attention has shifted to explore the effect these drugs have on the extracellular matrix (ECM). Within the ECM are unique structures arranged in a net-like manner, surrounding a subset of neurons called perineuronal nets (PNNs). This review focuses on drug-induced changes in PNNs, the molecules that regulate PNNs, and the expression of PNNs within brain circuitry mediating motivation, reward, and reinforcement as it pertains to addiction. Megan Slaker, Jordan M. Blacktop, and Barbara A. Sorg Copyright © 2016 Megan Slaker et al. All rights reserved. Background Noise Contributes to Organic Solvent Induced Brain Dysfunction Mon, 18 Jan 2016 09:02:40 +0000 Occupational exposure to complex blends of organic solvents is believed to alter brain functions among workers. However, work environments that contain organic solvents are also polluted with background noise which raises the issue of whether or not the noise contributed to brain alterations. The purpose of the current study was to determine whether or not repeated exposure to low intensity noise with and without exposure to a complex blend of organic solvents would alter brain activity. Female Fischer344 rats served as subjects in these experiments. Asynchronous volume conductance between the midbrain and cortex was evaluated with a slow vertex recording technique. Subtoxic solvent exposure, by itself, had no statistically significant effects. However, background noise significantly suppressed brain activity and this suppression was exacerbated with solvent exposure. Furthermore, combined exposure produced significantly slow neurotransmission. These abnormal neurophysiologic findings occurred in the absence of hearing loss and detectable damage to sensory cells. The observations from the current experiment raise concern for all occupations where workers are repeatedly exposed to background noise or noise combined with organic solvents. Noise levels and solvent concentrations that are currently considered safe may not actually be safe and existing safety regulations have failed to recognize the neurotoxic potential of combined exposures. O’neil W. Guthrie, Brian A. Wong, Shawn M. McInturf, James E. Reboulet, Pedro A. Ortiz, and David R. Mattie Copyright © 2016 O’neil W. Guthrie et al. All rights reserved. Plastic Change in the Auditory Minimum Threshold Induced by Intercollicular Effects in Mice Sun, 17 Jan 2016 12:15:02 +0000 In the auditory pathway, the commissure of the inferior colliculus (IC) interconnects the two ICs on both sides of the dorsal midbrain. This interconnection could mediate an interaction between the two ICs during sound signal processing. The intercollicular effects evoked by focal electric stimulation for 30 min could inhibit or facilitate auditory responses and induce plastic changes in the response minimum threshold (MT) of IC neurons. Changes in MT are dependent on the best frequency (BF) and MT difference. The MT shift is larger in IC neurons with BF differences ≤2 kHz than in those with BF differences >2 kHz. Moreover, MTs that shift toward electrically stimulated IC neurons increase with the increasing MT difference between the two ICs. The shift in MT lasts for a certain period of time and then returns to previous levels within ~150 min. The collicular interactions are either reciprocal or unilateral under alternate stimulating and recording conditions in both ICs. Our results suggest that intercollicular effects may be involved in the acoustic experience-dependent plasticity of the MT of IC neurons. Hui-Xian Mei, Jia Tang, Zi-Ying Fu, Liang Cheng, and Qi-Cai Chen Copyright © 2016 Hui-Xian Mei et al. All rights reserved. Linking Mitochondria to Synapses: New Insights for Stress-Related Neuropsychiatric Disorders Thu, 14 Jan 2016 14:22:13 +0000 The brain evolved cellular mechanisms for adapting synaptic function to energy supply. This is particularly evident when homeostasis is challenged by stress. Signaling loops between the mitochondria and synapses scale neuronal connectivity with bioenergetics capacity. A biphasic “inverted U shape” response to the stress hormone glucocorticoids is demonstrated in mitochondria and at synapses, modulating neural plasticity and physiological responses. Low dose enhances neurotransmission, synaptic growth, mitochondrial functions, learning, and memory whereas chronic, higher doses produce inhibition of these functions. The range of physiological effects by stress and glucocorticoid depends on the