Neural Plasticity The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Spinal Cord Hemisection Facilitates Aromatic L-Amino Acid Decarboxylase Cells to Produce Serotonin in the Subchronic but Not the Chronic Phase Sun, 04 Oct 2015 06:42:13 +0000 Neuromodulators, such as serotonin (5-hydroxytryptamine, 5-HT) and noradrenalin, play an essential role in regulating the motor and sensory functions in the spinal cord. We have previously shown that in the rat spinal cord the activity of aromatic L-amino acid decarboxylase (AADC) cells to produce 5-HT from its precursor (5-hydroxytryptophan, 5-HTP) is dramatically increased following complete spinal cord transection. In this study, we investigated whether a partial loss of 5-HT innervation could similarly increase AADC activity. Adult rats with spinal cord hemisected at thoracic level (T11/T12) were used with a postoperation interval at 5 days or 60 days. Using immunohistochemistry, first, we observed a significant reduction in the density of 5-HT-immunoreactive fibers in the spinal cord below the lesion on the injured side for both groups. Second, we found that the AADC cells were similarly expressed on both injured and uninjured sides in both groups. Third, increased production of 5-HT in AADC cells following 5-HTP was seen in 5-day but not in 60-day postinjury group. These results suggest that plastic changes of the 5-HT system might happen primarily in the subchronic phase and for longer period its function could be compensated by plastic changes of other intrinsic and/or supraspinal modulation systems. Bushra Azam, Jacob Wienecke, Dennis Bo Jensen, Aleena Azam, and Mengliang Zhang Copyright © 2015 Bushra Azam et al. All rights reserved. Contralateral Metabolic Activation Related to Plastic Changes in the Spinal Cord after Peripheral Nerve Injury in Rats Mon, 28 Sep 2015 08:43:23 +0000 We have previously reported the crossed-withdrawal reflex in which the rats with nerve injury developed behavioral pain responses of the injured paw to stimuli applied to the contralateral uninjured paw. This reflex indicates that contralateral plastic changes may occur in the spinal cord after unilateral nerve injury. The present study was performed to elucidate the mechanisms and morphological correlates underlying the crossed-withdrawal reflex by using quantitative 14C-2-deoxyglucose (2-DG) autoradiography which can examine metabolic activities and spatial patterns simultaneously. Under pentobarbital anesthesia, rats were subjected to unilateral nerve injury. Mechanical allodynia was tested for two weeks after nerve injury. After nerve injury, neuropathic pain behaviors developed progressively. The crossed-withdrawal reflex was observed at two weeks postoperatively. Contralateral enhancement of 2-DG uptake in the ventral horn of the spinal cord to electrical stimulation of the uninjured paw was observed. These results suggest that the facilitation of information processing from the uninjured side to the injured side may contribute to the crossed-withdrawal reflex by plastic changes in the spinal cord of nerve-injured rats. Ran Won and Bae Hwan Lee Copyright © 2015 Ran Won and Bae Hwan Lee. All rights reserved. Cortical Excitability Measured with nTMS and MEG during Stroke Recovery Sun, 27 Sep 2015 07:29:11 +0000 Objective. Stroke alters cortical excitability both in the lesioned and in the nonlesioned hemisphere. Stroke recovery has been studied using transcranial magnetic stimulation (TMS). Spontaneous brain oscillations and somatosensory evoked fields (SEFs) measured by magnetoencephalography (MEG) are modified in stroke patients during recovery. Methods. We recorded SEFs and spontaneous MEG activity and motor threshold (MT) short intracortical inhibition (SICI) and intracortical facilitation (ICF) with navigated TMS (nTMS) at one and three months after first-ever hemispheric ischemic strokes. Changes of MEG and nTMS parameters attributed to gamma-aminobutyrate and glutamate transmission were compared. Results. ICF correlated with the strength and extent of SEF source areas depicted by MEG at three months. The nTMS MT and event-related desynchronization (ERD) of beta-band MEG activity and SICI and the beta-band MEG event-related synchronization (ERS) were correlated, but less strongly. Conclusions. This first report using sequential nTMS and MEG in stroke recovery found intra- and interhemispheric correlations of nTMS and MEG estimates of cortical excitability. ICF and SEF parameters, MT and the ERD of the lesioned hemisphere, and SICI and ERS of the nonlesioned hemisphere were correlated. Covarying excitability in the lesioned and nonlesioned hemispheres emphasizes the importance of the hemispheric balance of the excitability of the sensorimotor system. Jyrki P. Mäkelä, Pantelis Lioumis, Kristina Laaksonen, Nina Forss, Turgut Tatlisumak, Markku Kaste, and Satu Mustanoja Copyright © 2015 Jyrki P. Mäkelä et al. All rights reserved. Plasticity-Related PKMζ Signaling in the Insular Cortex Is Involved in the Modulation of Neuropathic Pain after Nerve Injury Sun, 20 Sep 2015 09:50:16 +0000 The insular cortex (IC) is associated with important functions linked with pain and emotions. According to recent reports, neural plasticity in the brain including the IC can be induced by nerve injury and may contribute