scholarly journals Input-independent homeostasis of developing thalamocortical activity

2021 ◽  
Author(s):  
Pouria Riyahi ◽  
Marnie A Phillips ◽  
Matthew T Colonnese
Keyword(s):  
Visual Processing ◽  
Background Activity ◽  
Silent Period ◽  
Prognostic Indicator ◽  
Cortical Activity ◽  
Progressive Increase ◽  
Developmental Trajectory ◽  
Primary Input ◽  
Firing Rates

ABSTRACTThe isocortex of all mammals studied to date shows a progressive increase in the amount and continuity of background activity during early development. In humans the transition from a discontinuous (mostly silent, intermittently bursting) cortex to one that is continuously active is complete soon after birth and is a critical prognostic indicator in newborns. In the visual cortex of rodents this switch from discontinuous to continuous background activity occurs rapidly during the two days before eye-opening, driven by activity changes in relay thalamus. The factors that regulate the timing of continuity development, which enables mature visual processing, are unknown. Here we test the role of the retina, the primary input, in the development of continuous spontaneous activity in the visual system of mice using depth electrode recordings of cortical activity from enucleated mice in vivo. Bilateral enucleation at postnatal day (P)6, one week prior to the onset of continuous activity, acutely silences cortex, yet firing rates and early oscillations return to normal within two days and show a normal developmental trajectory through P12. Enucleated animals showed differences in silent period duration and continuity on P13 that resolved on P16, and an increase in low frequency power that did not. Our results show that the timing of cortical activity development is not determined by the major driving input to the system. Rather, homeostatic mechanisms in thalamocortex regulate firing rates and continuity even across periods of rapid maturation.

scholarly journals How synaptic strength, short-term plasticity, and temporal factors contribute to neuronal spike output

2021 ◽  
Author(s):  
Alexandra Gastone Guilabert ◽  
Benjamin Ehret ◽  
Moritz O. Buchholz ◽  
Gregor F.P. Schuhknecht
Keyword(s):  
Background Activity ◽  
Synaptic Strength ◽  
Temporal Coding ◽  
Excitatory Postsynaptic Potential ◽  
Short Term ◽  
Paired Pulse ◽  
Temporal Synchrony ◽  
Short Term Plasticity ◽  
Firing Rates

To compute spiking responses, neurons integrate inputs from thousands of synapses whose strengths span an order of magnitude. Intriguingly, in mouse neocortex, the small minority of 'strong' synapses is found predominantly between similarly tuned cells, suggesting they are the synapses that determine a neuron's spike output. This raises the question of how other computational primitives, such as 'background' activity from the majority of synapses, which are 'weak', short-term plasticity, and temporal synchrony contribute to spiking. First, we combined extracellular stimulation and whole-cell recordings in mouse barrel cortex to map the distribution of excitatory postsynaptic potential (EPSP) amplitudes and paired-pulse ratios of excitatory synaptic connections converging onto individual layer 2/3 (L2/3) neurons. While generally net short-term plasticity was weak, connections with EPSPs > 2 mV displayed pronounced paired-pulse depression. EPSP amplitudes and paired-pulse ratios of connections converging onto the same neurons spanned the full range observed across L2/3 and there was no indication that strong synapses nor those with particular short-term plasticity properties were associated with particular cells, which critically constrains theoretical models of cortical filtering. To investigate how different computational primitives of synaptic information processing interact to shape spiking, we developed a computational model of a pyramidal neuron in the rodent L2/3 circuitry: firing rates and pairwise correlations of presynaptic inputs were constrained by in vivo observations, while synaptic strength and short-term plasticity were set based on our experimental data. Importantly, we found that the ability of strong inputs to evoke spiking critically depended on their high temporal synchrony and high firing rates observed in vivo and on synaptic background activity - and not primarily on synaptic strength, which in turn further enhanced information transfer. Depression of strong synapses was critical for maintaining a neuron's responsivity and prevented runaway excitation. Our results provide a holistic framework of how cortical neurons exploit complex synergies between temporal coding, synaptic properties, and noise in order to transform synaptic inputs into output firing.