dose, duration, and context at exposure. These criteria are met by neuronal activity and the circadian, stress-sensitive and ultradian, stress-insensitive modes of glucocorticoid secretion. A major hallmark of stress-related neuropsychiatric disorders is the disrupted glucocorticoid rhythms and tissue resistance to signaling with the glucocorticoid receptor (GR). GR resistance could result from the loss of context-dependent glucocorticoid signaling mediated by the downregulation of the activity-dependent neurotrophin BDNF. The coincidence of BDNF and GR signaling changes glucocorticoid signaling output with consequences on mitochondrial respiration efficiency, synaptic plasticity, and adaptive trajectories. Freddy Jeanneteau and Margarita Arango-Lievano Copyright © 2016 Freddy Jeanneteau and Margarita Arango-Lievano. All rights reserved. Miglustat Reverts the Impairment of Synaptic Plasticity in a Mouse Model of NPC Disease Thu, 14 Jan 2016 14:17:40 +0000 Niemann-Pick type C disease is an autosomal recessive storage disorder, characterized by abnormal sequestration of unesterified cholesterol within the late endolysosomal compartment of cells and accumulation of gangliosides and other sphingolipids. Progressive neurological deterioration and insurgence of symptoms like ataxia, seizure, and cognitive decline until severe dementia are pathognomonic features of the disease. Here, we studied synaptic plasticity phenomena and evaluated ERKs activation in the hippocampus of BALB/c NPC1−/− mice, a well described animal model of the disease. Our results demonstrated an impairment of both induction and maintenance of long term synaptic potentiation in NPC1−/− mouse slices, associated with the lack of ERKs phosphorylation. We then investigated the effects of Miglustat, a recent approved drug for the treatment of NPCD. We found that in vivo Miglustat administration in NPC1−/− mice was able to rescue synaptic plasticity deficits, to restore ERKs activation and to counteract hyperexcitability. Overall, these data indicate that Miglustat may be effective for treating the neurological deficits associated with NPCD, such as seizures and dementia. G. D’Arcangelo, D. Grossi, M. Racaniello, A. Cardinale, A. Zaratti, S. Rufini, A. Cutarelli, V. Tancredi, D. Merlo, and C. Frank Copyright © 2016 G. D’Arcangelo et al. All rights reserved. Chondroitin 6-Sulfation Regulates Perineuronal Net Formation by Controlling the Stability of Aggrecan Thu, 14 Jan 2016 14:16:59 +0000 Perineuronal nets (PNNs) are lattice-like extracellular matrix structures composed of chondroitin sulfate proteoglycans (CSPGs). The appearance of PNNs parallels the decline of neural plasticity, and disruption of PNNs reactivates neural plasticity in the adult brain. We previously reported that sulfation patterns of chondroitin sulfate (CS) chains on CSPGs influenced the formation of PNNs and neural plasticity. However, the mechanism of PNN formation regulated by CS sulfation remains unknown. Here we found that overexpression of chondroitin 6-sulfotransferase-1 (C6ST-1), which catalyzes 6-sulfation of CS chains, selectively decreased aggrecan, a major CSPG in PNNs, in the aged brain without affecting other PNN components. Both diffuse and PNN-associated aggrecans were reduced by overexpression of C6ST-1. C6ST-1 increased 6-sulfation in both the repeating disaccharide region and linkage region of CS chains. Overexpression of 6-sulfation primarily impaired accumulation of aggrecan in PNNs, whereas condensation of other PNN components was not affected. Finally, we found that increased 6-sulfation accelerated proteolysis of aggrecan by a disintegrin and metalloproteinase domain with thrombospondin motif (ADAMTS) protease. Taken together, our results indicate that sulfation patterns of CS chains on aggrecan influenced the stability of the CSPG, thereby regulating formation of PNNs and neural plasticity. Shinji Miyata and Hiroshi Kitagawa Copyright © 2016 Shinji Miyata and Hiroshi Kitagawa. All rights reserved. Eyes Open on Sleep and Wake: In Vivo to In Silico Neural Networks Thu, 14 Jan 2016 13:12:36 +0000 Functional and effective connectivity of cortical areas are essential for normal brain function under different behavioral states. Appropriate cortical activity during sleep and wakefulness is ensured by the balanced activity of excitatory and inhibitory circuits. Ultimately, fast, millisecond cortical rhythmic oscillations shape cortical function in time and space. On a