to chronic pain. Continuous active kinase, protein kinase Mζ (PKMζ), has been known to maintain the long-term potentiation. This study was conducted to determine the role of PKMζ in the IC, which may be involved in the modulation of neuropathic pain. Mechanical allodynia test and immunohistochemistry (IHC) of zif268, an activity-dependent transcription factor required for neuronal plasticity, were performed after nerve injury. After ζ-pseudosubstrate inhibitory peptide (ZIP, a selective inhibitor of PKMζ) injection, mechanical allodynia test and immunoblotting of PKMζ, phospho-PKMζ (p-PKMζ), and GluR1 and GluR2 were observed. IHC demonstrated that zif268 expression significantly increased in the IC after nerve injury. Mechanical allodynia was significantly decreased by ZIP microinjection into the IC. The analgesic effect lasted for 12 hours. Moreover, the levels of GluR1, GluR2, and p-PKMζ were decreased after ZIP microinjection. These results suggest that peripheral nerve injury induces neural plasticity related to PKMζ and that ZIP has potential applications for relieving chronic pain. Jeongsoo Han, Minjee Kwon, Myeounghoon Cha, Motomasa Tanioka, Seong-Karp Hong, Sun Joon Bai, and Bae Hwan Lee Copyright © 2015 Jeongsoo Han et al. All rights reserved. Reactive Oxygen Species Donors Increase the Responsiveness of Dorsal Horn Neurons and Induce Mechanical Hyperalgesia in Rats Sun, 20 Sep 2015 09:33:40 +0000 Our previous studies suggest that reactive oxygen species (ROS) scavengers have analgesic effect on neuropathic pain through spinal mechanisms in the rat. The studies suggest that superoxide in spinal cord is one of important mediators of persistent pain. To test the hypothesis that increase of superoxide-derived intermediates leads to central sensitization and pain, the effects of an intrathecal injection of chemical ROS donors releasing either , , or H2O2 were examined on pain behaviors. Following treatment with t-BOOH ( donor), dorsal horn neuron responses to mechanical stimuli in normal rats and the changes of neuronal excitability were explored on substantia gelatinosa (SG) neurons using whole-cell patch clamping recordings. Intrathecal administration of t-BOOH or NaOCl ( donor), but not H2O2, significantly decreased mechanical thresholds of hind paws. The responses of wide dynamic range neurons to mechanical stimuli increased after a local application of t-BOOH. The t-BOOH increased the frequency and the amplitude of excitatory postsynaptic potentials, depolarized membrane potential in SG neurons, and increased the frequency of action potentials evoked by depolarizing current pulses. These results suggest that elevated ROS, especially , in the spinal cord sensitized dorsal horn neurons and produced hyperalgesia in normal rats. Hee Young Kim, Inhyung Lee, Sang Woo Chun, and Hee Kee Kim Copyright © 2015 Hee Young Kim et al. All rights reserved. Modulation of Spinal GABAergic Inhibition and Mechanical Hypersensitivity following Chronic Compression of Dorsal Root Ganglion in the Rat Mon, 14 Sep 2015 07:56:19 +0000 Chronic compression of dorsal root ganglion (CCD) results in neuropathic pain. We investigated the role of spinal GABA in CCD-induced pain using rats with unilateral CCD. A stereological analysis revealed that the proportion of GABA-immunoreactive neurons to total neurons at L4/5 laminae I–III on the injured side decreased in the early phase of CCD (post-CCD week 1) and then returned to the sham-control level in the late phase (post-CCD week 18). In the early phase, the rats showed an increase in both mechanical sensitivity of the hind paw and spinal WDR neuronal excitability on the injured side, and such increase was suppressed by spinally applied muscimol (GABA-A agonist, 5 nmol) and baclofen (GABA-B agonist, 25 nmol), indicating the reduced spinal GABAergic inhibition involved. In the late phase, the CCD-induced increase in mechanical sensitivity and neuronal excitability returned to pre-CCD levels, and such recovered responses were enhanced by spinally applied bicuculline (GABA-A antagonist, 15 nmol) and CGP52432 (GABA-B antagonist, 15 nmol), indicating the regained spinal GABAergic inhibition involved. In conclusion, the alteration of spinal GABAergic inhibition following CCD and leading to a gradual reduction over time of CCD-induced mechanical hypersensitivity is most likely due to changes in GABA content in spinal GABA neurons. Moon Chul Lee, Taick Sang Nam, Se Jung Jung, Young S. Gwak, and Joong Woo Leem Copyright © 2015 Moon Chul Lee et al. All rights reserved. PKA Inhibitor H89 (N-[2-p-bromocinnamylamino-ethyl]-5-isoquinolinesulfonamide) Attenuates Synaptic Dysfunction and Neuronal Cell Death following Ischemic Injury Sun, 13 Sep 2015 12:59:09 +0000 The cyclic AMP-dependent protein kinase (PKA), which activates prosurvival signaling proteins, has been implicated in the expression of long-term potentiation and hippocampal long-term memory. It has come to light that H89 commonly known as the PKA inhibitor have diverse roles in the nervous system that are unrelated to its role as a PKA inhibitor. We have investigated the role of H89 in ischemic and reperfusion injury. First, we examined the expression of postsynaptic density protein 95 (PSD95), microtubule-associated protein 2 (MAP2), and synaptophysin in