scholarly journals Prenatal androgen treatment does not alter the firing activity of hypothalamic arcuate kisspeptin neurons in female mice

2021 ◽  
Author(s):  
Amanda G Gibson ◽  
Jennifer Jaime ◽  
Laura L Burger ◽  
Suzanne M Moenter
Keyword(s):  
Firing Rate ◽  
Polycystic Ovary ◽  
Developmental Trajectory ◽  
Dependent Manner ◽  
Gnrh Neuron ◽  
Neuron Firing ◽  
Firing Rates ◽  
Gnrh Neurons ◽  
Kndy Neurons

Neuroendocrine control of reproduction is disrupted in many individuals with polycystic ovary syndrome, who present with increased luteinizing hormone (LH), and presumably gonadotropin-releasing hormone (GnRH), release frequency, and high androgen levels. Prenatal androgenization (PNA) recapitulates these phenotypes in primates and rodents. Female offspring of mice injected with dihydrotestosterone (DHT) on gestational D16-18 exhibit disrupted estrous cyclicity, increased LH and testosterone, and increased GnRH neuron firing rate as adults. PNA also alters the developmental trajectory of GnRH neuron firing rates, markedly blunting the prepubertal peak in firing that occurs in 3wk-old controls. GnRH neurons do not express detectable androgen receptors and are thus probably not the direct target of DHT. Rather, PNA likely alters GnRH neuronal activity by modulating upstream neurons, such as hypothalamic arcuate neurons co-expressing kisspeptin, neurokinin B (gene Tac2), and dynorphin, aka KNDy neurons. We hypothesized PNA treatment changes firing rates of KNDy neurons in a similar age-dependent manner as GnRH neurons. We conducted targeted extracellular recordings (0.5-2h) of Tac2-identified KNDy neurons from control and PNA mice at 3wks of age and in adulthood. About half of neurons were quiescent (<0.005Hz). Long-term firing rates of active cells varied, suggestive of episodic activity, but were not different among groups. Short-term burst firing was also similar. We thus reject the hypothesis that PNA alters the firing rate of KNDy neurons. This does not preclude altered neurosecretory output of KNDy neurons, involvement of other neuronal populations, or in-vivo networks as critical drivers of altered GnRH firing rates in PNA mice.

scholarly journals The somatosensory cortical activity in individuals with cerebral palsy displays an aberrant developmental trajectory

2020 ◽  
Author(s):  
Michael P. Trevarrow ◽  
Joseph Kleinsmith ◽  
Brittany K. Taylor ◽  
Tony W. Wilson ◽  
Max J. Kurz
Keyword(s):  
Cerebral Palsy ◽  
Cortical Activity ◽  
Developmental Trajectory

scholarly journals A deep convolutional visual encoding model of neuronal responses in the LGN

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Eslam Mounier ◽  
Bassem Abdullah ◽  
Hani Mahdi ◽  
Seif Eldawlatly
Keyword(s):  
Firing Rate ◽  
Visual Information ◽  
Visual Stimulation ◽  
Neuronal Population ◽  
Neuronal Firing ◽  
Electrode Arrays ◽  
Deep Convolutional Neural Networks ◽  
Firing Rates ◽  
Spatiotemporal Representation

