Time-Dependent, Layer-Specific Modulation of Sensory Responses Mediated by Neocortical Layer 1

2006 ◽  
Vol 96 (6) ◽  
pp. 3170-3182 ◽  
Author(s):  
Dan Shlosberg ◽  
Yael Amitai ◽  
Rony Azouz
Keyword(s):  
Somatosensory Cortex ◽  
Cortical Neurons ◽  
Sensory Information ◽  
Time Dependent ◽  
Inhibitory Influence ◽  
Sensory Responses ◽  
Specific Regulation ◽  
Sensory Evoked

An essential component of feedback and top-down information in the cortical column arrives at layer 1 (L1) where it contacts distal dendrites of pyramidal neurons. Although much is known about the anatomical organization of L1 fibers, their contribution to sensory information processing remains to be determined. We assessed the physiological significance of L1 inputs by performing extracellular recordings in vivo from neurons in the primary somatosensory cortex of rodents. We found that blocking activity in L1 increases whisker-evoked response magnitude and variance, suggesting that L1 exerts an inhibitory influence on whisker responses. However, when pairing L1 stimulation with whisker deflection, the interval between the stimuli determined the outcome of the interaction, with facilitation of sensory responses dominating the short intervals (≤10 ms) and suppression prevailing at longer intervals (>10 ms). These temporal interactions resulted in a time-dependent regulation of direction tuning of cortical neurons. The synaptic mechanisms underlying L1 inputs’ influences were examined using whole cell recordings in vitro while pairing L1 and white-matter stimulations. We found time-dependent, layer-specific differences in synaptic summation of the two inputs, with supralinearity at shorter intervals and sublinearity at longer intervals that resulted mainly from shunting inhibition. Taken together, our results demonstrate that L1 inputs impose a time- and layer-specific regulation on sensory-evoked responses. This in turn may lead to a dynamic transmission of sensory information in the somatosensory cortex.

scholarly journals Control of cerebellar granule cell output by sensory-evoked Golgi cell inhibition

2015 ◽  
Vol 112 (42) ◽  
pp. 13099-13104 ◽  
Author(s):  
Ian Duguid ◽  
Tiago Branco ◽  
Paul Chadderton ◽  
Charlotte Arlt ◽  
Kate Powell ◽  
...  
Keyword(s):  
Granule Cell ◽  
Granule Cells ◽  
Mossy Fiber ◽  
Feed Forward ◽  
Sensory Responses ◽  
Sensory Evoked ◽  
Cell Inhibition ◽  
Feed Forward Inhibition

Classical feed-forward inhibition involves an excitation–inhibition sequence that enhances the temporal precision of neuronal responses by narrowing the window for synaptic integration. In the input layer of the cerebellum, feed-forward inhibition is thought to preserve the temporal fidelity of granule cell spikes during mossy fiber stimulation. Although this classical feed-forward inhibitory circuit has been demonstrated in vitro, the extent to which inhibition shapes granule cell sensory responses in vivo remains unresolved. Here we combined whole-cell patch-clamp recordings in vivo and dynamic clamp recordings in vitro to directly assess the impact of Golgi cell inhibition on sensory information transmission in the granule cell layer of the cerebellum. We show that the majority of granule cells in Crus II of the cerebrocerebellum receive sensory-evoked phasic and spillover inhibition prior to mossy fiber excitation. This preceding inhibition reduces granule cell excitability and sensory-evoked spike precision, but enhances sensory response reproducibility across the granule cell population. Our findings suggest that neighboring granule cells and Golgi cells can receive segregated and functionally distinct mossy fiber inputs, enabling Golgi cells to regulate the size and reproducibility of sensory responses.

scholarly journals Chronic Ca2+ imaging of cortical neurons with long-term expression of GCaMP-X

2022 ◽  
Author(s):  
Jinli Geng ◽  
Wenxiang Li ◽  
Yingjun Tang ◽  
Yunming Gao ◽  
Yitong Lu ◽  
...  
Keyword(s):  
Neural Development ◽  
Cortical Neurons ◽  
Intracellular Signaling ◽  
Sensory Response ◽  
Imaging Data ◽  
Membrane Excitability ◽  
Sensory Evoked