much longer time scale, brain function also depends on prior sleep-wake history and circadian processes. However, much remains to be established on how the brain operates at the neuronal level in humans during sleep and wakefulness. A key limitation of human neuroscience is the difficulty in isolating neuronal excitation/inhibition drive in vivo. Therefore, computational models are noninvasive approaches of choice to indirectly access hidden neuronal states. In this review, we present a physiologically driven in silico approach, Dynamic Causal Modelling (DCM), as a means to comprehend brain function under different experimental paradigms. Importantly, DCM has allowed for the understanding of how brain dynamics underscore brain plasticity, cognition, and different states of consciousness. In a broader perspective, noninvasive computational approaches, such as DCM, may help to puzzle out the spatial and temporal dynamics of human brain function at different behavioural states. Amaury Vanvinckenroye, Gilles Vandewalle, Christophe Phillips, and Sarah L. Chellappa Copyright © 2016 Amaury Vanvinckenroye et al. All rights reserved. Functional Integration between Salience and Central Executive Networks: A Role for Action Video Game Experience Thu, 14 Jan 2016 13:08:09 +0000 Action video games (AVGs) have attracted increasing research attention as they offer a unique perspective into the relation between active learning and neural plasticity. However, little research has examined the relation between AVG experience and the plasticity of neural network mechanisms. It has been proposed that AVG experience is related to the integration between Salience Network (SN) and Central Executive Network (CEN), which are responsible for attention and working memory, respectively, two cognitive functions essential for AVG playing. This study initiated a systematic investigation of this proposition by analyzing AVG experts’ and amateurs’ resting-state brain functions through graph theoretical analyses and functional connectivity. Results reveal enhanced intra- and internetwork functional integrations in AVG experts compared to amateurs. The findings support the possible relation between AVG experience and the neural network plasticity. Diankun Gong, Hui He, Weiyi Ma, Dongbo Liu, Mengting Huang, Li Dong, Jinnan Gong, Jianfu Li, Cheng Luo, and Dezhong Yao Copyright © 2016 Diankun Gong et al. All rights reserved. Gender Differences in the Neurobiology of Anxiety: Focus on Adult Hippocampal Neurogenesis Thu, 14 Jan 2016 13:03:01 +0000 Although the literature reports a higher incidence of anxiety disorders in women, the majority of basic research has focused on male rodents, thus resulting in a lack of knowledge on the neurobiology of anxiety in females. Bridging this gap is crucial for the design of effective translational interventions in women. One of the key brain mechanisms likely to regulate anxious behavior is adult hippocampal neurogenesis (AHN). This review paper aims to discuss the evidence on the differences between male and female rodents with regard to anxiety-related behavior and physiology, with a special focus on AHN. The differences between male and female physiologies are greatly influenced by hormonal differences. Gonadal hormones and their fluctuations during the estrous cycle have often been identified as agents responsible for sexual dimorphism in behavior and AHN. During sexual maturity, hormone levels fluctuate cyclically in females more than in males, increasing the stress response and the susceptibility to anxiety. It is therefore of great importance that future research investigates anxiety and other neurophysiological aspects in the female model, so that results can be more accurately applicable to the female population. Alessandra Aparecida Marques, Mário Cesar do Nascimento Bevilaqua, Alberto Morais Pinto da Fonseca, Antonio Egidio Nardi, Sandrine Thuret, and Gisele Pereira Dias Copyright © 2016 Alessandra Aparecida Marques et al. All rights reserved. The Chemorepulsive Protein Semaphorin 3A and Perineuronal Net-Mediated Plasticity Thu, 14 Jan 2016 13:00:28 +0000 During postnatal development, closure of critical periods coincides with the appearance of extracellular matrix structures, called perineuronal nets (PNN), around various neuronal populations throughout the brain. The absence or presence of PNN strongly correlates with neuronal plasticity. It is not clear how PNN regulate plasticity. The repulsive axon