scholarly journals Impact of functional synapse clusters on neuronal response selectivity

2019 ◽  
Author(s):  
Balázs B Ujfalussy ◽  
Judit K Makara
Keyword(s):  
Large Scale ◽  
Pyramidal Neurons ◽  
Neuronal Response ◽  
Cluster Formation ◽  
Biophysical Model ◽  
Functional Clustering ◽  
Synaptic Interactions ◽  
Nonlinear Amplification ◽  
Output Transformation

SummaryClustering of functionally similar synapses in dendrites is thought to affect input-output transformation by inducing dendritic nonlinearities. However, neither the in vivo impact of synaptic clusters on somatic membrane potential (sVm), nor the rules of cluster formation are elucidated. We developed a computational approach to measure the effect of functional synaptic clusters on sVm response of biophysical model CA1 and L2/3 pyramidal neurons to behaviorally relevant in vivo-like inputs. Large-scale dendritic spatial inhomogeneities in synaptic tuning properties did influence sVm, but small synaptic clusters appearing randomly with unstructured connectivity did not. With structured connectivity, ~10-20 synapses per cluster was optimal for clustering-based tuning, but larger responses were achieved by 2-fold potentiation of the same synapses. We further show that without nonlinear amplification of the effect of random clusters, action potential-based, global plasticity rules can not generate functional clustering. Our results suggest that clusters likely form via local synaptic interactions, and have to be moderately large to impact sVm responses.

scholarly journals Impact of functional synapse clusters on neuronal response selectivity

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Balázs B. Ujfalussy ◽  
Judit K. Makara
Keyword(s):  
Pyramidal Neurons ◽  
Neuronal Response ◽  
Cluster Formation ◽  
Biophysical Model ◽  
Functional Clustering ◽  
State Dependent ◽  
Synaptic Interactions ◽  
Output Transformation ◽  
Random Connectivity

AbstractClustering of functionally similar synapses in dendrites is thought to affect neuronal input-output transformation by triggering local nonlinearities. However, neither the in vivo impact of synaptic clusters on somatic membrane potential (sVm), nor the rules of cluster formation are elucidated. We develop a computational approach to measure the effect of functional synaptic clusters on sVm response of biophysical model CA1 and L2/3 pyramidal neurons to in vivo-like inputs. We demonstrate that small synaptic clusters appearing with random connectivity do not influence sVm. With structured connectivity,  ~10–20 synapses/cluster are optimal for clustering-based tuning via state-dependent mechanisms, but larger selectivity is achieved by 2-fold potentiation of the same synapses. We further show that without nonlinear amplification of the effect of random clusters, action potential-based, global plasticity rules cannot generate functional clustering. Our results suggest that clusters likely form via local synaptic interactions, and have to be moderately large to impact sVm responses.

scholarly journals Chandelier cell anatomy and function reveal a variably distributed but common signal

2020 ◽  
Author(s):  
Casey M. Schneider-Mizell ◽  
Agnes L. Bodor ◽  
Forrest Collman ◽  
Derrick Brittain ◽  
Adam A. Bleckert ◽  
...  
Keyword(s):  
Large Scale ◽  
Pyramidal Neurons ◽  
Cell Activity ◽  
Cortical Cell ◽  
Cell Types ◽  
Structural Features ◽  
Target Neuron ◽  
Chandelier Cell ◽  
Chandelier Cells

AbstractThe activity and connectivity of inhibitory cells has a profound impact on the operation of neuronal networks. While the average connectivity of many inhibitory cell types has been characterized, we still lack an understanding of how individual interneurons distribute their synapses onto their targets and how heterogeneous the inhibition is onto different individual excitatory neurons. Here, we use large-scale volumetric electron microscopy (EM) and functional imaging to address this question for chandelier cells in layer 2/3 of mouse visual cortex. Using dense morphological reconstructions from EM, we mapped the complete chandelier input onto 153 pyramidal neurons. We find that the number of input synapses is highly variable across the population, but the variability is correlated with structural features of the target neuron: soma depth, soma size, and the number of perisomatic synapses received. Functionally, we found that chandelier cell activity in vivo was highly correlated and tracks pupil diameter, a proxy for arousal state. We propose that chandelier cells provide a global signal whose strength is individually adjusted for each target neuron. This approach, combining comprehensive structural analysis with functional recordings of identified cell types, will be a powerful tool to uncover the wiring rules across the diversity of cortical cell types.

