scholarly journals Modeling Attractor Deformation in the Rodent Head-Direction System

2000 ◽  
Vol 83 (6) ◽  
pp. 3402-3410 ◽  
Author(s):  
Jeremy P. Goodridge ◽  
David S. Touretzky
Keyword(s):  
Angular Velocity ◽  
Primary Source ◽  
Inhibitory Neurons ◽  
Surprising Result ◽  
Head Direction ◽  
Anterior Thalamus ◽  
Attractor Dynamics ◽  
Cell Firing

We present a model of the head-direction circuit in the rat that improves on earlier models in several respects. First, it provides an account of some of the unique characteristics of head-direction (HD) cell firing in the lateral mammillary nucleus and the anterior thalamus. Second, the model functions without making physiologically unrealistic assumptions. In particular, it implements attractor dynamics in postsubiculum and lateral mammillary nucleus without directionally tuned inhibitory neurons, which have never been observed in vivo, and it integrates angular velocity without the use of multiplicative synapses. The model allows us to examine the relationships among three HD areas and various properties of their representations. A surprising result is that certain combinations of purported HD cell properties are mutually incompatible, suggesting that the lateral mammillary nucleus may not be the primary source of head direction input to anterior thalamic HD cells.

scholarly journals How activity dependent feedback inhibition may maintain head direction signals in mouse presubiculum

2017 ◽  
Author(s):  
Jean Simonnet ◽  
Mérie Nassar ◽  
Federico Stella ◽  
Ivan Cohen ◽  
Bertrand Mathon ◽  
...  
Keyword(s):  
Feedback Inhibition ◽  
Head Direction ◽  
Synaptic Excitation ◽  
Anterior Thalamus ◽  
Neuron Activation ◽  
Synaptic Interactions ◽  
Attractor Dynamics ◽  
Direction Information ◽  
And Function ◽  
Activity Dependent

ABSTRACTOrientation in space is represented in specialized brain circuits. Persistent head direction signals are transmitted from anterior thalamus to the presubiculum, but the identity of the presubicular target neurons, their connectivity and function in local microcircuits are unknown. Here we examine how thalamic afferents recruit presubicular principal neurons and Martinotti interneurons and the ensuing synaptic interactions between these cells. Pyramidal neuron activation of Martinotti cells in superficial layers is strongly facilitating such that high frequency head directional stimulation efficiently unmutes synaptic excitation. Martinotti cell feedback plays a dual role: precisely timed spikes may not inhibit the firing of in-tune head direction cells, while exerting lateral inhibition. Autonomous attractor dynamics emerge from a modeled network implementing wiring motifs and timing sensitive synaptic interactions in the pyramidal - Martinotti cell feedback loop. This inhibitory microcircuit is therefore tuned to refine and maintain head direction information in the presubiculum.

Effects of Unfractionated and Low Molecular Weight Heparins on Platelet Thromboxane Biosynthesis “In Vivo”

1994 ◽  
Vol 72 (06) ◽  
pp. 942-946 ◽  
Author(s):  
Raffaele Landolfi ◽  
Erica De Candia ◽  
Bianca Rocca ◽  
Giovanni Ciabattoni ◽  
Armando Antinori ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Unfractionated Heparin ◽  
Low Molecular Weight Heparin ◽  
Primary Source ◽  
In Vivo Studies ◽  
Low Molecular Weight ◽  
Heparin Administration ◽  
To Receive

SummarySeveral “in vitro” and “in vivo” studies indicate that heparin administration may affect platelet function. In this study we investigated the effects of prophylactic heparin on thromboxane (Tx)A2 biosynthesis “in vivo”, as assessed by the urinary excretion of major enzymatic metabolites 11-dehydro-TxB2 and 2,3-dinor-TxB2. Twenty-four patients who were candidates for cholecystectomy because of uncomplicated lithiasis were randomly assigned to receive placebo, unfractionated heparin, low molecular weight heparin or unfractionaed heparin plus 100 mg aspirin. Measurements of daily excretion of Tx metabolites were performed before and during the treatment. In the groups assigned to placebo and to low molecular weight heparin there was no statistically significant modification of Tx metabolite excretion while patients receiving unfractionated heparin had a significant increase of both metabolites (11-dehydro-TxB2: 3844 ± 1388 vs 2092 ±777, p <0.05; 2,3-dinor-TxB2: 2737 ± 808 vs 1535 ± 771 pg/mg creatinine, p <0.05). In patients randomized to receive low-dose aspirin plus unfractionated heparin the excretion of the two metabolites was largely suppressed thus suggesting that platelets are the primary source of enhanced thromboxane biosynthesis associated with heparin administration. These data indicate that unfractionated heparin causes platelet activation “in vivo” and suggest that the use of low molecular weight heparin may avoid this complication.

