Neural Plasticity The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Animal Models of Subjective Tinnitus Wed, 16 Apr 2014 08:08:32 +0000 Tinnitus is one of the major audiological diseases, affecting a significant portion of the ageing society. Despite its huge personal and presumed economic impact there are only limited therapeutic options available. The reason for this deficiency lies in the very nature of the disease as it is deeply connected to elementary plasticity of auditory processing in the central nervous system. Understanding these mechanisms is essential for developing a therapy that reverses the plastic changes underlying the pathogenesis of tinnitus. This requires experiments that address individual neurons and small networks, something usually not feasible in human patients. However, in animals such invasive experiments on the level of single neurons with high spatial and temporal resolution are possible. Therefore, animal models are a very critical element in the combined efforts for engineering new therapies. This review provides an overview over the most important features of animal models of tinnitus: which laboratory species are suitable, how to induce tinnitus, and how to characterize the perceived tinnitus by behavioral means. In particular, these aspects of tinnitus animal models are discussed in the light of transferability to the human patients. Wolfger von der Behrens Copyright © 2014 Wolfger von der Behrens. All rights reserved. The Effects of Early-Life Predator Stress on Anxiety- and Depression-Like Behaviors of Adult Rats Tue, 15 Apr 2014 12:49:21 +0000 Childhood emotional trauma contributes significantly to certain psychopathologies, such as post-traumatic stress disorder. In experimental animals, however, whether or not early-life stress results in behavioral abnormalities in adult animals still remains controversial. Here, we investigated both short-term and long-term changes of anxiety- and depression-like behaviors of Wistar rats after being exposed to chronic feral cat stress in juvenile ages. The 2-week predator stress decreased spontaneous activities immediately following stress but did not increase depression- or anxiety-like behaviors 4 weeks after the stimulation in adulthood. Instead, juvenile predator stress had some protective effects, though not very obvious, in adulthood. We also exposed genetic depression model rats, Wistar Kyoto (WKY) rats, to the same predator stress. In WKY rats, the same early-life predator stress did not enhance anxiety- or depression-like behaviors in both the short-term and long-term. However, the stressed WKY rats showed slightly reduced depression-like behaviors in adulthood. These results indicate that in both normal Wistar rats and WKY rats, early-life predator stress led to protective, rather than negative, effects in adulthood. Lu-jing Chen, Bing-qing Shen, Dan-dan Liu, and Sheng-tian Li Copyright © 2014 Lu-jing Chen et al. All rights reserved. Polarity Specific Suppression Effects of Transcranial Direct Current Stimulation for Tinnitus Thu, 10 Apr 2014 00:00:00 +0000 Tinnitus is the perception of a sound in the absence of an external auditory stimulus and affects 10–15% of the Western population. Previous studies have demonstrated the therapeutic effect of anodal transcranial direct current stimulation (tDCS) over the left auditory cortex on tinnitus loudness, but the effect of this presumed excitatory stimulation contradicts with the underlying pathophysiological model of tinnitus. Therefore, we included 175 patients with chronic tinnitus to study polarity specific effects of a single tDCS session over the auditory cortex (39 anodal, 136 cathodal). To assess the effect of treatment, we used the numeric rating scale for tinnitus loudness and annoyance. Statistical analysis demonstrated a significant main effect for tinnitus loudness and annoyance, but for tinnitus annoyance anodal stimulation has a significantly more pronounced effect than cathodal stimulation. We hypothesize that the suppressive effect of tDCS on tinnitus loudness may be attributed to a disrupting effect of ongoing neural hyperactivity, independent of the inhibitory or excitatory effects and that the reduction of annoyance may be induced by influencing adjacent or functionally connected brain areas involved in the tinnitus related distress network. Further research is required to explain why only anodal stimulation has a suppressive effect on tinnitus annoyance. Kathleen Joos, Dirk De Ridder, Paul Van de Heyning, and Sven Vanneste Copyright © 2014 Kathleen Joos et al. All rights reserved. Comparing the Efficacy of Excitatory Transcranial Stimulation Methods Measuring Motor Evoked Potentials Thu, 03 Apr 2014 08:32:52 +0000 The common aim of transcranial stimulation methods is the induction or alterations of cortical excitability in a controlled way. Significant effects of each individual stimulation method have been published; however, conclusive direct comparisons of many of these methods are rare. The aim of the present study was to compare the efficacy of three widely applied stimulation methods inducing excitability enhancement in the motor cortex: 1 mA anodal transcranial direct