guidance proteins Semaphorin (Sema) 3A and Sema3B are also prominently expressed in the postnatal and adult brain. In the neocortex, Sema3A accumulates in the PNN that form around parvalbumin positive inhibitory interneurons during the closure of critical periods. Sema3A interacts with high-affinity with chondroitin sulfate E, a component of PNN. The localization of Sema3A in PNN and its inhibitory effects on developing neurites are intriguing features and may clarify how PNN mediate structural neural plasticity. In the cerebellum, enhanced neuronal plasticity as a result of an enriched environment correlates with reduced Sema3A expression in PNN. Here, we first review the distribution of Sema3A and Sema3B expression in the rat brain and the biochemical interaction of Sema3A with PNN. Subsequently, we review what is known so far about functional correlates of changes in Sema3A expression in PNN. Finally, we propose a model of how Semaphorins in the PNN may influence local connectivity. F. de Winter, J. C. F. Kwok, J. W. Fawcett, T. T. Vo, D. Carulli, and J. Verhaagen Copyright © 2016 F. de Winter et al. All rights reserved. Caffeine-Induced Suppression of GABAergic Inhibition and Calcium-Independent Metaplasticity Thu, 14 Jan 2016 12:59:30 +0000 GABAergic inhibition plays a critical role in the regulation of neuron excitability; thus, it is subject to modulations by many factors. Recent evidence suggests the elevation of intracellular calcium () and calcium-dependent signaling molecules underlie the modulations. Caffeine induces a release of calcium from intracellular stores. We tested whether caffeine modulated GABAergic transmission by increasing . A brief local puff-application of caffeine to hippocampal CA1 pyramidal cells transiently suppressed GABAergic inhibitory postsynaptic currents (IPSCs) by 73.2 ± 6.98%. Time course of suppression and the subsequent recovery of IPSCs resembled DSI (depolarization-induced suppression of inhibition), mediated by endogenous cannabinoids that require a rise. However, unlike DSI, caffeine-induced suppression of IPSCs (CSI) persisted in the absence of a rise. Intracellular applications of BAPTA and ryanodine (which blocks caffeine-induced calcium release from intracellular stores) failed to prevent the generation of CSI. Surprisingly, ruthenium red, an inhibitor of multiple calcium permeable/release channels including those of stores, induced metaplasticity by amplifying the magnitude of CSI independently of calcium. This metaplasticity was accompanied with the generation of a large inward current. Although ionic basis of this inward current is undetermined, the present result demonstrates that caffeine has a robust -independent inhibitory action on GABAergic inhibition and causes metaplasticity by opening plasma membrane channels. Masako Isokawa Copyright © 2016 Masako Isokawa. All rights reserved. Inhibition Plasticity in Older Adults: Practice and Transfer Effects Using a Multiple Task Approach Thu, 14 Jan 2016 11:03:22 +0000 Objective. To examine plasticity of inhibition, as indexed by practice effects of inhibition tasks and the associated transfer effects, using a multiple task approach in healthy older adults. Method. Forty-eight healthy older adults were evenly assigned to either a practice group or a no-contact control group. All participants completed pretest (2.5 hours) and posttest (2 hours) sessions, with a 2-week interval in between. During the 2-week interval, only the practice group completed six 30-minute practice sessions (three sessions per week for two consecutive weeks) of three lab-based inhibition tasks. Results. All three inhibition tasks demonstrated significant improvement across practice sessions, suggesting practice-induced plasticity. The benefit, however, only transferred to near-near tasks. The results are inconclusive with regard to the near-far and far-far transfer effects. Discussion. This study further extends literature on practice effects of inhibition in older adults by using a multiple task approach. Together with previous work, the current study suggests that older adults are able to improve inhibition performance through practice and transfer the practice gains to tasks that overlap in both target cognitive ability and task structure (i.e., near-near tasks). Andrea J. Wilkinson and Lixia Yang Copyright © 2016 Andrea J. Wilkinson and Lixia Yang. All rights reserved. Emerging Role of Spinal Cord TRPV1 in Pain Exacerbation Thu, 14 Jan 