10,209 results
Search Results
2. Interweaving Kids in Science--the Young Referees' Approach.
- Author
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Segev, Idan and Knight, Robert T.
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SCIENTIFIC knowledge ,SCIENTIFIC method ,BRAIN-computer interfaces ,PHENOMENOLOGICAL biology - Abstract
The article presents the discussion on sociological, economic, and ethical implications of these fast-paced science-driven changes. Topics include breakthroughs in machine learning, gene editing, brain–machine interface, brain organoids, and artificial wombs; and innovative scientific solutions have also surfaced in recent years such as climate change and aging.
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- 2023
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3. End of a [Paper] Era.
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Picciotto, Marina R.
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CHRONOLOGY , *READING , *NEUROSCIENTISTS - Abstract
An introduction is presented in which the editor discusses articles in the issue on topics including JNeurosci, Neuroscience, and eNeuro.
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- 2020
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4. Erratum: Seigneur and Südhof, "Genetic Ablation of All Cerebellins Reveals Synapse Organizer Functions in Multiple Regions throughout the Brain".
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SYNAPSES ,CONTROL boards (Electrical engineering) - Abstract
A correction is presented to the article errors in Figures 2 and 3 of the research paper "Genetic Ablation of All Cerebellins Reveals Synapse Organizer Functions in Multiple Regions throughout the Brain," correcting duplications across panels and providing clarifications.
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- 2024
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5. Transient Attention Gates Access Consciousness: Coupling N2pc and P3 Latencies Using Dynamic Time Warping.
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Hosseini, Mahan, Zivony, Alon, Eimer, Martin, Wyble, Brad, and Bowman, Howard
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CONSCIOUSNESS ,TIME management ,PYTHON programming language ,SELECTIVITY (Psychology) ,SHORT-term memory - Abstract
The N2pc and P3 event-related potentials (ERPs), used to index selective attention and access to working memory and conscious awareness, respectively, have been important tools in cognitive sciences. Although it is likely that these two components and the underlying cognitive processes are temporally and functionally linked, such links have not yet been convincingly demonstrated. Adopting a novel methodological approach based on dynamic time warping (DTW), we provide evidence that the N2pc and P3 ERP components are temporally linked. We analyzed data from an experiment where 23 participants (16 women) monitored bilateral rapid serial streams of letters and digits in order to report a target digit indicated by a shape cue, separately for trials with correct responses and trials where a temporally proximal distractor was reported instead (distractor intrusion). DTW analyses revealed that N2pc and P3 latencies were correlated in time, both when the target or a distractor was reported. Notably, this link was weaker on distractor intrusion trials. This N2pc–P3 association is discussed with respect to the relationship between attention and access consciousness. Our results demonstrate that our novel method provides a valuable approach for assessing temporal links between two cognitive processes and their underlying modulating factors. This method allows to establish links and their modulator for any two time-series across all domains of the field (general-purpose MATLAB functions and a Python module are provided alongside this paper). [ABSTRACT FROM AUTHOR]
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- 2024
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6. Erratum: Nora et al., "Impaired Cortical Tracking of Speech in Children with Developmental Language Disorder".
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LANGUAGE disorders ,CHILDREN'S language ,SPEECH ,CHILDREN with developmental disabilities - Abstract
A correction to the article "Impaired Cortical Tracking of Speech in Children with Developmental Language Disorder" in the May 29, 2024 issue is presented, which discusses the revised author contributions, clarifying that R.S. designed the research, A.N. wrote the first draft.
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- 2024
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7. Erratum: Montandon and Horner, “State-Dependent Contribution of the Hyperpolarization-Activated Na+ /K+ and Persistent Na+ Currents to Respiratory Rhythmogenesis In Vivo”.
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NEUROSCIENCES ,COLOR - Abstract
This document is an erratum for an article titled "State-Dependent Contribution of the Hyperpolarization-Activated Na+/K+ and Persistent Na+ Currents to Respiratory Rhythmogenesis In Vivo" by Gaspard Montandon and Richard L. Horner. The erratum states that there was an error in Figure 8 of the article, where incorrect images were inserted. The corrected Figure 8 is provided in the erratum. It is noted that this error does not impact the conclusions of the paper. [Extracted from the article]
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- 2024
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8. The Journal of Neuroscience's 40th Anniversary: Looking Back, Looking Forward.
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Carew, Thomas J.
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CLASSICAL conditioning ,NEUROSCIENCES ,NOBEL Prizes ,ANNIVERSARIES - Abstract
Some of us fortunate enough to have published a paper in The Journal of Neuroscience in its inaugural year (1981) have been asked to write a Progressions article addressing our views on the significance of the original work and how ideas about the topic of that work have evolved over the last 40 years. These questions cannot be effectively considered without placing them in the context of the incredible growth of the overall field of neuroscience over these last four decades. For openers, in 1981, the Nobel Prize was awarded to three neuroscience superstars: Roger Sperry, David Hubel, and Torsten Wiesel. Not a bad year to launch the Journal. With this as a backdrop, I divide this Progressions article into two parts. First, I discuss our original (1981) paper describing classical conditioning in Aplysia californica, and place our results in the context of the state of the field at the time. Second, I fast forward to the present and consider some of remarkable progress in the broad field of learning and memory that has occurred in the last 40 years. Along the way, I also reflect briefly on some of the amazing advances, both technical and conceptual, that we in neuroscience have witnessed. [ABSTRACT FROM AUTHOR]
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- 2021
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9. Mapping the Hypocretin/Orexin Neuronal System: An Unexpectedly Productive Journey.
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Peyron, Christelle and Kilduff, Thomas S.
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OREXINS ,NEURAL stem cells ,NEUROPEPTIDES ,NEUROSCIENCES ,NEUROANATOMY - Abstract
Early in 1998, we (de Lecea et al., 1998) and others (Sakurai et al., 1998) described the same hypothalamic neuropeptides, respectively called the hypocretins or orexins, which were discovered using two different approaches. In December of that year, we published the subject of this commentary in the Journal of Neuroscience: a highly detailed anatomical description of the extensive axonal projections of the hypocretin/orexin neurons. Although the function of this system was unknown at the time, a large body of literature today attests that the hypocretin/orexin neuropeptides play important roles in multiple physiological functions, particularly in sleep/wake regulation. Neuroanatomical studies are rarely frontline news, but the citation rate of this paper underscores the critical nature of such basic research. Based in part on this detailed description, the hypocretin/orexin neuropeptides have since been studied in many different areas of neuroscience research, including sleep/wake regulation, feeding, addiction, reward and motivation, anxiety and depression, cardiovascular regulation, pain, migraine, and neuroendocrine regulation, including reproduction. Thus, this paper has had a surprisingly broad impact on neuroscience research, particularly since it was originally rejected by the Journal! [ABSTRACT FROM AUTHOR]
- Published
- 2017
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10. The Life of a Trailing Spouse.
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Lemmon, Vance P.
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CELL adhesion molecules ,VISUAL cortex ,SPOUSES ,NEUROSCIENCES ,AXONS - Abstract
In 1981, I published a paper in the first issue of the Journal of Neuroscience with my postdoctoral mentor, Alan Pearlman. It reported a quantitative analysis of the receptive field properties of neurons in reeler mouse visual cortex and the surprising conclusion that although the neuronal somas were strikingly malpositioned, their receptive fields were unchanged. This suggested that in mouse cortex at least, neuronal circuits have very robust systems in place to ensure the proper formation of connections. This had the unintended consequence of transforming me from an electrophysiologist into a cellular and molecular neuroscientist who studied cell adhesion molecules and the molecular mechanisms they use to regulate axon growth. It took me a surprisingly long time to appreciate that your science is driven by the people around you and by the technologies that are locally available. As a professional puzzler, I like all different kinds of puzzles, but the most fun puzzles involve playing with other puzzlers. This is my story of learning how to find like-minded puzzlers to solve riddles about axon growth and regeneration. [ABSTRACT FROM AUTHOR]
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- 2021
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11. In Vivo Multi-Day Calcium Imaging of CA1 Hippocampus in Freely Moving Rats Reveals a High Preponderance of Place Cells with Consistent Place Fields.
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Wirtshafter, Hannah S. and Disterhoft, John F.