current stimulation (atDCS), intermittent theta burst stimulation (iTBS), and 1 mA transcranial random noise stimulation (tRNS) within one subject group. The effect of each stimulation condition was quantified by evaluating motor-evoked-potential amplitudes (MEPs) in a fixed time sequence after stimulation. The analyses confirmed a significant enhancement of the M1 excitability caused by all three types of active stimulations compared to sham stimulation. There was no significant difference between the types of active stimulations, although the time course of the excitatory effects slightly differed. Among the stimulation methods, tRNS resulted in the strongest and atDCS significantly longest MEP increase compared to sham. Different time courses of the applied stimulation methods suggest different underlying mechanisms of action. Better understanding may be useful for better targeting of different transcranial stimulation techniques. Vera Moliadze, Georg Fritzsche, and Andrea Antal Copyright © 2014 Vera Moliadze et al. All rights reserved. Reduced Renshaw Recurrent Inhibition after Neonatal Sciatic Nerve Crush in Rats Sun, 23 Mar 2014 08:25:14 +0000 Renshaw recurrent inhibition (RI) plays an important gated role in spinal motion circuit. Peripheral nerve injury is a common disease in clinic. Our current research was designed to investigate the change of the recurrent inhibitory function in the spinal cord after the peripheral nerve crush injury in neonatal rat. Sciatic nerve crush was performed on 5-day-old rat puppies and the recurrent inhibition between lateral gastrocnemius-soleus (LG-S) and medial gastrocnemius (MG) motor pools was assessed by conditioning monosynaptic reflexes (MSR) elicited from the sectioned dorsal roots and recorded either from the LG-S and MG nerves by antidromic stimulation of the synergist muscle nerve. Our results demonstrated that the MSR recorded from both LG-S or MG nerves had larger amplitude and longer latency after neonatal sciatic nerve crush. The RI in both LG-S and MG motoneuron pools was significantly reduced to virtual loss (15–20% of the normal RI size) even after a long recovery period upto 30 weeks after nerve crush. Further, the degree of the RI reduction after tibial nerve crush was much less than that after sciatic nerve crush indicatig that the neuron-muscle disconnection time is vital to the recovery of the spinal neuronal circuit function during reinnervation. In addition, sciatic nerve crush injury did not cause any spinal motor neuron loss but severally damaged peripheral muscle structure and function. In conclusion, our results suggest that peripheral nerve injury during neonatal early development period would cause a more sever spinal cord inhibitory circuit damage, particularly to the Renshaw recurrent inhibition pathway, which might be the target of neuroregeneration therapy. Liang Shu, Jingjing Su, Lingyan Jing, Ying Huang, Yu Di, Lichao Peng, and Jianren Liu Copyright © 2014 Liang Shu et al. All rights reserved. Involvement of Thalamus in Initiation of Epileptic Seizures Induced by Pilocarpine in Mice Thu, 20 Mar 2014 09:58:26 +0000 Studies have suggested that thalamus is involved in temporal lobe epilepsy, but the role of thalamus is still unclear. We obtained local filed potentials (LFPs) and single-unit activities from CA1 of hippocampus and parafascicular nucleus of thalamus during the development of epileptic seizures induced by pilocarpine in mice. Two measures, redundancy and directionality index, were used to analyze the electrophysiological characters of neuronal activities and the information flow between thalamus and hippocampus. We found that LFPs became more regular during the seizure in both hippocampus and thalamus, and in some cases LFPs showed a transient disorder at seizure onset. The variation tendency of the peak values of cross-correlation function between neurons matched the variation tendency of the redundancy of LFPs. The information tended to flow from thalamus to hippocampus during seizure initiation period no matter what the information flow direction was before the seizure. In some cases the information flow was symmetrically bidirectional, but none was found in which the information flowed from hippocampus to thalamus during the seizure initiation period. In addition, inactivation of thalamus by tetrodotoxin (TTX) resulted in a suppression of seizures. These results suggest that thalamus may play an important role in the initiation of epileptic seizures. Yong-Hua Li, Jia-Jia Li, Qin-Chi Lu, Hai-Qing Gong, Pei-Ji Liang, and Pu-Ming Zhang Copyright © 2014 Yong-Hua Li et al. All rights reserved. Surveillance, Phagocytosis, and Inflammation: How Never-Resting Microglia Influence Adult Hippocampal Neurogenesis Wed, 19 Mar 2014 08:26:38 +0000 Microglia cells are the major orchestrator of the brain inflammatory response. As such, they are traditionally studied in various contexts of trauma, injury, and disease, where they are well-known for regulating a wide range of physiological processes by their release of proinflammatory cytokines, reactive oxygen species, and trophic factors, among other crucial mediators. In the last few years, however, this