SECRETION OF PROGESTERONE DURING GESTATION IN THE RAT

1978 ◽  
Vol 79 (2) ◽  
pp. 179-190 ◽  
Author(s):  
MRINAL K. SANYAL
Keyword(s):  
Abdominal Aorta ◽  
Primary Source ◽  
Solvent System ◽  
Peripheral Circulation ◽  
Systemic Circulation ◽  
Maternal Circulation ◽  
Secondary Importance ◽  
System Hexane ◽  
Venous Plasma

The concentrations of progesterone and 5α-pregnane-3,20-dione in ovarian and uterine venous plasma and in the systemic circulation were measured during gestation in the rat. The steroids were quantified by radioimmunoassay after separation on silicic acid microcolumns with the solvent system hexane: ethyl acetate (5: 2, v/v). The concentration of progesterone in the systemic circulation was highest on days 3–4 and 13–17 of pregnancy; throughout gestation, the concentration of 5α-pregnane-3,20-dione was low in relation to that of progesterone and showed no marked changes as gestation proceeded. The level of progesterone in ovarian venous effluent was 10–20 times higher than that in the uterine vein and 20–50 times greater than that in the systemic circulation. The rate of secretion of progesterone by the ovary was highest during days 13–17 of gestation and ovariectomy during this period markedly reduced the levels of progesterone in the peripheral circulation. The concentration of progesterone in the uterine venous effluent was raised compared with the concentration in plasma from the abdominal aorta, especially on days 7 and 9 of pregnancy. These results suggest that, in vivo, the rat placenta synthesizes small amounts of progesterone and secretes it into the maternal circulation. The ovary is the primary source of progesterone during pregnancy and the placental contribution is of secondary importance. Although 4-ene-5α-reductase enzyme(s) is present in the ovary and placenta, significant quantities of the reduced progestin 5α-pregnane-3,20-dione are not secreted into the systemic circulation during gestation in the rat.

Targeting TAZ and YAP as a New Therapeutic Approach to Diabetic Nephropathy

2018 ◽  
Author(s):  
Lauren Chan
Keyword(s):  
Transforming Growth Factor ◽  
Primary Source ◽  
Transforming Growth Factor Β ◽  
Mechanical Stimuli ◽  
Nuclear Retention ◽  
Retention Factors ◽  
Smad Signaling Pathway ◽  
Nuclear Location ◽  
Smad 3

Introduction Fibrosis is a major contributor to chronic kidney disease (CKD), for which no effective clinical treatment exists. The primary source of fibrosis is the activation of fibroblasts to the myofibroblast state. Fibroblast-myofibroblast transition requires transforming growth factor-β (TGF-β) and its canonical Smad signaling pathway.   Purpose Recent findings suggest that mechanical stimuli affect fibroblast behavior. Nuclear localization of YAP/TAZ, closely associated mechanosensitive transcriptional co-factors, are regulated by substrate stiffness. As YAP/TAZ are Smad nuclear retention factors promoting TGF- β signaling, we hypothesized that YAP/TAZ inhibition could attenuate stiffness-mediated, TGF- β induced pro-fibrotic responses.   Methods Immunostaining and immunoblotting were used to analyze localization and activity of YAP/TAZ and Smad levels, respectively.   Results YAP/TAZ are in an active nuclear location in fibroblasts grown on stiff, fibrotic-like substrates (100kPa). In fibroblasts grown on soft substrates (2kPa), YAP/TAZ are primarily in an inactive cytosolic position. Cells grown on soft surfaces demonstrated strongly attenuated nuclear Smad 2/3 translocation and Smad-3 dependent transcription upon TGF-β stimulation, indicating impaired pro-fibrotic signaling. Verteporfin, a clinically approved drug with YAP inhibitory properties, was used to test the role of YAP/TAZ in reduced TGF-β signaling. Verteporfin reduced TGF-β-induced nuclear Smad2/3 accumulation and Smad3-mediated  transcription in fibroblasts grown on stiff surfaces. In vivo, Verteporfin significantly reduces markers of renal fibrosis.   Conclusions Soft, healthy kidney-like substrates inhibit, while stiff fibrotic-like substrates promote, pro-fibrotic TGF-β Smad signalling. Verteporfin inactivates the YAP/TAZ fibroblast mechanosensor, reduces stiffness-augmented fibroblast responses to TGF-β through blockade of Smad signalling, and may be a novel anti-fibrotic agent for CKD.