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CALCIUM ,HIPPOCAMPUS (Brain) ,RATS ,CELL imaging ,IMAGING systems in biology ,NEURAL codes - Abstract
Calcium imaging using GCaMP indicators and miniature microscopes has been used to image cellular populations during long timescales and in different task phases, as well as to determine neuronal circuit topology and organization. Because the hippocampus (HPC) is essential for tasks of memory, spatial navigation, and learning, calcium imaging of large populations of HPC neurons can provide new insight on cell changes over time during these tasks. All reported HPC in vivo calcium imaging experiments have been done in mouse. However, rats have many behavioral and physiological experimental advantages over mice. In this paper, we present the first (to our knowledge) in vivo calcium imaging from CA1 HPC in freely moving male rats. Using the UCLA Miniscope, we demonstrate that, in rat, hundreds of cells can be visualized and held across weeks. We show that calcium events in these cells are highly correlated with periods of movement, with few calcium events occurring during periods without movement. We additionally show that an extremely large percent of cells recorded during a navigational task are place cells (77.3 6 5.0%, surpassing the percent seen during mouse calcium imaging), and that these cells enable accurate decoding of animal position and can be held over days with consistent place fields in a consistent spatial map. A detailed protocol is included, and implications of these advancements on in vivo imaging and place field literature are discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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12. Erratum: Burré et al., "Definition of a Molecular Pathway Mediating α-Synuclein Neurotoxicity".
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ALPHA-synuclein ,NEUROTOXICOLOGY ,DEFINITIONS ,NEUROSCIENCES - Abstract
A correction is presented to the article errors found in Figure 5A of the research paper "Definition of a Molecular Pathway Mediating α-Synuclein Neurotoxicity," clarifying the duplication of panels in mutant groups and providing the corrected version of the figure.
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- 2024
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13. A Computational Model of Direction Selectivity in Macaque V1 Cortex Based on Dynamic Differences between On and Off Pathways.
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Chariker, Logan, Shapley, Robert, Hawken, Michael, and Lai-Sang Young
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LATERAL geniculate body ,MACAQUES ,VISUAL cortex ,CELL populations - Abstract
This paper is about neural mechanisms of direction selectivity (DS) in macaque primary visual cortex, V1. We present data (on male macaque) showing strong DS in a majority of simple cells in V1 layer 4Cα, the cortical layer that receives direct afferent input from the magnocellular division of the lateral geniculate nucleus (LGN). Magnocellular LGN cells are not direction-selective. To understand the mechanisms of DS, we built a large-scale, recurrent model of spiking neurons called DSV1. Like its predecessors, DSV1 reproduces many visual response properties of V1 cells including orientation selectivity. Two important new features of DSV1 are (1) DS is initiated by small, consistent dynamic differences in the visual responses of OFF and ON Magnocellular LGN cells, and (2) DS in the responses of most model simple cells is increased over those of their feedforward inputs; this increase is achieved through dynamic interaction of feedforward and intracortical synaptic currents without the use of intracortical direction-specific connections. The DSV1 model emulates experimental data in the following ways: (1) most 4Cα Simple cells were highly direction-selective but 4Cα Complex cells were not; (2) the preferred directions of the model's direction-selective Simple cells were invariant with spatial and temporal frequency (TF); (3) the distribution of the preferred/opposite ratio across the model's population of cells was very close to that found in experiments. The strong quantitative agreement between DS in data and in model simulations suggests that the neural mechanisms of DS in DSV1 may be similar to those in the real visual cortex. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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14. Sex-Dependent Synaptic Alterations in a Mouse Model of Alzheimer’s Disease.
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Dugan, Brittany J. and Dockery, Myles
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NEURAL circuitry ,ALZHEIMER'S disease ,CYTOLOGY ,TAU proteins ,HIPPOCAMPUS (Brain) ,ENTORHINAL cortex ,WAKEFULNESS - Abstract
A recent study published in the Journal of Neuroscience examined sex-dependent synaptic alterations in a mouse model of Alzheimer's disease (AD). The study found that female mice exhibited increased amyloid burden and fewer presynaptic connections to the subiculum, a region of the brain involved in memory formation. These findings suggest that reduced input to the subiculum may be an underlying mechanism in memory impairment that worsens throughout the progression of AD. The study also highlighted the importance of investigating sex differences in AD research and the potential impact of synaptic alterations on sleep disturbances in women with AD. [Extracted from the article]
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- 2024
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15. Brain State-Dependent Modulation of Thalamic Visual Processing by Cortico-Thalamic Feedback.
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Reinhold, Kimberly, Resulaj, Arbora, and Scanziani, Massimo
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VISUAL perception ,VISUAL cortex ,THALAMUS - Abstract
The behavioral state of a mammal impacts how the brain responds to visual stimuli as early as in the dorsolateral geniculate nucleus of the thalamus (dLGN), the primary relay of visual information to the cortex. A clear example of this is the markedly stronger response of dLGN neurons to higher temporal frequencies of the visual stimulus in alert as compared with quiescent animals. The dLGN receives strong feedback from the visual cortex, yet whether this feedback contributes to these state-dependent responses to visual stimuli is poorly understood. Here, we show that in male and female mice, silencing cortico- thalamic feedback profoundly reduces state-dependent differences in the response of dLGN neurons to visual stimuli. This holds true for dLGN responses to both temporal and spatial features of the visual stimulus. These results reveal that the state-dependent shift of the response to visual stimuli in an early stage of visual processing depends on cortico-thalamic feedback. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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16. Neuroscience Research and Mentoring in Puerto Rico: What Succeeds in This Environment?
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Quirk, Gregory J.
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Twenty years ago, I arrived in Puerto Rico from New York City to establish a neuroscience laboratory and research program on extinction of conditioned fear. The lab's first research paper appeared in the Journal of Neuroscience (Quirk et al., 2000) and has been cited >900 times. The success of this project in Puerto Rico far surpassed my original expectations. Therefore, I thought it might be useful to identify the factors responsible for this success, with the hope of facilitating the development of laboratories in diverse settings. A description of our lab practices is interspersed with personal statements from trainees hailing from Puerto Rico and other parts of Latin America. Creating an effective research and training environment depends less on the director's personality and more on the proper practice of activities that foster intellectual growth, such as journal clubs, lab meetings, and philosophy of science retreats. On a personal level, this project has been enormously gratifying. The unique environment in Puerto Rico fostered my best work, and I am very happy to have established my laboratory here. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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17. On the Road from Phenotypic Plasticity to Stem Cell Therapy.
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Iacovitti, Lorraine
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PHENOTYPIC plasticity ,STEM cell treatment ,NEURAL crest ,PHENOTYPES ,TISSUE culture - Abstract
In 1981, I published a paper in the first issue of The Journal of Neuroscience with my postdoctoral mentor, Richard Bunge. At that time, the long-standing belief that each neuron expressed only one neurotransmitter, known as Dale's Principle (Dale, 1935), was being hotly debated following a report by French embryologist Nicole Le Douarin showing that neural crest cells destined for one transmitter phenotype could express characteristics of another if transplanted to alternate sites in the developing embryo (Le Douarin, 1980). In the Bunge laboratory, we were able to more directly test the question of phenotypic plasticity in the controlled environment of the tissue culture dish. Thus, in our paper, we grew autonomic catecholaminergic neurons in culture under conditions which promoted the acquisition of cholinergic traits and showed that cells did not abandon their inherited phenotype to adopt a new one but instead were capable of dual transmitter expression. In this Progressions article, I detail the path that led to these findings and how this study impacted the direction I followed for the next 40 years. This is my journey from phenotypic plasticity to the promise of a stem cell therapy. [ABSTRACT FROM AUTHOR]
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- 2021
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18. Neural Contributions to Reduced Fluid Intelligence across the Adult Lifespan.