classical view of microglia was challenged by a series of discoveries showing their active and positive contribution to normal brain functions. In light of these discoveries, surveillant microglia are now emerging as an important effector of cellular plasticity in the healthy brain, alongside astrocytes and other types of inflammatory cells. Here, we will review the roles of microglia in adult hippocampal neurogenesis and their regulation by inflammation during chronic stress, aging, and neurodegenerative diseases, with a particular emphasis on their underlying molecular mechanisms and their functional consequences for learning and memory. Amanda Sierra, Sol Beccari, Irune Diaz-Aparicio, Juan M. Encinas, Samuel Comeau, and Marie-Ève Tremblay Copyright © 2014 Amanda Sierra et al. All rights reserved. Glia and the Synapse: Plasticity and Disease Tue, 18 Mar 2014 08:07:47 +0000 Irina Nikonenko, Emma Victoria Jones, Hubert Fiumelli, and Yann Bernardinelli Copyright © 2014 Irina Nikonenko et al. All rights reserved. Fluoxetine Dose and Administration Method Differentially Affect Hippocampal Plasticity in Adult Female Rats Mon, 17 Mar 2014 10:03:34 +0000 Selective serotonin reuptake inhibitor medications are one of the most common treatments for mood disorders. In humans, these medications are taken orally, usually once per day. Unfortunately, administration of antidepressant medications in rodent models is often through injection, oral gavage, or minipump implant, all relatively stressful procedures. The aim of the present study was to investigate how administration of the commonly used SSRI, fluoxetine, via a wafer cookie, compares to fluoxetine administration using an osmotic minipump, with regards to serum drug levels and hippocampal plasticity. For this experiment, adult female Sprague-Dawley rats were divided over the two administration methods: (1) cookie and (2) osmotic minipump and three fluoxetine treatment doses: 0, 5, or 10 mg/kg/day. Results show that a fluoxetine dose of 5 mg/kg/day, but not 10 mg/kg/day, results in comparable serum levels of fluoxetine and its active metabolite norfluoxetine between the two administration methods. Furthermore, minipump administration of fluoxetine resulted in higher levels of cell proliferation in the granule cell layer (GCL) at a 5 mg dose compared to a 10 mg dose. Synaptophysin expression in the GCL, but not CA3, was significantly lower after fluoxetine treatment, regardless of administration method. These data suggest that the administration method and dose of fluoxetine can differentially affect hippocampal plasticity in the adult female rat. Jodi L. Pawluski, Eva van Donkelaar, Zipporah Abrams, Virginie Houbart, Marianne Fillet, Harry W. M. Steinbusch, and Thierry D. Charlier Copyright © 2014 Jodi L. Pawluski et al. All rights reserved. Downregulated GABA and BDNF-TrkB Pathway in Chronic Cyclothiazide Seizure Model Thu, 13 Mar 2014 08:14:59 +0000 Cyclothiazide (CTZ) has been reported to simultaneously enhance glutamate receptor excitation and inhibit GABAA receptor inhibition, and in turn it evokes epileptiform activities in hippocampal neurons. It has also been shown to acutely induce epileptic seizure behavior in freely moving rats. However, whether CTZ induced seizure rats could develop to have recurrent seizure still remains unknown. In the current study, we demonstrated that 46% of the CTZ induced seizure rats developed to have recurrent seizure behavior as well as epileptic EEG with a starting latency between 2 weeks and several months. In those chronic seizure rats 6 months after the seizure induction by the CTZ, our immunohistochemistry results showed that both GAD and GAT-1 were significantly decreased across CA1, CA3, and dentate gyrus area of the hippocampus studied. In addition, both BDNF and its receptor TrkB were also decreased in hippocampus of the chronic CTZ seizure rats. Our results indicate that CTZ induced seizure is capable of developing to have recurrent seizure, and the decreased GABA synthesis and transport as well as the impaired BDNF-TrkB signaling pathway may contribute to the development of the recurrent seizure. Thus, CTZ seizure rats may provide a novel animal model for epilepsy study and anticonvulsant drug testing in the future. Shuzhen Kong, Zhihua Cheng, Jianhui Liu, and Yun Wang Copyright © 2014 Shuzhen Kong et al. All rights reserved. Ion Channel Modulation in Spinal/Trigeminal Synaptic Plasticity Wed, 12 Mar 2014 13:28:21 +0000 Dong-ho Youn, Gábor Gerber, and William A. Sather Copyright © 2014 Dong-ho Youn et al. All rights reserved. Active Calcium/Calmodulin-Dependent Protein Kinase II (CaMKII) Regulates NMDA Receptor Mediated Postischemic Long-Term Potentiation (i-LTP) by Promoting the Interaction between CaMKII and NMDA Receptors in Ischemia Mon, 10 Mar 2014 12:26:44 +0000 Active calcium/calmodulin-dependent protein kinase II (CaMKII) has been reported to take a critical role in the induction of long-term potentiation (LTP). Changes in CaMKII activity were detected in various ischemia models. It is tempting to know whether and how CaMKII takes a role in NMDA receptor (NMDAR)-mediated postischemic long-term potentiation (NMDA i-LTP). Here, we