Neuroreport (Neuroreport Rapid Comm Neurosci Res)

Publications in this journal

• Article: Pertussis toxin attenuates experimental autoimmune encephalomyelitis by upregulating neuronal vascular endothelial growth factor.

  Zhiwei Tang, Jun-Xiang Yin, Pengcheng Han, Yan Gan, Stephen W Coons, Chongqian Wang, Marwan Maalouf, Jiong Shi
  [show abstract] [hide abstract]
  ABSTRACT: We have reported earlier that pertussis toxin (PTx) attenuates the motor deficits in experimental autoimmune encephalomyelitis (EAE), an animal model for human multiple sclerosis. PTx protects neurons from inflammatory insults. Vascular endothelial growth factor (VEGF) is also neuroprotective. However, the effect of PTx on VEGF has never been studied. We investigated whether PTx modulates neuronal VEGF expression and how it affects the pathogenesis of EAE. EAE was induced by injecting myelin oligodendrocyte glycoprotein 35-55 peptides with adjuvants into C57BL/6 mice. Clinical scores of EAE were evaluated daily for 19 days. Brain and spinal cord samples were collected and assessed for inflammation and demyelination. VEGF, NeuN for neurons, and Caspase-3 for apoptosis were stained for localization using immunohistochemistry techniques, followed by western blot analysis for quantification. Primary neurons were cultured to assess the direct effect of PTx on neuronal VEGF expression. PTx treatment increases neuronal VEGF expression by up to ∼75% in vitro and ∼60% in vivo, preventing neurons from apoptosis. This leads to resolution in inflammation and remyelination and amendment in motor deficits. Our findings suggest that upregulation of endogenous neuronal VEGF by PTx protects motor deficits in EAE and it is a potential therapeutic option for multiple sclerosis.
  Neuroreport 06/2013; 24(9):469-75.
• Article: Musical expertise affects attention as reflected by auditory-evoked gamma-band activity in human EEG.

  Cyrill G M Ott, Christina Stier, Christoph S Herrmann, Lutz Jäncke
  [show abstract] [hide abstract]
  ABSTRACT: Musical expertise has been shown to induce widespread structural and functional alterations in the brain, even-handedly affecting top-down and bottom-up factors. At the same time, it is known that the early evoked gamma-band response (GBR) can be modulated by top-down as well as bottom-up factors such as attention and sound intensity. In this study, we examined the effects of musicianship and attention on the intensity modulation of the auditory-evoked GBR. We compared the electroencephalogram of 17 professional musicians with that of 17 musical laymen obtained during either a forced-choice discrimination task (active) or a passive listening condition. Pure 1000 Hz sine tones were presented at three systematically varied sound intensities (40, 60, and 80 dB sound pressure levels). The results of auditory-evoked potentials and evoked GBRs obtained in the active condition predominantly corresponded to the findings of previous studies. Besides the already known augmentation of the early evoked GBR because of enhanced intertrial phase coherence with increasing sound intensity, we also observed stronger GBRs and enhanced phase locking under the active condition compared with passive listening, whereas the general shape of intensity modulation was comparable between the two conditions. In addition, phase locking to stimulus onset was increased for stimuli of all three intensities when attended, whereas in musicians, only stimuli of the highest intensity (80 dB) induced significantly increased phase locking under the active condition. Taken together, our results suggest that musical expertise influences attention effects on the intensity-modulated early auditory-evoked GBR with respect to intertrial phase coherence.
  Neuroreport 06/2013; 24(9):445-50.
• Article: Sex matters: n-back modulates emotional mismatch negativity.

  Yang-Teng Fan, Ya-Yu Hsu, Yawei Cheng
  [show abstract] [hide abstract]
  ABSTRACT: This work investigates the impact of task load on irrelevant emotional voice processing between the sexes. The working memory task was manipulated by asking participants to evaluate the position of a visual stimulus (0-back) and compare the position of the current stimulus with the one or two trials before (1-back and 2-back). We recorded auditory event-related potentials while presenting the emotionally spoken syllables 'dada' and acoustically matched nonvocal sounds to healthy adults. Women, not men, showed larger amplitudes of emotional mismatch negativity (MMN), presumed to reflect preattentive auditory change detection, during the 1-back task than the 0-back and 2-back tasks. Among women only weaker emotional MMN amplitudes were associated with a higher 2-back accuracy. Neither task difficulty nor sex had any effect on MMN when responding to nonvocal sounds. Our findings suggest that there are sex differences in preattentive emotional voice processing under varying levels of task load.
  Neuroreport 06/2013; 24(9):457-63.
• Article: No association of SORT1 gene polymorphism with sporadic Alzheimer's disease in the Chinese Han population.