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Mitchell, Daniel J., Mousley, Alexa L. S., Shafto, Meredith A., and Duncan, John
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FLUID intelligence ,LARGE-scale brain networks ,ADULTS ,PHYSICAL activity ,FUNCTIONAL magnetic resonance imaging - Abstract
Fluid intelligence, the ability to solve novel, complex problems, declines steeply during healthy human aging. Using fMRI, fluid intelligence has been repeatedly associated with activation of a frontoparietal brain network, and impairment following focal damage to these regions suggests that fluid intelligence depends on their integrity. It is therefore possible that age-related functional differences in frontoparietal activity contribute to the reduction in fluid intelligence. This paper reports on analysis of the Cambridge Center for Ageing and Neuroscience data, a large, population-based cohort of healthy males and females across the adult lifespan. The data support a model in which age-related differences in fluid intelligence are partially mediated by the responsiveness of frontoparietal regions to novel problem-solving. We first replicate a prior finding of such mediation using an independent sample. We then precisely localize the mediating brain regions, and show that mediation is specifically associated with voxels most activated by cognitive demand, but not with voxels suppressed by cognitive demand. We quantify the robustness of this result to potential unmodeled confounders, and estimate the causal direction of the effects. Finally, exploratory analyses suggest that neural mediation of age-related differences in fluid intelligence is moderated by the variety of regular physical activities, more reliably than by their frequency or duration. An additional moderating role of the variety of nonphysical activities emerged when controlling for head motion. A better understanding of the mechanisms that link healthy aging with lower fluid intelligence may suggest strategies for mitigating such decline. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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19. Corticotropin Releasing Factor (CRF) Coexpression in GABAergic, Glutamatergic, and GABA/Glutamatergic Subpopulations in the Central Extended Amygdala and Ventral Pallidum of Young Male Primates.
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Fudge, Julie L., Kelly, Emily A., and Hackett, Troy A.
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CORTICOTROPIN releasing hormone ,AMYGDALOID body ,GLOBUS pallidus ,GABA transporters ,GLUTAMATE transporters ,MONOAMINE transporters ,METHYL aspartate receptors - Abstract
The central extended amygdala (CEA) and ventral pallidum (VP) are involved in diverse motivated behaviors based on rodent models. These structures are conserved, but expanded, in higher primates, including human. Corticotropin releasing factor (CRF), a canonical "stress molecule" associated with the CEA and VP circuitry across species, is dynamically regulated by stress and drugs of abuse and misuse. CRF's effects on circuits critically depend on its colocation with primary "fast" transmitters, making this crucial for understanding circuit effects. We surveyed the distribution and colocalization of CRF-, VGluT2- (vesicular glutamate transporter 2), and VGAT- (vesicular GABA transporter) mRNA in specific subregions of the CEA and VP in young male monkeys. Although CRF-containing neurons were clustered in the lateral central bed nucleus (BSTLcn), the majority were broadly dispersed throughout other CEA subregions, and the VP. CRF/VGAT-only neurons were highest in the BSTLcn, lateral central amygdala nucleus (CeLcn), and medial central amygdala nucleus (CeM) (74%, 73%, and 85%, respectively). In contrast, lower percentages of CRF/VGAT only neurons populated the sublenticular extended amygdala (SLEAc), ventrolateral bed nucleus (BSTLP), and VP (53%, 54%, 17%, respectively), which had higher complements of CRF/VGAT/VGluT2-labeled neurons (33%, 29%, 67%, respectively). Thus, the majority of CRF-neurons at the "poles" (BSTLcn and CeLcn/CeM) of the CEA are inhibitory, while the "extended" BSTLP and SLEAc subregions, and neighboring VP, have a more complex profile with admixtures of "multiplexed" excitatory CRF neurons. CRF's colocalization with its various fast transmitters is likely circuit-specific, and relevant for understanding CRF actions on specific target sites. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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20. The Theta Paradox: 4-8 Hz EEG Oscillations Reflect Both Sleep Pressure and Cognitive Control.
- Author
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Snipes, Sophia, Krugliakova, Elena, Meier, Elias, and Huber, Reto
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CONTROL (Psychology) ,COGNITIVE ability ,PRESSURE control ,SLEEP deprivation ,MOTOR cortex ,SLEEP hygiene ,SLEEP - Abstract
Human electroencephalographic (EEG) oscillations characterize specific behavioral and vigilance states. The frequency of these oscillations is typically sufficient to distinguish a given state; however, theta oscillations (4-8 Hz) have instead been found in near-opposite conditions of drowsiness during sleep deprivation and alert cognitive control. While the latter has been extensively studied and is often referred to as "frontal midline theta," (fmTheta) the former has been investigated far less but is considered a marker for sleep pressure during wake. In this study we investigated to what extent theta oscillations differed during cognitive tasks and sleep deprivation. We measured high-density EEG in 18 young healthy adults (nine female) performing six tasks under three levels of sleep deprivation. We found both cognitive load and sleep deprivation increased theta power in medial prefrontal cortical areas; however, sleep deprivation caused additional increases in theta in many other, predominantly frontal, areas. The sources of sleep deprivation theta (sdTheta) were task dependent, with a visual-spatial task and short-term memory (STM) task showing the most widespread effects. Notably, theta was highest in supplementary motor areas during passive music listening, and highest in the inferior temporal cortex (responsible for object recognition) during a spatial game. Furthermore, while changes in task performance were correlated with increases in theta during sleep deprivation, this relationship was not specific to the EEG of the same task and did not survive correction for multiple comparisons. Altogether, these results suggest that both during sleep deprivation and cognition theta oscillations may preferentially occur in cortical areas not involved in ongoing behavior. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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21. Erratum.
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MACAQUES ,CEREBELLUM - Abstract
The article presents the discussion on correction notice "Closed-Loop Optogenetic Perturbation of Macaque Oculomotor Cerebellum: Evidence for an Internal Saccade Model" published in the February 7, 2024 issue.
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- 2024
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22. The Development of Neuronal Polarity: A Retrospective View.
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Banker, Gary
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NEURONS ,CELL polarity ,HIPPOCAMPUS (Brain) ,AXONS ,DENDRITES - Abstract
In 1988, Carlos Dotti, Chris Sullivan, and I published a paper on the establishment of polarity by hippocampal neurons in culture, which continues to be frequently cited 30 years later (Dotti et al., 1988). By following individual neurons from the time of plating until they had formed well developed axonal and dendritic arbors, we identified the five stages of development that lead to the mature expression of neuronal polarity. We were surprised to find that, before axon formation, the cells pass through a multipolar phase, in which several, apparently identical short neurites undergo periods of extension and retraction. Then one of these neurites begins a period of prolonged growth, becoming the definitive axon; the remaining neurites subsequently become dendrites. This observation suggested that any of the initial neurites were capable of becoming axons, a hypothesis confirmed by later work. In this Progressions article, I will try to recall the circumstances that led to this work, recapture some of the challenges we faced in conducting these experiments, and consider why some of today's neuroscientists still find this paper relevant. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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23. Differential Alterations in Striatal Direct and Indirect Pathways Mediate Two Autism-like Behaviors in Valproate-Exposed Mice.
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Yuanyuan Di, Zhijun Diao, Qi Zheng, Jin Li, Qiangqiang Cheng, Zhongqi Li, Suwen Fang, Hao Wang, Chunling Wei, Qiaohua Zheng, Yingxun Liu, Jing Han, Zhiqiang Liu, Juan Fan, Wei Ren, and Yingfang Tian
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MICE ,VALPROIC acid ,AUTISM - Abstract
Autism is characterized by two key diagnostic criteria including social deficits and repetitive behaviors. Although recent studies implicated ventral striatum in social deficits and dorsal striatum in repetitive behaviors, here we revealed coexisting and opposite morphologic and functional alterations in the dorsostriatal direct and indirect pathways, and such alterations in these two pathways were found to be responsible, respectively, for the two abovementioned different autism-like behaviors exhibited by male mice prenatally exposed to valproate. The alteration in direct pathway was characterized by a potentiated state of basal activity, with impairment in transient responsiveness of D1-MSNs during social exploration. Concurrent alteration in indirect pathway was a depressed state of basal activity, with enhancement in transient responsiveness of D2-MSNs during repetitive behaviors. A causal relationship linking such differential alterations in these two pathways to the coexistence of these two autism-like behaviors was demonstrated by the cell type-specific correction of abnormal basal activity in the D1-MSNs and D2-MSNs of valproate-exposed mice. The findings support those differential alterations in two striatal pathways mediate the two coexisting autism-like behavioral abnormalities, respectively. This result will help in developing therapeutic options targeting these circuit alterations. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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24. Erratum: Nomi et al., "Moment-to-Moment BOLD Signal Variability Reflects Regional Changes in Neural Flexibility across the Lifespan".