mouse brain after middle cerebral artery occlusion injury. Next, we examined the role of H89 pretreatment on the expression of brain-derived neurotrophic factor (BDNF), PSD95, MAP2, and the apoptosis regulators Bcl2 and cleaved caspase-3 in cultured neuroblastoma cells exposed to hypoxia and reperfusion injury. In addition, we investigated the alteration of AKT activation in H89 pretreated neuroblastoma cells under hypoxia and reperfusion injury. The data suggest that H89 may contribute to brain recovery after ischemic stroke by regulating neuronal death and proteins related to synaptic plasticity. Juhyun Song, So Yeong Cheon, Won Taek Lee, Kyung Ah Park, and Jong Eun Lee Copyright © 2015 Juhyun Song et al. All rights reserved. Statins Promote Long-Term Recovery after Ischemic Stroke by Reconnecting Noradrenergic Neuronal Circuitry Thu, 10 Sep 2015 14:33:40 +0000 Inhibitors of HMG-CoA reductase (statins), widely used to lower cholesterol in coronary heart and vascular disease, are effective drugs in reducing the risk of stroke and improving its outcome in the long term. After ischemic stroke, cardiac autonomic dysfunction and psychological problems are common complications related to deficits in the noradrenergic (NA) system. This study investigated the effects of statins on the recovery of NA neuron circuitry and its function after transient focal cerebral ischemia (tFCI). Using the wheat germ agglutinin (WGA) transgene technique combined with the recombinant adenoviral vector system, NA-specific neuronal pathways were labeled, and were identified in the locus coeruleus (LC), where NA neurons originate. NA circuitry in the atorvastatin-treated group recovered faster than in the vehicle-treated group. The damaged NA circuitry was partly reorganized with the gradual recovery of autonomic dysfunction and neurobehavioral deficit. Newly proliferated cells might contribute to reorganizing NA neurons and lead anatomic and functional recovery of NA neurons. Statins may be implicated to play facilitating roles in the recovery of the NA neuron and its function. Kyoung Joo Cho, So Young Cheon, and Gyung Whan Kim Copyright © 2015 Kyoung Joo Cho et al. All rights reserved. Altered Recruitment of the Attention Network Is Associated with Disability and Cognitive Impairment in Pediatric Patients with Acquired Brain Injury Thu, 10 Sep 2015 09:50:35 +0000 We assessed abnormalities of brain functional magnetic resonance imaging (fMRI) activity during a sustained attention task (Conners’ Continuous Performance Test (CCPT)) in 20 right-handed pediatric acquired brain injury (ABI) patients versus 7 right-handed age-matched healthy controls, and we estimated the correlation of such abnormalities with clinical and cognitive deficits. Patients underwent the Wechsler Intelligence Scale for Children (WISC), Wisconsin Card Sorting Test, and Functional Independence Measure (FIM) evaluations. During fMRI, patients and controls activated regions of the attention network. Compared to controls, ABI patients experienced a decreased average fMRI recruitment of the left cerebellum and a decreased deactivation of the left anterior cingulate cortex. With increasing task demand, compared to controls, ABI patients had an impaired ability to increase the recruitment of several posterior regions of the attention network. They also experienced a greater activation of frontal regions, which was correlated with worse performance on FIM, WISC, and fMRI CCPT. Such abnormal brain recruitment was significantly influenced by the type of lesion (focal versus diffuse axonal injury) and time elapsed from the event. Pediatric ABI patients experienced an inability to optimize attention network recruitment, especially when task difficulty was increased, which likely contributes to their clinical and cognitive deficits. Sandra Strazzer, Maria A. Rocca, Erika Molteni, Ermelinda De Meo, Monica Recla, Paola Valsasina, Filippo Arrigoni, Susanna Galbiati, Alessandra Bardoni, and Massimo Filippi Copyright © 2015 Sandra Strazzer et al. All rights reserved. Audiomotor Integration in Minimally Conscious State: Proof of Concept! Thu, 03 Sep 2015 06:36:41 +0000 Patients suffering from chronic disorders of consciousness (DOC) are characterized by profound unawareness and an impairment of large-scale cortical and subcortical connectivity. In this study, we applied an electrophysiological approach aimed at identifying the residual audiomotor connectivity patterns that are thought to be linked to awareness. We measured some markers of audiomotor integration (AMI) in 20 patients affected by DOC, before and after the application of a repetitive transcranial magnetic stimulation protocol (rTMS) delivered over the left primary motor area (M1), paired to a transauricular alternating current stimulation. Our protocol induced potentiating of the electrophysiological markers of AMI and M1 excitability, paired to a clinical improvement, in all of the patients with minimally conscious state (MCS) but in none of those suffering from unresponsive wakefulness syndrome (UWS). Our protocol could be a promising approach to potentiate the functional connectivity within large-scale audiomotor networks, thus allowing clinicians to differentiate patients affected by MCS from UWS, besides the clinical assessment. Antonino