  Fan Zeng, Yong-Ping Deng, Xu Yi, Hong-Yuan Cao, Hai-Qiang Zou, Xin Wang, Chun-Rong Liang, Ye-Ran Wang, Li-Li Zhang, Chang-Yue Gao, Zhi-Qiang Xu, Yan Lian, Lin Wang, Xin-Fu Zhou, Hua-Dong Zhou, Yan-Jiang Wang
  [show abstract] [hide abstract]
  ABSTRACT: Increasing evidence shows that sortilin (encoded by SORT1 gene), a member of the vacuolar protein sorting 10 family of sorting receptors, can modulate amyloid-β peptides (Aβ) metabolism and clearance, as well as mediate the neurotoxicity of the Aβ oligomer and proneurotrophins, thus playing diverse roles in the pathogenesis of Alzheimer's disease. To assess the association between single nucleotide polymorphism (SNP) of the SORT1 gene and sporadic Alzheimer's disease (sAD) in the Chinese Han population, a case-control study was carried out including 220 sAD patients and 245 controls. One tag SNP was selected from the entire SORT1 gene through construction of linkage disequilibrium blocks, and three SNPs located in the vicinity of SORT1 that affect its expression were also selected. The four target SNPs were genotyped using a multiplex PCR-ligase detection reaction method, yielding no significant association between them or haplotypes containing three of them, and the risk of sAD. The results of this study indicate that polymorphisms of the SORT1 gene are unlikely to confer the risk of sAD in the Chinese Han population.
  Neuroreport 06/2013; 24(9):464-8.
• Article: The developmental regulation of glutamate receptor-mediated calcium signaling in primary cultured rat hippocampal neurons.

  Zhi Y Guo, Cheng Z Li, Xiao J Li, Ya L Wang, Mark P Mattson, Cheng B Lu
  [show abstract] [hide abstract]
  ABSTRACT: We have studied the developmental changes of glutamate-induced calcium (Ca) response in primary cultured hippocampal neurons at three different stages of cultures, 3, 7-8, and 14-16 days in vitro (DIV), using fura-2 single-cell digital micro-fluorimetry. We found that glutamate-induced Ca signaling was altered during development, and that two different ionotropic glutamate receptors, α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPARs) and N-methyl-D-aspartate receptors (NMDARs), were differently involved in the modulation of calcium response at different stages of neuronal culture. In the stages of culture at 3 and 8 DIV, glutamate-induced Ca influx was mostly because of AMPAR activation and subsequent opening of voltage-dependent calcium channels, as Ca response can be largely reduced by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and by nifedipine. In the advanced culture (14-17 DIV), glutamate-induced Ca response was less sensitive to 6-cyano-7-nitroquinoxaline-2,3-dione and nifedipine. Furthermore, AMPA-induced Ca response increased in a time-dependent manner during the cultures of 3-8 DIV and then reduced in the advanced culture of 14-17 DIV. NMDA-induced Ca influx increased in a time-dependent manner, with a marked increase in the advanced culture (14-17 DIV). These results suggest that glutamate-induced Ca signaling switched from AMPA-voltage-dependent calcium channel to NMDA-calcium signaling during development.
  Neuroreport 06/2013; 24(9):492-7.
• Article: Influence of stimulation intensity on paired-pulse suppression of human median nerve somatosensory evoked potentials.