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NEUROPLASTICITY ,TIME series analysis - Abstract
A correction to the article "Moment-to-Moment BOLD Signal Variability Reflects Regional Changes in Neural Flexibility across the Lifespan" that was published in the The Journal of Neuroscience, February 26,2020 issue is presented.
- Published
- 2020
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25. The p75NTR Influences Cerebellar Circuit Development and Adult Behavior via Regulation of Cell Cycle Duration of Granule Cell Progenitors.
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Zanin, Juan P., Verpeut, Jessica L., Ying Li, Shiflett, Michael W., Wang, Samuel S.-H., Santhakumar, Viji, and Friedman, Wilma J.
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CELL cycle regulation ,GRANULE cells ,PROGENITOR cells ,ADULT development ,NEUROTROPHIN receptors - Abstract
Development of brain circuitry requires precise regulation and timing of proliferation and differentiation of neural progenitor cells. The p75 neurotrophin receptor (p75NTR) is highly expressed in the proliferating granule cell precursors (GCPs) during development of the cerebellum. In a previous paper, we showed that proNT3 promoted GCP cell cycle exit via p75NTR. Here we used genetically modified rats and mice of both sexes to show that p75NTR regulates the duration of the GCP cell cycle, requiring activation of RhoA. Rats and mice lacking p75NTR have dysregulated GCP proliferation, with deleterious effects on cerebellar circuit development and behavioral consequences persisting into adulthood. In the absence of p75NTR, the GCP cell cycle is accelerated, leading to delayed cell cycle exit, prolonged GCP proliferation, increased glutamatergic input to Purkinje cells, and a deficit in delay eyeblink conditioning, a cerebellum-dependent form of learning. These results demonstrate the necessity of appropriate developmental timing of the cell cycle for establishment of proper connectivity and associated behavior. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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26. Biophysical and Architectural Mechanisms of Subthalamic Theta under Response Conflict.
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Moolchand, Prannath, Jones, Stephanie R., and Frank, Michael J.
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SUBTHALAMIC nucleus ,CONTROL (Psychology) ,CONDITIONED response ,FRONTAL lobe ,COMPULSIVE behavior - Abstract
The cortico-basal ganglia circuit is needed to suppress prepotent actions and to facilitate controlled behavior. Under conditions of response conflict, the frontal cortex and subthalamic nucleus (STN) exhibit increased spiking and theta band power, which are linked to adaptive regulation of behavioral output. The electrophysiological mechanisms underlying these neural signatures of impulse control remain poorly understood. To address this lacuna, we constructed a novel large-scale, biophysically principled model of the subthalamopallidal (STN-globus pallidus externus) network and examined the mechanisms that modulate theta power and spiking in response to cortical input. Simulations confirmed that theta power does not emerge from intrinsic network dynamics but is robustly elicited in response to cortical input as burst events representing action selection dynamics. Rhythmic burst events of multiple cortical populations, representing a state of conflict where cortical motor plans vacillate in the theta range, led to prolonged STN theta and increased spiking, consistent with empirical literature. Notably, theta band signaling required NMDA, but not AMPA, currents, which were in turn related to a triphasic STN response characterized by spiking, silence, and bursting periods. Finally, theta band resonance was also strongly modulated by architectural connectivity, with maximal theta arising when multiple cortical populations project to individual STN “conflict detector” units because of an NMDA-dependent supralinear response. Our results provide insights into the biophysical principles and architectural constraints that give rise to STN dynamics during response conflict, and how their disruption can lead to impulsivity and compulsivity. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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27. ASD/OCD-Linked Protocadherin-10 Regulates Synapse, But Not Axon, Development in the Amygdala and Contributes to Fear- and Anxiety-Related Behaviors.
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Naosuke Hoshina, Johnson-Venkatesh, Erin M., Rally, Veronica R., Sant, Jaanvi, Hoshina, Miyuki, Seiglie, Mariel P., and Umemori, Hisashi
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CELL adhesion molecules ,AMYGDALOID body ,SYNAPSES ,AUTISM spectrum disorders ,OBSESSIVE-compulsive disorder ,FEAR ,IMMOBILIZATION stress - Abstract
The Protocadherin-10 (PCDH10) gene is associated with autism spectrum disorder (ASD), obsessive-compulsive disorder (OCD), and major depression (MD). The PCDH10 protein is a homophilic cell adhesion molecule that belongs to the d2-protocadherin family. PCDH10 is highly expressed in the developing brain, especially in the basolateral nucleus of the amygdala (BLA). However, the role of PCDH10 in vivo has been debatable: one paper reported that a Pcdh10 mutant mouse line showed changes in axonal projections; however, another Pcdh10 mutant mouse line was reported to have failed to detect axonal phenotypes. Therefore, the actual roles of PCDH10 in the brain remain to be elucidated. We established a new Pcdh10 KO mouse line using the CRISPR/Cas9 system, without inserting gene cassettes to avoid nonspecific effects, examined the roles of PCDH10 in the brain, and studied the behavioral consequences of Pcdh10 inactivation. Here, we show that Pcdh10 KO mice do not show defects in axonal development. Instead, we find that Pcdh10 KO mice exhibit impaired development of excitatory synapses in the dorsal BLA. We further demonstrate that male Pcdh10 KO mice exhibit reduced anxiety-related behaviors, impaired fear conditioning, decreased stress-coping responses, and mildly impaired social recognition and communication. These results indicate that PCDH10 plays a critical role in excitatory synapse development, but not axon development, in the dorsal BLA and that PCDH10 regulates anxiety-related, fear-related, and stress-related behaviors. Our results reveal the roles of PCDH10 in the brain and its relationship to relevant psychiatric disorders such as ASD, OCD, and MD. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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28. The Nogo-66 Receptors NgR1 and NgR3 Are Required for Commissural Axon Pathfinding.
- Author
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Vaccaro, Giuseppe, Dumoulin, Alexandre, Zuñiga, Nikole R., Bandtlow, Christine E., and Stoeckli, Esther T.
- Abstract
Nogo-66 receptors (NgR1-3) are glycosylphosphatidyl inositol-linked proteins that belong to the leucine-rich repeat superfamily. Through binding to myelin-associated inhibitors, NgRs contribute to the inhibition of axonal regeneration after spinal cord injury. Their role in limiting synaptic plasticity and axonal outgrowth in the adult CNS has been described previously, but not much is known about their role during the development of the nervous system. Here, we show that NgR1 and NgR3 mRNAs are expressed during spinal cord development of the chicken embryo. In particular, they are expressed in the dI1 subpopulation of commissural neurons during the time when their axons navigate toward and across the floorplate, the ventral midline of the spinal cord. To assess a potential role of NgR1 and NgR3 in axon guidance, we downregulated them using in ovo RNAi and analyzed the trajectory of commissural axons by tracing them in open-book preparations of spinal cords. Our results show that loss of either NgR1 or NgR3 causes axons to stall in the midline area and to interfere with the rostral turn of postcrossing axons. In addition, we also show that NgR1, but not NgR3, requires neuronal PlexinA2 for the regulation of commissural axon guidance. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
29. The Quest for the FFA and Where It Led.
- Author
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Kanwisher, Nancy
- Subjects
FUSIFORM gyrus ,CEREBRAL cortex ,FUNCTIONAL magnetic resonance imaging ,POSITRON emission tomography ,BRAIN function localization - Abstract
This article tells the story behind our first paper on the fusiform face area (FFA): how we chose the question, developed the methods, and followed the data to find the FFA and subsequently many other functionally specialized cortical regions. The paper's impact had less to do with the particular findings in the paper itself and more to do with the method that it promoted and the picture of the human mind and brain that it led to. The use of a functional localizer to define a candidate region in each subject individually enabled us not just to make pictures of brain activation, but also to ask principled, hypothesis-driven questions about a thing in nature. This method enabled stronger and more extensive tests of the function of each cortical region than had been possible before in humans and, as a result, has produced a large body of evidence that the human cortex contains numerous regions that are specifically engaged in particular mental processes. The growing inventory of cortical regions with distinctive and often very specific functions can be seen as an initial sketch of the basic components of the human mind. This sketch also serves as a roadmap into the vast and exciting new landscape of questions about the computations, structural connections, time course, development, plasticity, and evolution of each of these regions, as well as the hardest question of all: how do these regions work together to produce human intelligence? [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
30. A Critical Period for Development of Cerebellar-Mediated Autism-Relevant Social Behavior.
- Author
-
Gibson, Jennifer M., Howland, Cleone P., Chongyu Ren, Howland, Cyrena, Vernino, Alexandra, and Tsai, Peter T.
