bluuebunny/crossref_metadata_2025 huggingface dataset:
Neural Correlates of Induced Motion Perception in the Human Brain
Authors: Takemura Hiromasa , Ashida Hiroshi , Amano Kaoru , Kitaoka Akiyoshi , Murakami Ikuya
Published: October 2012

A physically stationary stimulus surrounded by a moving stimulus appears to move in the opposite direction. There are similarities between the characteristics of this phenomenon of induced motion and surround suppression of directionally selective neurons in the brain. Here, functional magnetic resonance imaging was used to investigate the link between the subjective perception of induced motion and cortical activity. The visual stimuli consisted of a central drifting sinusoid surrounded by a moving random-dot pattern. The change in cortical activity in response to changes in speed and direction of the central stimulus was measured. The human cortical area hMT+ showed the greatest activation when the central stimulus moved at a fast speed in the direction opposite to that of the surround. More importantly, the activity in this area was the lowest when the central stimulus moved in the same direction as the surround and at a speed such that the central stimulus appeared to be stationary. The results indicate that the activity in hMT+ is related to perceived speed modulated by induced motion rather than to physical speed or a kinetic boundary. Early visual areas (V1, V2, V3, and V3A) showed a similar pattern; however, the relationship to perceived speed was not as clear as that in hMT+. These results suggest that hMT+ may be a neural correlate of induced motion perception and play an important role in contrasting motion signals in relation to their surrounding context and adaptively modulating our motion perception depending on the spatial context.
BDNF Promotes Differentiation and Maturation of Adult-born Neurons through GABAergic Transmission
Authors: Waterhouse Emily G. , An Juan Ji , Orefice Lauren L. , Baydyuk Maryna , Liao Guey-Ying , Zheng Kang , Lu Bai , Xu Baoji
Published: October 2012

Brain-derived neurotrophic factor (BDNF) has been implicated in regulating adult neurogenesis in the subgranular zone (SGZ) of the dentate gyrus; however, the mechanism underlying this regulation remains unclear. In this study, we found thatBdnfmRNA localized to distal dendrites of dentate gyrus granule cells isolated from wild-type (WT) mice, but not fromBdnfklox/kloxmice where the long 3′ untranslated region (UTR) ofBdnfmRNA is truncated. KCl-induced membrane depolarization stimulated release of dendritic BDNF translated from long 3′ UTRBdnfmRNA in cultured hippocampal neurons, but not from short 3′ UTRBdnfmRNA.Bdnfklox/kloxmice exhibited reduced expression of glutamic acid decarboxylase 65 (a GABA synthase), increased proliferation of progenitor cells, and impaired differentiation and maturation of newborn neurons in the SGZ. These deficits in adult neurogenesis were rescued with administration of phenobarbital, an enhancer of GABAAreceptor activity. Furthermore, we observed similar neurogenesis deficits in mice where the receptor for BDNF, TrkB, was selectively abolished in parvalbumin (PV)-expressing GABAergic interneurons. Thus, our data suggest that locally synthesized BDNF in dendrites of granule cells promotes differentiation and maturation of progenitor cells in the SGZ by enhancing GABA release, at least in part, from PV-expressing GABAergic interneurons.
Dopamine Modulates Episodic Memory Persistence in Old Age
Authors: Chowdhury Rumana , Guitart-Masip Marc , Bunzeck Nico , Dolan Raymond J. , Düzel Emrah
Published: October 2012

Activation of the hippocampus is required to encode memories for new events (or episodes). Observations from animal studies suggest that, for these memories to persist beyond 4–6 h, a release of dopamine generated by strong hippocampal activation is needed. This predicts that dopaminergic enhancement should improve human episodic memory persistence also for events encoded with weak hippocampal activation. Here, using pharmacological functional MRI (fMRI) in an elderly population in which there is a loss of dopamine neurons as part of normal aging, we show this very effect. The dopamine precursor levodopa led to a dose-dependent (inverted U-shape) persistent episodic memory benefit for images of scenes when tested after 6 h, independent of whether encoding-related hippocampal fMRI activity was weak or strong (U-shaped dose–response relationship). This lasting improvement even for weakly encoded events supports a role for dopamine in human episodic memory consolidation, albeit operating within a narrow dose range.
The Relationship between Slow Photoresponse Recovery Rate and Temporal Resolution of Vision
Authors: Umino Yumiko , Herrmann Rolf , Chen Ching-Kang , Barlow Robert B. , Arshavsky Vadim Y. , Solessio Eduardo
Published: October 2012

The rate at which photoreceptors recover from excitation is thought to be critical for setting the temporal resolution of vision. Indeed, mutations in RGS9 (regulator of G-protein signaling 9) and R9AP (RGS9 anchor protein) proteins mediating rapid photoresponse recovery impair patients' ability to see moving objects. In this study, we analyzed temporal properties of retinal sensitivity and spatiotemporal aspects of visual behavior in R9AP knock-out mice. Surprisingly, we have found that this knock-out does not affect dim-light vision mediated by rods acting as single-photon counters. Under these conditions, vision was also unaffected in mice overexpressing R9AP in rods, which causes accelerated photoresponse recovery. However, in brighter light, slow photoresponse recovery in rods and cones impaired visual responses to high temporal frequency stimuli, as reported for the daylight vision of human patients. Therefore, the speed of photoresponse recovery can affect temporal resolution and motion detection when photoreceptors integrate signals from multiple photons but not when they act as single-photon counters.
Age-Dependent MicroRNA Control of Synaptic Plasticity in 22q11 Deletion Syndrome and Schizophrenia
Authors: Earls Laurie R. , Fricke R. Gaines , Yu Jing , Berry Raymond B. , Baldwin Lisa T. , Zakharenko Stanislav S.
Published: October 2012