2016 08:18:11 +0000 TRPV1 is well known as a sensor ion channel that transduces a potentially harmful environment into electrical depolarization of the peripheral terminal of the nociceptive primary afferents. Although TRPV1 is also expressed in central regions of the nervous system, its roles in the area remain unclear. A series of recent reports on the spinal cord synapses have provided evidence that TRPV1 plays an important role in synaptic transmission in the pain pathway. Particularly, in pathologic pain states, TRPV1 in the central terminal of sensory neurons and interneurons is suggested to commonly contribute to pain exacerbation. These observations may lead to insights regarding novel synaptic mechanisms revealing veiled roles of spinal cord TRPV1 and may offer another opportunity to modulate pathological pain by controlling TRPV1. In this review, we introduce historical perspectives of this view and details of the recent promising results. We also focus on extended issues and unsolved problems to fully understand the role of TRPV1 in pathological pain. Together with recent findings, further efforts for fine analysis of TRPV1’s plastic roles in pain synapses at different levels in the central nervous system will promote a better understanding of pathologic pain mechanisms and assist in developing novel analgesic strategies. Seung-In Choi, Ji Yeon Lim, Sungjae Yoo, Hyun Kim, and Sun Wook Hwang Copyright © 2016 Seung-In Choi et al. All rights reserved. The Right Hemisphere Planum Temporale Supports Enhanced Visual Motion Detection Ability in Deaf People: Evidence from Cortical Thickness Thu, 14 Jan 2016 06:28:43 +0000 After sensory loss, the deprived cortex can reorganize to process information from the remaining modalities, a phenomenon known as cross-modal reorganization. In blind people this cross-modal processing supports compensatory behavioural enhancements in the nondeprived modalities. Deaf people also show some compensatory visual enhancements, but a direct relationship between these abilities and cross-modally reorganized auditory cortex has only been established in an animal model, the congenitally deaf cat, and not in humans. Using T1-weighted magnetic resonance imaging, we measured cortical thickness in the planum temporale, Heschl’s gyrus and sulcus, the middle temporal area MT+, and the calcarine sulcus, in early-deaf persons. We tested for a correlation between this measure and visual motion detection thresholds, a visual function where deaf people show enhancements as compared to hearing. We found that the cortical thickness of a region in the right hemisphere planum temporale, typically an auditory region, was greater in deaf individuals with better visual motion detection thresholds. This same region has previously been implicated in functional imaging studies as important for functional reorganization. The structure-behaviour correlation observed here demonstrates this area’s involvement in compensatory vision and indicates an anatomical correlate, increased cortical thickness, of cross-modal plasticity. Martha M. Shiell, François Champoux, and Robert J. Zatorre Copyright © 2016 Martha M. Shiell et al. All rights reserved. The Role of Hypothalamic Neuropeptides in Neurogenesis and Neuritogenesis Wed, 13 Jan 2016 13:26:20 +0000 The hypothalamus is a source of neural progenitor cells which give rise to different populations of specialized and differentiated cells during brain development. Newly formed neurons in the hypothalamus can synthesize and release various neuropeptides. Although term neuropeptide recently undergoes redefinition, small-size hypothalamic neuropeptides remain major signaling molecules mediating short- and long-term effects on brain development. They represent important factors in neurite growth and formation of neural circuits. There is evidence suggesting that the newly generated hypothalamic neurons may be involved in regulation of metabolism, energy balance, body weight, and social behavior as well. Here we review recent data on the role of hypothalamic neuropeptides in adult neurogenesis and neuritogenesis with special emphasis on the development of food intake and social behavior related brain circuits. Jan Bakos, Martina Zatkova, Zuzana Bacova, and Daniela Ostatnikova Copyright © 2016 Jan Bakos et al. All rights reserved. Multilevel Deficiency of White Matter Connectivity Networks in Alzheimer’s Disease: A Diffusion MRI Study with DTI and HARDI Models Wed, 13 