Fast Inhibition Alters First Spike Timing in Auditory Brainstem Neurons

2004 ◽  
Vol 92 (4) ◽  
pp. 2615-2621 ◽  
Author(s):  
Antonio G. Paolini ◽  
Janine C. Clarey ◽  
Karina Needham ◽  
Graeme M. Clark
Keyword(s):  
Lateral Inhibition ◽  
Cochlear Nucleus ◽  
Stellate Cell ◽  
Discharge Rate ◽  
Stellate Cells ◽  
Auditory Pathway ◽  
Auditory Brainstem ◽  
Spike Timing ◽  
Inhibitory Neurons

Within the first processing site of the central auditory pathway, inhibitory neurons (D stellate cells) broadly tuned to tonal frequency project on narrowly tuned, excitatory output neurons (T stellate cells). The latter is thought to provide a topographic representation of sound spectrum, whereas the former is thought to provide lateral inhibition that improves spectral contrast, particularly in noise. In response to pure tones, the overall discharge rate in T stellate cells is unlikely to be suppressed dramatically by D stellate cells because they respond primarily to stimulus onset and provide fast, short-duration inhibition. In vivo intracellular recordings from the ventral cochlear nucleus (VCN) showed that, when tones were presented above or below the characteristic frequency (CF) of a T stellate neuron, they were inhibited during depolarization. This resulted in a delay in the initial action potential produced by T stellate cells. This ability of fast inhibition to alter the first spike timing of a T stellate neuron was confirmed by electrically activating the D stellate cell pathway that arises in the contralateral cochlear nucleus. Delay was also induced when two tones were presented: one at CF and one outside the frequency response area of the T stellate neuron. These findings suggest that the traditional view of lateral inhibition within the VCN should incorporate delay as one of its principle outcomes.

scholarly journals Statistical Comparison of Spike Responses to Natural Stimuli in Monkey Area V1 With Simulated Responses of a Detailed Laminar Network Model for a Patch of V1

2011 ◽  
Vol 105 (2) ◽  
pp. 757-778 ◽  
Author(s):  
Malte J. Rasch ◽  
Klaus Schuch ◽  
Nikos K. Logothetis ◽  
Wolfgang Maass
Keyword(s):  
Network Model ◽  
Network Models ◽  
Cortical Network ◽  
Inhibitory Neurons ◽  
Sensory Stimuli ◽  
Natural Stimuli ◽  
Cortical Areas ◽  
Model Response ◽  
Spiking Activity

