bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retinoic Acid Receptor β Controls Development of Striatonigral Projection Neurons through FGF-Dependent and Meis1-Dependent Mechanisms
Authors: Rataj-Baniowska Monika , Niewiadomska-Cimicka Anna , Paschaki Marie , Szyszka-Niagolov Monika , Carramolino Laura , Torres Miguel , Dollé Pascal , Krężel Wojciech 
Published: October 2015

The mammalian striatum controls sensorimotor and psychoaffective functions through coordinated activities of its two striatonigral and striatopallidal output pathways. Here we show that retinoic acid receptor β (RARβ) controls development of a subpopulation of GABAergic,Gad65-positive striatonigral projection neurons. InRarb−/−knock-out mice, concomitant reduction ofGad65, dopamine receptor D1 (Drd1), and substance P expression at different phases of prenatal development was associated with reduced number ofDrd1-positive cells at birth, in contrast to normal numbers of striatopallidal projection neurons expressing dopamine receptor D2. Fate mapping using BrdU pulse-chase experiments revealed that such deficits may originate from compromised proliferation of late-born striosomal neurons and lead to decreased number ofDrd1-positive cells retaining BrdU in postnatal day (P) 0Rarb−/−striatum. Reduced expression ofFgf3in the subventricular zone of the lateral ganglionic eminence (LGE) at embryonic day 13.5 may underlie such deficits by inducing premature differentiation of neuronal progenitors, as illustrated by reduced expression of the proneural gene Ascl1 (Mash1) and increased expression of Meis1, a marker of postmitotic LGE neurons. In agreement with a critical role of FGF3 in this control, reduced number of Ascl1-expressing neural progenitors, and a concomitant increase of Meis1-expressing cells, were observed in primary cell cultures ofRarb−/−LGE. This defect was normalized by addition of fibroblast growth factor (FGF). Such data point to role of Meis1 in striatal development, also supported by reduced neuronal differentiation in the LGE ofMeis1−/−embryos. Our data unveil a novel mechanism of development of striatonigral projection neurons involving retinoic acid and FGF, two signals required for positioning the boundaries of Meis1-expressing cells.SIGNIFICANCE STATEMENTWe provide the first evidence that retinoic acid signaling controls development of striatonigral projection neurons, which constitute one of the two major output pathways of the striatum. Our data point to retinoic acid receptor β (RARβ) as novel determinant of striatonigral pathway development, and indicate that such activities of RARβ are mediated by abnormal FGF3 and Meis1 signaling, but do not involve Isl1, Ctip2, or Ebf1, the only factors known so far to control development of these neurons. Furthermore, present data support possibility that lateral ganglionic eminence development is controlled by gradients of fibroblast growth factor and RA signaling.
Voltage-Mediated Control of Spontaneous Bundle Oscillations in Saccular Hair Cells
Authors: Meenderink Sebastiaan W. F. , Quiñones Patricia M. , Bozovic Dolores 
Published: October 2015

Hair cells of the vertebrate vestibular and auditory systems convert mechanical inputs into electrical signals that are relayed to the brain. This transduction involves mechanically gated ion channels that open following the deflection of mechanoreceptive hair bundles that reside on top of these cells. The mechano-electrical transduction includes one or more active feedback mechanisms to keep the mechanically gated ion channels in their most sensitive operating range. Coupling between the gating of the mechanosensitive ion channels and this adaptation mechanism leads to the occurrence of spontaneous limit-cycle oscillations, which indeed have been observedin vitroin hair cells from the frog sacculus and the turtle basilar papilla. We obtained simultaneous optical and electrophysiological recordings from bullfrog saccular hair cells with such spontaneously oscillating hair bundles. The spontaneous bundle oscillations allowed us to characterize several properties of mechano-electrical transduction without artificial loading the hair bundle with a mechanical stimulus probe. We show that the membrane potential of the hair cell can modulate or fully suppress innate oscillations, thus controlling the dynamic state of the bundle. We further demonstrate that this control is exerted by affecting the internal calcium concentration, which sets the resting open probability of the mechanosensitive channels. The auditory and vestibular systems could use the membrane potential of hair cells, possibly controlled via efferent innervation, to tune the dynamic states of the cells.SIGNIFICANCE STATEMENTThe sensation of sound and balance starts by converting minute mechanical motions into electrical signals. This is accomplished by sensory hair cells, in which the opening and closing of mechanosensitive channels follows the motion of their hair bundles. These hair bundles can exhibit motility without an external drive. Underlying these spontaneous bundle oscillations are two coupled feedback mechanisms that improve the cell's response when mechanically stimulated. Here, we present synchronized optical and electrical recordings from cells with spontaneously oscillating bundles and show that the membrane potential may be a control parameter, tuning the cell's feedback processes. This control comes from modulation of the channel's open probability, which is affected by the concentration of calcium inside the cell.
Spatial Correlations in Natural Scenes Modulate Response Reliability in Mouse Visual Cortex
Authors: Rikhye Rajeev V. , Sur Mriganka 
Published: October 2015