monitored changes in NMDAR-mediated field excitatory postsynaptic potentials (NMDA fEPSPs) at different time points following ischemia onset in vitro oxygen and glucose deprivation (OGD) ischemia model. We found that 10 min OGD treatment induced significant i-LTP in NMDA fEPSPs, whereas shorter (3 min) or longer (25 min) OGD treatment failed to induce prominent NMDA i-LTP. CaMKII activity or CaMKII autophosphorylation displays a similar bifurcated trend at different time points following onset of ischemia both in vitro OGD or in vivo photothrombotic lesion (PT) models, suggesting a correlation of increased CaMKII activity or CaMKII autophosphorylation with NMDA i-LTP. Disturbing the association between CaMKII and GluN2B subunit of NMDARs with short cell-permeable peptides Tat-GluN2B reversed NMDA i-LTP induced by OGD treatment. The results provide support to a notion that increased interaction between NMDAR and CaMKII following ischemia-induced increased CaMKII activity and autophosphorylation is essential for induction of NMDA i-LTP. Ning Wang, Linlin Chen, Nan Cheng, Jingyun Zhang, Tian Tian, and Wei Lu Copyright © 2014 Ning Wang et al. All rights reserved. Effect of the Entorhinal Cortex on Ictal Discharges in Low-Mg2+-Induced Epileptic Hippocampal Slice Models Mon, 03 Mar 2014 11:50:19 +0000 The hippocampus plays an important role in the genesis of mesial temporal lobe epilepsy, and the entorhinal cortex (EC) may affect the hippocampal network activity because of the heavy interconnection between them. However, the mechanism by which the EC affects the discharge patterns and the transmission mode of epileptiform discharges within the hippocampus needs further study. Here, multielectrode recording techniques were used to study the spatiotemporal characteristics of epileptiform discharges in adult mouse hippocampal slices and combined EC-hippocampal slices and determine whether and how the EC affects the hippocampal neuron discharge patterns. The results showed that low-Mg2+ artificial cerebrospinal fluid induced interictal discharges in hippocampal slices, whereas, in combined EC-hippocampal slices the discharge pattern was alternated between interictal and ictal discharges, and ictal discharges initiated in the EC and propagated to the hippocampus. The pharmacological effect of the antiepileptic drug valproate (VPA) was tested. VPA reversibly suppressed the frequency of interictal discharges but did not change the initiation site and propagation speed, and it completely blocked ictal discharges. Our results suggested that EC was necessary for the hippocampal ictal discharges, and ictal discharges were more sensitive than interictal discharges in response to VPA. Ye-Jun Shi, Xin-Wei Gong, Hai-Qing Gong, Pei-Ji Liang, Pu-Ming Zhang, and Qin-Chi Lu Copyright © 2014 Ye-Jun Shi et al. All rights reserved. Chronic Fluoxetine Treatment Suppresses Plasticity (Long-Term Potentiation) in the Mature Rodent Primary Auditory Cortex In Vivo Tue, 25 Feb 2014 09:40:33 +0000 Several recent studies have provided evidence that chronic treatment with the selective serotonin reuptake inhibitor (SSRI) fluoxetine can facilitate synaptic plasticity (e.g., ocular dominance shifts) in the adult central nervous system. Here, we assessed whether fluoxetine enhances long-term potentiation (LTP) in the thalamocortical auditory system of mature rats, a developmentally regulated form of plasticity that shows a characteristic decline during postnatal life. Adult rats were chronically treated with fluoxetine (administered in the drinking water, 0.2 mg/mL, four weeks of treatment). Electrophysiological assessments were conducted using an anesthetized (urethane) in vivo preparation, with LTP of field potentials in the primary auditory cortex (A1) induced by theta-burst stimulation of the medial geniculate nucleus. We find that, compared to water-treated control animals, fluoxetine-treated rats did not express higher levels of LTP and, in fact, exhibited reduced levels of potentiation at presumed intracortical A1 synapses. Bioactivity of fluoxetine was confirmed by a reduction of weight gain and fluid intake during the four-week treatment period. We conclude that chronic fluoxetine treatment fails to enhance LTP in the mature rodent thalamocortical auditory system, results that bring into question the notion that SSRIs act as general facilitators of synaptic plasticity in the mammalian forebrain. Hans C. Dringenberg, Leora R. Branfield Day, and Deanna H. Choi Copyright © 2014 Hans C. Dringenberg et al. All rights reserved. Modulation of Cortical Interhemispheric Interactions by Motor Facilitation or Restraint Mon, 24 Feb 2014 12:14:24 +0000 Cortical interhemispheric interactions in motor control are still poorly understood and it is important to clarify how these depend on inhibitory/facilitatory limb movements and motor expertise, as reflected by limb dominance. Here we addressed this problem using functional magnetic resonance imaging (fMRI) and a task involving dominant/nondominant limb mobilization in the presence/absence of contralateral limb restraint. In this way we could modulate excitation/deactivation of the contralateral hemisphere. Blocks of arm elevation