Dynamic Ca2+ signals reflect acute changes in membrane excitability (e.g. sensory response), and also mediate intracellular signaling cascades normally of longer time scales (e.g., Ca2+- dependent neuritogenesis). In both cases, chronic Ca2+ imaging has been often desired, but largely hindered by unexpected cytotoxicity intrinsic to GCaMP, a popular series of genetically-encoded Ca2+ indicators. Here, we demonstrate that the recently developed GCaMP-X outperforms GCaMP in long-term probe expression and/or chronic Ca2+ imaging. GCaMP-X shows much improved compatibility with neurons and thus more reliable than GCaMP as demonstrated in vivo by acute Ca2+ responses to whisker deflection or spontaneous Ca2+ fluctuations over an extended time frame. Chronic Ca2+ imaging data (≥1 month) are acquired from the same set of cultured cortical neurons, unveiling that spontaneous/local Ca2+ activities would progressively develop into autonomous/global Ca2+ oscillations. Besides the morphological indices of neurite length or soma size, the major metrics of oscillatory Ca2+, including rate, amplitude, synchrony among different neurons or organelles have also been examined along with the developmental stages. Both neuritogenesis and Ca2+ signals are dysregulated by GCaMP in virus-infected or transgenic neurons, in direct contrast to GCaMP-X without any noticeable side-effect. Such in vitro data altogether consolidate the unique importance of oscillatory Ca2+ to activity-dependent neuritogenesis, as one major factor responsible for the distinctions between GCaMP vs GCaMP-X in vivo. For the first time with GCaMP-X of long-term expression in neurons, spontaneous and sensory-evoked Ca2+ activities are imaged and evaluated both in vitro and in vivo, providing new opportunities to monitor neural development or other chronic processes concurrently with Ca2+ dynamics.

scholarly journals TRAF3 mediates neuronal apoptosis in early brain injury following subarachnoid hemorrhage via targeting TAK1-dependent MAPKs and NF-κB pathways

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yan Zhou ◽  
Tao Tao ◽  
Guangjie Liu ◽  
Xuan Gao ◽  
Yongyue Gao ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Therapeutic Target ◽  
Cortical Neurons ◽  
Neuronal Apoptosis ◽  
Early Brain Injury ◽  
Neurological Deficits ◽  
Human Brain Tissue

AbstractNeuronal apoptosis has an important role in early brain injury (EBI) following subarachnoid hemorrhage (SAH). TRAF3 was reported as a promising therapeutic target for stroke management, which covered several neuronal apoptosis signaling cascades. Hence, the present study is aimed to determine whether downregulation of TRAF3 could be neuroprotective in SAH-induced EBI. An in vivo SAH model in mice was established by endovascular perforation. Meanwhile, primary cultured cortical neurons of mice treated with oxygen hemoglobin were applied to mimic SAH in vitro. Our results demonstrated that TRAF3 protein expression increased and expressed in neurons both in vivo and in vitro SAH models. TRAF3 siRNA reversed neuronal loss and improved neurological deficits in SAH mice, and reduced cell death in SAH primary neurons. Mechanistically, we found that TRAF3 directly binds to TAK1 and potentiates phosphorylation and activation of TAK1, which further enhances the activation of NF-κB and MAPKs pathways to induce neuronal apoptosis. Importantly, TRAF3 expression was elevated following SAH in human brain tissue and was mainly expressed in neurons. Taken together, our study demonstrates that TRAF3 is an upstream regulator of MAPKs and NF-κB pathways in SAH-induced EBI via its interaction with and activation of TAK1. Furthermore, the TRAF3 may serve as a novel therapeutic target in SAH-induced EBI.

scholarly journals Machine learning-based classification of mitochondrial morphology in primary neurons and brain

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Garrett M. Fogo ◽  
Anthony R. Anzell ◽  
Kathleen J. Maheras ◽  
Sarita Raghunayakula ◽  
Joseph M. Wider ◽  
...  
Keyword(s):  
Image Analysis ◽  
Cortical Neurons ◽  
Mitochondrial Dynamics ◽  
Automated Image Analysis ◽  
Mitochondrial Morphology ◽  
Analysis Pipeline ◽  
Genetic Ablation ◽  
Block Face

AbstractThe mitochondrial network continually undergoes events of fission and fusion. Under physiologic conditions, the network is in equilibrium and is characterized by the presence of both elongated and punctate mitochondria. However, this balanced, homeostatic mitochondrial profile can change morphologic distribution in response to various stressors. Therefore, it is imperative to develop a method that robustly measures mitochondrial morphology with high accuracy. Here, we developed a semi-automated image analysis pipeline for the quantitation of mitochondrial morphology for both in vitro and in vivo applications. The image analysis pipeline was generated and validated utilizing images of primary cortical neurons from transgenic mice, allowing genetic ablation of key components of mitochondrial dynamics. This analysis pipeline was further extended to evaluate mitochondrial morphology in vivo through immunolabeling of brain sections as well as serial block-face scanning electron microscopy. These data demonstrate a highly specific and sensitive method that accurately classifies distinct physiological and pathological mitochondrial morphologies. Furthermore, this workflow employs the use of readily available, free open-source software designed for high throughput image processing, segmentation, and analysis that is customizable to various biological models.