The 22q11 deletion syndrome (22q11DS) is characterized by multiple physical and psychiatric abnormalities and is caused by the hemizygous deletion of a 1.5–3 Mb region of chromosome 22. It constitutes one of the strongest known genetic risks for schizophrenia; schizophrenia arises in as many as 30% of patients with 22q11DS during adolescence or early adulthood. A mouse model of 22q11DS displays an age-dependent increase in hippocampal long-term potentiation (LTP), a form of synaptic plasticity underlying learning and memory. The sarco(endo)plasmic reticulum Ca2+ATPase (SERCA2), which is responsible for loading Ca2+into the endoplasmic reticulum (ER), is elevated in this mouse model. The resulting increase in ER Ca2+load leads to enhanced neurotransmitter release and increased LTP. However, the mechanism by which the 22q11 microdeletion leads to SERCA2 overexpression and LTP increase has not been determined. Screening of multiple mutant mouse lines revealed that haploinsufficiency ofDgcr8, a microRNA (miRNA) biogenesis gene in the 22q11DS disease-critical region, causes age-dependent, synaptic SERCA2 overexpression and increased LTP. We found that miR-25 and miR-185, regulators of SERCA2, are depleted in mouse models of 22q11DS. Restoration of these miRNAs to presynaptic neurons rescues LTP inDgcr8+/−mice. Finally, we show that SERCA2 is elevated in the brains of patients with schizophrenia, providing a link between mouse model findings and the human disease. We conclude that miRNA-dependent SERCA2 dysregulation is a pathogenic event in 22q11DS and schizophrenia.
Melanopsin and Rod–Cone Photoreceptors Play Different Roles in Mediating Pupillary Light Responses during Exposure to Continuous Light in Humans
Authors: Gooley Joshua J. , Ho Mien Ivan , St. Hilaire Melissa A. , Yeo Sing-Chen , Chua Eric Chern-Pin , van Reen Eliza , Hanley Catherine J. , Hull Joseph T. , Czeisler Charles A. , Lockley Steven W.
Published: October 2012

In mammals, the pupillary light reflex is mediated by intrinsically photosensitive melanopsin-containing retinal ganglion cells that also receive input from rod–cone photoreceptors. To assess the relative contribution of melanopsin and rod–cone photoreceptors to the pupillary light reflex in humans, we compared pupillary light responses in normally sighted individuals (n= 24) with a blind individual lacking rod–cone function. Here, we show that visual photoreceptors are required for normal pupillary responses to continuous light exposure at low irradiance levels, and for sustained pupillary constriction during exposure to light in the long-wavelength portion of the visual spectrum. In the absence of rod–cone function, pupillomotor responses are slow and sustained, and cannot track intermittent light stimuli, suggesting that rods/cones are required for encoding fast modulations in light intensity. In sighted individuals, pupillary constriction decreased monotonically for at least 30 min during exposure to continuous low-irradiance light, indicating that steady-state pupillary responses are an order of magnitude slower than previously reported. Exposure to low-irradiance intermittent green light (543 nm; 0.1–4 Hz) for 30 min, which was given to activate cone photoreceptors repeatedly, elicited sustained pupillary constriction responses that were more than twice as great compared with exposure to continuous green light. Our findings demonstrate nonredundant roles for rod–cone photoreceptors and melanopsin in mediating pupillary responses to continuous light. Moreover, our results suggest that it might be possible to enhance nonvisual light responses to low-irradiance exposures by using intermittent light to activate cone photoreceptors repeatedly in humans.
Alpha-Band Phase Synchrony Is Related to Activity in the Fronto-Parietal Adaptive Control Network
Authors: Sadaghiani Sepideh , Scheeringa René , Lehongre Katia , Morillon Benjamin , Giraud Anne-Lise , D'Esposito Mark , Kleinschmidt Andreas
Published: October 2012

Neural oscillations in the alpha band (8–12 Hz) are increasingly viewed as an active inhibitory mechanism that gates and controls sensory information processing as a function of cognitive relevance. Extending this view, phase synchronization of alpha oscillations across distant cortical regions could regulate integration of information. Here, we investigated whether such long-range cross-region coupling in the alpha band is intrinsically and selectively linked to activity in a distinct functionally specialized brain network. If so, this would provide new insight into the functional role of alpha band phase synchrony. We adapted the phase-locking value to assess fluctuations in synchrony that occur over time in ongoing activity. Concurrent EEG and functional magnetic resonance imaging (fMRI) were recorded during resting wakefulness in 26 human subjects. Fluctuations in global synchrony in the upper alpha band correlated positively with activity in several prefrontal and parietal regions (as measured by fMRI). fMRI intrinsic connectivity analysis confirmed that these regions correspond to the well known fronto-parietal (FP) network. Spectral correlations with this network's activity confirmed that no other frequency band showed equivalent results. This selective association supports an intrinsic relation between large-scale alpha phase synchrony and cognitive functions associated with the FP network. This network has been suggested to implement phasic aspects of top-down modulation such as initiation and change in moment-to-moment control. Mechanistically, long-range upper alpha band synchrony is well suited to support these functions. Complementing our previous findings that related alpha oscillation power to neural structures serving tonic control, the current findings link alpha phase synchrony to neural structures underpinning phasic control of alertness and task requirements.
Pituitary Adenylate Cyclase-Activating Polypeptide Induces Postsynaptically Expressed Potentiation in the Intra-amygdala Circuit
Authors: Cho Jun-Hyeong , Zushida Ko , Shumyatsky Gleb P. , Carlezon William A. , Meloni Edward G. , Bolshakov Vadim Y.
Published: October 2012

