Browsing by Subject "inhibition"

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    Behavioral state and stimulus strength regulate the role of somatostatin interneurons in stabilizing network activity.
    (bioRxiv, 2024-09-10) Cammarata, Celine M; Pei, Yingming; Shields, Brenda C; Lim, Shaun SX; Hawley, Tammy; Li, Jennifer Y; St Amand, David; Brunel, Nicolas; Tadross, Michael R; Glickfeld, Lindsey L
    Inhibition stabilization enables cortical circuits to encode sensory signals across diverse contexts. Somatostatin-expressing (SST) interneurons are well-suited for this role through their strong recurrent connectivity with excitatory pyramidal cells. We developed a cortical circuit model predicting that SST cells become increasingly important for stabilization as sensory input strengthens. We tested this prediction in mouse primary visual cortex by manipulating excitatory input to SST cells, a key parameter for inhibition stabilization, with a novel cell-type specific pharmacological method to selectively block glutamatergic receptors on SST cells. Consistent with our model predictions, we find antagonizing glutamatergic receptors drives a paradoxical facilitation of SST cells with increasing stimulus contrast. In addition, we find even stronger engagement of SST-dependent stabilization when the mice are aroused. Thus, we reveal that the role of SST cells in cortical processing gradually switches as a function of both input strength and behavioral state.
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    Blood flow controls coagulation onset via the positive feedback of factor VII activation by factor Xa
    (2010) Shibeko, Alexey M; Lobanova, Ekaterina S; Panteleev, Mikhail A; Ataullakhanov, Fazoil I
    Background: Blood coagulation is a complex network of biochemical reactions, which is peculiar in that it is time- and space-dependent, and has to function in the presence of rapid flow. Recent experimental reports suggest that flow plays a significant role in its regulation. The objective of this study was to use systems biology techniques to investigate this regulation and to identify mechanisms creating a flow-dependent switch in the coagulation onset. Results: Using a detailed mechanism-driven model of tissue factor (TF)-initiated thrombus formation in a two-dimensional channel we demonstrate that blood flow can regulate clotting onset in the model in a threshold-like manner, in agreement with existing experimental evidence. Sensitivity analysis reveals that this is achieved due to a combination of the positive feedback of TF-bound factor VII activation by activated factor X (Xa) and effective removal of factor Xa by flow from the activating patch depriving the feedback of "ignition". The level of this trigger (i.e. coagulation sensitivity to flow) is controlled by the activity of tissue factor pathway inhibitor. Conclusions: This mechanism explains the difference between red and white thrombi observed in vivo at different shear rates. It can be speculated that this is a special switch protecting vascular system from uncontrolled formation and spreading of active coagulation factors in vessels with rapidly flowing blood.