Kir6.2-containing ATP-sensitive potassium channels protect cortical neurons from ischemic/anoxic injury in vitro and in vivo

Neuroscience ◽  
2007 ◽  
Vol 144 (4) ◽  
pp. 1509-1515 ◽  
Author(s):  
H.-S. Sun ◽  
Z.-P. Feng ◽  
P.A. Barber ◽  
A.M. Buchan ◽  
R.J. French
Keyword(s):  
Potassium Channels ◽  
Cortical Neurons ◽  
Anoxic Injury

scholarly journals Metformin Inhibited Growth, Invasion and Metastasis of Esophageal Squamous Cell Carcinoma in Vitro and in Vivo

2018 ◽  
Vol 51 (3) ◽  
pp. 1276-1286 ◽  
Author(s):  
Feng Liang ◽  
Yu-Gang Wang ◽  
Changcheng Wang
Keyword(s):  
Squamous Cell Carcinoma ◽  
Plasma Glucose Level ◽  
Caspase 3 ◽  
Time Dependent ◽  
Dependent Manner ◽  
Metformin Treatment ◽  
Invasion And Migration ◽  
And Migration

Background/Aims: This study aimed at investigating the effects of metformin on the growth and metastasis of esophageal squamous cell carcinoma (ESCC) in vitro and in vivo. Methods: Two human ESCC cell lines EC9706 and Eca109 were selected and challenged with metformin in this study. Western blot assay was performed to detect th level of Bcl-2, Bax and Caspase-3. Scratch wound assay, transwell assay and Millicell invasion assay were used to assay the invasion and migration of EC9706 and Eca109 cells. Nude mice tumor models were used to assay the growth and lung metastasis of ESCC cells after metformin treatment. The plasma glucose level was also assayed. Results: We found that metformin significantly inhibited proliferation and induced apoptosis of both ESCC cell lines in a dose- and time-dependent manner, and the expression of Bcl-2 was down-regulated and Bax and Caspase-3 were up-regulated. Metformin significantly inhibited the invasion and migration of EC9706 and Eca109 cells (p < 0.05). mRNA and protein levels of MMP-2 and MMP-9 decreased significantly upon treatment with metformin of 10mM for 12, 24 and 48h in a time-dependent manner (p < 0.05). In line with in vitro results, in vivo experiments demonstrated that metformin inhibited tumorigenicity, inhibited lung metastasis and down-regulated the expression of MMP-2 and MMP-9. Moreover, we showed that metformin treatment did not cause significant alteration in liver and renal functions and plasma glucose level. Conclusion: Our study for the first time demonstrated the anti-invasive and anti-metastatic effects of metformin on human ESCC cells both in vitro and in vivo, which might be associated with the down-regulation of MMP-2 and MMP-9. As a whole, our results indicate the potential of metformin to be developed as a chemotherapeutic agent for patients with ESCC and might stimulate future studies on this area.

scholarly journals Optogenetic Modulation of a Minor Fraction of Parvalbumin-Positive Interneurons Specifically Affects Spatiotemporal Dynamics of Spontaneous and Sensory-Evoked Activity in Mouse Somatosensory Cortex in Vivo

2017 ◽  
Vol 27 (12) ◽  
pp. 5784-5803 ◽  
Author(s):  
Jenq-Wei Yang ◽  
Pierre-Hugues Prouvot ◽  
Vicente Reyes-Puerta ◽  
Maik C Stüttgen ◽  
Albrecht Stroh ◽  
...  
Keyword(s):  
Somatosensory Cortex ◽  
Spatiotemporal Dynamics ◽  
Minor Fraction ◽  
Evoked Activity ◽  
Sensory Evoked ◽  
A Minor

Thyroid hormone modulates androgen and oestrogen receptor content in the Sertoli cells of peripubertal rats