were alternated with absent/present restraint of the contralateral limb in 17 participants. We found the expected activation of contralateral sensorimotor cortex and ipsilateral cerebellum during arm elevation. In addition, only the dominant arm elevation (hold period) was accompanied by deactivation of ipsilateral sensorimotor cortex, irrespective of presence/absence of contralateral restraint, although the latter increased deactivation. In contrast, the nondominant limb yielded absent deactivation and reduced area of contralateral activation upon restriction. Our results provide evidence for a difference in cortical communication during motor control (action facilitation/inhibition), depending on the “expertise” of the hemisphere that controls action (dominant versus nondominant). These results have relevant implications for the development of facilitation/inhibition strategies in neurorehabilitation, namely, in stroke, given that fMRI deactivations have recently been shown to reflect decreases in neural responses. Ana Cristina Vidal, Paula Banca, Augusto Gil Pascoal, Gustavo Cordeiro, João Sargento-Freitas, and Miguel Castelo-Branco Copyright © 2014 Ana Cristina Vidal et al. All rights reserved. Nociceptive Neurons Differentially Express Fast and Slow T-Type Ca2+ Currents in Different Types of Diabetic Neuropathy Tue, 18 Feb 2014 11:56:17 +0000 T-type Ca2+ channels are known as important participants of nociception and their remodeling contributes to diabetes-induced alterations of pain sensation. In this work we have established that about 30% of rat nonpeptidergic thermal C-type nociceptive (NTCN) neurons of segments L4–L6 express a slow T-type Ca2+ current (T-current) while a fast T-current is expressed in the other 70% of these neurons. Streptozotocin-induced diabetes in young rats resulted in thermal hyperalgesia, hypoalgesia, or normalgesia 5-6 weeks after the induction. Our results show that NTCN neurons obtained from hyperalgesic animals do not express the slow T-current. Meanwhile, the fraction of neurons expressing the slow T-current did not significantly change in the hypo- and normalgesic diabetic groups. Moreover, the peak current density of fast T-current was significantly increased only in the neurons of hyperalgesic group. In contrast, the peak current density of slow T-current was significantly decreased in the hypo- and normalgesic groups. Experimental diabetes also resulted in a depolarizing shift of steady-state inactivation of fast T-current in the hyperalgesic group and slow T-current in the hypo- and normalgesic groups. We suggest that the observed changes may contribute to expression of different types of peripheral diabetic neuropathy occurring during the development of diabetes mellitus. Eugen V. Khomula, Anya L. Borisyuk, Viacheslav Y. Viatchenko-Karpinski, Andrea Briede, Pavel V. Belan, and Nana V. Voitenko Copyright © 2014 Eugen V. Khomula et al. All rights reserved. Comment to “Ultrasonic Assessment of Females with Carpal Tunnel Syndrome Proved by Nerve Conduction Study” Thu, 16 Jan 2014 13:45:19 +0000 Daniele Coraci, Valter Santilli, Paola de Franco, and Luca Padua Copyright © 2014 Daniele Coraci et al. All rights reserved. Astrocyte-Secreted Matricellular Proteins in CNS Remodelling during Development and Disease Thu, 16 Jan 2014 12:29:15 +0000 Matricellular proteins are secreted, nonstructural proteins that regulate the extracellular matrix (ECM) and interactions between cells through modulation of growth factor signaling, cell adhesion, migration, and proliferation. Despite being well described in the context of nonneuronal tissues, recent studies have revealed that these molecules may also play instrumental roles in central nervous system (CNS) development and diseases. In this minireview, we discuss the matricellular protein families SPARC (secreted protein acidic and rich in cysteine), Hevin/SC1 (SPARC-like 1), TN-C (Tenascin C), TSP (Thrombospondin), and CCN (CYR61/CTGF/NOV), which are secreted by astrocytes during development. These proteins exhibit a reduced expression in adult CNS but are upregulated in reactive astrocytes following injury or disease, where they are well placed to modulate the repair processes such as tissue remodeling, axon regeneration, glial scar formation, angiogenesis, and rewiring of neural circuitry. Conversely, their reexpression in reactive astrocytes may also lead to detrimental effects and promote the progression of neurodegenerative diseases. Emma V. Jones and David S. Bouvier Copyright © 2014 Emma V. Jones and David S. Bouvier. All rights reserved. G-Protein Coupled Receptor-Evoked Glutamate Exocytosis from Astrocytes: Role of Prostaglandins Thu, 16 Jan 2014 08:20:01 +0000 Astrocytes are highly secretory cells, participating in rapid brain communication by releasing glutamate. Recent evidences have suggested that this process is largely mediated by Ca2+-dependent regulated exocytosis of VGLUT-positive vesicles. Here by taking advantage of VGLUT1-pHluorin and TIRF illumination, we characterized mechanisms of glutamate exocytosis evoked by endogenous transmitters (glutamate and ATP), which are known to stimulate Ca2+ elevations in astrocytes. At first we