  Mario A Gatica Tossi, Ann-Sophie Lillemeier, Hubert R Dinse
  [show abstract] [hide abstract]
  ABSTRACT: Paired-pulse stimulation, the application of two stimuli in close succession, is a useful tool to investigate cortical excitability. Suppression of the second response after short interstimulus intervals characterizes paired-pulse behavior. Although paired-pulse suppression is often studied as a marker of cortical excitability in humans, little is known about the influence of stimulation intensity on paired-pulse suppression. To systematically explore the effect of stimulus intensity on paired-pulse suppression of median nerve somatosensory evoked potentials (MNSEPs), we recorded single-pulse or paired-pulse MNSEPs in healthy volunteers using stimulation intensities ranging from the sensory threshold to 1.2 times the motor threshold using interstimulus intervals of 10, 30, and 100 ms. Of the various somatosensory evoked potential components, only the N20-P25 component showed an effect of intensity, where higher intensities resulted in stronger paired-pulse suppression. However, when only intermediate intensities were considered, paired-pulse suppression was not or only weakly influenced. Our data suggest that stimulation intensity in contrast to single pulse-evoked MNSEPs has only a weak influence on the paired-pulse suppression of early MNSEPs. Paired-pulse suppression is believed to arise from inhibition generated by intracortical networks. The lack of intensity dependence within the range tested can be considered as a step toward creating invariance against fluctuations of stimulus intensity. Thus, intracortical computations as apparent in paired-pulse behavior might be characterized by different properties compared with feed-forward processing.
  Neuroreport 06/2013; 24(9):451-6.
• Article: Altered semantic integration in autism beyond language: a cross-modal event-related potentials study.

  Tatiane C Ribeiro, Claudia A Valasek, Ludovico Minati, Paulo S Boggio
  [show abstract] [hide abstract]
  ABSTRACT: Autism spectrum disorders (ASDs) are characterized by impaired communication, particularly pragmatic and semantic language, resulting in verbal comprehension deficits. Semantic processing in these conditions has been studied extensively, but mostly limited only to linguistic material. Emerging evidence, however, suggests that semantic integration deficits may extend beyond the verbal domain. Here, we explored cross-modal semantic integration using visual targets preceded by musical and linguistic cues. Particularly, we have recorded the event-related potentials to evaluate whether the N400 and late positive potential (LPP) components, two widely studied electrophysiological markers of semantic processing, are differently sensitive to congruence with respect to typically developing children. Seven ASD patients and seven neurotypical participants matched by age, education and intelligence quotient provided usable data. Neuroelectric activity was recorded in response to visual targets that were related or unrelated to a preceding spoken sentence or musical excerpt. The N400 was sensitive to semantic congruence in the controls but not the patients, whereas the LPP showed a complementary pattern. These results suggest that semantic processing in ASD children is also altered in the context of musical and visual stimuli, and point to a functional decoupling between the generators of the N400 and LPP, which may indicate delayed semantic processing. These novel findings underline the importance of exploring semantic integration across multiple modalities in ASDs and provide motivation for further investigation in large clinical samples.
  Neuroreport 05/2013; 24(8):414-8.
• Article: Metformin inhibits glioma cell U251 invasion by downregulation of fibulin-3.

  Lian-Bo Gao, Shen Tian, Hong-Hua Gao, Yan-Yuan Xu
  [show abstract] [hide abstract]
  ABSTRACT: Fibulin-3 has been considered as a regulator of glioma cell invasion, but little is known about the molecules regulating fibulin-3 expression. Metformin, an oral antidiabetic drug in the biguanide class, is known to inhibit proliferation and metastasis in a variety of cancer cells. In the present study, we determined the effect of metformin on the expression of fibulin-3 in U251 Human glioma cells. Metformin potently suppressed U251 cell adhesion and invasion. Metformin inhibited the expression of fibulin-3 at the transcriptional level. Moreover, metformin abolished the protein expression of fibulin-3 in a concentration-dependent manner. Furthermore, this compound suppressed the expression of matrix metalloproteinase-2, a key effector of glioma cell invasion, regulated by fibulin-3. Taken together, our results suggest that metformin abolishes fibulin-3 expression and subsequently inhibits invasion of glioma cells.
  Neuroreport 05/2013;
• Article: Age differences in thalamic low-frequency fluctuations.