scholarly journals Optimization of a novel biophysical model using large scale in vivo antisense hybridization data displays improved prediction capabilities of structurally accessible RNA regions

2017 ◽  
Vol 45 (9) ◽  
pp. 5523-5538 ◽  
Author(s):  
Jorge Vazquez-Anderson ◽  
Mia K. Mihailovic ◽  
Kevin C. Baldridge ◽  
Kristofer G. Reyes ◽  
Katie Haning ◽  
...  
Keyword(s):  
Large Scale ◽  
Biophysical Model ◽  
Hybridization Data

scholarly journals Efficient Position Decoding Methods Based on Fluorescence Calcium Imaging in the Mouse Hippocampus

2020 ◽  
Vol 32 (6) ◽  
pp. 1144-1167
Author(s):  
Mengyu Tu ◽  
Ruohe Zhao ◽  
Avital Adler ◽  
Wen-Biao Gan ◽  
Zhe S. Chen
Keyword(s):  
Calcium Imaging ◽  
Large Scale ◽  
Pyramidal Neurons ◽  
Signal To Noise Ratio ◽  
Frame Rate ◽  
Mouse Hippocampus ◽  
Time Position ◽  
In Vivo Calcium Imaging

Large-scale fluorescence calcium imaging methods have become widely adopted for studies of long-term hippocampal and cortical neuronal dynamics. Pyramidal neurons of the rodent hippocampus show spatial tuning in freely foraging or head-fixed navigation tasks. Development of efficient neural decoding methods for reconstructing the animal's position in real or virtual environments can provide a fast readout of spatial representations in closed-loop neuroscience experiments. Here, we develop an efficient strategy to extract features from fluorescence calcium imaging traces and further decode the animal's position. We validate our spike inference-free decoding methods in multiple in vivo calcium imaging recordings of the mouse hippocampus based on both supervised and unsupervised decoding analyses. We systematically investigate the decoding performance of our proposed methods with respect to the number of neurons, imaging frame rate, and signal-to-noise ratio. Our proposed supervised decoding analysis is ultrafast and robust, and thereby appealing for real-time position decoding applications based on calcium imaging.

scholarly journals Feedback inhibition and its control in an insect olfactory circuit

2019 ◽  
Author(s):  
Subhasis Ray ◽  
Zane N. Aldworth ◽  
Mark A. Stopfer
Keyword(s):  
Large Scale ◽  
Dynamic Range ◽  
Feedback Inhibition ◽  
Inhibitory Neurons ◽  
Biophysical Model ◽  
Intrinsic Properties ◽  
Olfactory Pathway ◽  
Olfactory Responses ◽  
Electrophysiological Recordings

AbstractInhibitory neurons play critical roles in regulating and shaping olfactory responses in vertebrates and invertebrates. In insects, these roles are performed by relatively few neurons, which can be interrogated efficiently, revealing fundamental principles of olfactory coding. Here, with electrophysiological recordings from the locust and a large-scale biophysical model, we analyzed the properties and functions of GGN, a unique giant GABAergic neuron that plays a central role in structuring olfactory codes in the locust mushroom body. Analysis of our in vivo recordings and simulations of our model of the olfactory network suggests that GGN extends the dynamic range of KCs, and leads us to predict the existence of a yet undiscovered olfactory pathway. Our analysis of GGN’s intrinsic properties, inputs, and outputs, in vivo and in silico, reveals basic new features of this critical neuron and the olfactory network that surrounds it.