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a pleiotropic neuropeptide expressed in the brain, where it may act as a neuromodulator or neurotransmitter contributing to different behavioral processes and stress responses. PACAP is highly expressed in the amygdala, a subcortical brain area involved in both innate and learned fear, suggesting a role for PACAP-mediated signaling in fear-related behaviors. It remains unknown, however, whether and how PACAP affects neuronal and synaptic functions in the amygdala. In this study, we focused on neurons in the lateral division of the central nucleus (CeL), where PACAP-positive presynaptic terminals were predominantly found within the amygdala. In our experiments on rat brain slices, exogenous application of PACAP did not affect either resting membrane potential or membrane excitability of CeL neurons. PACAP enhanced, however, excitatory synaptic transmission in projections from the basolateral nucleus (BLA) to the CeL, while inhibitory transmission in the same pathway was unaffected. PACAP-induced potentiation of glutamatergic synaptic responses persisted after the washout of PACAP and was blocked by the VPAC1 receptor antagonist, suggesting that VPAC1 receptors might mediate synaptic effects of PACAP in the CeL. Moreover, potentiation of synaptic transmission by PACAP was dependent on postsynaptic activation of protein kinase A and calcium/calmodulin-dependent protein kinase II, as well as synaptic targeting of GluR1 subunit-containing AMPA receptors. Thus, PACAP may upregulate excitatory neurotransmission in the BLA–CeL pathway postsynaptically, consistent with the known roles of PACAP in control of fear-related behaviors.
Endocannabinoid-Mediated Long-Term Depression of Afferent Excitatory Synapses in Hippocampal Pyramidal Cells and GABAergic Interneurons
Authors: Péterfi Zoltán , Urbán Gabriella M. , Papp Orsolya I. , Németh Beáta , Monyer Hannah , Szabó Gábor , Erdélyi Ferenc , Mackie Ken , Freund Tamás F. , Hájos Norbert , Katona István
Published: October 2012

Although endocannabinoids have emerged as essential retrograde messengers in several forms of synaptic plasticity, it remains controversial whether they mediate long-term depression (LTD) of glutamatergic synapses onto excitatory and inhibitory neurons in the hippocampus. Here, we show that parvalbumin- and somatostatin/metabotropic glutamate receptor 1a(mGlu1a)-positive GABAergic interneurons express diacylglycerol lipase-α (DGL-α), a synthesizing enzyme of the endocannabinoid 2-arachidonoylglycerol (2-AG), albeit at lower levels than principal cells. Moreover, this lipase accumulates postsynaptically around afferent excitatory synapses in all three cell types. To address the role of retrograde 2-AG signaling in LTD, we investigated two forms: (1) produced by postsynaptic spiking paired with subsequent presynaptic stimulation or (2) induced by group I mGlu activation by (S)-3,5-dihydroxyphenylglycine (DHPG). Neither form of LTD was evoked in the presence of the mGlu5antagonist MPEP [2-methyl-6-(phenylethynyl)-pyridine], the DGL inhibitor THL [N-formyl-l-leucine (1S)-1-[[(2S,3S)-3-hexyl-4-oxo-2-oxetanyl]methyl]dodecyl ester], or the intracellularly applied Ca2+chelator BAPTA in CA1 pyramidal cells, fast-spiking interneurons (representing parvalbumin-containing cells) and interneurons projecting to stratum lacunosum-moleculare (representing somatostatin/mGlu1a-expressing interneurons). Both forms of LTD were completely absent in CB1cannabinoid receptor knock-out mice, whereas pharmacological blockade of CB1led to inconsistent results. Notably, in accordance with their lower DGL-α level, a higher stimulation frequency or higher DHPG concentration was required for LTD induction in interneurons compared with pyramidal cells. These findings demonstrate that hippocampal principal cells and interneurons produce endocannabinoids to mediate LTD in a qualitatively similar, but quantitatively different manner. The shifted induction threshold implies that endocannabinoid-LTD contributes to cortical information processing during distinct network activity patterns in a cell type-specific manner.
Features versus Feelings: Dissociable Representations of the Acoustic Features and Valence of Aversive Sounds
Authors: Kumar Sukhbinder , von Kriegstein Katharina , Friston Karl , Griffiths Timothy D.
Published: October 2012

This study addresses the neuronal representation of aversive sounds that are perceived as unpleasant. Functional magnetic resonance imaging in humans demonstrated responses in the amygdala and auditory cortex to aversive sounds. We show that the amygdala encodes both the acoustic features of a stimulus and its valence (perceived unpleasantness). Dynamic causal modeling of this system revealed that evoked responses to sounds are relayed to the amygdala via auditory cortex. While acoustic features modulate effective connectivity from auditory cortex to the amygdala, the valence modulates the effective connectivity from amygdala to the auditory cortex. These results support a complex (recurrent) interaction between the auditory cortex and amygdala based on object-level analysis in the auditory cortex that portends the assignment of emotional valence in amygdala that in turn influences the representation of salient information in auditory cortex.
Dynamic Regulation of Synaptic Maturation State by Voltage-Gated A-Type K+Channels in CA1 Hippocampal Pyramidal Neurons
Authors: Kim Eunyoung , Hoffman Dax A.
Published: October 2012