characterized the VGLUT1-pHluorin expressing vesicles and found that VGLUT1-positive vesicles were a specific population of small synaptic-like microvesicles containing glutamate but which do not express VGLUT2. Endogenous mediators evoked a burst of exocytosis through activation of G-protein coupled receptors. Subsequent glutamate exocytosis was reduced by about 80% upon pharmacological blockade of the prostaglandin-forming enzyme, cyclooxygenase. On the other hand, receptor stimulation was accompanied by extracellular release of prostaglandin E2 (PGE2). Interestingly, administration of exogenous PGE2 produced per se rapid, store-dependent burst exocytosis of glutamatergic vesicles in astrocytes. Finally, when PGE2-neutralizing antibody was added to cell medium, transmitter-evoked exocytosis was again significantly reduced (by about 50%). Overall these data indicate that cyclooxygenase products are responsible for a major component of glutamate exocytosis in astrocytes and that large part of such component is sustained by autocrine/paracrine action of PGE2. Corrado Cali, Jan Lopatar, Francesco Petrelli, Luca Pucci, and Paola Bezzi Copyright © 2014 Corrado Cali et al. All rights reserved. Auditory-Cortex Short-Term Plasticity Induced by Selective Attention Sun, 12 Jan 2014 00:00:00 +0000 The ability to concentrate on relevant sounds in the acoustic environment is crucial for everyday function and communication. Converging lines of evidence suggests that transient functional changes in auditory-cortex neurons, “short-term plasticity”, might explain this fundamental function. Under conditions of strongly focused attention, enhanced processing of attended sounds can take place at very early latencies (~50 ms from sound onset) in primary auditory cortex and possibly even at earlier latencies in subcortical structures. More robust selective-attention short-term plasticity is manifested as modulation of responses peaking at ~100 ms from sound onset in functionally specialized nonprimary auditory-cortical areas by way of stimulus-specific reshaping of neuronal receptive fields that supports filtering of selectively attended sound features from task-irrelevant ones. Such effects have been shown to take effect in ~seconds following shifting of attentional focus. There are findings suggesting that the reshaping of neuronal receptive fields is even stronger at longer auditory-cortex response latencies (~300 ms from sound onset). These longer-latency short-term plasticity effects seem to build up more gradually, within tens of seconds after shifting the focus of attention. Importantly, some of the auditory-cortical short-term plasticity effects observed during selective attention predict enhancements in behaviorally measured sound discrimination performance. Iiro P. Jääskeläinen and Jyrki Ahveninen Copyright © 2014 Iiro P. Jääskeläinen and Jyrki Ahveninen. All rights reserved. Dual Effect of Exogenous Nitric Oxide on Neuronal Excitability in Rat Substantia Gelatinosa Neurons Wed, 08 Jan 2014 16:31:06 +0000 Nitric oxide (NO) is an important signaling molecule involved in nociceptive transmission. It can induce analgesic and hyperalgesic effects in the central nervous system. In this study, patch-clamp recording was used to investigate the effect of NO on neuronal excitability in substantia gelatinosa (SG) neurons of the spinal cord. Different concentrations of sodium nitroprusside (SNP; NO donor) induced a dual effect on the excitability of neuronal membrane: 1 mM of SNP evoked membrane hyperpolarization and an outward current, whereas 10 µM induced depolarization of the membrane and an inward current. These effects were prevented by hemoglobin and 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide potassium salt (c-PTIO) (NO scavengers), phenyl N-tert-butylnitrone (PBN; nonspecific reactive oxygen species scavenger), and through inhibition of soluble guanylyl cyclase (sGC). Pretreatment with n-ethylmaleimide (NEM; thiol-alkylating agent) also decreased effects of both 1 mM and 10 µM SNP, suggesting that these responses were mediated by direct S-nitrosylation. Charybdotoxin (CTX) and tetraethylammonium (TEA) (large-conductance Ca2+-activated K+ channel blockers) and glybenclamide (ATP-sensitive K+ channel blocker) decreased SNP-induced hyperpolarization. La3+ (nonspecific cation channel blocker), but not Cs+ (hyperpolarization-activated K+ channel blocker), blocked SNP-induced membrane depolarization. In conclusion, NO dually affects neuronal excitability in a concentration-dependent manner via modification of various K+ channels. A-Reum Park, Hae In Lee, Dejidnorov Semjid, Do Kyung Kim, and Sang Woo Chun Copyright © 2014 A-Reum Park et al. All rights reserved. Astrocyte-Synapse Structural Plasticity Wed, 08 Jan 2014 16:28:03 +0000 The function and efficacy of synaptic transmission are determined not only by the composition and activity of pre- and postsynaptic components but also by the environment in which a synapse is embedded. Glial cells constitute an important part of this environment and participate in several aspects of synaptic functions. Among the glial cell family, the roles played by astrocytes at the synaptic level are particularly