Naro, Antonino Leo, Antonino Cannavò, Antonio Buda, Rocco Bruno, Carlo Salviera, Placido Bramanti, and Rocco Salvatore Calabrò Copyright © 2015 Antonino Naro et al. All rights reserved. Corrigendum to “Efficacy and Interindividual Variability in Motor-Cortex Plasticity following Anodal tDCS and Paired-Associative Stimulation” Wed, 02 Sep 2015 10:11:04 +0000 Wolfgang Strube, Tilmann Bunse, Berend Malchow, and Alkomiet Hasan Copyright © 2015 Wolfgang Strube et al. All rights reserved. Brain and Behavior Plasticity: From Fundamental Science to Health Outcomes Tue, 01 Sep 2015 07:54:43 +0000 Keh-chung Lin, Steven L. Wolf, Chetwyn Chan, Ching-yi Wu, and Ching-Po Lin Copyright © 2015 Keh-chung Lin et al. All rights reserved. Neural Plastic Effects of Cognitive Training on Aging Brain Mon, 31 Aug 2015 09:39:16 +0000 Increasing research has evidenced that our brain retains a capacity to change in response to experience until late adulthood. This implies that cognitive training can possibly ameliorate age-associated cognitive decline by inducing training-specific neural plastic changes at both neural and behavioral levels. This longitudinal study examined the behavioral effects of a systematic thirteen-week cognitive training program on attention and working memory of older adults who were at risk of cognitive decline. These older adults were randomly assigned to the Cognitive Training Group () and the Active Control Group (). Findings clearly indicated that training induced improvement in auditory and visual-spatial attention and working memory. The training effect was specific to the experience provided because no significant difference in verbal and visual-spatial memory between the two groups was observed. This pattern of findings is consistent with the prediction and the principle of experience-dependent neuroplasticity. Findings of our study provided further support to the notion that the neural plastic potential continues until older age. The baseline cognitive status did not correlate with pre- versus posttraining changes to any cognitive variables studied, suggesting that the initial cognitive status may not limit the neuroplastic potential of the brain at an old age. Natalie T. Y. Leung, Helena M. K. Tam, Leung W. Chu, Timothy C. Y. Kwok, Felix Chan, Linda C. W. Lam, Jean Woo, and Tatia M. C. Lee Copyright © 2015 Natalie T. Y. Leung et al. All rights reserved. Restoration of Central Programmed Movement Pattern by Temporal Electrical Stimulation-Assisted Training in Patients with Spinal Cerebellar Atrophy Mon, 31 Aug 2015 09:28:14 +0000 Disrupted triphasic electromyography (EMG) patterns of agonist and antagonist muscle pairs during fast goal-directed movements have been found in patients with hypermetria. Since peripheral electrical stimulation (ES) and motor training may modulate motor cortical excitability through plasticity mechanisms, we aimed to investigate whether temporal ES-assisted movement training could influence premovement cortical excitability and alleviate hypermetria in patients with spinal cerebellar ataxia (SCA). The EMG of the agonist extensor carpi radialis muscle and antagonist flexor carpi radialis muscle, premovement motor evoked potentials (MEPs) of the flexor carpi radialis muscle, and the constant and variable errors of movements were assessed before and after 4 weeks of ES-assisted fast goal-directed wrist extension training in the training group and of general health education in the control group. After training, the premovement MEPs of the antagonist muscle were facilitated at 50 ms before the onset of movement. In addition, the EMG onset latency of the antagonist muscle shifted earlier and the constant error decreased significantly. In summary, temporal ES-assisted training alleviated hypermetria by restoring antagonist premovement and temporal triphasic EMG patterns in SCA patients. This technique may be applied to treat hypermetria in cerebellar disorders. (This trial is registered with NCT01983670.) Ying-Zu Huang, Yao-Shun Chang, Miao-Ju Hsu, Alice M. K. Wong, and Ya-Ju Chang Copyright © 2015 Ying-Zu Huang et al. All rights reserved. Coincidence Anticipation Timing Performance during an Acute Bout of Brisk Walking in Older Adults: Effect of Stimulus Speed Mon, 31 Aug 2015 09:15:45 +0000 This study examined coincidence anticipation timing (CAT) performance at slow and fast stimulus speeds before, during, and after an acute bout of walking in adults aged 60–76 years. Results from a series of repeated measures ANOVAs indicated significant rest versus exercise × stimulus speed × time interactions for absolute and variable errors (both ) whereby absolute and variable error scores, when stimulus speed was slow, improved as the duration of exercise increased. When stimulus speed was fast there were significantly greater absolute and variable errors at 18 minutes of the walking bout. There was also greater error at 18 minutes during walking compared to rest. These results suggest that, in a task involving walking and CAT, stimulus speeds plays an important role; specifically walking (exercise) enhances CAT performance at slow stimulus speeds but reduces CAT performance at fast stimulus speeds. The implications are that in everyday situations, where events require dual-task responses to be made at different