A major goal of computational neuroscience is the creation of computer models for cortical areas whose response to sensory stimuli resembles that of cortical areas in vivo in important aspects. It is seldom considered whether the simulated spiking activity is realistic (in a statistical sense) in response to natural stimuli. Because certain statistical properties of spike responses were suggested to facilitate computations in the cortex, acquiring a realistic firing regimen in cortical network models might be a prerequisite for analyzing their computational functions. We present a characterization and comparison of the statistical response properties of the primary visual cortex (V1) in vivo and in silico in response to natural stimuli. We recorded from multiple electrodes in area V1 of 4 macaque monkeys and developed a large state-of-the-art network model for a 5 × 5-mm patch of V1 composed of 35,000 neurons and 3.9 million synapses that integrates previously published anatomical and physiological details. By quantitative comparison of the model response to the “statistical fingerprint” of responses in vivo, we find that our model for a patch of V1 responds to the same movie in a way which matches the statistical structure of the recorded data surprisingly well. The deviation between the firing regimen of the model and the in vivo data are on the same level as deviations among monkeys and sessions. This suggests that, despite strong simplifications and abstractions of cortical network models, they are nevertheless capable of generating realistic spiking activity. To reach a realistic firing state, it was not only necessary to include both N -methyl-d-aspartate and GABAB synaptic conductances in our model, but also to markedly increase the strength of excitatory synapses onto inhibitory neurons (>2-fold) in comparison to literature values, hinting at the importance to carefully adjust the effect of inhibition for achieving realistic dynamics in current network models.

scholarly journals Seizures start as silent microseizures by neuronal ensembles

2018 ◽  
Author(s):  
Michael Wenzel ◽  
Jordan P. Hamm ◽  
Darcy S. Peterka ◽  
Rafael MD Yuste
Keyword(s):  
Calcium Imaging ◽  
Travelling Wave ◽  
Inhibitory Neurons ◽  
Neural Activation ◽  
Calcium Dynamics ◽  
Neuronal Ensembles ◽  
Two Photon ◽  
Step Model

AbstractUnderstanding seizure formation and spread remains a critical goal of epilepsy research. While many studies have documented seizure spread, it remains mysterious how they start. We used fast in-vivo two-photon calcium imaging to reconstruct, at cellular resolution, the dynamics of focal cortical seizures as they emerge in epileptic foci (intrafocal), and subsequently propagate (extrafocal). We find that seizures start as intrafocal coactivation of small numbers of neurons (ensembles), which are electrographically silent. These silent “microseizures” expand saltatorily until they break into neighboring cortex, where they progress smoothly and first become detectable by LFP. Surprisingly, we find spatially heterogeneous calcium dynamics of local PV interneuron sub-populations, which rules out a simple role of inhibitory neurons during seizures. We propose a two-step model for the circuit mechanisms of focal seizures, where neuronal ensembles first generate a silent microseizure, followed by widespread neural activation in a travelling wave, which is then detected electrophysiologically.

scholarly journals Molecular Characterization of Superficial Layers of the Presubiculum During Development

2021 ◽  
Vol 15 ◽  
Author(s):  
Jiayan Liu ◽  
Tetsuhiko Kashima ◽  
Shota Morikawa ◽  
Asako Noguchi ◽  
Yuji Ikegaya ◽  
...  
Keyword(s):  
Spatial Representation ◽  
Critical Role ◽  
Glutamate Transporter ◽  
Direction Selectivity ◽  
Inhibitory Neurons ◽  
Head Direction ◽  
Anterior Thalamic Nucleus ◽  
Functional Development ◽  
Eye Opening ◽  
Anterograde Tracer

The presubiculum, a subarea of the parahippocampal region, plays a critical role in spatial navigation and spatial representation. An outstanding aspect of presubicular spatial codes is head-direction selectivity of the firing of excitatory neurons, called head-direction cells. Head-direction selectivity emerges before eye-opening in rodents and is maintained in adulthood through neurophysiological interactions between excitatory and inhibitory neurons. Although the presubiculum has been physiologically profiled in terms of spatial representation during development, the histological characteristics of the developing presubiculum are poorly understood. We found that the expression of vesicular glutamate transporter 2 (VGluT2) could be used to delimit the superficial layers of the presubiculum, which was identified using an anterograde tracer injected into the anterior thalamic nucleus (ATN). Thus, we immunostained slices from mice ranging in age from neonates to adults using an antibody against VGluT2 to evaluate the VGluT2-positive area, which was identified as the superficial layers of the presubiculum, during development. We also immunostained the slices using antibodies against parvalbumin (PV) and somatostatin (SOM) and found that in the presubicular superficial layers, PV-positive neurons progressively increased in number during development, whereas SOM-positive neurons exhibited no increasing trend. In addition, we observed repeating patch structures in presubicular layer III from postnatal days 12. The abundant expression of VGluT2 suggests that the presubicular superficial layers are regulated primarily by VGluT2-mediated excitatory neurotransmission. Moreover, developmental changes in the densities of PV- and SOM-positive interneurons and the emergence of the VGluT2-positive patch structures during adolescence may be associated with the functional development of spatial codes in the superficial layers of the presubiculum.