Intrinsic neuronal variability significantly limits information encoding in the primary visual cortex (V1). Certain stimuli can suppress this intertrial variability to increase the reliability of neuronal responses. In particular, responses to natural scenes, which have broadband spatiotemporal statistics, are more reliable than responses to stimuli such as gratings. However, very little is known about which stimulus statistics modulate reliable coding and how this occurs at the neural ensemble level. Here, we sought to elucidate the role that spatial correlations in natural scenes play in reliable coding. We developed a novel noise-masking method to systematically alter spatial correlations in natural movies, without altering their edge structure. Using high-speed two-photon calcium imagingin vivo, we found that responses in mouse V1 were much less reliable at both the single neuron and population level when spatial correlations were removed from the image. This change in reliability was due to a reorganization of between-neuron correlations. Strongly correlated neurons formed ensembles that reliably and accurately encoded visual stimuli, whereas reducing spatial correlations reduced the activation of these ensembles, leading to an unreliable code. Together with an ensemble-specific normalization model, these results suggest that the coordinated activation of specific subsets of neurons underlies the reliable coding of natural scenes.SIGNIFICANCE STATEMENTThe natural environment is rich with information. To process this information with high fidelity, V1 neurons have to be robust to noise and, consequentially, must generate responses that are reliable from trial to trial. While several studies have hinted that both stimulus attributes and population coding may reduce noise, the details remain unclear. Specifically, what features of natural scenes are important and how do they modulate reliability? This study is the first to investigate the role of spatial correlations, which are a fundamental attribute of natural scenes, in shaping stimulus coding by V1 neurons. Our results provide new insights into how stimulus spatial correlations reorganize the correlated activation of specific ensembles of neurons to ensure accurate information processing in V1.
Consolidation of Complex Events via Reinstatement in Posterior Cingulate Cortex
Authors: Bird Chris M. , Keidel James L. , Ing Leslie P. , Horner Aidan J. , Burgess Neil 
Published: October 2015

It is well-established that active rehearsal increases the efficacy of memory consolidation. It is also known that complex events are interpreted with reference to prior knowledge. However, comparatively little attention has been given to the neural underpinnings of these effects. In healthy adults humans, we investigated the impact of effortful, active rehearsal on memory for events by showing people several short video clips and then asking them to recall these clips, either aloud (Experiment 1) or silently while in an MRI scanner (Experiment 2). In both experiments, actively rehearsed clips were remembered in far greater detail than unrehearsed clips when tested a week later. In Experiment 1, highly similar descriptions of events were produced across retrieval trials, suggesting a degree of semanticization of the memories had taken place. In Experiment 2, spatial patterns of BOLD signal in medial temporal and posterior midline regions were correlated when encoding and rehearsing the same video. Moreover, the strength of this correlation in the posterior cingulate predicted the amount of information subsequently recalled. This is likely to reflect a strengthening of the representation of the video's content. We argue that these representations combine both new episodic information and stored semantic knowledge (or “schemas”). We therefore suggest that posterior midline structures aid consolidation by reinstating and strengthening the associations between episodic details and more generic schematic information. This leads to the creation of coherent memory representations of lifelike, complex events that are resistant to forgetting, but somewhat inflexible and semantic-like in nature.SIGNIFICANCE STATEMENTMemories are strengthened via consolidation. We investigated memory for lifelike events using video clips and showed that rehearsing their content dramatically boosts memory consolidation. Using MRI scanning, we measured patterns of brain activity while watching the videos and showed that, in a network of brain regions, similar patterns of brain activity are reinstated when rehearsing the same videos. Within the posterior cingulate, the strength of reinstatement predicted how well the videos were remembered a week later. The findings extend our knowledge of the brain regions important for creating long-lasting memories for complex, lifelike events.
Expression of ESR1 in Glutamatergic and GABAergic Neurons Is Essential for Normal Puberty Onset, Estrogen Feedback, and Fertility in Female Mice
Authors: Cheong Rachel Y. , Czieselsky Katja , Porteous Robert , Herbison Allan E. 
Published: October 2015