important, ranging from the trophic support to the fine-tuning of transmission. Astrocytic structures are frequently observed in close association with glutamatergic synapses, providing a morphological entity for bidirectional interactions with synapses. Experimental evidence indicates that astrocytes sense neuronal activity by elevating their intracellular calcium in response to neurotransmitters and may communicate with neurons. The precise role of astrocytes in regulating synaptic properties, function, and plasticity remains however a subject of intense debate and many aspects of their interactions with neurons remain to be investigated. A particularly intriguing aspect is their ability to rapidly restructure their processes and modify their coverage of the synaptic elements. The present review summarizes some of these findings with a particular focus on the mechanisms driving this form of structural plasticity and its possible impact on synaptic structure and function. Yann Bernardinelli, Dominique Muller, and Irina Nikonenko Copyright © 2014 Yann Bernardinelli et al. All rights reserved. Noninvasive Strategies to Optimise Brain Plasticity: From Basic Research to Clinical Perspectives Mon, 30 Dec 2013 09:07:22 +0000 Alessandro Sale, Anthony J. Hannan, Lamberto Maffei, and Andrea Guzzetta Copyright © 2013 Alessandro Sale et al. All rights reserved. Methylcobalamin: A Potential Vitamin of Pain Killer Thu, 26 Dec 2013 10:08:47 +0000 Methylcobalamin (MeCbl), the activated form of vitamin B12, has been used to treat some nutritional diseases and other diseases in clinic, such as Alzheimer’s disease and rheumatoid arthritis. As an auxiliary agent, it exerts neuronal protection by promoting regeneration of injured nerves and antagonizing glutamate-induced neurotoxicity. Recently several lines of evidence demonstrated that MeCbl may have potential analgesic effects in experimental and clinical studies. For example, MeCbl alleviated pain behaviors in diabetic neuropathy, low back pain and neuralgia. MeCbl improved nerve conduction, promoted the regeneration of injured nerves, and inhibited ectopic spontaneous discharges of injured primary sensory neurons. This review aims to summarize the analgesic effect and mechanisms of MeCbl at the present. Ming Zhang, Wenjuan Han, Sanjue Hu, and Hui Xu Copyright © 2013 Ming Zhang et al. All rights reserved. Ipsilateral and Contralateral Auditory Brainstem Response Reorganization in Hemispherectomized Patients Mon, 23 Dec 2013 09:06:08 +0000 Background. Cortical hemispherectomy leads to degeneration of ipsilateral subcortical structures, which can be observed long term after the operation. Therefore, reorganization of the brainstem auditory pathway might occur. The aim of this study was to assess reorganization of brainstem auditory pathways by measuring the auditory brainstem response (ABR) in long-term hemispherectomized patients. Methods. We performed bilateral monaural stimulation and measured bilateral ABR in 8 patients ~20 years after hemispherectomy and 10 control subjects. Magnetic resonance imaging (MRI) was performed in patients to assess structural degeneration. Results. All patients showed degenerated ipsilateral brainstem structures by MRI but no significant differences in bilateral recording ABR wave latencies. However, nonsurgical-side stimulation elicited significantly longer wave V latencies compared to surgical-side stimulation. Differences in bilateral ABR were observed between hemispherectomized patients and control subjects. Waves III and V latencies elicited by nonsurgical-side stimulation were significantly longer than those in control subjects; surgical-side stimulation showed no significant differences. Conclusions. (1) Differences in ABR latency elicited by unilateral stimulation are predominantly due to bilateral brainstem auditory pathway activity rather than to changes in brainstem volume; (2) ABR Waves III and V originate predominantly in the contralateral brainstem; and (3) subcortical auditory pathways appear to reorganize after long term hemispherectomy. Ning Yao, Hui Qiao, Ping Li, Yang Liu, Liang Wu, Xiaofeng Deng, Zide Wang, Daxing Chen, Xianzeng Tong, Yuan Liu, Chenlong Yang, and Yulun Xu Copyright © 2013 Ning Yao et al. All rights reserved. Microglia in Neuronal Circuits Sun, 22 Dec 2013 10:20:31 +0000 Long-Jun Wu, Beth Stevens, Shumin Duan, and Brian A. MacVicar Copyright © 2013 Long-Jun Wu et al. All rights reserved. Microglia and Synapse: Interactions in Health and Neurodegeneration Wed, 11 Dec 2013 13:18:28 +0000 A series of discoveries spanning for the last few years has challenged our view of microglial function, the main form of immune defense in the brain. The surveillance of neuronal circuits executed by each microglial cell overseeing its territory occurs in the form of regular, dynamic interactions. Microglial contacts with individual neuronal compartments, such as dendritic spines and axonal terminals, ensure that redundant or dysfunctional elements are recognized and eliminated from the brain. Microglia take on a new shape that is large and amoeboid when a threat to brain integrity is detected. In this defensive form, they migrate to the endangered