AbstractThe Lateral Geniculate Nucleus (LGN) represents one of the major processing sites along the visual pathway. Despite its crucial role in processing visual information and its utility as one target for recently developed visual prostheses, it is much less studied compared to the retina and the visual cortex. In this paper, we introduce a deep learning encoder to predict LGN neuronal firing in response to different visual stimulation patterns. The encoder comprises a deep Convolutional Neural Network (CNN) that incorporates visual stimulus spatiotemporal representation in addition to LGN neuronal firing history to predict the response of LGN neurons. Extracellular activity was recorded in vivo using multi-electrode arrays from single units in the LGN in 12 anesthetized rats with a total neuronal population of 150 units. Neural activity was recorded in response to single-pixel, checkerboard and geometrical shapes visual stimulation patterns. Extracted firing rates and the corresponding stimulation patterns were used to train the model. The performance of the model was assessed using different testing data sets and different firing rate windows. An overall mean correlation coefficient between the actual and the predicted firing rates of 0.57 and 0.7 was achieved for the 10 ms and the 50 ms firing rate windows, respectively. Results demonstrate that the model is robust to variability in the spatiotemporal properties of the recorded neurons outperforming other examined models including the state-of-the-art Generalized Linear Model (GLM). The results indicate the potential of deep convolutional neural networks as viable models of LGN firing.

scholarly journals TRIM27 interacts with Iκbα to promote the growth of human renal cancer cells through regulating the NF-κB pathway

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chengwu Xiao ◽  
Wei Zhang ◽  
Meimian Hua ◽  
Huan Chen ◽  
Bin Yang ◽  
...  
Keyword(s):  
Cell Lines ◽  
Prognostic Indicator ◽  
The Cancer Genome Atlas ◽  
Mrna Levels ◽  
Loss Of Function ◽  
Protein Levels ◽  
Kaplan Meier ◽  
Cancer Genome Atlas

Abstract Background The tripartite motif (TRIM) family proteins exhibit oncogenic roles in various cancers. The roles of TRIM27, a member of the TRIM super family, in renal cell carcinoma (RCC) remained unexplored. In the current study, we aimed to investigate the clinical impact and roles of TRIM27 in the development of RCC. Methods The mRNA levels of TRIM27 and Kaplan–Meier survival of RCC were analyzed from The Cancer Genome Atlas database. Real-time PCR and Western blotting were used to measure the mRNA and protein levels of TRIM27 both in vivo and in vitro. siRNA and TRIM27 were exogenously overexpressed in RCC cell lines to manipulate TRIM27 expression. Results We discovered that TRIM27 was elevated in RCC patients, and the expression of TRIM27 was closely correlated with poor prognosis. The loss of function and gain of function results illustrated that TRIM27 promotes cell proliferation and inhibits apoptosis in RCC cell lines. Furthermore, TRIM27 expression was positively associated with NF-κB expression in patients with RCC. Blocking the activity of NF-κB attenuated the TRIM27-mediated enhancement of proliferation and inhibition of apoptosis. TRIM27 directly interacted with Iκbα, an inhibitor of NF-κB, to promote its ubiquitination, and the inhibitory effects of TRIM27 on Iκbα led to NF-κB activation. Conclusions Our results suggest that TRIM27 exhibits an oncogenic role in RCC by regulating NF-κB signaling. TRIM27 serves as a specific prognostic indicator for RCC, and strategies targeting the suppression of TRIM27 function may shed light on future therapeutic approaches.

scholarly journals Overexpressed P75CUX1 promotes EMT in glioma infiltration by activating β-catenin

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Anqi Xu ◽  
Xizhao Wang ◽  
Jie Luo ◽  
Mingfeng Zhou ◽  
Renhui Yi ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Tumor Grade ◽  
Prognostic Indicator ◽  
Migration And Invasion ◽  
Poor Overall Survival ◽  
Mesenchymal Transition ◽  
Kaplan Meier ◽  
Homeobox Protein

AbstractThe homeobox protein cut-like 1 (CUX1) comprises three isoforms and has been shown to be involved in the development of various types of malignancies. However, the expression and role of the CUX1 isoforms in glioma remain unclear. Herein, we first identified that P75CUX1 isoform exhibited consistent expression among three isoforms in glioma with specifically designed antibodies to identify all CUX1 isoforms. Moreover, a significantly higher expression of P75CUX1 was found in glioma compared with non-tumor brain (NB) tissues, analyzed with western blot and immunohistochemistry, and the expression level of P75CUX1 was positively associated with tumor grade. In addition, Kaplan–Meier survival analysis indicated that P75CUX1 could serve as an independent prognostic indicator to identify glioma patients with poor overall survival. Furthermore, CUX1 knockdown suppressed migration and invasion of glioma cells both in vitro and in vivo. Mechanistically, this study found that P75CUX1 regulated epithelial–mesenchymal transition (EMT) process mediated via β-catenin, and CUX1/β-catenin/EMT is a novel signaling cascade mediating the infiltration of glioma. Besides, CUX1 was verified to promote the progression of glioma via multiple other signaling pathways, such as Hippo and PI3K/AKT. In conclusion, we suggested that P75CUX1 could serve as a potential prognostic indicator as well as a novel treatment target in malignant glioma.