Circulating estradiol exerts a profound influence on the activity of the gonadotropin-releasing hormone (GnRH) neuronal network controlling fertility. Using genetic strategies enabling neuron-specific deletion of estrogen receptor α (Esr1), we examine here whether estradiol-modulated GABA and glutamate transmission are critical for the functioning of the GnRH neuron network in the female mouse. UsingVgat- andVglut2-ires-Cre knock-in mice and ESR1 immunohistochemistry, we demonstrate that subpopulations of GABA and glutamate neurons throughout the limbic forebrain express ESR1, with ESR1-GABAergic neurons being more widespread and numerous than ESR1-glutamatergic neurons. We crossedVgat- andVglut2-ires-Cre mice with anEsr1lox/loxline to generate animals with GABA-neuron-specific or glutamate-neuron-specific deletion ofEsr1. Vgat-ires-Cre;Esr1lox/loxmice were infertile, with abnormal estrous cycles, and exhibited a complete failure of the estrogen positive feedback mechanism responsible for the preovulatory GnRH surge. However, puberty onset and estrogen negative feedback were normal.Vglut2-ires-Cre;Esr1lox/loxmice were also infertile but displayed a wider range of deficits, including advanced puberty onset, abnormal negative feedback, and abolished positive feedback. Whereas <25% of preoptic kisspeptin neurons expressed Cre inVgat- andVglut2-ires-Cre lines, ∼70% of arcuate kisspeptin neurons were targeted inVglut2-ires-Cre;Esr1lox/loxmice, possibly contributing to their advanced puberty phenotype. These observations show that, unexpectedly, ESR1-GABA neurons are only essential for the positive feedback mechanism. In contrast, we reveal the key importance of ESR1 in glutamatergic neurons for multiple estrogen feedback loops within the GnRH neuronal network required for fertility in the female mouse.SIGNIFICANCE STATEMENTCirculating estradiol acts upon the brain to regulate the functioning of many neuronal networks, including those controlling reproduction. Acting in classic homeostatic negative or positive feedback modes, estradiol variably suppresses or enhances the activity of the gonadotropin-releasing hormone (GnRH) neurons throughout the ovarian cycle. We show here that estrogen receptor α (ESR1) within glutamate (VGLUT2) neurons is essential for both the negative and positive estradiol feedback loops. In contrast, ESR1 in GABA neurons is only required for estradiol positive feedback. These studies emphasize the importance of estradiol-modulated amino-acidergic neurons within the GnRH neuronal network and highlight an unexpected prominent role for ESR1-expressing glutamate neurons in fertility control.
Attention Modulates TMS-Locked Alpha Oscillations in the Visual Cortex
Authors: Herring Jim D. , Thut Gregor , Jensen Ole , Bergmann Til O. 
Published: October 2015