Neuronal activity is critical for the formation and modification of neural circuits during brain development. In hippocampal CA1 pyramidal dendrites, A-type voltage-gated K+currents, formed primarily by Kv4.2 subunits, control excitability. Here we used Kv4.2 knock-out (Kv4.2-KO) mice along with acutein vivoexpression of Kv4.2 or its dominant-negative pore mutant to examine the role of Kv4.2 in the development of CA1 synapses. We found that Kv4.2 expression induces synaptic maturation in juvenile WT mice and rescues developmentally delayed synapses in adult Kv4.2-KO mice. In addition, we show that NMDAR subunit composition can be reverted back to the juvenile form in WT adult synapses by functionally downregulating Kv4.2 levels. These results suggest that Kv4.2 regulation of excitability determines synaptic maturation state, which can be bidirectionally adjusted into adulthood.
Novel Animal Models of Acute and Chronic Cancer Pain: A Pivotal Role for PAR2
Authors: Lam David K. , Dang Dongmin , Zhang Jianan , Dolan John C. , Schmidt Brian L.
Published: October 2012

Targeted therapy to prevent the progression from acute to chronic pain in cancer patients remains elusive. We developed three novel cancer models in mice that together recapitulate the anatomical, temporal, and functional characteristics of acute and chronic head and neck cancer pain in humans. Using pharmacologic and genetic approaches in these novel cancer models, we identified the interaction between protease-activated receptor 2 (PAR2) and serine proteases to be of central importance. We show that serine proteases such as trypsin induce acute cancer pain in a PAR2-dependent manner. Chronic cancer pain is associated with elevated serine proteases in the cancer microenvironment and PAR2 upregulation in peripheral nerves. Serine protease inhibition greatly reduces the severity of persistent cancer pain in wild-type mice, but most strikingly, the development of chronic cancer pain is prevented in PAR2-deficient mice. Our results demonstrate a direct role for PAR2 in acute cancer pain and suggest that PAR2 upregulation may favor the development and maintenance of chronic cancer pain. Targeting the PAR2–serine protease interaction is a promising approach to the treatment of acute cancer pain and prevention of chronic cancer pain.
A Knock-In Model of Human Epilepsy inDrosophilaReveals a Novel Cellular Mechanism Associated with Heat-Induced Seizure
Authors: Sun Lei , Gilligan Jeff , Staber Cynthia , Schutte Ryan J. , Nguyen Vivian , O'Dowd Diane K. , Reenan Robert
Published: October 2012

Over 40 missense mutations in the humanSCN1Asodium channel gene are linked to an epilepsy syndrome termed genetic epilepsy with febrile seizures plus (GEFS+). Inheritance of GEFS+ is dominant, but the underlying cellular mechanisms remain poorly understood. Here we report that knock-in of a GEFS+SCN1Amutation (K1270T) into theDrosophilasodium channel gene,para, causes a semidominant temperature-induced seizure phenotype. Electrophysiological studies of GABAergic interneurons in the brains of adult GEFS+ flies reveal a novel cellular mechanism underlying heat-induced seizures: the deactivation threshold for persistent sodium currents reversibly shifts to a more negative voltage when the temperature is elevated. This leads to sustained depolarizations in GABAergic neurons and reduced inhibitory activity in the central nervous system. Furthermore, our data indicate a natural temperature-dependent shift in sodium current deactivation (exacerbated by mutation) may contribute to febrile seizures in GEFS+ and perhaps normal individuals.
Localization of PDZD7 to the Stereocilia Ankle-Link Associates this Scaffolding Protein with the Usher Syndrome Protein Network
Authors: Grati M'hamed , Shin Jung-Bum , Weston Michael D. , Green James , Bhat Manzoor A. , Gillespie Peter G. , Kachar Bechara
Published: October 2012

Usher syndrome is the leading cause of genetic deaf–blindness. Monoallelic mutations inPDZD7increase the severity of Usher type II syndrome caused by mutations inUSH2AandGPR98, which respectively encode usherin and GPR98. PDZ domain-containing 7 protein (PDZD7) is a paralog of the scaffolding proteins harmonin and whirlin, which are implicated in Usher type 1 and type 2 syndromes. While usherin and GPR98 have been reported to form hair cell stereocilia ankle-links, harmonin localizes to the stereocilia upper tip-link density and whirlin localizes to both tip and ankle-link regions. Here, we used mass spectrometry to show that PDZD7 is expressed in chick stereocilia at a comparable molecular abundance to GPR98. We also show by immunofluorescence and by overexpression of tagged proteins in rat and mouse hair cells that PDZD7 localizes to the ankle-link region, overlapping with usherin, whirlin, and GPR98. Finally, we show in LLC-PK1 cells that cytosolic domains of usherin and GPR98 can bind to both whirlin and PDZD7. These observations are consistent withPDZD7being a modifier and candidate gene for USH2, and suggest that PDZD7 is a second scaffolding component of the ankle-link complex.
Expanding the Ig Superfamily Code for Laminar Specificity in Retina: Expression and Role of Contactins
Authors: Yamagata Masahito , Sanes Joshua R.
Published: October 2012