  Mara Mather, Lin Nga
  [show abstract] [hide abstract]
  ABSTRACT: The thalamus plays a role in many different types of cognitive processes and is critical for communication between disparate cortical regions. Given its critical role in coordinating cognitive processes, it is important to understand how its function might be affected by aging. In the present study, we examined whether there are age differences in low-frequency fluctuations during rest in the thalamus. Across independent data sets, we found that the amplitude of low-frequency (0.01-0.10 Hz) oscillations was greater in the thalamus among older than younger adults. Breaking this low-frequency range down further revealed that this increase in amplitude with age in the thalamus was most pronounced at the low end of the frequency range (0.010-0.027 Hz), whereas in the higher low-frequency range (0.198-0.250 Hz) younger adults showed greater amplitude than older adults. These shifts in thalamic low-frequency oscillatory activity likely influence the complex dynamics of coordinated brain activity and influence cognitive performance.
  Neuroreport 05/2013; 24(7):349-53.
• Article: Human cytomegalovirus infection modulates thrombospondins 1 and 2 in primary fetal astrocytes.

  Li Zhang, Ling Li, Bin Wang, Dong-Meng Qian, Xu-Mia Song, Ming Hu
  [show abstract] [hide abstract]
  ABSTRACT: Transmission of human cytomegalovirus (HCMV) to the fetus is the most common type of intrauterine infection; the mechanism of HCMV pathogenesis in the developing central nervous system remains unclear. Thrombospondins 1 and 2 (TSP1, TSP2) produced by immature astrocytes are critical for fetal synaptogenesis. To examine the effect of HCMV on fetal astrocytes, human fetal astrocytes were isolated and cultured with HCMV AD169. Cells were harvested at different time points. Protein and mRNA expressions of TSP1 and TSP2 were determined using RT-qPCR, western blotting analysis, and enzyme-linked immunosorbent assay. The results showed that HCMV infection induced time-dependent decreases in mRNA and protein expressions of both TSP1 and TSP2 in astrocytes. Flow cytometry was used to detect apoptosis of HCMV-infected astrocytes, and the result indicated that there was no linkage between cell apoptosis and the decrease in TSP1 and TSP2 expressions induced by HCMV infection. When ganciclovir treatment was performed on HCMV-infected astrocytes, results showed that ganciclovir treatment inhibited the reduction of TSP1 and TSP2 expression in astrocytes. In the further study, pEGFP-N3-IE1 was transfected into astrocytes to identify that it was not IE1 but active viral replication that was essential in the continuous decrease of TSP1 and TSP2 expressions in HCMV-infected astrocytes.
  Neuroreport 05/2013;
• Article: Benevolent sexism alters executive brain responses.

  Benoit Dardenne, Muriel Dumont, Marie Sarlet, Christophe Phillips, Evelyne Balteau, Christian Degueldre, André Luxen, Eric Salmon, Pierre Maquet, Fabienne Collette
  [show abstract] [hide abstract]
  ABSTRACT: Benevolence is widespread in our societies. It is defined as considering a subordinate group nicely but condescendingly, that is, with charity. Deleterious consequences for the target have been reported in the literature. In this experiment, we used functional MRI (fMRI) to identify whether being the target of (sexist) benevolence induces changes in brain activity associated with a working memory task. Participants were confronted by benevolent, hostile, or neutral comments before and while performing a reading span test in an fMRI environment. fMRI data showed that brain regions associated previously with intrusive thought suppression (bilateral, dorsolateral, prefrontal, and anterior cingulate cortex) reacted specifically to benevolent sexism compared with hostile sexism and neutral conditions during the performance of the task. These findings indicate that, despite being subjectively positive, benevolence modifies task-related brain networks by recruiting supplementary areas likely to impede optimal cognitive performance.
  Neuroreport 05/2013;
• Article: Acute ketamine-induced neuroplasticity: ribosomal protein S6 phosphorylation expression in drug addiction-related rat brain areas.