Jan 2016 13:10:05 +0000 Alzheimer’s disease (AD) is the most common form of dementia in elderly people. It is an irreversible and progressive brain disease. In this paper, we utilized diffusion-weighted imaging (DWI) to detect abnormal topological organization of white matter (WM) structural networks. We compared the differences between WM connectivity characteristics at global, regional, and local levels in 26 patients with probable AD and 16 normal control (NC) elderly subjects, using connectivity networks constructed with the diffusion tensor imaging (DTI) model and the high angular resolution diffusion imaging (HARDI) model, respectively. At the global level, we found that the WM structural networks of both AD and NC groups had a small-world topology; however, the AD group showed a significant decrease in both global and local efficiency, but an increase in clustering coefficient and the average shortest path length. We further found that the AD patients had significantly decreased nodal efficiency at the regional level, as well as weaker connections in multiple local cortical and subcortical regions, such as precuneus, temporal lobe, hippocampus, and thalamus. The HARDI model was found to be more advantageous than the DTI model, as it was more sensitive to the deficiencies in AD at all of the three levels. Tao Wang, Feng Shi, Yan Jin, Pew-Thian Yap, Chong-Yaw Wee, Jianye Zhang, Cece Yang, Xia Li, Shifu Xiao, and Dinggang Shen Copyright © 2016 Tao Wang et al. All rights reserved. Spindle Bursts in Neonatal Rat Cerebral Cortex Wed, 13 Jan 2016 07:02:23 +0000 Spontaneous and sensory evoked spindle bursts represent a functional hallmark of the developing cerebral cortex in vitro and in vivo. They have been observed in various neocortical areas of numerous species, including newborn rodents and preterm human infants. Spindle bursts are generated in complex neocortical-subcortical circuits involving in many cases the participation of motor brain regions. Together with early gamma oscillations, spindle bursts synchronize the activity of a local neuronal network organized in a cortical column. Disturbances in spindle burst activity during corticogenesis may contribute to disorders in cortical architecture and in the activity-dependent control of programmed cell death. In this review we discuss (i) the functional properties of spindle bursts, (ii) the mechanisms underlying their generation, (iii) the synchronous patterns and cortical networks associated with spindle bursts, and (iv) the physiological and pathophysiological role of spindle bursts during early cortical development. Jenq-Wei Yang, Vicente Reyes-Puerta, Werner Kilb, and Heiko J. Luhmann Copyright © 2016 Jenq-Wei Yang et al. All rights reserved. N100 Repetition Suppression Indexes Neuroplastic Defects in Clinical High Risk and Psychotic Youth Tue, 12 Jan 2016 13:54:58 +0000 Highly penetrant mutations leading to schizophrenia are enriched for genes coding for N-methyl-D-aspartate receptor signaling complex (NMDAR-SC), implicating plasticity defects in the disease’s pathogenesis. The importance of plasticity in neurodevelopment implies a role for therapies that target these mechanisms in early life to prevent schizophrenia. Testing such therapies requires noninvasive methods that can assess engagement of target mechanisms. The auditory N100 is an obligatory cortical response whose amplitude decreases with tone repetition. This adaptation may index the health of plasticity mechanisms required for normal development. We exposed participants aged 5 to 17 years with psychosis , at clinical high risk (CHR) for psychosis , and healthy controls to an auditory tone repeated 450 times and measured N100 adaptation (mean amplitude during first 150 tones − mean amplitude during last 150 tones). N100 adaptation was reduced in CHR and psychosis, particularly among participants <13 years old. Initial N100 blunting partially accounted for differences. Decreased change in the N100 amplitude with tone repetition may be a useful marker of defects in neuroplastic mechanisms measurable early in life. Joseph Gonzalez-Heydrich, Michelle Bosquet Enlow, Eugene D’Angelo, Larry J. Seidman, Sarah Gumlak, April Kim, Kristen A. Woodberry, Ashley Rober, Sahil Tembulkar, Kyle O’Donnell, Hesham M. Hamoda, Kara Kimball, Alexander Rotenberg, Lindsay M. Oberman, Alvaro Pascual-Leone, Matcheri S. Keshavan, and Frank H. Duffy Copyright © 2016 Joseph Gonzalez-Heydrich et al. All rights reserved.