speeds, for example, walking on the pavement whilst avoiding a crowd, compared to crossing a busy road, an understanding of how different stimulus speeds influence dual-task performance is extremely important, particularly in the older adult population. Michael J. Duncan, Michelle Stanley, Mike Smith, Michael J. Price, and Sheila Leddington Wright Copyright © 2015 Michael J. Duncan et al. All rights reserved. An Influence of Birth Weight, Gestational Age, and Apgar Score on Pattern Visual Evoked Potentials in Children with History of Prematurity Mon, 31 Aug 2015 09:03:18 +0000 Purpose. The objective of our study was to examine a possible influence of gestational age, birth weight, and Apgar score on amplitudes and latencies of P100 wave in preterm born school-age children. Materials and Methods. We examined the following group of school-age children: 28 with history of prematurity (mean age 10.56 ± 1.66 years) and 25 born at term (mean age 11.2 ± 1.94 years). The monocular PVEP was performed in all children. Results. The P100 wave amplitudes and latencies significantly differ between preterm born school-age children and those born at term. There was an essential positive linear correlation of the P100 wave amplitudes with birth weight, gestational age, and Apgar score. There were the negative linear correlations of P100 latencies in 15-minute stimulation from O1 and Oz electrode with Apgar score and O1 and O2 electrode with gestational age. Conclusions. PVEP responses vary in preterm born children in comparison to term. Low birth weight, early gestational age, and poor baseline output seem to be the predicting factors for the developmental rate of a brain function in children with history of prematurity. Further investigations are necessary to determine perinatal factors that can affect the modified visual system function in preterm born children. Marta Michalczuk, Beata Urban, Beata Chrzanowska-Grenda, Monika Oziębło-Kupczyk, and Alina Bakunowicz-Łazarczyk Copyright © 2015 Marta Michalczuk et al. All rights reserved. Age-Related Reduced Somatosensory Gating Is Associated with Altered Alpha Frequency Desynchronization Mon, 31 Aug 2015 09:02:28 +0000 Sensory gating (SG), referring to an attenuated neural response to the second identical stimulus, is considered as preattentive processing in the central nervous system to filter redundant sensory inputs. Insufficient somatosensory SG has been found in the aged adults, particularly in the secondary somatosensory cortex (SII). However, it remains unclear which variables leading to the age-related somatosensory SG decline. There has been evidence showing a relationship between brain oscillations and cortical evoked excitability. Thus, this study used whole-head magnetoencephalography to record responses to paired-pulse electrical stimulation to the left median nerve in healthy young and elderly participants to test whether insufficient stimulus 1- (S1-) induced event-related desynchronization (ERD) contributes to a less-suppressed stimulus 2- (S2-) evoked response. Our analysis revealed that the minimum norm estimates showed age-related reduction of SG in the bilateral SII regions. Spectral power analysis showed that the elderly demonstrated significantly reduced alpha ERD in the contralateral SII (SIIc). Moreover, it was striking to note that lower S1-induced alpha ERD was associated with higher S2-evoked amplitudes in the SIIc among the aged adults. Conclusively, our findings suggest that age-related decline of somatosensory SG is partially attributed to the altered S1-induced oscillatory activity. Chia-Hsiung Cheng, Pei-Ying S. Chan, Sylvain Baillet, and Yung-Yang Lin Copyright © 2015 Chia-Hsiung Cheng et al. All rights reserved. Plasticity of GABAA Receptors during Pregnancy and Postpartum Period: From Gene to Function Sun, 30 Aug 2015 12:45:05 +0000 Pregnancy needs complex pathways that together play a role in proper growth and protection of the fetus preventing its premature loss. Changes during pregnancy and postpartum period include the manifold machinery of neuroactive steroids that plays a crucial role in neuronal excitability by local modulation of specific inhibitory receptors: the GABAA receptors. Marked fluctuations in both blood and brain concentration of neuroactive steroids strongly contribute to GABAA receptor function and plasticity. In this review, we listed several interesting results regarding the regulation and plasticity of GABAA receptor function during pregnancy and postpartum period in rats. The increase in brain levels of neuroactive steroids during pregnancy and their sudden decrease immediately before delivery are causally related to changes in the expression/function of specific GABAA receptor subunits in the hippocampus. These data suggest that alterations in GABAA receptor expression and function may be related to neurological and psychiatric disorders associated with crucial periods in women. These findings could help to provide potential new treatments for these women’s disabling syndromes. Valentina Licheri, Giuseppe Talani, Ashish A. Gorule, Maria Cristina Mostallino, Giovanni Biggio, and Enrico Sanna Copyright © 2015 Valentina Licheri et al. All rights reserved. Molecular Mechanisms of Memory Consolidation, Reconsolidation, and Persistence Wed, 26 Aug 