  Vincenzo Tedesco, Chiara Ravagnani, Daniele Bertoglio, Cristiano Chiamulera
  [show abstract] [hide abstract]
  ABSTRACT: Recent clinical studies show that a low dose of dissociative anesthetic ketamine (KET) induced a rapid antidepressant response that lasted for up to 7 days. This effect could be related to the capacity of KET to acutely induce molecular mechanisms of neuroplasticity engaged after chronic treatments. KET produces its actions by binding to the glutamate N-methyl-D-aspartic acid receptor, leading to increased activation of the mammalian target of rapamycin. Ribosomal protein S6 phosphorylation (rpS6P) is downstream to mammalian target of rapamycin and p70S6K activation, a molecular mechanism correlating synaptic protein synthesis and neuroplasticity. As neuroplasticity is also a key mechanism of addiction development, and considering the increasing abuse of KET, our aim was to examine the effect of acute KET administration on the expression of rpS6 in drug addiction-related cerebral areas. We tested in rats the effect of different KET doses (5 or 10 mg/kg, intraperitoneally) on rpS6P expression by immunolocalization in prelimbic (PRL) and infralimbic (IL) cortices, nucleus accumbens core (NAcC) and nucleus accumbens shell (NAcS), hippocampus (CA1 and CA3), and basolateral amygdala (BLA). Expression levels of rpS6 were quantified. A significant dose-related increase in rpS6P expression in PRL, IL, BLA, NAcC but not in the NAcS and hippocampus was found after acute KET. These data confirm acute KET-induced neuroplasticity effects, and extend these findings to drug addiction-related brain areas.
  Neuroreport 05/2013; 24(7):388-93.
• Article: Continuous theta-burst stimulation over the primary somatosensory cortex modulates interhemispheric inhibition.

  Christopher M Zapallow, Mark F Jacobs, Kevin G H Lee, Michael J Asmussen, Philemon Tsang, Aimee J Nelson
  [show abstract] [hide abstract]
  ABSTRACT: One mechanism thought to mediate hand and upper limb control across motor cortices is called interhemispheric inhibition (IHI). Somatosensory cortices are important in the motor control of the hand, although the neural mechanisms by which somatic loci act are not fully understood. In the present study, we study the possibility that the primary somatosensory cortex (SI) influences IHI as one mechanism to modulate hand control. IHI from the motor cortices was measured before and after continuous theta-burst stimulation (cTBS) was delivered over the left-hemisphere SI. IHI was evoked using paired-pulse transcranial magnetic stimulation and measured using electromyography electrodes over the first dorsal interosseous muscles of both hands at short (10 ms) and long (40 ms) intervals to evoke short interval IHI and long interval IHI, respectively. Measures were taken before and for up to 1 h after 600 pulse cTBS was delivered over SI. Results indicate that cTBS over SI increases short interval IHI in the left hand (i.e. ipsilateral to cTBS) for 45-60 min after stimulation. These results indicate that SI is indeed able to modify IHI, and this is therefore one neural mechanism by which SI may influence hand control.
  Neuroreport 05/2013; 24(7):394-8.
• Article: Neonatal SVZ EGFP-labeled cells produce neurons in the olfactory bulb and astrocytes in the cerebral cortex by in-vivo electroporation.

  Xijuan Wang, Liwen Chang, Zhibao Guo, Wenbin Li, Wei Liu, Baohuan Cai, Jing Wang
  [show abstract] [hide abstract]
  ABSTRACT: Neural progenitors/stem cells (NSCs) exist in neonatal mouse subventricular zone (SVZ). To explore the differentiation of the NSCs in neonatal mouse SVZ and the distribution of the progeny cells derived from these NSCs in early adulthood, the enhanced green fluorescent protein (EGFP) plasmid was transferred into the NSCs in the lateral ventricle of newborn mice (P0) by in-vivo electroporation to trace these cells and their progeny cells. Thirty days after electroporation, histological sections of mouse brain were prepared for immunofluorescence with cell-specific antibodies to identify the type(s) of cells that were marked by EGFP. The results showed that EGFP-positive cells were distributed mainly in the olfactory bulb (OB), cortex, and SVZ, and double labeled with NeuN (neuron marker) in OB, glial fibrillary acidic protein (GFAP) (astrocyte marker) in the cortex, and Blbp and GFAP (astrocyte marker) in SVZ. However, there was no-EGFP-positive cell in the hippocampus. The present results indicate that the NSCs in SVZ of the neonatal mouse can give rise to neurons in the OB and astrocytes in the cortex in early adulthood, but not generate progeny cells residing in the hippocampus. In addition, there are still neural progenitors in SVZ until early adulthood.
  Neuroreport 05/2013; 24(7):381-7.
• Article: Motor and perceptual sequence learning: different time course of parallel processes.