Cortical oscillations, such as 8–12 Hz alpha-band activity, are thought to subserve gating of information processing in the human brain. While most of the supporting evidence is correlational, causal evidence comes from attempts to externally drive (“entrain”) these oscillations by transcranial magnetic stimulation (TMS). Indeed, the frequency profile of TMS-evoked potentials (TEPs) closely resembles that of oscillations spontaneously emerging in the same brain region. However, it is unclear whether TMS-locked and spontaneous oscillations are produced by the same neuronal mechanisms. If so, they should react in a similar manner to top-down modulation by endogenous attention. To test this prediction, we assessed the alpha-like EEG response to TMS of the visual cortex during periods of high and low visual attention while participants attended to either the visual or auditory modality in a cross-modal attention task. We observed a TMS-locked local oscillatory alpha response lasting several cycles after TMS (but not after sham stimulation). Importantly, TMS-locked alpha power was suppressed during deployment of visual relative to auditory attention, mirroring spontaneous alpha amplitudes. In addition, the early N40 TEP component, located at the stimulation site, was amplified by visual attention. The extent of attentional modulation for both TMS-locked alpha power and N40 amplitude did depend, with opposite sign, on the individual ability to modulate spontaneous alpha power at the stimulation site. We therefore argue that TMS-locked and spontaneous oscillations are of common neurophysiological origin, whereas the N40 TEP component may serve as an index of current cortical excitability at the time of stimulation.SIGNIFICANCE STATEMENTRhythmic transcranial magnetic stimulation (TMS) is a promising tool to experimentally “entrain” cortical activity. If TMS-locked oscillatory responses actually recruit the same neuronal mechanisms as spontaneous cortical oscillations, they qualify as a valid tool to study the causal role of neuronal oscillations in cognition but also to enable new treatments targeting aberrant oscillatory activity in, for example, neurological conditions. Here, we provide first-time evidence that TMS-locked and spontaneous oscillations are indeed tightly related and are likely to rely on the same neuronal generators. In addition, we demonstrate that an early local component of the TMS-evoked potential (the N40) may serve as a new objective and noninvasive probe of visual cortex excitability, which so far was only accessible via subjective phosphene reports.
Transcranial Stimulation over Frontopolar Cortex Elucidates the Choice Attributes and Neural Mechanisms Used to Resolve Exploration–Exploitation Trade-Offs
Authors: Raja Beharelle Anjali , Polanía Rafael , Hare Todd A. , Ruff Christian C. 
Published: October 2015

Optimal behavior requires striking a balance between exploiting tried-and-true options or exploring new possibilities. Neuroimaging studies have identified different brain regions in humans where neural activity is correlated with exploratory or exploitative behavior, but it is unclear whether this activity directly implements these choices or simply reflects a byproduct of the behavior. Moreover, it remains unknown whether arbitrating between exploration and exploitation can be influenced with exogenous methods, such as brain stimulation. In our study, we addressed these questions by selectively upregulating and downregulating neuronal excitability with anodal or cathodal transcranial direct current stimulation over right frontopolar cortex during a reward-learning task. This caused participants to make slower, more exploratory or faster, more exploitative decisions, respectively. Bayesian computational modeling revealed that stimulation affected how much participants took both expected and obtained rewards into account when choosing to exploit or explore: Cathodal stimulation resulted in an increased focus on the option expected to yield the highest payout, whereas anodal stimulation led to choices that were less influenced by anticipated payoff magnitudes and were more driven by recent negative reward prediction errors. These findings suggest that exploration is triggered by a neural mechanism that is sensitive to prior less-than-expected choice outcomes and thus pushes people to seek out alternative courses of action. Together, our findings establish a parsimonious neurobiological mechanism that causes exploration and exploitation, and they provide new insights into the choice features used by this mechanism to direct decision-making.SIGNIFICANCE STATEMENTWe often must choose whether to try something new (exploration) or stick with a proven strategy (exploitation). Balancing this trade-off is important for survival and growth across species because, without exploration, we would perseverate with the same strategies and never discover better options. Which brain mechanisms are responsible for our ability to make these decisions? We show that applying different types of noninvasive brain stimulation over frontopolar cortex causes participants to explore more or less in uncertain environments. These changes in exploration reflect how much participants focus on expected payoffs and on memory of recent disappointments. Thus, our results characterize a neural mechanism that systematically incorporates anticipated rewards and past experiences to trigger exploration of alternative courses of action.
A Lognormal Recurrent Network Model for Burst Generation during Hippocampal Sharp Waves
Authors: Omura Yoshiyuki , Carvalho Milena M. , Inokuchi Kaoru , Fukai Tomoki 
Published: October 2015