Bipolar, amacrine, and retinal ganglion cells elaborate arbors and form synapses within the inner plexiform layer (IPL) of the vertebrate retina. Specific subsets of these neuronal types synapse in one or a few of the ≥10 sublaminae of the IPL. Four closely related Ig superfamily transmembrane adhesion molecules—Sidekick1 (Sdk1), Sdk2, Dscam, and DscamL—are expressed by non-overlapping subsets of chick retinal neurons and promote their lamina-specific arborization (Yamagata and Sanes, 2008). Here, we asked whether contactins (Cntns), six homologs of Sdks and Dscams, are expressed by and play roles in other subsets.In situhybridization showed thatcntn1–5were differentially expressed by subsets of amacrine cells. Immunohistochemistry showed that each Cntn protein was concentrated in a subset of IPL sublaminae. To assess roles of Cntns in retinal development, we focused on Cntn2. Depletion of Cntn2 by RNA interference markedly reduced the ability of Cntn2-positive cells to restrict their arbors to appropriate sublaminae. Conversely, ectopic expression ofcntn2redirected neurites of transduced neurons to the Cntn2-positive sublaminae. Thus, both loss- and gain-of-function strategies implicate Cntn2 in lamina-specific neurite targeting. Studies in heterologous cells showed that Cntn2 mediates homophilic adhesion, but does not bind detectably to Sdks, Dscams, or other Cntns. Overexpression analysis showed that Cntns1 and 3 can also redirect neurites to appropriate sublaminae. We propose that Cntns, Sdks, and Dscams comprise an Ig superfamily code that uses homophilic interactions to promote lamina-specific targeting of retinal dendrites in IPL.
Treatment of Neurodevelopmental Disorders in Adulthood
Authors: Castrén Eero , Elgersma Ype , Maffei Lamberto , Hagerman Randi
Published: October 2012

Brain development in neurodevelopmental disorders has been considered to comprise a sequence of critical periods, and abnormalities occurring during early development have been considered irreversible in adulthood. However, findings in mouse models of neurodevelopmental disorders, including fragile X, Rett syndrome, Down syndrome, and neurofibromatosis type I suggest that it is possible to reverse certain molecular, electrophysiological, and behavioral deficits associated with these disorders in adults by genetic or pharmacological manipulations. Furthermore, recent studies have suggested that critical period-like plasticity can be reactivated in the adult brain by environmental manipulations or by pharmacotherapy. These studies open up a tantalizing possibility that targeted pharmacological treatments in combination with regimes of training or rehabilitation might alleviate or reverse the symptoms of neurodevelopmental disorders even after the end of critical developmental periods. Even though translation from animal experimentation to clinical practice is challenging, these results suggest a rational basis for treatment of neurodevelopmental disorders in adulthood.
Integrative Approaches Utilizing Oxytocin to Enhance Prosocial Behavior: From Animal and Human Social Behavior to Autistic Social Dysfunction
Authors: Yamasue Hidenori , Yee Jason R. , Hurlemann René , Rilling James K. , Chen Frances S. , Meyer-Lindenberg Andreas , Tost Heike
Published: October 2012

The prevalence of autism spectrum disorder (ASD) is as high as 1 in 100 individuals and is a heavy burden to society. Thus, identifying causes and treatments is imperative. Here, we briefly review the topics covered in our 2012 Society for Neuroscience Mini-Symposium entitled “Integrative Approaches Using Oxytocin to Enhance Prosocial Behavior: From Animal and Human Social Behavior to ASD's Social Dysfunction.” This work is not meant to be a comprehensive review of oxytocin and prosocial behavior. Instead, we wish to share the newest findings on the effects of oxytocin on social behavior, the brain, and the social dysfunction of ASD at the molecular, genetic, systemic, and behavior levels, in varied subjects ranging from animal models to humans suffering from autism for the purpose of promoting further study for developing the clinical use of oxytocin in treating ASD.
Illuminating Vertebrate Olfactory Processing
Authors: Spors Hartwig , Albeanu Dinu Florin , Murthy Venkatesh N. , Rinberg Dmitry , Uchida Naoshige , Wachowiak Matt , Friedrich Rainer W.
Published: October 2012

The olfactory system encodes information about molecules by spatiotemporal patterns of activity across distributed populations of neurons and extracts information from these patterns to control specific behaviors. Recent studies usedin vivorecordings, optogenetics, and other methods to analyze the mechanisms by which odor information is encoded and processed in the olfactory system, the functional connectivity within and between olfactory brain areas, and the impact of spatiotemporal patterning of neuronal activity on higher-order neurons and behavioral outputs. The results give rise to a faceted picture of olfactory processing and provide insights into fundamental mechanisms underlying neuronal computations. This review focuses on some of this work presented in a Mini-Symposium at the Annual Meeting of the Society for Neuroscience in 2012.
Inhibition of Fear by Learned Safety Signals: A Mini-Symposium Review
Authors: Christianson John P. , Fernando Anushka B. P. , Kazama Andy M. , Jovanovic Tanja , Ostroff Linnaea E. , Sangha Susan
Published: October 2012

Safety signals are learned cues that predict the nonoccurrence of an aversive event. As such, safety signals are potent inhibitors of fear and stress responses. Investigations of safety signal learning have increased over the last few years due in part to the finding that traumatized persons are unable to use safety cues to inhibit fear, making it a clinically relevant phenotype. The goal of this review is to present recent advances relating to the neural and behavioral mechanisms of safety learning, and expression in rodents, nonhuman primates, and humans.
How Do Short-Term Changes at Synapses Fine-Tune Information Processing?
Authors: Klug Achim , Borst J. Gerard G. , Carlson Bruce A. , Kopp-Scheinpflug Cornelia , Klyachko Vitaly A. , Xu-Friedman Matthew A.
Published: October 2012

Synaptic transmission is highly dependent on recent activity and can lead to depression or facilitation of synaptic strength. This phenomenon is called “short-term synaptic plasticity” and is shown at all synapses. While much work has been done to understand the mechanisms of short-term changes in the state of synapses, short-term plasticity is often thought of as a mechanistic consequence of the design of a synapse. This review will attempt to go beyond this view and discuss how, on one hand, complex neuronal activity affects the short-term state of synapses, but also how these dynamic changes in synaptic strength affect information processing in return.
Layer-Specific CREB Target Gene Induction in Human Neocortical Epilepsy
Authors: Beaumont Thomas L. , Yao Bin , Shah Aashit , Kapatos Gregory , Loeb Jeffrey A.
Published: October 2012

