scholarly journals Optimizing computer models of corticospinal neurons to replicate in vitro dynamics

2017 ◽  
Vol 117 (1) ◽  
pp. 148-162 ◽  
Author(s):  
Samuel A. Neymotin ◽  
Benjamin A. Suter ◽  
Salvador Dura-Bernal ◽  
Gordon M. G. Shepherd ◽  
Michele Migliore ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Pyramidal Neurons ◽  
Computer Models ◽  
Cortical Layer ◽  
Cortical Layers ◽  
Electrophysiological Properties ◽  
Full Reconstruction ◽  
Resonance Properties ◽  
Oscillation Frequencies

Corticospinal neurons (SPI), thick-tufted pyramidal neurons in motor cortex layer 5B that project caudally via the medullary pyramids, display distinct class-specific electrophysiological properties in vitro: strong sag with hyperpolarization, lack of adaptation, and a nearly linear frequency-current ( F– I) relationship. We used our electrophysiological data to produce a pair of large archives of SPI neuron computer models in two model classes: 1) detailed models with full reconstruction; and 2) simplified models with six compartments. We used a PRAXIS and an evolutionary multiobjective optimization (EMO) in sequence to determine ion channel conductances. EMO selected good models from each of the two model classes to form the two model archives. Archived models showed tradeoffs across fitness functions. For example, parameters that produced excellent F– I fit produced a less-optimal fit for interspike voltage trajectory. Because of these tradeoffs, there was no single best model but rather models that would be best for particular usages for either single neuron or network explorations. Further exploration of exemplar models with strong F– I fit demonstrated that both the detailed and simple models produced excellent matches to the experimental data. Although dendritic ion identities and densities cannot yet be fully determined experimentally, we explored the consequences of a demonstrated proximal to distal density gradient of Ih, demonstrating that this would lead to a gradient of resonance properties with increased resonant frequencies more distally. We suggest that this dynamical feature could serve to make the cell particularly responsive to major frequency bands that differ by cortical layer. NEW & NOTEWORTHY We developed models of motor cortex corticospinal neurons that replicate in vitro dynamics, including hyperpolarization-induced sag and realistic firing patterns. Models demonstrated resonance in response to synaptic stimulation, with resonance frequency increasing in apical dendrites with increasing distance from soma, matching the increasing oscillation frequencies spanning deep to superficial cortical layers. This gradient may enable specific corticospinal neuron dendrites to entrain to relevant oscillations in different cortical layers, contributing to appropriate motor output commands.

scholarly journals Diversity amongst human cortical pyramidal neurons revealed via their sag currents and frequency preferences

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Homeira Moradi Chameh ◽  
Scott Rich ◽  
Lihua Wang ◽  
Fu-Der Chen ◽  
Liang Zhang ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Theta Oscillations ◽  
Cortical Layers ◽  
Electrophysiological Properties ◽  
Theta Frequency ◽  
Subthreshold Resonance ◽  
Cortical Pyramidal Neurons ◽  
Whole Cell Recordings

AbstractIn the human neocortex coherent interlaminar theta oscillations are driven by deep cortical layers, suggesting neurons in these layers exhibit distinct electrophysiological properties. To characterize this potential distinctiveness, we use in vitro whole-cell recordings from cortical layers 2 and 3 (L2&3), layer 3c (L3c) and layer 5 (L5) of the human cortex. Across all layers we observe notable heterogeneity, indicating human cortical pyramidal neurons are an electrophysiologically diverse population. L5 pyramidal cells are the most excitable of these neurons and exhibit the most prominent sag current (abolished by blockade of the hyperpolarization activated cation current, Ih). While subthreshold resonance is more common in L3c and L5, we rarely observe this resonance at frequencies greater than 2 Hz. However, the frequency dependent gain of L5 neurons reveals they are most adept at tracking both delta and theta frequency inputs, a unique feature that may indirectly be important for the generation of cortical theta oscillations.

scholarly journals Dendritic spikes in apical oblique dendrites of cortical layer 5 pyramidal neurons

2020 ◽  
Author(s):  
Michael Lawrence G. Castañares ◽  
Greg J. Stuart ◽  
Vincent R. Daria
Keyword(s):  
Sensory Processing ◽  
Pyramidal Neurons ◽  
Low Frequency ◽  
Cortical Layer ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels ◽  
Basal Dendrites ◽  
Dendritic Spikes ◽  
Specific Computation

AbstractDendritic spikes in layer 5 pyramidal neurons (L5PNs) play a major role in cortical computation. While dendritic spikes have been studied extensively in apical and basal dendrites of L5PNs, whether oblique dendrites, which ramify in the input layers of the cortex, also generate dendritic spikes is unknown. Here we report the existence of dendritic spikes in apical oblique dendrites of L5PNs. In silico investigations indicate that oblique branch spikes are triggered by brief, low-frequency action potential (AP) trains (~40 Hz) and are characterized by a fast sodium spike followed by activation of voltage-gated calcium channels. In vitro experiments confirmed the existence of oblique branch spikes in L5PNs during brief AP trains at frequencies of around 60 Hz. Oblique branch spikes offer new insights into branch-specific computation in L5PNs and may be critical for sensory processing in the input layers of the cortex.