1996 ◽  
Vol 148 (1) ◽  
pp. 43-50 ◽  
Author(s):  
M L Panno ◽  
D Sisci ◽  
M Salerno ◽  
M Lanzino ◽  
V Pezzi ◽  
...  
Keyword(s):  
Sertoli Cells ◽  
Oestrogen Receptor ◽  
Age Groups ◽  
Strong Relationship ◽  
Inhibitory Influence ◽  
Aromatase Activity ◽  
Severe Impairment ◽  
Cellular Compartments

Abstract A possible role of tri-iodothyronine (T3) on the interplay between testicular steroids and Sertoli cells has been investigated on the basis of previous findings demonstrating a direct inhibitory influence of T3 on aromatase activity and oestradiol production in peripuberal Sertoli cells. In this context, the present study was focused on the effects of T3 on oestrogen receptor (ER) and androgen receptor (AR) contents in the cytosol and nucleus of Sertoli cells isolated from 2-, 3- and 4-week-old euthyroid, hypothyroid and hypothyroid treated rats. Hypothyroidism was induced by the oral administration of 0·025% methimazole (MMI) from birth until the rats were killed at 2, 3 and 4 weeks of age. Half of the MMI-treated animals were injected i.p. with l-tri-iodothyronine (T3; 3 μg/100 g body weight) during the last week before death. Sertoli cells from all groups were initially cultured under basal conditions for the first 24 h and subsequently in the presence of testosterone with or without T3 for an additional 24 h. Hypothyroidism was associated with severe impairment of body as well as testicular growth. Euthyroid ERs showed an elevated Kd (0·76 nm) which was similar in the different age groups investigated. The in vitro addition of T3 or testosterone induced a decrease in ER content and this decrease was greater after exposure to both hormones. In 2- and 3-week-old hypothyroid rats, ER content was markedly increased and was reversed in euthyroid rats when T3 was given in vivo. When ERs were assayed in the Sertoli cell nucleus and cytoplasm of 2- and 3-week-old animals, a strong relationship in ER content in the two cellular compartments was observed. Neither of the hormones tested seemed to affect the AR content in the nucleus significantly, while the in vitro addition of testosterone or T3 or both hormones together augmented the ARs in the cytosol to a greater extent, resulting in an increase in their total (cytosolic and nuclear) content in the cells. The present data suggest that T3 down-regulates ERs and up-regulates ARs in peripuberal Sertoli cells. The additive effect of testosterone and T3 in up-regulating ARs could possibly involve a role for T3 in influencing the androgen responsiveness of the Sertoli cells during spermatogenesis. Journal of Endocrinology (1996) 148, 43–50

scholarly journals KBP interacts with SCG10, linking Goldberg–Shprintzen syndrome to microtubule dynamics and neuronal differentiation

2010 ◽  
Vol 19 (18) ◽  
pp. 3642-3651 ◽  
Author(s):  
Maria M. Alves ◽  
Grzegorz Burzynski ◽  
Jean-Marie Delalande ◽  
Jan Osinga ◽  
Annemieke van der Goot ◽  
...  
Keyword(s):  
Nervous System ◽  
Enteric Nervous System ◽  
Neuronal Differentiation ◽  
Cortical Neurons ◽  
Neuronal Development ◽  
Direct Interaction ◽  
Clinical Disorder ◽  
Neurite Development

Abstract Goldberg–Shprintzen syndrome (GOSHS) is a rare clinical disorder characterized by central and enteric nervous system defects. This syndrome is caused by inactivating mutations in the Kinesin Binding Protein (KBP) gene, which encodes a protein of which the precise function is largely unclear. We show that KBP expression is up-regulated during neuronal development in mouse cortical neurons. Moreover, KBP-depleted PC12 cells were defective in nerve growth factor-induced differentiation and neurite outgrowth, suggesting that KBP is required for cell differentiation and neurite development. To identify KBP interacting proteins, we performed a yeast two-hybrid screen and found that KBP binds almost exclusively to microtubule associated or related proteins, specifically SCG10 and several kinesins. We confirmed these results by validating KBP interaction with one of these proteins: SCG10, a microtubule destabilizing protein. Zebrafish studies further demonstrated an epistatic interaction between KBP and SCG10 in vivo . To investigate the possibility of direct interaction between KBP and microtubules, we undertook co-localization and in vitro binding assays, but found no evidence of direct binding. Thus, our data indicate that KBP is involved in neuronal differentiation and that the central and enteric nervous system defects seen in GOSHS are likely caused by microtubule-related defects.

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