Epilepsy is a disorder of recurrent seizures that affects 1% of the population. To understand why some areas of cerebral cortex produce seizures and others do not, we identified differentially expressed genes in human epileptic neocortex compared with nearby regions that did not produce seizures. The transcriptome that emerged strongly implicates MAPK signaling and CREB-dependent transcription, with 74% of differentially expressed genes containing a cAMP response element (CRE) in their proximal promoter, more than half of which are conserved. Despite the absence of recent seizures in these patients, epileptic brain regions prone to seizures showed persistent activation of ERK and CREB. Persistent CREB activation was directly linked to CREB-dependent gene transcription by chromatin immunoprecipitation that showed phosphorylated CREB constitutively associated with the proximal promoters of many of the induced target genes involved in neuronal signaling, excitability, and synaptic plasticity. A distinct spatial pattern of ERK activation was seen in superficial axodendritic processes of epileptic neocortex that colocalized with both CREB phosphorylation and CREB target gene induction in well demarcated populations of layer 2/3 neurons. These same neuronal lamina showed a marked increase in synaptic density. The findings generated in this study generate a robust and spatially restricted pattern of epileptic biomarkers and associated synaptic changes that could lead to new mechanistic insights and potential therapeutic targets for human epilepsy.
Conjunctions between Motion and Disparity Are Encoded with the Same Spatial Resolution As Disparity Alone
Authors: Allenmark Fredrik , Read Jenny C. A.
Published: October 2012

Neurons in cortical area MT respond well to transparent streaming motion in distinct depth planes, such as caused by observer self-motion, but do not contain subregions excited by opposite directions of motion. We therefore predicted that spatial resolution for transparent motion/disparity conjunctions would be limited by the size of MT receptive fields, just as spatial resolution for disparity is limited by the much smaller receptive fields found in primary visual cortex, V1. We measured this using a novel “joint motion/disparity grating,” on which human observers detected motion/disparity conjunctions in transparent random-dot patterns containing dots streaming in opposite directions on two depth planes. Surprisingly, observers showed the same spatial resolution for these as for pure disparity gratings. We estimate the limiting receptive field diameter at 11 arcmin, similar to V1 and much smaller than MT. Higher internal noise for detecting joint motion/disparity produces a slightly lower high-frequency cutoff of 2.5 cycles per degree (cpd) versus 3.3 cpd for disparity. This suggests that information on motion/disparity conjunctions is available in the population activity of V1 and that this information can be decoded for perception even when it is invisible to neurons in MT.
Distinct Neurochemical and Functional Properties of GAD67-Containing 5-HT Neurons in the Rat Dorsal Raphe Nucleus
Authors: Shikanai Hiroki , Yoshida Takayuki , Konno Kohtarou , Yamasaki Miwako , Izumi Takeshi , Ohmura Yu , Watanabe Masahiko , Yoshioka Mitsuhiro
Published: October 2012

The serotonergic (5-HTergic) system arising from the dorsal raphe nucleus (DRN) is implicated in various physiological and behavioral processes, including stress responses. The DRN is comprised of several subnuclei, serving specific functions with distinct afferent and efferent connections. Furthermore, subsets of 5-HTergic neurons are known to coexpress other transmitters, including GABA, glutamate, or neuropeptides, thereby generating further heterogeneity. However, despite the growing evidence for functional variations among DRN subnuclei, relatively little is known about how they map onto neurochemical diversity of 5-HTergic neurons. In the present study, we characterized functional properties of GAD67-expressing 5-HTergic neurons (5-HT/GAD67 neurons) in the rat DRN, and compared with those of neurons expressing 5-HTergic molecules (5-HT neurons) or GAD67 alone. While 5-HT/GAD67 neurons were absent in the dorsomedial (DRD) or ventromedial (DRV) parts of the DRN, they were selectively distributed in the lateral wing of the DRN (DRL), constituting 12% of the total DRL neurons. They expressed plasmalemmal GABA transporter 1, but lacked vesicular inhibitory amino acid transporter. By using whole-cell patch-clamp recording, we found that 5-HT/GAD67 neurons had lower input resistance and firing frequency than 5-HT neurons. As revealed by c-Fos immunohistochemistry, neurons in the DRL, particularly 5-HT/GAD67 neurons, showed higher responsiveness to exposure to an open field arena than those in the DRD and DRV. By contrast, exposure to contextual fear conditioning stress showed no such regional differences. These findings indicate that 5-HT/GAD67 neurons constitute a unique neuronal population with distinctive neurochemical and electrophysiological properties and high responsiveness to innocuous stressor.
Miniature IPSCs in Hippocampal Granule Cells Are Triggered by Voltage-Gated Ca2+Channels via Microdomain Coupling
Authors: Goswami Sarit Pati , Bucurenciu Iancu , Jonas Peter
Published: October 2012