- Subjects
TUBEROUS sclerosis ,AUTISM spectrum disorders ,RAPAMYCIN ,MALE models ,LABORATORY mice ,CEREBELLUM - Abstract
The cerebellum has been increasingly implicated in autism spectrum disorder (ASD) with many ASD-linked genes impacting both cerebellar function and development. However, the precise timing and critical periods of when abnormal cerebellar neurodevelopment contributes to ASD-relevant behaviors remains poorly understood. In this study, we identify a critical period for the development of ASD-relevant behaviors in a cerebellar male mouse model of tuberous sclerosis complex (TSC), by using the mechanistic target of rapamycin (mTOR) inhibitor, rapamycin, to pharmacologically inhibit dysregulated downstream signaling. We find independent critical periods during which abnormal ASD-relevant behaviors develop for the two core ASD diagnostic criteria, social impairments and behavioral flexibility, and delineate an anatomic, physiological, and behavioral framework. These findings not only further our understanding of the genetic mechanisms underlying the timing of ASD-relevant behaviors but also have the capacity to inform potential therapies to optimize treatment interventions. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
31. Cortical Granularity Shapes the Organization of Afferent Paths to the Amygdala and Its Striatal Targets in Nonhuman Primate.
- Author
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McHale, A. C., Cho, Y. T., and Fudge, J. L.
- Subjects
AMYGDALOID body ,BASAL ganglia ,AFFERENT pathways ,PREFRONTAL cortex ,PRIMATES - Abstract
The prefrontal cortex (PFC) and insula, amygdala, and striatum form interconnected networks that drive motivated behaviors. We previously found a connectional trend in which granularity of the ventromedial and orbital PFC/insula predicted connections to the amygdala, and also the breadth of amygdalo-striatal efferents, including projections beyond the “classic” ventral striatum. To further interrogate connectional relationships among the cortex, amygdala, and striatum, and to further define the “limbic” (amygdala-recipient) striatum, we conducted tract tracing studies in two cohorts of macaques (male n = 14, female n = 1). We focused on the cortico-amygdalo-striatal (indirect) and cortico-“limbic” striatal (direct) paths originating in the entire PFC and insula. Larger datasets and a quantitative approach revealed “cortical rules” in which cortical granularity predicts the complexity and location of projections to both the basal nucleus of the amygdala and striatum. Remarkably, projections from “cortical-like” basal nucleus to the striatum followed similar patterns. In both “direct” and “indirect” paths to the “limbic” striatum, agranular cortices formed a “foundational,” broad projection, and were joined by inputs from progressively more differentiated cortices. In amygdalo-striatal paths, the ventral basal nucleus was the “foundational” input, with progressively more dorsal basal nucleus regions gradually adding inputs as the “limbic” striatum extended caudally. Together, the “indirect” and “direct” paths followed consistent principles in which cortical granularity dictated the strength and complexity of projections at their targets. Cluster analyses independently confirmed these connectional trends, and also highlighted connectional features that predicted termination in specific subregions of the basal nucleus and “limbic” striatum. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
32. Dynamic Causal Modelling of Active Vision.
- Author
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Parr, Thomas, Mirza, M. Berk, Cagnan, Hayriye, and Friston, Karl J.
- Subjects
CAUSAL models ,DYNAMIC models ,MOVEMENT sequences ,VISION ,EYE movements - Abstract
In this paper, we draw from recent theoretical work on active perception, which suggests that the brain makes use of an internal (i.e., generative) model to make inferences about the causes of sensations. This view treats visual sensations as consequent on action (i.e., saccades) and implies that visual percepts must be actively constructed via a sequence of eye movements. Oculomotor control calls on a distributed set of brain sources that includes the dorsal and ventral frontoparietal (attention) networks. We argue that connections from the frontal eye fields to ventral parietal sources represent the mapping from "where", fixation location to information derived from "what" representations in the ventral visual stream. During scene construction, this mapping must be learned, putatively through changes in the effective connectivity of these synapses. Here, we test the hypothesis that the coupling between the dorsal frontal cortex and the right temporoparietal cortex is modulated during saccadic interrogation of a simple visual scene. Using dynamic causal modeling for magnetoencephalography with (male and female) human participants, we assess the evidence for changes in effective connectivity by comparing models that allow for this modulation with models that do not. We find strong evidence for modulation of connections between the two attention networks; namely, a disinhibition of the ventral network by its dorsal counterpart. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
33. Adult Hippocampal Neurogenesis: A Coming-of-Age Story.
- Author
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Kuhn, H. Georg, Gage, Fred H., and Toda, Tomohisa
- Abstract
What has become standard textbook knowledge over the last decade was a hotly debated matter a decade earlier: the proposition that new neurons are generated in the adult mammalian CNS. The early discovery by Altman and colleagues in the 1960s was vulnerable to criticism due to the lack of technical strategies for unequivocal demonstration, quantification, and physiological analysis of newly generated neurons in adult brain tissue. After several technological advancements had been made in the field, we published a paper in 1996 describing the generation of new neurons in the adult rat brain and the decline of hippocampal neurogenesis during aging. The paper coincided with the publication of several other studies that together established neurogenesis as a cellular mechanism in the adult mammalian brain. I n this Progressions article, which is by no means a comprehensive review, we recount our personal view of the initial setting that led to our study and we discuss some of its implications and developments that followed. We also address questions that remain regarding the regulation and function of neurogenesis in the adult mammalian brain, in particular the existence of neurogenesis in the adult human brain. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
34. Sex, Impulsivity, and Anxiety: Interplay between Ventral Striatum and Amygdala Reactivity in Sexual Behaviors.
- Author
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Gola, Mateusz, Makoto Miyakoshi, and Sescousse, Guillaume
- Subjects
MEDICAL research ,SEX customs ,HUMAN beings ,COMORBIDITY ,ANXIETY disorders ,SUBSTANCE abuse - Abstract
The article discusses various research papers that were conducted for analyzing sexual behavior of human beings. Various aspects that were analyzed includes comorbidity of mood, addictive behavior and anxiety disorders. Papers of various researchers that were discussed include E. C. Victor, N. Prause and Y. S. Nikolova.
- Published
- 2015
- Full Text
- View/download PDF
35. Attention Differentially Affects Acoustic and Phonetic Feature Encoding in a Multispeaker Environment.
- Author
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Teoh, Emily S., Ahmed, Farhin, and Lalor, Edmund C.
- Subjects
ATTENTION ,COCKTAIL parties ,PHONETICS ,ENCODING ,NEUROLINGUISTICS ,DATABASES - Abstract
Humans have the remarkable ability to selectively focus on a single talker in the midst of other competing talkers. The neural mechanisms that underlie this phenomenon remain incompletely understood. In particular, there has been longstanding debate over whether attention operates at an early or late stage in the speech processing hierarchy. One way to better understand this is to examine how attention might differentially affect neurophysiological indices of hierarchical acoustic and linguistic speech representations. In this study, we do this by using encoding models to identify neural correlates of speech processing at various levels of representation. Specifically, we recorded EEG from fourteen human subjects (nine female and five male) during a “cocktail party” attention experiment. Model comparisons based on these data revealed phonetic feature processing for attended, but not unattended speech. Furthermore, we show that attention specifically enhances isolated indices of phonetic feature processing, but that such attention effects are not apparent for isolated measures of acoustic processing. These results provide new insights into the effects of attention on different prelexical representations of speech, insights that complement recent anatomic accounts of the hierarchical encoding of attended speech. Furthermore, our findings support the notion that, for attended speech, phonetic features are processed as a distinct stage, separate from the processing of the speech acoustics. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
36. Hand Shape Representations in the Human Posterior Parietal Cortex.
- Author
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Klaes, Christian, Kellis, Spencer, Aflalo, Tyson, Lee, Brian, Pejsa, Kelsie, Shanfield, Kathleen, Hayes-Jackson, Stephanie, Aisen, Mindy, Heck, Christi, Liu, Charles, and Andersen, Richard A.
