scholarly journals In silico voltage-sensitive dye imaging reveals the emergent dynamics of cortical populations

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Taylor H. Newton ◽  
Michael W. Reimann ◽  
Marwan Abdellah ◽  
Grigori Chevtchenko ◽  
Eilif B. Muller ◽  
...  

AbstractVoltage-sensitive dye imaging (VSDI) is a powerful technique for interrogating membrane potential dynamics in assemblies of cortical neurons, but with effective resolution limits that confound interpretation. To address this limitation, we developed an in silico model of VSDI in a biologically faithful digital reconstruction of rodent neocortical microcircuitry. Using this model, we extend previous experimental observations regarding the cellular origins of VSDI, finding that the signal is driven primarily by neurons in layers 2/3 and 5, and that VSDI measurements do not capture individual spikes. Furthermore, we test the capacity of VSD image sequences to discriminate between afferent thalamic inputs at various spatial locations to estimate a lower bound on the functional resolution of VSDI. Our approach underscores the power of a bottom-up computational approach for relating scales of cortical processing.

2019 ◽  
Author(s):  
Taylor H. Newton ◽  
Marwan Abdellah ◽  
Grigori Chevtchenko ◽  
Eilif B. Muller ◽  
Henry Markram

AbstractVoltage-sensitive dye imaging (VSDI) is a powerful technique for interrogating membrane potential dynamics in assemblies of cortical neurons, but with effective resolution limits that confound interpretation. In particular, it is unclear how VSDI signals relate to population firing rates. To address this limitation, we developed an in silico model of VSDI in a biologically faithful digital reconstruction of rodent neocortical microcircuitry. Using this model, we extend previous experimental observations regarding the cellular origins of VSDI, finding that the signal is driven primarily by neurons in layers 2/3 and 5. We proceed by exploring experimentally inaccessible circuit properties to show that during periods of spontaneous activity, membrane potential fluctuations are anticorrelated with population firing rates. Furthermore, we manipulate network connections to show that this effect depends on recurrent connectivity and is modulated by external input. We conclude that VSDI primarily reflects inhibitory responses to ongoing excitatory dynamics.


BIO-PROTOCOL ◽  
2016 ◽  
Vol 6 (3) ◽  
Author(s):  
Takayuki Suzuki ◽  
Masanori Murayama

2021 ◽  
Vol 22 (11) ◽  
pp. 5645
Author(s):  
Stefano Morotti ◽  
Haibo Ni ◽  
Colin H. Peters ◽  
Christian Rickert ◽  
Ameneh Asgari-Targhi ◽  
...  

Background: The mechanisms underlying dysfunction in the sinoatrial node (SAN), the heart’s primary pacemaker, are incompletely understood. Electrical and Ca2+-handling remodeling have been implicated in SAN dysfunction associated with heart failure, aging, and diabetes. Cardiomyocyte [Na+]i is also elevated in these diseases, where it contributes to arrhythmogenesis. Here, we sought to investigate the largely unexplored role of Na+ homeostasis in SAN pacemaking and test whether [Na+]i dysregulation may contribute to SAN dysfunction. Methods: We developed a dataset-specific computational model of the murine SAN myocyte and simulated alterations in the major processes of Na+ entry (Na+/Ca2+ exchanger, NCX) and removal (Na+/K+ ATPase, NKA). Results: We found that changes in intracellular Na+ homeostatic processes dynamically regulate SAN electrophysiology. Mild reductions in NKA and NCX function increase myocyte firing rate, whereas a stronger reduction causes bursting activity and loss of automaticity. These pathologic phenotypes mimic those observed experimentally in NCX- and ankyrin-B-deficient mice due to altered feedback between the Ca2+ and membrane potential clocks underlying SAN firing. Conclusions: Our study generates new testable predictions and insight linking Na+ homeostasis to Ca2+ handling and membrane potential dynamics in SAN myocytes that may advance our understanding of SAN (dys)function.


PLoS ONE ◽  
2011 ◽  
Vol 6 (10) ◽  
pp. e26158 ◽  
Author(s):  
Markus Rothermel ◽  
Benedict Shien Wei Ng ◽  
Agnieszka Grabska-Barwińska ◽  
Hanns Hatt ◽  
Dirk Jancke

Sign in / Sign up

Export Citation Format

Share Document