The coupling between presynaptic Ca2+channels and Ca2+sensors of exocytosis is a key determinant of synaptic transmission. Evoked release from parvalbumin (PV)-expressing interneurons is triggered by nanodomain coupling of P/Q-type Ca2+channels, whereas release from cholecystokinin (CCK)-containing interneurons is generated by microdomain coupling of N-type channels. Nanodomain coupling has several functional advantages, including speed and efficacy of transmission. One potential disadvantage is that stochastic opening of presynaptic Ca2+channels may trigger spontaneous transmitter release. We addressed this possibility in rat hippocampal granule cells, which receive converging inputs from different inhibitory sources. Both reduction of extracellular Ca2+concentration and the unselective Ca2+channel blocker Cd2+reduced the frequency of miniature IPSCs (mIPSCs) in granule cells by ∼50%, suggesting that the opening of presynaptic Ca2+channels contributes to spontaneous release. Application of the selective P/Q-type Ca2+channel blocker ω-agatoxin IVa had no detectable effects, whereas both the N-type blocker ω-conotoxin GVIa and the L-type blocker nimodipine reduced mIPSC frequency. Furthermore, both the fast Ca2+chelator BAPTA-AM and the slow chelator EGTA-AM reduced the mIPSC frequency, suggesting that Ca2+-dependent spontaneous release is triggered by microdomain rather than nanodomain coupling. The CB1receptor agonist WIN 55212-2 also decreased spontaneous release; this effect was occluded by prior application of ω-conotoxin GVIa, suggesting that a major fraction of Ca2+-dependent spontaneous release was generated at the terminals of CCK-expressing interneurons. Tonic inhibition generated by spontaneous opening of presynaptic N- and L-type Ca2+channels may be important for hippocampal information processing.
A New Vesicular Scaffolding Complex Mediates the G-Protein-Coupled 5-HT1AReceptor Targeting to Neuronal Dendrites
Authors: Al Awabdh Sana , Miserey-Lenkei Stéphanie , Bouceba Tahar , Masson Justine , Kano Fumi , Marinach-Patrice Carine , Hamon Michel , Emerit Michel Boris , Darmon Michèle
Published: October 2012

Although essential for their neuronal function, the molecular mechanisms underlying the dendritic targeting of serotonin G-protein-coupled receptors are poorly understood. Here, we characterized a Yif1B-dependent vesicular scaffolding complex mediating the intracellular traffic of the rat 5-HT1Areceptor (5-HT1AR) toward dendrites. By combining directed mutagenesis, GST-pull down, and surface plasmon resonance, we identified a tribasic motif in the C-tail of the 5-HT1AR on which Yif1B binds directly with high affinity (KD≈ 37 nm). Moreover, we identified Yip1A, Rab6, and Kif5B as new partners of the 5-HT1AR/Yif1B complex, and showed that their expression in neurons is also crucial for the dendritic targeting of the 5-HT1AR. Live videomicroscopy revealed that 5-HT1AR, Yif1B, Yip1A, and Rab6 traffic in vesicles exiting the soma toward the dendritic tree, and also exhibit bidirectional motions, sustaining their role in 5-HT1AR dendritic targeting. Hence, we propose a new trafficking pathway model in which Yif1B is the scaffold protein recruiting the 5-HT1AR in a complex including Yip1A and Rab6, with Kif5B and dynein as two opposite molecular motors coordinating the traffic of vesicles along dendritic microtubules. This targeting pathway opens new insights for G-protein-coupled receptors trafficking in neurons.
Epidemiological evidence against a role for C-reactive protein causing leptin resistance
Authors: Rutter M K , Sattar N , Tajar A , O'Neill T W , Lee D M , Bartfai G , Boonen S , Casanueva F F , Finn J D , Forti G , Giwercman A , Han T S , Huhtaniemi I T , Kula K , Lean M E J , Pendleton N , Punab M , Silman A J , Vanderschueren D , Lowe G , O'Rahilly S , Morris R W , Wu F C , Wannamethee S G , _ _
Published: October 2012

Objective

It has been suggested that elevated levels of C-reactive protein (CRP) might interfere with leptin signalling and contribute to leptin resistance. Our aim was to assess whether plasma levels of CRP influence leptin resistance in humans, and our hypothesis was that CRP levels would modify the cross-sectional relationships between leptin and measures of adiposity.

Design and methods

We assessed four measures of adiposity: BMI, waist circumference, fat mass and body fat (%) in 2113 British Regional Heart Study (BRHS) men (mean (s.d.) age 69 (5) years), with replication in 760 (age 69 (6) years) European Male Ageing Study (EMAS) subjects.

Results

In BRHS subjects, leptin correlated with CRP (Spearman'sr=0.22,P<0.0001). Leptin and CRP correlated with all four measures of adiposity (rvalue range: 0.22–0.57, allP<0.0001). Age-adjusted mean levels for adiposity measures increased in relation to leptin levels, but CRP level did not consistently influence the β-coefficients of the regression lines in a CRP-stratified analysis. In BRHS subjects, the BMI vs leptin relationship demonstrated a weak statistical interaction with CRP (P=0.04). We observed no similar interaction in EMAS subjects and no significant interactions with other measures of adiposity in BRHS or EMAS cohorts.