- Subjects
PARIETAL lobe ,PRIMATES ,AUDITORY cortex ,NEUROPROSTHESES ,MOTOR neurons - Abstract
Humans shape their hands to grasp, manipulate objects, and to communicate. From nonhuman primate studies, we know that visual and motor properties for grasps can be derived from cells in the posterior parietal cortex (PPC). Are non-grasp-related hand shapes in humans represented similarly? Here we show for the first time how single neurons in the PPC of humans are selective for particular imagined hand shapes independent of graspable objects. We find that motor imagery to shape the hand can be successfully decoded from the PPC by implementing a version of the popular Rock-Paper-Scissors game and its extension Rock-Paper-Scissors-Lizard-Spock. By simultaneous presentation of visual and auditory cues, we can discriminate motor imagery from visual information and show differences in auditory and visual information processing in the PPC. These results also demonstrate that neural signals from human PPC can be used to drive a dexterous cortical neuroprosthesis. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
37. Hippocampal Connectivity with Retrosplenial Cortex is Linked to Neocortical Tau Accumulation and Memory Function.
- Author
-
Ziontz, Jacob, Adams, Jenna N., Harrison, Theresa M., Baker, Suzanne L., and Jagust, William J.
- Subjects
CINGULATE cortex ,TAU proteins ,PARIETAL lobe ,EPISODIC memory ,POSITRON emission tomography ,FUNCTIONAL magnetic resonance imaging - Abstract
The mechanisms underlying accumulation of Alzheimer's disease (AD)-related tau pathology outside of the medial temporal lobe (MTL) in older adults are unknown but crucial to understanding cognitive decline. A growing body of evidence from human and animal studies strongly implicates neural connectivity in the propagation of tau in humans, but the pathways of neocortical tau spread and its consequences for cognitive function are not well understood. Using resting state functional magnetic resonance imaging (fMRI) and tau PET imaging from a sample of 97 male and female cognitively normal older adults, we examined MTL structures involved in medial parietal tau accumulation and associations with memory function. Functional connectivity between hippocampus (HC) and retrosplenial cortex (RsC), a key region of the medial parietal lobe, was associated with tau in medial parietal lobe. By contrast, connectivity between entorhinal cortex (EC) and RsC did not correlate with medial parietal lobe tau. Further, greater hippocampal-retrosplenial (HC-RsC) connectivity was associated with a stronger correlation between MTL and medial parietal lobe tau. Finally, an interaction between connectivity strength and medial parietal tau was associated with episodic memory performance, particularly in the visuospatial domain. This pattern of tau accumulation thus appears to reflect pathways of neural connectivity, and propagation of tau from EC to medial parietal lobe via the HC may represent a critical process in the evolution of cognitive dysfunction in aging and AD. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
38. Impaired Refinement of Kinematic Variability in Huntington Disease Mice on an Automated Home Cage Forelimb Motor Task.
- Author
-
Woodard, Cameron L., Sepers, Marja D., and Raymond, Lynn A.
- Subjects
HUNTINGTON disease ,FORELIMB ,ANIMAL behavior ,MOUSE diseases ,LABORATORY mice ,VARIABILITY (Psychometrics) ,COMPULSIVE hair pulling - Abstract
The effective development of novel therapies in mouse models of neurologic disorders relies on behavioral assessments that provide accurate read-outs of neuronal dysfunction and/or degeneration. We designed an automated behavioral testing system (PiPaw), which integrates an operant lever-pulling task directly into the mouse home cage. This task is accessible to grouphoused mice 24 h per day, enabling high-throughput longitudinal analysis of forelimb motor learning. Moreover, this design eliminates the need for exposure to novel environments and minimizes experimenter interaction, significantly reducing two of the largest stressors associated with animal behavior. Male mice improved their performance of this task over 1 week of testing by reducing intertrial variability of reward-related kinematic parameters (pull amplitude or peak velocity). In addition, mice displayed short-term improvements in reward rate, and a concomitant decrease in movement variability, over the course of brief bouts of task engagement. We used this system to assess motor learning in mouse models of the inherited neurodegenerative disorder, Huntington disease (HD). Despite having no baseline differences in task performance, male Q175-FDN HD mice were unable to modulate the variability of their movements to increase reward on either short or long timescales. Task training was associated with a decrease in the amplitude of spontaneous excitatory activity recorded from striatal medium spiny neurons in the hemisphere contralateral to the trained forelimb in WT mice; however, no such changes were observed in Q175-FDN mice. This behavioral screening platform should prove useful for preclinical drug trials toward improved treatments in HD and other neurologic disorders. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
39. Postmitotic Prox1 Expression Controls the Final Specification of Cortical VIP Interneuron Subtypes.
- Author
-
Stachniak, Tevye Jason, Kastli, Rahel, Hanley, Olivia, Argunsah, Ali Özgür, van der Valk, Elianne Grietje Theodora, Kanatouris, George, and Karayannis, Theofanis
- Subjects
GENE expression ,TRANSCRIPTION factors ,BIPOLAR cells ,RNA sequencing ,DEVELOPMENTAL biology ,SYNAPSES ,NEURAL transmission - Abstract
Throughout development, neuronal identity is controlled by key transcription factors that determine the unique properties of a cell. During embryogenesis, the transcription factor Prox1 regulates VIP-positive cortical interneuron migration, survival, and connectivity. Here, we explore the role of Prox1 as a regulator of genetic programs that guide the final specification of VIP interneuron subtypes in early postnatal life. Synaptic in vitro electrophysiology in male and female mice shows that postnatal Prox1 removal differentially affects the dynamics of excitatory inputs onto VIP bipolar and multipolar subtypes. RNA sequencing reveals that one of the downstream targets of Prox1 is the postsynaptic protein Elfn1, a constitutive regulator of presynaptic release probability. Further genetic, pharmacological, and electrophysiological experiments demonstrate that removing Prox1 reduces Elfn1 function in VIP multipolar but not in bipolar cells. Finally, overexpression experiments and analysis of native Elfn1 mRNA expression reveal that Elfn1 levels are differentially controlled at the post-transcriptional stage. Thus, in addition to activity-dependent processes that contribute to the developmental trajectory of VIP cells, genetic programs engaged by Prox1 control the final differentiation of multipolar and bipolar subtypes. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
40. Suppressing the Morning Cortisol Rise After Memory Reactivation at 4 A.M. enhances Episodic Memory Reconsolidation in Humans.
- Author
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Antypa, Despina, Perrault, Aurore A., Vuilleumier, Patrik, Schwartz, Sophie, and Rimmele, Ulrike
- Subjects
MEMORY ,EPISODIC memory ,HYDROCORTISONE ,MORNING ,LABORATORY animals ,HUMAN experimentation - Abstract
Evidence from animal and human research shows that established memories can undergo changes after reactivation through a process called reconsolidation. Alterations of the level of the stress hormone cortisol may provide a way to manipulate reconsolidation in humans. Here, in a double-blind, within-subject design, we reactivated a 3-d-old memory at 3:55 A.M. in sixteen men and four women, immediately followed by oral administration of metyrapone versus placebo, to examine whether metyrapone-induced suppression of the morning cortisol rise may influence reconsolidation processes during and after early morning sleep. Crucially, reactivation followed by cortisol suppression versus placebo resulted in enhanced memory for the reactivated episode tested 4 d after reactivation. This enhancement after cortisol suppression was specific for the reactivated episode versus a non-reactivated episode. These findings suggest that when reactivation of memories is immediately followed by suppression of cortisol levels during early morning sleep in humans, reconsolidation processes change in a way that leads to the strengthening of episodic memory traces. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
41. A Search for a Cortical Map of Auditory Space.
- Author
-
Middlebrooks, John C.