scholarly journals Global, multiplexed dendritic computations under in vivo-like conditions

2017 ◽  
Author(s):  
Balázs B Ujfalussy ◽  
Máté Lengyel ◽  
Tiago Branco
Keyword(s):  
Synaptic Input ◽  
Biophysical Model ◽  
Single Neurons ◽  
Input Output ◽  
Linear Integration ◽  
Cortical Circuit ◽  
Spatio Temporal ◽  
Somatic Response ◽  
Output Transformation

AbstractDendrites integrate inputs in highly non-linear ways, but it is unclear how these non-linearities contribute to the overall input-output transformation of single neurons. Here, we developed statistically principled methods using a hierarchical cascade of linear-nonlinear subunits (hLN) to model the dynamically evolving somatic response of neurons receiving complex spatio-temporal synaptic input patterns. We used the hLN to predict the membrane potential of a detailed biophysical model of a L2/3 pyramidal cell receiving in vivo-like synaptic input and reproducing in vivo dendritic recordings. We found that more than 90% of the somatic response could be captured by linear integration followed a single global non-linearity. Multiplexing inputs into parallel processing channels could improve prediction accuracy by as much as additional layers of local non-linearities. These results provide a data-driven characterisation of a key building block of cortical circuit computations: dendritic integration and the input-output transformation of single neurons during in vivo-like conditions.

Minimal Models of Adapted Neuronal Response to In Vivo–Like Input Currents

2004 ◽  
Vol 16 (10) ◽  
pp. 2101-2124 ◽  
Author(s):  
Giancarlo La Camera ◽  
Alexander Rauch ◽  
Hans-R. Lüscher ◽  
Walter Senn ◽  
Stefano Fusi
Keyword(s):  
Pyramidal Neurons ◽  
Neuronal Response ◽  
Large Population ◽  
Time Varying ◽  
Minimal Models ◽  
Stationary Model ◽  
The Central Nervous System ◽  
Mechanisms Of Adaptation ◽  
Reversal Potentials

Rate models are often used to study the behavior of large networks of spiking neurons. Here we propose a procedure to derive rate models that take into account the fluctuations of the input current and firing-rate adaptation, two ubiquitous features in the central nervous system that have been previously overlooked in constructing rate models. The procedure is general and applies to any model of firing unit. As examples, we apply it to the leaky integrate-and-fire (IF) neuron, the leaky IF neuron with reversal potentials, and to the quadratic IF neuron. Two mechanisms of adaptation are considered, one due to an after hyperpolarization current and the other to an adapting threshold for spike emission. The parameters of these simple models can be tuned to match experimental data obtained from neocortical pyramidal neurons. Finally, we show how the stationary model can be used to predict the time-varying activity of a large population of adapting neurons.

Purification of the Antihemophilic Factor by Gel Filtration on Agarose

1969 ◽  
Vol 22 (03) ◽  
pp. 577-583 ◽  
Author(s):  
M.M.P Paulssen ◽  
A.C.M.G.B Wouterlood ◽  
H.L.M.A Scheffers
Keyword(s):  
Factor Viii ◽  
Plasma Proteins ◽  
Large Scale ◽  
Gel Filtration ◽  
Large Scale Preparation ◽  
Scale Preparation ◽  
Antihemophilic Factor

SummaryFactor VIII can be isolated from plasma proteins, including fibrinogen by chromatography on agarose. The best results were obtained with Sepharose 6B. Large scale preparation is also possible when cryoprecipitate is separated by chromatography. In most fractions containing factor VIII a turbidity is observed which may be due to the presence of chylomicrons.The purified factor VIII was active in vivo as well as in vitro.