  Georg Dirnberger, Judith Novak-Knollmueller
  [show abstract] [hide abstract]
  ABSTRACT: The aim was to determine the extent and time course of motor and perceptual learning in a procedural learning task, and the relation of these two processes. Because environmental constraints modulate the relative impact of different learning mechanisms, we chose a simple learning task similar to real-life exercise. Thirty-four healthy individuals performed a visuomotor serial reaction time task. Learning blocks with high stimulus-response compatibility were practiced repeatedly; in between these, participants performed test blocks with the same or a different (mirror-inverted, or new) stimulus sequence and/or with the same or a different (mirror-inverted) stimulus-response allocation. This design allowed us to measure the progress of motor learning and perceptual learning independently. Results showed that in the learning blocks, a steady reduction of the reaction times indicated that-as expected-participants improved their skills continuously. Analysis of the test blocks indicated that both motor learning and perceptual learning were significant. The two mechanisms were correlated (r=0.62, P<0.001). However, their time course was different: the impact of motor learning increased strongly from earlier to later intervals, whereas the progress of perceptual learning was more stable but slower. In conclusion, in a simple visuomotor learning task, participants can learn the motor sequence and the stimulus sequence in parallel. The positive correlation of motor and perceptual learning suggests that the two mechanisms act in synergy and are not alternative opposing strategies. The impact of these two learning mechanisms changes over time: motor learning sets in later and becomes relevant only in the course of training.
  Neuroreport 05/2013;
• Article: From brain topography to brain topology: relevance of graph theory to functional neuroscience.

  Ludovico Minati, Giulia Varotto, Ludovico D'Incerti, Ferruccio Panzica, Dennis Chan
  [show abstract] [hide abstract]
  ABSTRACT: Although several brain regions show significant specialization, higher functions such as cross-modal information integration, abstract reasoning and conscious awareness are viewed as emerging from interactions across distributed functional networks. Analytical approaches capable of capturing the properties of such networks can therefore enhance our ability to make inferences from functional MRI, electroencephalography and magnetoencephalography data. Graph theory is a branch of mathematics that focuses on the formal modelling of networks and offers a wide range of theoretical tools to quantify specific features of network architecture (topology) that can provide information complementing the anatomical localization of areas responding to given stimuli or tasks (topography). Explicit modelling of the architecture of axonal connections and interactions among areas can furthermore reveal peculiar topological properties that are conserved across diverse biological networks, and highly sensitive to disease states. The field is evolving rapidly, partly fuelled by computational developments that enable the study of connectivity at fine anatomical detail and the simultaneous interactions among multiple regions. Recent publications in this area have shown that graph-based modelling can enhance our ability to draw causal inferences from functional MRI experiments, and support the early detection of disconnection and the modelling of pathology spread in neurodegenerative disease, particularly Alzheimer's disease. Furthermore, neurophysiological studies have shown that network topology has a profound link to epileptogenesis and that connectivity indices derived from graph models aid in modelling the onset and spread of seizures. Graph-based analyses may therefore significantly help understand the bases of a range of neurological conditions. This review is designed to provide an overview of graph-based analyses of brain connectivity and their relevance to disease aimed principally at general neuroscientists and clinicians.
  Neuroreport 05/2013;
• Article: Investigation of APOE isoforms and the association between APOE E3 and E4 with migraine in the Australian Caucasian population.

  Shani Stuart, Bianca Donges, Melanie Murrell, Larisa M Haupt, Rod A Lea, Lyn R Griffiths
  [show abstract] [hide abstract]
  ABSTRACT: Migraine is a debilitating neurovascular disease that is associated with pulsating head pain accompanied by nausea, vomiting, photophobia, phonophobia and sometimes visual sensory disturbances. Because of its role in nitric oxide regulation and interleukin release, apolipoprotein E (APOE) has been suggested to play a role in the migraine pathogenesis pathway. This study evaluated the potential role of three APOE variants in an Australian population and the role that they may play in susceptibility to migraine. The study found no significant association between the tested variants and migraine for any of the APOE variants investigated.
  Neuroreport 05/2013;
• Article: Do canonical transient receptor potential channels mediate cholinergic excitation of cortical pyramidal neurons?