- Subjects
AUDITORY cortex ,GENERAL anesthesia - Abstract
This is the story of a search for a cortical map of auditory space. The search began with a study that was reported in the first issue of The Journal of Neuroscience (Middlebrooks and Pettigrew, 1981). That paper described some unexpected features of spatial sensitivity in the auditory cortex while failing to demonstrate the expected map. In the ensuing 40 years, we have encountered the following: panoramic spatial coding by single neurons; a rich variety of response patterns that are unmasked in the absence of general anesthesia; sharpening of spatial sensitivity when an animal is engaged in a listening task; and reorganization of spatial sensitivity in the presence of competing sounds. We have not encountered a map, but not through lack of trying. On the basis of years of negative results by our group and others, and positive results that are inconsistent with static point-to-point topography, we are confident in concluding that there just ain't no map. Instead, we have come to appreciate the highly dynamic spatial properties of cortical neurons, which serve the needs of listeners in a changing sonic environment. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
42. Presynaptic Inhibitory Effects of Acetylcholine in the Hippocampus: A 40-Year Evolution of a Serendipitous Finding.
- Author
-
Valentino, Rita J. and Dingledine, Raymond J.
- Subjects
ACETYLCHOLINE ,PYRAMIDAL neurons ,HIPPOCAMPUS (Brain) ,HIPPOCAMPAL innervation ,DENDRITES - Abstract
Cholinergic regulation of hippocampal circuit activity has been an active area of neurophysiological research for decades. The prominent cholinergic innervation of intrinsic hippocampal circuitry, potent effects of cholinomimetic drugs, and behavioral responses to cholinergic modulation of hippocampal circuitry have driven investigators to discover diverse cellular actions of acetylcholine in distinct sites within hippocampal circuitry. Further research has illuminated how these actions organize circuit activity to optimize encoding of new information, promote consolidation, and coordinate this with recall of prior memories. The development of the hippocampal slice preparation was a major advance that accelerated knowledge of how hippocampal circuits functioned and how acetylcholine modulated these circuits. Using this preparation in the early 1980s, we made a serendipitous finding of a novel presynaptic inhibitory effect of acetylcholine on Schaffer collaterals, the projections from CA3 pyramidal neurons to dendrites of CA1 pyramidal cells. We characterized this effect at cellular and pharmacological levels, published the findings in the first volume of the Journal of Neuroscience, and proceeded to pursue other scientific directions. We were surprised and thrilled to see that, nearly 40 years later, the paper is still being cited and downloaded because the data became an integral piece of the foundation of the science of cholinergic regulation of hippocampal function in learning and memory. This Progressions article is a story of how single laboratory findings evolve through time to be confirmed, challenged, and reinterpreted by other laboratories to eventually become part of the basis of fundamental concepts related to important brain functions. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
43. Contribution of Postsynaptic Molecules to AMPA Receptor Nanodomain Organization.
- Author
-
Alvaro Barrera-Ocampo and Chater, Thomas E.
- Subjects
POSTSYNAPTIC potential ,SCAFFOLD proteins ,SYNAPSES ,AMINO acids ,HYDROXY acids - Abstract
The article presents a research paper that focuses on the role of postsynaptic molecules to amino-hydroxy-methyl-isoxazolepropionic acid receptor (AMPAR) nanodomain organization. The paper also looks at topics such as influence of AMPARs interaction with multiple auxiliary and scaffolding proteins on trafficking and stabilization of the receptors at synapses, expression patterns of subunits of AMPARs across the brain, and levels of AMPAR confinement at synapses.
- Published
- 2013
- Full Text
- View/download PDF
44. Palmitoylation Controls NMDA Receptor Function and Steroid Sensitivity.
- Author
-
Hubalkova, Pavla, Ladislav, Marek, Vyklicky, Vojtech, Smejkalova, Tereza, Krausova, Barbora Hrcka, Kysilov, Bohdan, Krusek, Jan, Naimová, Zaneta, Korinek, Miloslav, Chodounska, Hana, Kudova, Eva, Cerny, Jiri, and Vyklicky Jr, Ladislav
- Subjects
PALMITOYLATION ,METHYL aspartate receptors ,STEROID receptors ,LIGAND-gated ion channels ,NEUROPLASTICITY - Abstract
NMDARs are ligand-gated ion channels that cause an influx of Na
+ and Ca2+ into postsynaptic neurons. The resulting intracellular Ca2+ transient triggers synaptic plasticity. When prolonged, it may induce excitotoxicity, but it may also activate negative feedback to control the activity of NMDARs. Here, we report that a transient rise in intracellular Ca2+ (Ca2+ challenge) increases the sensitivity of NMDARs but not AMPARs/kainate receptors to the endogenous inhibitory neurosteroid 20-oxo-5b-pregnan-3a-yl 3-sulfate and to its synthetic analogs, such as 20-oxo-5b-pregnan-3a-yl 3-hemipimelate (PAhPim). In cultured hippocampal neurons, 30 lM PAhPim had virtually no effect on NMDAR responses; however, following the Ca21 challenge, it inhibited the responses by 62%; similarly, the Ca2+ challenge induced a 3.7-fold decrease in the steroid IC50 on recombinant GluN1/GluN2B receptors. The increase in the NMDAR sensitivity to PAhPim was dependent on three cysteines (C849, C854, and C871) located in the carboxy-terminal domain of the GluN2B subunit, previously identified to be palmitoylated (Hayashi et al., 2009). Our experiments suggested that the Ca2+ challenge induced receptor depalmitoylation, and single-channel analysis revealed that this was accompanied by a 55% reduction in the probability of channel opening. Results of in silico modeling indicate that receptor palmitoylation promotes anchoring of the GluN2B subunit carboxy-terminal domain to the plasma membrane and facilitates channel opening. Depalmitoylation-induced changes in the NMDAR pharmacology explain the neuroprotective effect of PAhPim on NMDA-induced excitotoxicity. We propose that palmitoylation-dependent changes in the NMDAR sensitivity to steroids serve as an acute endogenous mechanism that controls NMDAR activity. [ABSTRACT FROM AUTHOR]- Published
- 2021
- Full Text
- View/download PDF
45. Tuba Activates Cdc42 during Neuronal Polarization Downstream of the Small GTPase Rab8a.
- Author
-
Urrutia, Pamela J., Bodaleo, Felipe, Bórquez, Daniel A., Homma, Yuta, Rozes-Salvador, Victoria, Villablanca, Cristopher, Conde, Cecilia, Mitsunori Fukuda, and González-Billault, Christian
- Subjects
GUANOSINE triphosphatase ,AXONS ,RHO GTPases ,NEURONAL differentiation ,GUANINE - Abstract
The acquisition of neuronal polarity is a complex molecular process that depends on changes in cytoskeletal dynamics and directed membrane traffic, regulated by the Rho and Rab families of small GTPases, respectively. However, during axon specification, a molecular link that couples these protein families has yet to be identified. In this paper, we describe a new positive feedback loop between Rab8a and Cdc42, coupled by Tuba, a Cdc42-specific guanine nucleotide-exchange factor (GEF), that ensures a single axon generation in rodent hippocampal neurons from embryos of either sex. Accordingly, Rab8a or Tuba gain-of-function generates neurons with supernumerary axons whereas Rab8a or Tuba loss-of-function abrogated axon specification, phenocopying the well-established effect of Cdc42 on neuronal polarity. Although Rab8 and Tuba do not interact physically, the activity of Rab8 is essential to generate a proximal to distal axonal gradient of Tuba in cultured neurons. Tuba-associated and Rab8a-associated polarity defects are also evidenced in vivo, since dominant negative (DN) Rab8a or Tuba knock-down impairs cortical neuronal migration in mice. Our results suggest that Tuba coordinates directed vesicular traffic and cytoskeleton dynamics during neuronal polarization. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
46. A Model for the Origin of Motion Direction Selectivity in Visual Cortex.
- Author
-
Freeman, Alan W.