The strength of cortical synapses distributes lognormally, with a long tail of strong synapses. Various properties of neuronal activity, such as the average firing rates of neurons, the rate and magnitude of spike bursts, the magnitude of population synchrony, and the correlations between presynaptic and postsynaptic spikes, also obey lognormal-like distributions reported in the rodent hippocampal CA1 and CA3 areas. Theoretical models have demonstrated how such a firing rate distribution emerges from neural network dynamics. However, how the other properties also display lognormal patterns remain unknown. Because these features are likely to originate from neural dynamics in CA3, we model a recurrent neural network with the weights of recurrent excitatory connections distributed lognormally to explore the underlying mechanisms and their functional implications. Using multi-timescale adaptive threshold neurons, we construct a low-frequency spontaneous firing state of bursty neurons. This state well replicates the observed statistical properties of population synchrony in hippocampal pyramidal cells. Our results show that the lognormal distribution of synaptic weights consistently accounts for the observed long-tailed features of hippocampal activity. Furthermore, our model demonstrates that bursts spread over the lognormal network much more effectively than single spikes, implying an advantage of spike bursts in information transfer. This efficiency in burst propagation is not found in neural network models with Gaussian-weighted recurrent excitatory synapses. Our model proposes a potential network mechanism to generate sharp waves in CA3 and associated ripples in CA1 because bursts occur in CA3 pyramidal neurons most frequently during sharp waves.SIGNIFICANCE STATEMENTThe wiring structure of local cortical networks is known to be far from random. Here, we propose a recurrent neural network model with a long-tailed synaptic weight distribution to account for various properties of the synchronous firing of hippocampal neurons observed typically during sharp wave ripples. Furthermore, the model predicts that pathways of strong synapses route spike bursts much more efficiently than single spikes. Sharp wave ripples are crucial for memory encoding, but the underlying mechanism remains unknown. Our model suggests the crucial role of internal dynamics of nonrandom hippocampal circuits in generating and routing such activity patterns. Our results will have significant implications in understanding the mechanism of memory encoding by the hippocampus.
Evaluación de la estrategia de rehabilitación de base comunitaria (RBC) desde la perspectiva de la comunidad y los equipos locales de rehabilitación
Authors: Guajardo Alejandro , Recabarren-Hernández Eladio , Asún Salazar Domingo , Zamora-Astudillo Cristian , Cottet-Soto Pablo 
Published: October 2015

<p>A través de este proyecto de investigación se evalúo, desde la perspectiva de la comunidad y los equipos locales de rehabilitación en Chile, los distintos niveles de intervención de la RBC. Así, el objetivo que guío esta investigación fue evaluar el impacto social percibido y la aceptabilidad social de la estrategia de Rehabilitación de Base Comunitaria (RBC) desde la perspectiva de la comunidad y los equipos locales de rehabilitación.</p><p>El marco metodológico fue definido bajo los parámetros de una investigación cualitativa de carácter descriptivo y transversal. El universo de estudio correspondió a las comunas que contaban con programas de RBC que se desarrollan a nivel nacional como parte de la política nacional de discapacidad y rehabilitación en salud. Los criterios que guiaron el proceso de muestreo fueron los de pertinencia y suficiencia de la información, por lo que se optó por un muestreo estructural. El procesamiento de los datos se realizó mediante análisis de contenido semánticamente orientado, siguiendo una estratega intensiva, es decir, se analizó toda la información producida durante la fase de terreno.</p><p>Los resultados dan cuenta de la RBC como una estrategia con variadas formas de implementación y desarrollo que se relaciona con la historia local, el perfil de la comunidad, perfil del centro, perfil de usuarias/ios y las características de vinculación municipal con el programa de rehabilitación. El estudio identifica en la estrategia de RBC tres modelos de acción: biomédico, biopsicosocial y comunitario.</p>