Conclusion

We have shown that plasma CRP has little influence on the relationship between measures of adiposity and serum leptin levels in these middle-aged and elderly male European cohorts. This study provides epidemiological evidence against CRP having a significant role in causing leptin resistance.
Thermal, Optical, and Film Properties of a Ladder-like Polysilsesquioxane as Flexible Electronic Device Substrates
Authors: Lee Albert S. , Choi Seung-Sock , Lee He Seung , Jeon Hyeon Yeol , Baek Kyung-Youl , Hwang Seung Sang
Published: October 2012

A high molecular weight, photocurable inorganic-organic hybrid based on ladder-like poly(phenyl6-co-methacrylate4)silsesquioxanes (LPPMA64) was investigated as a flexible display substrate. Photocured free standing films with 40μm thickness showed high transparency (>95%), excellent thermal stability (Td >450°C), and low coefficient of thermal expansion (38ppm/K) without the use of reinforced glass fibers. Furthermore, these ladder-like structured materials did not require any thermal treatment processes due to the negligible amounts of uncondensed groups, thus simplifying manufacturing processing. These novel hybrid films present an alternative to organic plastics as flexible electronic device substrates due to their excellent optical and thermal properties.
Analysis of Electron Traps in a-IGZO Thin Films after High Pressure Vapor Annealing by Capacitance–Voltage Method
Authors: Ueoka Yoshihiro , Fujii Mami , Yamazaki Haruka , Horita Masahiro , Ishikawa Yasuaki , Uraoka Yukiharu
Published: October 2012

Effect of high-pressure water vapor (HPV) annealing is discussed from density of state (DOS) by capacitance–voltage (C–V) method and ΔVFB by the cyclic C–V measurement. The DOS of HPV samples were smaller than that of conventional atmosphere (AT) annealing around conduction band minimum (Ec). The ΔVFB of HPV samples were also smaller than that of AT. This suggests that HPV annealing is an effective method to decrease electron trap density as compared with AT condition. Especially, HPV 0.5 MPa sample was lower electron trap density and more stable than the other pressure HPV samples. Therefore, it is considered that the HPV in 0.5 MPa is the most promising condition. In addition, we succeeded in demonstrating the analysis of trap density in thin film by C–V method and cyclic C–V measurement.
Theoretical Approach for the Development of Organic Semiconductors on the Basis of the MO Symmetry: Thienoacene as an Example
Authors: Kojima Hirotaka , Mori Takehiko
Published: October 2012

We have explored materials for organic field-effect transistors (OFETs) from the viewpoint of theoretical calculations. The herringbone structure, which realizes two-dimensional conduction, is investigated in detail. Transfer integrals (t) are calculated systematically as a function of the dihedral angle between the molecular planes (θ) and the displacement along the molecular long axis (D). Acenes, oligothiophenes, thienoacenes and tetrathiafulvalenes are investigated, and are discussed from the molecular orbital (MO) symmetry. Thienoacenes (nTAs) are particularly examined as a candidate of OFET materials from the calculations of transfer integrals and reorganization energies (λ) based on the energy levels and the MO symmetry. LUMO of nTAs have MO symmetry suitable for conduction, but these orbitals are usually not related to the conduction. We have investigated the electronic properties of the derivatives with dicarboximide moiety. nTA-tetracarboxydiimide is expected to show the herringbone structure and exhibit n-type transport from the properties of LUMO.
Nanoscale Observation of the Distribution Polarization in Lithium Niobate Thin Films
Authors: Kiselev Dmitry A. , Zhukov Roman N. , Bykov Alexander S. , Malinkovich Mikhail D. , Parkhomenko Yuriy N.
Published: October 2012

In this work, an Atomic Force Microscope in the so-called Piezoresponse mode and Kelvin mode is used to image the grains, ferroelectric domains and surface potential in lithium niobate thin films. A RF magnetron sputter system was used to deposit LiNbO3 thin films on (100)-oriented Si substrates with SiO2 layer. The surface of the sample shows small grains which diameter ranges from 70 nm to 150 nm and roughness is less than 13 nm. Using the electric field from a biased conducting AFM tip, we show that possible to form and subsequently to visualize ferroelectric state. Also, we report surface charge retention on ferroelectric thin films by Kelvin probe microscope in comparison with the piezoresponse signal.
Electronic characterization of single-layer MoS2 sheets exfoliated on SrTiO3
Authors: Bußmann Benedict Kleine , Marinov Kolyo , Ochedowski Oliver , Scheuschner Nils , Maultzsch Janina , Schleberger Marika
Published: October 2012

Single layer regions of MoS2 on SiO2 and SrTiO3 were identified by Raman spectroscopy and μ-photoluminescence before Kelvin probe force microscopy was performed. For the already known system MoS2/SiO2 we find 1.839 eV for the direct bandgap, in good agreement with earlier results. On MoS2/SrTiO3 the direct bandgap was determined to be 1.829 eV. From our Kelvin probe data we infer that the SrTiO3 substrate leads to a dipole layer at the interface of the MoS2 single layer. The corresponding μ-PL measurements however show no significant decrease of the bandgap. This shows, that in the case of MoS2 the carrier type as well as concentration is not significantly influenced by the choice of SrTiO3 as the substrate compared to SiO2.
Competitive Role of Impurities on the Electrical Activity of as-grown Σ=13, Σ=25 and Deformed Σ=9 Grain boundaries in p-type Silicon Bi-crystals
Authors: Gaiaschi S. , El Kouadri Boudjelthia A. , Regula G. , Burle N. , Mesli A. , Neisius T. , Acciarri M. , Mong The Yen V. , Palais O. , Ntsoenzok E. , Pichaud B.
Published: October 2012

Electrical properties of grain boundaries grown by Czochralski process were studied by microwave phase shift (μW-PS) and electron beam induced current (EBIC), before and after gold diffusion at 700°C. As-grown samples had similar doping levels determined by four-point probe measurements but somewhat different oxygen concentrations, obtained by Fourier transform infrared spectroscopy (FTIR). It is shown that the increase of the grain boundary activity due to Au gathering at this planar defect can be hindered by native impurities (likely oxygen). EBIC and μW-PS techniques gave respectively electron diffusion lengths and lifetime values, both in good agreement. EBIC images on deformed Σ =9 showed that extrinsic dislocations do not activate the grain boundary at 300K.