scholarly journals HNRNPH1-stabilized LINC00662 promotes ovarian cancer progression by activating the GRP78/p38 pathway

Oncogene ◽  
2021 ◽  
Author(s):  
Yong Wu ◽  
Qinhao Guo ◽  
Xingzhu Ju ◽  
Zhixiang Hu ◽  
Lingfang Xia ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Progression ◽  
Prognostic Indicator ◽  
Mapk Signaling ◽  
The Cancer Genome Atlas ◽  
Cancer Genome Atlas ◽  
Proliferation And Metastasis ◽  
Nuclear Ribonucleoprotein

AbstractNumerous studies suggest an important role for copy number alterations (CNAs) in cancer progression. However, CNAs of long intergenic noncoding RNAs (lincRNAs) in ovarian cancer (OC) and their potential functions have not been fully investigated. Here, based on analysis of The Cancer Genome Atlas (TCGA) database, we identified in this study an oncogenic lincRNA termed LINC00662 that exhibited a significant correlation between its CNA and its increased expression. LINC00662 overexpression is highly associated with malignant features in OC patients and is a prognostic indicator. LINC00662 significantly promotes OC cell proliferation and metastasis in vitro and in vivo. Mechanistically, LINC00662 is stabilized by heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1). Moreover, LINC00662 exerts oncogenic effects by interacting with glucose-regulated protein 78 (GRP78) and preventing its ubiquitination in OC cells, leading to activation of the oncogenic p38 MAPK signaling pathway. Taken together, our results define an oncogenic role for LINC00662 in OC progression mediated via GRP78/p38 signaling, with potential implications regarding therapeutic targets for OC.

scholarly journals Netrin-1 in Atherosclerosis: Relationship between Human Macrophage Intracellular Levels and In Vivo Plaque Morphology

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 168
Author(s):  
Susanna Fiorelli ◽  
Nicola Cosentino ◽  
Benedetta Porro ◽  
Franco Fabbiocchi ◽  
Giampaolo Niccoli ◽  
...  
Keyword(s):  
Progressive Increase ◽  
Human Macrophage ◽  
Plaque Morphology ◽  
Artery Disease ◽  
Atherosclerotic Process ◽  
And Function ◽  
And Control ◽  
Macrophage Accumulation

Netrin-1 is a laminin-like protein that plays a pivotal role in cell migration and, according to the site of its release, exerts both pro and anti-atherosclerotic functions. Macrophages, key cells in atherosclerosis, are heterogeneous in morphology and function and different subpopulations may support plaque progression, stabilization, and/or regression. Netrin-1 was evaluated in plasma and, together with its receptor UNC5b, in both spindle and round monocyte-derived macrophages (MDMs) morphotypes from coronary artery disease (CAD) patients and control subjects. In CAD patients, plaque features were detected in vivo by optical coherence tomography. CAD patients had lower plasma Netrin-1 levels and a higher MDMs expression of both protein and its receptor compared to controls. Specifically, a progressive increase in Netrin-1 and UNC5b was evidenced going from controls to stable angina (SA) and acute myocardial infarction (AMI) patients. Of note, spindle MDMs of AMI showed a marked increase of both Netrin-1 and its receptor compared to spindle MDMs of controls. UNC5b expression is always higher in spindle compared to round MDMs, regardless of the subgroup. Finally, CAD patients with higher intracellular Netrin-1 levels showed greater intraplaque macrophage accumulation in vivo. Our findings support the role of Netrin-1 and UNC5b in the atherosclerotic process.