2015 12:12:37 +0000 Emiliano Merlo, Pedro Bekinschtein, Sietse Jonkman, and Jorge H. Medina Copyright © 2015 Emiliano Merlo et al. All rights reserved. Genotype-Dependent Difference in 5-HT2C Receptor-Induced Hypolocomotion: Comparison with 5-HT2A Receptor Functional Activity Wed, 26 Aug 2015 08:37:14 +0000 In the present study behavioral effects of the 5-HT2C serotonin receptor were investigated in different mouse strains. The 5-HT2C receptor agonist MK-212 applied intraperitoneally induced significant dose-dependent reduction of distance traveled in the open field test in CBA/Lac mice. This effect was receptor-specific because it was inhibited by the 5-HT2C receptor antagonist RS102221. To study the role of genotype in 5-HT2C receptor-induced hypolocomotion, locomotor activity of seven inbred mouse strains was measured after MK-212 acute treatment. We found that the 5-HT2C receptor stimulation by MK-212 decreased distance traveled in the open field test in CBA/Lac, C57Bl/6, C3H/He, and ICR mice, whereas it failed to affect locomotor activity in DBA/2J, Asn, and Balb/c mice. We also compared the interstrain differences in functional response to 5-HT2C and 5-HT2A receptors activation measured by the quantification of receptor-mediated head-twitches. These experiments revealed significant positive correlation between 5-HT2C and 5-HT2A receptors functional responses for all investigated mouse strains. Moreover, we found that 5-HT2A receptor activation with DOI did not change locomotor activity in CBA/Lac mice. Taken together, our data indicate the implication of 5-HT2C receptors in regulation of locomotor activity and suggest the shared mechanism for functional responses mediated by 5-HT2C and 5-HT2A receptors. Darya V. Bazovkina, Elena M. Kondaurova, Vladimir S. Naumenko, and Evgeni Ponimaskin Copyright © 2015 Darya V. Bazovkina et al. All rights reserved. Behavioral Tagging: A Translation of the Synaptic Tagging and Capture Hypothesis Tue, 25 Aug 2015 14:01:03 +0000 Similar molecular machinery is activated in neurons following an electrical stimulus that induces synaptic changes and after learning sessions that trigger memory formation. Then, to achieve perdurability of these processes protein synthesis is required for the reinforcement of the changes induced in the network. The synaptic tagging and capture theory provided a strong framework to explain synaptic specificity and persistence of electrophysiological induced plastic changes. Ten years later, the behavioral tagging hypothesis (BT) made use of the same argument, applying it to learning and memory models. The hypothesis postulates that the formation of lasting memories relies on at least two processes: the setting of a learning tag and the synthesis of plasticity related proteins, which once captured at tagged sites allow memory consolidation. BT explains how weak events, only capable of inducing transient forms of memories, can result in lasting memories when occurring close in time with other behaviorally relevant experiences that provide proteins. In this review, we detail the findings supporting the existence of BT process in rodents, leading to the consolidation, persistence, and interference of a memory. We focus on the molecular machinery taking place in these processes and describe the experimental data supporting the BT in humans. Diego Moncada, Fabricio Ballarini, and Haydée Viola Copyright © 2015 Diego Moncada et al. All rights reserved. Retrosplenial Cortex and Long-Term Memory: Molecules to Behavior Tue, 25 Aug 2015 08:41:19 +0000 The retrosplenial cortex (RSC) is reciprocally connected with the hippocampus and various parahippocampal cortical regions, suggesting that RSC is well-positioned to contribute to hippocampal-dependent memory. Consistent with this, substantial behavioral evidence indicates that RSC is essential for consolidating and/or retrieving contextual and spatial memories. In addition, there is growing evidence that RSC neurons undergo activity-dependent plastic changes during memory formation and retrieval. In this paper we review both the behavioral and cellular/molecular data and posit that the RSC has a particularly important role in the storage and retrieval of spatial and contextual memories perhaps due its involvement in binding together multiple cues in the environment. We identify remaining questions and avenues for future research that take advantage of emerging methods to selectively manipulate RSC neurons both spatially and temporally and to image the RSC in awake, behaving animals. Travis P. Todd and David J. Bucci Copyright © 2015 Travis P. Todd and David J. Bucci. All rights reserved. Involvement of Adult Hippocampal Neurogenesis in Learning and Forgetting Tue, 25 Aug 2015 06:50:18 +0000 Adult hippocampal neurogenesis is a process involving the continuous generation of newborn neurons in the hippocampus of adult animals. Mounting evidence has suggested that hippocampal neurogenesis contributes to some forms of hippocampus-dependent learning and memory; however, the detailed mechanism concerning how this small number of newborn neurons could affect learning and memory remains unclear. In this review, we discuss the relationship between adult-born neurons and learning and memory, with a highlight on recently discovered potential roles