sites, where they help to minimize the extent of the brain insult. However, in neurodegenerative diseases that are associated with misfolding and aggregation of synaptic proteins, these vital defensive functions appear to be compromised. Many microglial functions, such as phagocytosis, might be overwhelmed during exposure to the abnormal levels of misfolded proteins in their proximity. This might prevent them from attending to their normal duties, such as the stripping of degenerating synaptic terminals, before neuronal function is irreparably impaired. In these conditions microglia become chronically activated and appear to take on new, destructive roles by direct or indirect inflammatory attack. Zuzana Šišková and Marie-Ève Tremblay Copyright © 2013 Zuzana Šišková and Marie-Ève Tremblay. All rights reserved. GluN3A: An NMDA Receptor Subunit with Exquisite Properties and Functions Mon, 09 Dec 2013 08:37:55 +0000 N-methyl-D-aspartate receptors (NMDAR) are pivotal for synaptic plasticity and memory formation. Conventional NMDAR consist of heterotetrameric structures composed of GluN1 and GluN2 subunits. A third subunit, GluN3, can also assemble with NMDAR subunits giving a remarkable modification of their heteromeric structure, forming a “nonconventional” NMDAR. As a consequence, the stoichiometry and kinetic properties of the receptors are dramatically changed. Among the GluN3 family, the GluN3A subunit has been the focus of a large amount of studies during recent years. These studies reveal that GluN3A is transiently expressed during development and could play a role in the fine tuning of neuronal networks as well as associated diseases. Moreover, GluN3A distribution outside the postsynaptic densities, including perisynaptic astrocytes, places it at a strategic position to play an important role in the interactions between neurons and glial cells. This review highlights GluN3A properties and addresses its role in neurophysiology and associated pathologies. Laura A. Kehoe, Yann Bernardinelli, and Dominique Muller Copyright © 2013 Laura A. Kehoe et al. All rights reserved. The Role of Astrocytes in the Regulation of Synaptic Plasticity and Memory Formation Wed, 04 Dec 2013 10:56:38 +0000 Astrocytes regulate synaptic transmission and play a role in the formation of new memories, long-term potentiation (LTP), and functional synaptic plasticity. Specifically, astroglial release of glutamate, ATP, and cytokines likely alters the survivability and functioning of newly formed connections. Among these pathways, regulation of glutamate appears to be most directly related to the promotion of LTP, which is highly dependent on the synchronization of synaptic receptors through the regulation of excitatory postsynaptic potentials. Moreover, regulation of postsynaptic glutamate receptors, particularly AMPA receptors, is dependent on signaling by ATP synthesized in astrocytes. Finally, cytokine signaling is also implicated in regulating LTP, but is likely most important in plasticity following tissue damage. Despite the role of these signaling factors in regulating LTP and functional plasticity, an integrative model of these factors has not yet been elucidated. In this review, we seek to summarize the current body of evidence on astrocytic mechanisms for regulation of LTP and functional plasticity, and provide an integrative model of the processes. Yusuke Ota, Alexander T. Zanetti, and Robert M. Hallock Copyright © 2013 Yusuke Ota et al. All rights reserved. Brain Reorganization following Intervention in Children with Congenital Hemiplegia: A Systematic Review Tue, 03 Dec 2013 08:53:17 +0000 Noninvasive rehabilitation strategies for children with unilateral cerebral palsy are routinely used to improve hand motor function, activity, and participation. Nevertheless, the studies exploring their effects on brain structure and function are very scarce. Recently, structural neuroplasticity was demonstrated in adult poststroke patients, in response to neurorehabilitation. Our purpose is to review current evidence on the effects of noninvasive intervention strategies on brain structure or function, in children with unilateral cerebral palsy. The main literature databases were searched up to October 2013. We included studies where the effects of upper limb training were evaluated at neurofunctional and/or neurostructural levels. Only seven studies met our selection criteria; selected studies were case series, six using the intervention of the constraint-induced movement therapy (CIMT) and one used virtual reality therapy (VR). CIMT and VR seem to produce measurable neuroplastic changes in sensorimotor cortex associated with enhancement of motor skills in the affected limb. However, the level of evidence is limited, due to methodological weaknesses and small sample sizes of available studies. Well-designed and larger experimental studies, in particular RCTs, are needed to strengthen the generalizability of the findings and to better understand the mechanism of intervention-related brain plasticity in children with brain injury. E. Inguaggiato, G. Sgandurra, S. Perazza, A. Guzzetta, and G. Cioni Copyright © 2013 E. Inguaggiato et al. All rights reserved.