  Sameera Dasari, Joel Abramowitz, Lutz Birnbaumer, Allan T Gulledge
  [show abstract] [hide abstract]
  ABSTRACT: Activation of M1-type muscarinic acetylcholine receptors excites neocortical pyramidal neurons, in part by gating a nonselective cation conductance that produces calcium-dependent 'afterdepolarizing potentials' (ADPs) following short trains of action potentials. Although the identity of the cation conductance mediating the ADP is not known, previous work has implicated canonical transient receptor potential (TRPC) channels, specifically the TRPC5 and TRPC6 subtypes. Using pharmacological and genetic approaches, we tested the role of TRPC channels in generating cholinergic ADPs in layer 5 pyramidal neurons in the mouse medial prefrontal cortex (mPFC). A variety of compounds that block TRPC channels, including 2-aminoethoxydiphenyl borate, flufenamic acid, lanthanum, SKF-96365, and Pyr-3, had little, if any, impact on cholinergic ADPs. Similarly, genetic deletion of several TRPC subunits, including TPRC1, TRPC5, and TRPC6 (single knockouts), or both TRPC5 and TRPC6 together (double knockout), failed to reduce the amplitude of cholinergic ADPs. These data suggest that TRPC5 and TRPC6 subunits are not required for cholinergic excitation of layer 5 pyramidal neurons in the mouse mPFC and that the focus of future work should be expanded to test the involvement of other potential ionic effectors.
  Neuroreport 05/2013;
• Article: Sequence representation during response preparation in the serial reaction time task.

  Wei Hu, Yong Lu, Lihong Wang, John X Zhang
  [show abstract] [hide abstract]
  ABSTRACT: The type of representations involved in implicit learning during the response preparation stage of sequence learning was studied using the response-locked lateralized readiness potential (LRP-R) as an index. Participants performed a modified serial reaction time task on an eight-letter sequence; half were informed to look for patterns in the sequence and half were not. The standard sequence was occasionally replaced by one of two deviant sequences and the LRP-R elicited was analyzed. When comparing across three sequence conditions, namely, a perceptual deviant sequence, a motor deviant sequence, and a standard sequence (as control), the onset latency and the mean amplitude of the LRP-R were similar for all three conditions and for both explicit and implicit learners. The perceptual deviant sequence group showed a longer response preparation time than the motor deviant group and the standard sequence group, but the latter two were not significantly different. The perceptual deviant sequence group showed more negative LRP-R amplitude than the other two groups that did not differ from each other. The finding of similar LRP-R profiles between implicit and explicit learners suggests that stimulus representation (S-S association) is the main form of representation supporting sequence learning in the response preparation stage.
  Neuroreport 05/2013;
• Article: Lithium normalizes amphetamine-induced changes in striatal FoxO1 phosphorylation and behaviors in rats.

  Wenhua Zheng, Zhiwen Zeng, Sanjeev K Bhardwaj, Sara Jamali, Lalit K Srivastava
  [show abstract] [hide abstract]
  ABSTRACT: Administration of the psychostimulant drug amphetamine (AMPH) to animals causes hyperactivity and deficit in prepulse inhibition (PPI) of startle, behaviors that are often observed in neuropsychiatric disorders such as schizophrenia and bipolar disorder. Enhanced central dopamine (DA) transmission is believed to mediate AMPH-induced behavioral alterations. Lithium, a drug used primarily in the treatment of bipolar disorder, is reported to interact with the DA system and antagonize some DA-related behaviors. Here, we provide evidence that AMPH and lithium reciprocally regulate the activity of the transcription factor forkhead box, class O1 (FoxO1), a downstream target of Akt. Administration of d-AMPH (3 mg/kg, intraperitoneally) to Sprague-Dawley rats resulted in a concomitant decrease in levels of phosphorylated (p) Akt as well as p-FoxO1 in the striatum, whereas lithium chloride (LiCl,100 mg/kg, intraperitoneally) exerted the opposite effect, that is, it increased levels of p-Akt and p-FoxO1. Pretreatment of animals with lithium prevented an AMPH-induced decrease in striatal p-Akt and p-FoxO1 levels. Pretreatment of animals with lithium also attenuated AMPH-induced locomotor activity and decreased prepulse inhibition. These in-vivo data suggest that the Akt-FoxO1 pathway may be a common target for the action of dopaminergic and antidopaminergic drugs, and its modulation may be relevant to the treatment of neuropsychiatric disorders.
  Neuroreport 05/2013;