Physiology and Morphology of Shared and Specialized Spinal Interneurons for Locomotion and Scratching

2008 ◽  
Vol 99 (6) ◽  
pp. 2887-2901 ◽  
Author(s):  
Ari Berkowitz
Keyword(s):  
Direct Evidence ◽  
Ventral Horn ◽  
Morphological Properties ◽  
Rhythmic Movements ◽  
Potential Oscillations ◽  
Spinal Interneurons ◽  
Firing Rates ◽  
Motor Outputs ◽  
Membrane Potential Oscillations

Distinct types of rhythmic movements that use the same muscles are typically generated largely by shared multifunctional neurons in invertebrates, but less is known for vertebrates. Evidence suggests that locomotion and scratching are produced partly by shared spinal cord interneuronal circuity, although direct evidence with intracellular recording has been lacking. Here, spinal interneurons were recorded intracellularly during fictive swimming and fictive scratching in vivo and filled with Neurobiotin. Some interneurons that were rhythmically activated during both swimming and scratching had axon terminal arborizations in the ventral horn of the hindlimb enlargement, indicating their likely contribution to hindlimb motor outputs during both behaviors. We previously described a morphological group of spinal interneurons (“transverse interneurons” or T neurons) that were rhythmically activated during all forms of fictive scratching at higher peak firing rates and with larger membrane potential oscillations than scratch-activated spinal interneurons with different dendritic orientations. The current study demonstrates that T neurons are activated during both swimming and scratching and thus are components of the shared circuitry. Many spinal interneurons activated during fictive scratching are also activated during fictive swimming (scratch/swim neurons), but others are suppressed during swimming (scratch-specialized neurons). The current study demonstrates that some scratch-specialized neurons receive strong and long-lasting hyperpolarizing inhibition during fictive swimming and are also morphologically distinct from T neurons. Thus this study indicates that locomotion and scratching are produced by a combination of shared and dedicated interneurons whose physiological and morphological properties are beginning to be revealed.

Gender differences in cortical representation of rectal distension in healthy humans

2001 ◽  
Vol 281 (6) ◽  
pp. G1512-G1523 ◽  
Author(s):  
Mark K. Kern ◽  
Safwan Jaradeh ◽  
Ronald C. Arndorfer ◽  
Andrzej Jesmanowicz ◽  
James Hyde ◽  
...  
Keyword(s):  
Cortical Activity ◽  
Progressive Increase ◽  
Cortical Activation ◽  
Anterior Cingulate ◽  
Visceral Afferents ◽  
Rectal Distension ◽  
Perception Threshold ◽  
Healthy Humans ◽  
Signal Change ◽  
Female Subjects

Cerebral cortical processing of information relayed via visceral afferents is poorly understood. We determined and compared cortical activity caused by various levels of rectal distension in healthy male and female subjects. Twenty-eight healthy, young (20–44 yr) volunteer subjects (13 male, 15 female) were studied with a paradigm-driven functional magnetic resonance imaging (fMRI) technique during barostat-controlled rectal distension at perception threshold and 10 mmHg below and above perception threshold. Male subjects showed localized clusters of fMRI activity primarily in the sensory and parietooccipital regions, whereas female subjects also showed activity in the anterior cingulate and insular regions. A progressive increase in maximum percent fMRI signal change and total volume of cortical activity was associated with the intensity of rectal distension pressure in both genders. Regions of cortical activity for below-threshold stimuli showed less substantial signal intensity and volume than responses for threshold and above-threshold stimuli. Volume of cortical activity during rectal distension in women was significantly higher than that for men for all distensions. We conclude that 1) there are substantial differences in female cortical activation topography during rectal distension compared with males; 2) intensity and volume of registered cortical activity due to rectal stimulation are directly related to stimulus strength; and 3) rectal stimulation below perception level is registered in the cerebral cortex.

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