Ca 21 spikes initiated in the distal trunk of layer 5 pyramidal cells (PCs) underlie nonlinear dynamic changes in the gain of cellular response, critical for top-down control of cortical processing. Detailed models with many compartments and dozens of ionic channels can account for this Ca 21 spike-dependent gain and associated critical frequency. However, current models do not account for all known Ca 21 -dependent features. Previous attempts to include more features have required increasing complexity, limiting their interpretability and utility for studying large population dynamics. We overcome these limitations in a minimal two-compartment biophysical model. In our model, a basal-dendrites/somatic compartment included fast-inactivating Na 1 and delayed-rectifier K 1 conductances, while an apical-dendrites/trunk compartment included persistent Na 1 , hyperpolarization-activated cation (I h ), slow-inactivating K 1 , muscarinic K 1 , and Ca 21 L-type. The model replicated the Ca 21 spike morphology and its critical frequency plus three other defining features of layer 5 PC synaptic integration: linear frequency-current relationships, back-propagation-activated Ca 21 spike firing, and a shift in the critical frequency by blocking I h . Simulating 1000 synchronized layer 5 PCs, we reproduced the current source density patterns evoked by Ca 21 spikes and describe resulting medial-frontal EEG on a male macaque monkey. We reproduced changes in the current source density when I h was blocked. Thus, a two-compartment model with five crucial ionic currents in the apical dendrites reproduces all features of these neurons. We discuss the utility of this minimal model to study the microcircuitry of agranular areas of the frontal lobe involved in cognitive control and responsible for event-related potentials, such as the error-related negativity.
21Ca 2+ spikes initiated in the apical dendrites of layer-5 pyramidal cells (PC) underlie 22 nonlinear dynamic changes in the gain of cellular response, which is critical for top-down cognitive 23 control. Detailed models with several compartments and dozens of ionic channels have been 24 proposed to account for this Ca 2+ spike-dependent gain with its associated critical frequency. 25However, current models do not account for all known Ca 2+ -dependent features. Previous attempts 26 to include more features have required increasing complexity, limiting their interpretability and 27 utility for studying large population dynamics. We present a minimal 2-compartment biophysical 28 model, overcoming these limitations. In our model, a basal-dendritic/somatic compartment 29 included typical Na + and K + conductances, while an apical-dendritic/trunk compartment included 30 persistent Na + , hyperpolarization-activated cation (Ih), slow inactivation K + , muscarinic K + , and 31 Ca 2+ L-type. The model replicated the Ca 2+ spike morphology and its critical frequency plus three 32 other defining features of layer-5 PC synaptic integration: linear frequency-current relationships, 33 backpropagation-activated Ca 2+ spike firing, and a shift in the critical frequency by blocking Ih. 34Simulating 1,000 synchronized layer-5 PCs, we reproduced the current source density patterns 35 evoked by Ca 2+ -spikes both with and without Ih current. Thus, a 2-compartment model with five 36 non-classic ionic currents in the apical-dendrites reproduces all features of these neurons. We 37 discuss the utility of this minimal model to study the microcircuitry of agranular areas of the frontal 38 lobe involved in cognitive control and responsible for event-related potentials such as the error-39 related negativity. 40 Key words 41 pyramidal cells; LFP sources; cortical microcircuitry; biophysical modeling; cognitive 42 control 43 44 3 Significance Statement 45 A tractable model of layer-5 pyramidal cells replicates all known features crucial for distal 46 synaptic integration in these neurons. This minimal model enables new multi-scale investigations 47 of microcircuit functions with associated current flows measured by intracranial local field 48 potentials. It thus establishes a foundation for the future computational evaluation of scalp 49 electroencephalogram signatures imprinted by Ca 2+ spikes in pyramidal cells, a phenomenon 50 underlying many brain cognitive processes. 51
Event-related potentials (ERP) are among the most widely measured indices for studying human cognition. While their timing and magnitude provide valuable insights, their usefulness is limited by our understanding of their neural generators at the circuit level. Inverse source localization offers insights into such generators, but their solutions are not unique. To address this problem, scientists have assumed the source space generating such signals comprises a set of discrete equivalent current dipoles, representing the activity of small cortical regions. Based on this notion, theoretical studies have employed forward modeling of scalp potentials to understand how changes in circuit-level dynamics translate into macroscopic ERPs. However, experimental validation is lacking because it requires in vivo measurements of intracranial brain sources. Laminar local field potentials (LFP) offer a mechanism for estimating intracranial current sources. Yet, a theoretical link between LFPs and intracranial brain sources is missing. Here, we present a forward modeling approach for estimating mesoscopic intracranial brain sources from LFPs and predict their contribution to macroscopic ERPs. We evaluate the accuracy of this LFP-based representation of brain sources utilizing synthetic laminar neurophysiological measurements and then demonstrate the power of the approach in vivo to clarify the source of a representative cognitive ERP component. To that end, LFP was measured across the cortical layers of visual area V4 in macaque monkeys performing an attention demanding task. We show that area V4 generates dipoles through layer-specific transsynaptic currents that biophysically recapitulate the ERP component through the detailed forward modeling. The constraints imposed on EEG production by this method also revealed an important dissociation between computational and biophysical contributors. As such, this approach represents an important bridge from the mesoscopic activity of cortical columns to the patterns of EEG we measure at the scalp.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.