The Effect of Active Site-inhibited Factor VIIa on Tissue Factor-initiated Coagulation Using Platelets before and after Aspirin Administration

1997 ◽  
Vol 78 (04) ◽  
pp. 1202-1208 ◽  
Author(s):  
Marianne Kjalke ◽  
Julie A Oliver ◽  
Dougald M Monroe ◽  
Maureane Hoffman ◽  
Mirella Ezban ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Active Site ◽  
Large Scale ◽  
Thrombin Generation ◽  
Factor Viia ◽  
Dependent Manner ◽  
Antithrombotic Agent ◽  
Before And After ◽  
Ic50 Values

SummaryActive site-inactivated factor VIIa has potential as an antithrombotic agent. The effects of D-Phe-L-Phe-L-Arg-chloromethyl ketone-treated factor VIla (FFR-FVIIa) were evaluated in a cell-based system mimicking in vivo initiation of coagulation. FFR-FVIIa inhibited platelet activation (as measured by expression of P-selectin) and subsequent large-scale thrombin generation in a dose-dependent manner with IC50 values of 1.4 ± 0.8 nM (n = 8) and 0.9 ± 0.7 nM (n = 7), respectively. Kd for factor VIIa binding to monocytes ki for FFR-FVIIa competing with factor VIIa were similar (11.4 ± 0.8 pM and 10.6 ± 1.1 pM, respectively), showing that FFR-FVIIa binds to tissue factor in the tenase complex with the same affinity as factor VIIa. Using platelets from volunteers before and after ingestion of aspirin (1.3 g), there were no significant differences in the IC50 values of FFR-FVIIa [after aspirin ingestion, the IC50 values were 1.7 ± 0.9 nM (n = 8) for P-selectin expression, p = 0.37, and 1.4 ± 1.3 nM (n = 7) for thrombin generation, p = 0.38]. This shows that aspirin treatment of platelets does not influence the inhibition of tissue factor-initiated coagulation by FFR-FVIIa, probably because thrombin activation of platelets is not entirely dependent upon expression of thromboxane A2.

Naphthoquinones and derivatives for chemotherapy: perspectives and limitations of their anti-trypanosomatids activities

2020 ◽  
Vol 26 ◽  
Author(s):  
Luíza Dantas-Pereira ◽  
Edézio F. Cunha-Junior ◽  
Valter V. Andrade-Neto ◽  
John F. Bower ◽  
Guilherme A. M. Jardim ◽  
...  
Keyword(s):  
Large Scale ◽  
Neglected Tropical Diseases ◽  
Folk Medicine ◽  
Leishmania Species ◽  
Parasitic Infections ◽  
Mechanistic Analysis ◽  
Leishmania Spp ◽  
Nanomolar Range

: Chagas disease, Sleeping sickness and Leishmaniasis, caused by trypanosomatids Trypanosoma cruzi, Trypanosoma brucei and Leishmania spp., respectively, are considered neglected tropical diseases, and they especially affect impoverished populations in the developing world. The available chemotherapies are very limited and a search for alternatives is still necessary. In folk medicine, natural naphthoquinones have been employed for the treatment of a great variety of illnesses, including parasitic infections. This review is focused on the anti-trypanosomatid activity and mechanistic analysis of naphthoquinones and derivatives. Among all the series of derivatives tested in vitro, naphthoquinone-derived 1,2,3-triazoles were very active on T. cruzi infective forms in blood bank conditions, as well as in amastigotes of Leishmania spp. naphthoquinones containing a CF3 on a phenyl amine ring inhibited T. brucei proliferation in the nanomolar range, and naphthopterocarpanquinones stood out for their activity on a range of Leishmania species. Some of these compounds showed a promising selectivity index (SI) (30 to 1900), supporting further analysis in animal models. Indeed, high toxicity to the host and inactivation by blood components are crucial obstacles to be overcome to use naphthoquinones and/or their derivatives for chemotherapy. Multidisciplinary initiatives embracing medicinal chemistry, bioinformatics, biochemistry, and molecular and cellular biology need to be encouraged to allow the optimization of these compounds. Large scale automated tests are pivotal for the efficiency of the screening step, and subsequent evaluation of both the mechanism of action in vitro and pharmacokinetics in vivo are essential for the development of a novel, specific and safe derivative, minimizing adverse effects.

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