of neurogenesis in pattern separation and forgetting. Suk-yu Yau, Ang Li, and Kwok-Fai So Copyright © 2015 Suk-yu Yau et al. All rights reserved. Muscarinic ACh Receptors Contribute to Aversive Olfactory Learning in Drosophila Tue, 25 Aug 2015 06:48:04 +0000 The most studied form of associative learning in Drosophila consists in pairing an odorant, the conditioned stimulus (CS), with an unconditioned stimulus (US). The timely arrival of the CS and US information to a specific Drosophila brain association region, the mushroom bodies (MB), can induce new olfactory memories. Thus, the MB is considered a coincidence detector. It has been shown that olfactory information is conveyed to the MB through cholinergic inputs that activate acetylcholine (ACh) receptors, while the US is encoded by biogenic amine (BA) systems. In recent years, we have advanced our understanding on the specific neural BA pathways and receptors involved in olfactory learning and memory. However, little information exists on the contribution of cholinergic receptors to this process. Here we evaluate for the first time the proposition that, as in mammals, muscarinic ACh receptors (mAChRs) contribute to memory formation in Drosophila. Our results show that pharmacological and genetic blockade of mAChRs in MB disrupts olfactory aversive memory in larvae. This effect is not explained by an alteration in the ability of animals to respond to odorants or to execute motor programs. These results show that mAChRs in MB contribute to generating olfactory memories in Drosophila. Bryon Silva, Claudia Molina-Fernández, María Beatriz Ugalde, Eduardo I. Tognarelli, Cristian Angel, and Jorge M. Campusano Copyright © 2015 Bryon Silva et al. All rights reserved. Autobiographical Memory Disturbances in Depression: A Novel Therapeutic Target? Tue, 25 Aug 2015 06:01:35 +0000 Major depressive disorder (MDD) is characterized by a dysfunctional processing of autobiographical memories. We review the following core domains of deficit: systematic biases favoring materials of negative emotional valence; diminished access and response to positive memories; a recollection of overgeneral memories in detriment of specific autobiographical memories; and the role of ruminative processes and avoidance when dealing with autobiographical memories. Furthermore, we review evidence from functional neuroimaging studies of neural circuits activated by the recollection of autobiographical memories in both healthy and depressive individuals. Disruptions in autobiographical memories predispose and portend onset and maintenance of depression. Thus, we discuss emerging therapeutics that target memory difficulties in those with depression. We review strategies for this clinical domain, including memory specificity training, method-of-loci, memory rescripting, and real-time fMRI neurofeedback training of amygdala activity in depression. We propose that the manipulation of the reconsolidation of autobiographical memories in depression might represent a novel yet largely unexplored, domain-specific, therapeutic opportunity for depression treatment. Cristiano A. Köhler, André F. Carvalho, Gilberto S. Alves, Roger S. McIntyre, Thomas N. Hyphantis, and Martín Cammarota Copyright © 2015 Cristiano A. Köhler et al. All rights reserved. Evidence of Maintenance Tagging in the Hippocampus for the Persistence of Long-Lasting Memory Storage Tue, 25 Aug 2015 06:00:07 +0000 The synaptic tagging and capture (STC) hypothesis provides a compelling explanation for synaptic specificity and facilitation of long-term potentiation. Its implication on long-term memory (LTM) formation led to postulate the behavioral tagging mechanism. Here we show that a maintenance tagging process may operate in the hippocampus late after acquisition for the persistence of long-lasting memory storage. The proposed maintenance tagging has several characteristics: (1) the tag is transient and time-dependent; (2) it sets in a late critical time window after an aversive training which induces a short-lasting LTM; (3) exposing rats to a novel environment specifically within this tag time window enables the consolidation to a long-lasting LTM; (4) a familiar environment exploration was not effective; (5) the effect of novelty on the promotion of memory persistence requires dopamine D1/D5 receptors and Arc expression in the dorsal hippocampus. The present results can be explained by a broader version of the behavioral tagging hypothesis and highlight the idea that the durability of a memory trace depends either on late tag mechanisms induced by a training session or on events experienced close in time to this tag. Micol Tomaiuolo, Cynthia Katche, Haydee Viola, and Jorge H. Medina Copyright © 2015 Micol Tomaiuolo et al. All rights reserved. New Insights on Retrieval-Induced and Ongoing Memory Consolidation: Lessons from Arc Mon, 24 Aug 2015 14:30:25 +0000 The mainstream view on the neurobiological mechanisms underlying memory formation states that memory traces reside on the network of cells activated during initial acquisition that becomes active again upon retrieval (reactivation). These activation and reactivation processes have been called “conjunctive trace.” This process implies that singular molecular events must occur during acquisition, strengthening the