scholarly journals Subanesthetic ketamine reactivates adult cortical plasticity to restore vision from amblyopia

2020 ◽  
Author(s):  
Steven F. Grieco ◽  
Xin Qiao ◽  
Xiaoting Zheng ◽  
Yongjun Liu ◽  
Lujia Chen ◽  
...  
Keyword(s):  
Functional Recovery ◽  
Neural Plasticity ◽  
Cortical Plasticity ◽  
Brain Plasticity ◽  
Excitatory Input ◽  
Inhibitory Neurons ◽  
List Type ◽  
Visual Cortical

SummarySubanesthetic ketamine evokes rapid and long-lasting antidepressant effects in human patients. The mechanism for ketamine’s effects remains elusive, but ketamine may broadly modulate brain plasticity processes. We show that single-dose ketamine reactivates adult mouse visual cortical plasticity and promotes functional recovery of visual acuity defects from amblyopia. Ketamine specifically induces down-regulation of neuregulin-1 (NRG1) expression in parvalbumin-expressing (PV) inhibitory neurons in mouse visual cortex. NRG1 downregulation in PV neurons co-tracks both the fast onset and sustained decreases in synaptic inhibition to excitatory neurons, along with reduced synaptic excitation to PV neurons in vitro and in vivo following a single ketamine treatment. These effects are blocked by exogenous NRG1 as well as PV targeted receptor knockout. Thus ketamine reactivation of adult visual cortical plasticity is mediated through rapid and sustained cortical disinhibition via downregulation of PV-specific NRG1 signaling. Our findings reveal the neural plasticity-based mechanism for ketamine-mediated functional recovery from adult amblyopia.Highlights○ Disinhibition of excitatory cells by ketamine occurs in a fast and sustained manner○ Ketamine evokes NRG1 downregulation and excitatory input loss to PV cells○ Ketamine induced plasticity is blocked by exogenous NRG1 or its receptor knockout○ PV inhibitory cells are the initial functional locus underlying ketamine’s effects

scholarly journals Cytoplasmic accumulation of FUS triggers early behavioral alterations linked to cortical neuronal hyperactivity and defects in inhibitory synapses

2020 ◽  
Author(s):  
Jelena Scekic-Zahirovic ◽  
Inmaculada Sanjuan-Ruiz ◽  
Vanessa Kan ◽  
Salim Megat ◽  
Pierre De Rossi ◽  
...  
Keyword(s):  
Neuronal Activity ◽  
Rna Binding ◽  
Gene Mutations ◽  
Neuronal Loss ◽  
Inhibitory Neurons ◽  
Inhibitory Synapses ◽  
Behavioral Alterations ◽  
Behavioral Abnormalities ◽  
Cytoplasmic Accumulation

AbstractGene mutations causing cytoplasmic mislocalization of the RNA-binding protein FUS, lead to severe forms of amyotrophic lateral sclerosis (ALS). Cytoplasmic accumulation of FUS is also observed in other diseases, with unknown consequences. Here, we show that cytoplasmic mislocalization of FUS drives behavioral abnormalities in knock-in mice, including locomotor hyperactivity and alterations in social interactions, in the absence of widespread neuronal loss. Mechanistically, we identified a profound increase in neuronal activity in the frontal cortex of Fus knock-in mice in vivo. Importantly, RNAseq analysis suggested involvement of defects in inhibitory neurons, that was confirmed by ultrastructural and morphological defects of inhibitory synapses and increased synaptosomal levels of mRNAs involved in inhibitory neurotransmission. Thus, cytoplasmic FUS triggers inhibitory synaptic deficits, leading to increased neuronal activity and behavioral phenotypes. FUS mislocalization may trigger deleterious phenotypes beyond motor neuron impairment in ALS, but also in other neurodegenerative diseases with FUS mislocalization.

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