- Subjects
VISUAL cortex ,MOTION ,LEAD time (Supply chain management) ,NEURONS - Abstract
Motion perception is a vital part of our sensory repertoire in that it contributes to navigation, awareness of moving objects, and communication. Motion sense in carnivores and primates originates with primary visual cortical neurons selective for motion direction. More than 60 years after the discovery of these neurons, there is still no consensus on the mechanism underlying direction selectivity. This paper describes a model of the cat's visual system in which direction selectivity results from the well-documented orientation selectivity of inhibitory neurons: inhomogeneities in the orientation preference map for inhibitory neurons leads to spatially asymmetric inhibition, and thus to direction selectivity. Stimulation of the model with a drifting grating shows that direction selectivity results from the relative timing of excitatory and inhibitory inputs to a neuron. Using a stationary contrast-reversing grating reveals that the inhibitory input is spatially displaced in the preferred direction relative to the excitatory input, and that this asymmetry leads to the timing difference. More generally, the model yields physiologically realistic estimates of the direction selectivity index, and it reproduces the critical finding with contrastreversing gratings that response phase advances with grating spatial phase. It is concluded that a model based on intracortical inhibition can account well for the known properties of direction selectivity in carnivores and primates. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
47. Neuronal SIRT3 Deletion Predisposes to Female-Specific Alterations in Cellular Metabolism, Memory, and Network Excitability.
- Author
-
Pearson-Smith, Jennifer N., Fulton, Ruth, Huynh, Christopher Q., Figueroa, Anna G., Huynh, Gia B., Li-Ping Liang, Gano, Lindsey B., Michel, Cole R., Reisdorph, Nichole, Reisdorph, Richard, Fritz, Kristofer S., Verdin, Eric, and Patel, Manisha
- Subjects
COGNITIVE testing ,METABOLISM ,SPATIAL memory ,PROTEIN metabolism ,SHORT-term memory - Abstract
Mitochondrial dysfunction is an early event in the pathogenesis of neurologic disorders and aging. Sirtuin 3 (SIRT3) regulates mitochondrial function in response to the cellular environment through the reversible deacetylation of proteins involved in metabolism and reactive oxygen species detoxification. As the primary mitochondrial deacetylase, germline, or peripheral tissue-specific deletion of SIRT3 produces mitochondrial hyperacetylation and the accelerated development of age-related diseases. Given the unique metabolic demands of neurons, the role of SIRT3 in the brain is only beginning to emerge. Using mass spectrometry-based acetylomics, high-resolution respirometry, video-EEG, and cognition testing, we report targeted deletion of SIRT3 from select neurons in the cortex and hippocampus produces altered neuronal excitability and metabolic dysfunction in female mice. Targeted deletion of SIRT3 from neuronal helix-loop-helix 1 (NEX)-expressing neurons resulted in mitochondrial hyperacetylation, female-specific superoxide dismutase-2 (SOD2) modification, increased steady-state superoxide levels, metabolic reprogramming, altered neuronal excitability, and working spatial memory deficits. Inducible neuronal deletion of SIRT3 likewise produced female-specific deficits in spatial working memory. Together, the data demonstrate that deletion of SIRT3 from forebrain neurons selectively predisposes female mice to deficits in mitochondrial and cognitive function. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
48. Cortical Parvalbumin-Positive Interneuron Development and Function Are Altered in the APC Conditional Knockout Mouse Model of Infantile and Epileptic Spasms Syndrome.
- Author
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Ryner, Rachael F., Derera, Isabel D., Armbruster, Moritz, Kansara, Anar, Sommer, Mary E., Pirone, Antonella, Noubary, Farzad, Jacob, Michele, and Dulla, Chris G.
- Subjects
EPILEPSY ,INFANTILE spasms ,ADENOMATOUS polyposis coli ,KNOCKOUT mice ,LABORATORY mice ,PYRAMIDAL neurons - Abstract
Infantile and epileptic spasms syndrome (IESS) is a childhood epilepsy syndrome characterized by infantile or late-onset spasms, abnormal neonatal EEG, and epilepsy. Few treatments exist for IESS, clinical outcomes are poor, and the molecular and circuit-level etiologies of IESS are not well understood. Multiple human IESS risk genes are linked to Wnt/b-catenin signaling, a pathway that controls developmental transcriptional programs and promotes glutamatergic excitation via b-catenin's role as a synaptic scaffold. We previously showed that deleting adenomatous polyposis coli (APC), a component of the b-catenin destruction complex, in excitatory neurons (APC cKO mice, APC
fl/fl x CaMKIIaCre ) increased b-catenin levels in developing glutamatergic neurons and led to infantile behavioral spasms, abnormal neonatal EEG, and adult epilepsy. Here, we tested the hypothesis that the development of GABAergic interneurons (INs) is disrupted in APC cKO male and female mice. IN dysfunction is implicated in human IESS, is a feature of other rodent models of IESS, and may contribute to the manifestation of spasms and seizures. We found that parvalbuminpositive INs (PV+ INs), an important source of cortical inhibition, were decreased in number, underwent disproportionate developmental apoptosis, and had altered dendrite morphology at P9, the peak of behavioral spasms. PV+ INs received excessive excitatory input, and their intrinsic ability to fire action potentials was reduced at all time points examined (P9, P14, P60). Subsequently, GABAergic transmission onto pyramidal neurons was uniquely altered in the somatosensory cortex of APC cKO mice at all ages, with both decreased IPSC input at P14 and enhanced IPSC input at P9 and P60. These results indicate that inhibitory circuit dysfunction occurs in APC cKOs and, along with known changes in excitation, may contribute to IESS-related phenotypes. [ABSTRACT FROM AUTHOR]- Published
- 2023
- Full Text
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49. Muscarinic Acetylcholine Receptors Modulate HCN Channel Properties in Vestibular Ganglion Neurons.
- Author
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Bronson, Daniel and Kalluri, Radha
- Subjects
HYPERPOLARIZATION (Cytology) ,MUSCARINIC acetylcholine receptors ,MEMBRANE potential ,NEURONS ,GANGLIA ,POTASSIUM channels - Abstract
Efferent modulation of vestibular afferent excitability is linked to muscarinic signaling cascades that close low-voltage-gated potassium channels (i.e., KCNQ). Here, we show that muscarinic signaling cascades also depolarize the activation range of hyperpolarization-activated cyclic-nucleotide gated (HCN) channels. We compared the voltage activation range and kinetics of HCN channels and induced firing patterns before and after administering the muscarinic acetylcholine receptor (mAChR) agonist oxotremorine-M (Oxo-M) in dissociated vestibular ganglion neurons (VGNs) from rats of either sex using perforated whole-cell patch-clamp methods. Oxo-M depolarized HCN channels' half-activation voltage (V
1/2 ) and sped up the rate of activation near resting potential twofold. HCN channels in large-diameter and/or transient firing VGN (putative cell bodies of irregular firing neuron from central epithelial zones) had relatively depolarized V1/2 in control solution and were less sensitive to mAChR activation than those found in small-diameter VGN with sustained firing patterns (putatively belonging to regular firing afferents). The impact of mAChR on HCN channels is not a direct consequence of closing KCNQ channels since pretreating the cells with Linopirdine, a KCNQ channel blocker, did not prevent HCN channel depolarization by Oxo-M. Efferent signaling promoted ion channel configurations that were favorable to highly regular spiking in some VGN, but not others. This is consistent with previous observations that low-voltage gated potassium currents in VGN are conducted by mAChR agonist-sensitive and -insensitive channels. Connecting efferent signaling to HCN channels is significant because of the channel's impact on spike-timing regularity and nonchemical transmission between Type I hair cells and vestibular afferents. [ABSTRACT FROM AUTHOR]- Published
- 2023
- Full Text
- View/download PDF
50. Lipid Raft-Excluded GFRα1/Ret Fails to Transmit GDNF Signaling In Vivo.
- Author
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Morales, Daniel
- Subjects
MEMBRANE lipids ,LIPID rafts ,MEMBRANE microdomains ,GLIAL cell line-derived neurotrophic factor ,NEUROTROPHINS - Abstract
The article discusses research paper that studies asymmetric cellular lipid trafficking and membrane fractionation, led to the formulation of the lipid raft hypothesis. It informs that persuasive arguments for lipid rafts exist some of which emerge from glial cell line derived neurotrophic factor (GDNF). The study also raises question whether lipid raft targeting enable effector binding.
- Published
- 2016
- Full Text
- View/download PDF
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