connection between the implicated cells whose synchronous activity must underlie subsequent reactivations. The strongest experimental support for the conjunctive trace model comes from the study of immediate early genes such as c-fos, zif268, and activity-regulated cytoskeletal-associated protein. The expressions of these genes are reliably induced by behaviorally relevant neuronal activity and their products often play a central role in long-term memory formation. In this review, we propose that the peculiar characteristics of Arc protein, such as its optimal expression after ongoing experience or familiar behavior, together with its versatile and central functions in synaptic plasticity could explain how familiarization and recognition memories are stored and preserved in the mammalian brain. Jean-Pascal Morin, Kioko Guzmán-Ramos, and Federico Bermudez-Rattoni Copyright © 2015 Jean-Pascal Morin et al. All rights reserved. Hippocampal Infusion of Zeta Inhibitory Peptide Impairs Recent, but Not Remote, Recognition Memory in Rats Mon, 24 Aug 2015 14:16:45 +0000 Spatial memory in rodents can be erased following the infusion of zeta inhibitory peptide (ZIP) into the dorsal hippocampus via indwelling guide cannulas. It is believed that ZIP impairs spatial memory by reversing established late-phase long-term potentiation (LTP). However, it is unclear whether other forms of hippocampus-dependent memory, such as recognition memory, are also supported by hippocampal LTP. In the current study, we tested recognition memory in rats following hippocampal ZIP infusion. In order to combat the limited targeting of infusions via cannula, we implemented a stereotaxic approach for infusing ZIP throughout the dorsal, intermediate, and ventral hippocampus. Rats infused with ZIP 3–7 days after training on the novel object recognition task exhibited impaired object recognition memory compared to control rats (those infused with aCSF). In contrast, rats infused with ZIP 1 month after training performed similar to control rats. The ability to form new memories after ZIP infusions remained intact. We suggest that enhanced recognition memory for recent events is supported by hippocampal LTP, which can be reversed by hippocampal ZIP infusion. Jena B. Hales, Amber C. Ocampo, Nicola J. Broadbent, and Robert E. Clark Copyright © 2015 Jena B. Hales et al. All rights reserved. Effects of Exercise in Immersive Virtual Environments on Cortical Neural Oscillations and Mental State Thu, 20 Aug 2015 14:51:17 +0000 Virtual reality environments are increasingly being used to encourage individuals to exercise more regularly, including as part of treatment those with mental health or neurological disorders. The success of virtual environments likely depends on whether a sense of presence can be established, where participants become fully immersed in the virtual environment. Exposure to virtual environments is associated with physiological responses, including cortical activation changes. Whether the addition of a real exercise within a virtual environment alters sense of presence perception, or the accompanying physiological changes, is not known. In a randomized and controlled study design, moderate-intensity Exercise (i.e., self-paced cycling) and No-Exercise (i.e., automatic propulsion) trials were performed within three levels of virtual environment exposure. Each trial was 5 minutes in duration and was followed by posttrial assessments of heart rate, perceived sense of presence, EEG, and mental state. Changes in psychological strain and physical state were generally mirrored by neural activation patterns. Furthermore, these changes indicated that exercise augments the demands of virtual environment exposures and this likely contributed to an enhanced sense of presence. Tobias Vogt, Rainer Herpers, Christopher D. Askew, David Scherfgen, Heiko K. Strüder, and Stefan Schneider Copyright © 2015 Tobias Vogt et al. All rights reserved. Neural Plasticity in Common Forms of Chronic Headaches Thu, 20 Aug 2015 12:21:51 +0000 Headaches are universal experiences and among the most common disorders. While headache may be physiological in the acute setting, it can become a pathological and persistent condition. The mechanisms underlying the transition from episodic to chronic pain have been the subject of intense study. Using physiological and imaging methods, researchers have identified a number of different forms of neural plasticity associated with migraine and other headaches, including peripheral and central sensitization, and alterations in the endogenous mechanisms of pain modulation. While these changes have been proposed to contribute to headache and pain chronification, some findings are likely the results of repetitive noxious stimulation, such as atrophy of brain areas involved in pain perception and modulation. In this review, we provide a narrative overview of recent advances on the neuroimaging, electrophysiological and genetic aspects of neural plasticity associated with the most common forms of chronic headaches, including migraine, cluster headache, tension-type headache, and medication overuse headache. Tzu-Hsien Lai, Ekaterina Protsenko, Yu-Chen Cheng, Marco L. Loggia, Gianluca Coppola, and Wei-Ta Chen Copyright © 2015 Tzu-Hsien Lai et al. All rights reserved.