scholarly journals Transduction of inflammation from peripheral immune cells to the hippocampus induces neuronal hyperexcitability mediated by Caspase-1 activation

2020 ◽  
Author(s):  
Tarek Shaker ◽  
Bidisha Chattopadhyaya ◽  
Bénédicte Amilhon ◽  
Graziella Di Cristo ◽  
Alexander G. Weil
Keyword(s):  
Pyramidal Neurons ◽  
Mononuclear Cells ◽  
Culture Media ◽  
Cortical Layer ◽  
Peripheral Inflammation ◽  
Potential Contribution ◽  
Peripheral Blood Mononuclear ◽  
Caspase 1 ◽  
Therapeutic Benefits

Abstract 1.1. Background Recent studies report infiltration of peripheral blood mononuclear cells (PBMCs) into the central nervous system (CNS) in epileptic disorders, suggestive of a potential contribution of PBMC extravasation to the generation of seizures. Nevertheless, the underlying mechanisms involved in PBMC infiltrates promoting neuronal predisposition to ictogenesis remain unclear. Therefore, we developed an in vitro model mimicking infiltration of activated PBMCs into the brain in order to investigate potential transduction of inflammatory signals from PBMCs to the CNS.1.2. Methods To establish our model, we first extracted PBMCs from rat spleen, then, immunologically primed PBMCs with lipopolysaccharide (LPS), followed by further activation with nigericin. Thereafter, we co-cultured these activated PBMCs with organotypic cortico-hippocampal brain slice cultures (OCHSCs) derived from the same rat, and compared PBMC-OCHSC co-cultures to OCHSCs exposed to PBMCs in the culture media. We further targeted a potential molecular pathway underlying transduction of peripheral inflammation to OCHSCs by incubating OCHSCs with the Caspase-1 inhibitor VX-765 prior to co-culturing PBMCs with OCHSCs. After 24 hours, we analyzed inflammation markers in the cortex and the hippocampus using semiquantitative immunofluorescence. In addition, we analyzed neuronal activity by whole-cell patch-clamp recordings in cortical layer II/III and hippocampal CA1 pyramidal neurons.1.3. Results In the cortex, co-culturing immunoreactive PBMCs treated with LPS + nigericin on top of OCHSCs upregulated inflammatory markers and enhanced neuronal excitation. In contrast, no excitability changes were detected after adding primed PBMCs (i.e. treated with LPS only), to OCHSCs. Strikingly, in the hippocampus, both immunoreactive and primed PBMCs elicited similar pro-inflammatory and pro-excitatory effects. However, when immunoreactive and primed PBMCs were cultured in the media separately from OCHSCs, only immunoreactive PBMCs gave rise to neuroinflammation and hyperexcitability in the hippocampus, whereas primed PBMCs failed to produce any significant changes. Finally, VX-765 application to OCHSCs, co-cultured with either immunoreactive or primed PBMCs, protected them from neuroinflammation and hippocampal hyperexcitability.1.4. Conclusions Our study shows a higher susceptibility of the hippocampus to peripheral inflammation as compared to the cortex, mediated via Caspase-1-dependent signaling pathways. Thus, our findings suggest that Caspase-1 inhibition may potentially provide therapeutic benefits during hippocampal neuroinflammation and hyperexcitability secondary to peripheral innate immunity.

scholarly journals Studying Synaptically Evoked Cortical Responses ex vivo With Combination of a Single Neuron Recording (Whole-Cell) and Population Voltage Imaging (Genetically Encoded Voltage Indicator)

2021 ◽  
Vol 15 ◽  
Author(s):  
Jinyoung Jang ◽  
Mei Hong Zhu ◽  
Aditi H. Jogdand ◽  
Srdjan D. Antic
Keyword(s):  
Pyramidal Neurons ◽  
Ex Vivo ◽  
Brain Slices ◽  
Dendritic Tree ◽  
Response Speed ◽  
Optical Signal ◽  
Cortical Layer ◽  
Cortical Layers ◽  
Whole Cell ◽  
Voltage Imaging

In a typical electrophysiology experiment, synaptic stimulus is delivered in a cortical layer (1–6) and neuronal responses are recorded intracellularly in individual neurons. We recreated this standard electrophysiological paradigm in brain slices of mice expressing genetically encoded voltage indicators (GEVIs). This allowed us to monitor membrane voltages in the target pyramidal neurons (whole-cell), and population voltages in the surrounding neuropil (optical imaging), simultaneously. Pyramidal neurons have complex dendritic trees that span multiple cortical layers. GEVI imaging revealed areas of the brain slice that experienced the strongest depolarization on a specific synaptic stimulus (location and intensity), thus identifying cortical layers that contribute the most afferent activity to the recorded somatic voltage waveform. By combining whole-cell with GEVI imaging, we obtained a crude distribution of activated synaptic afferents in respect to the dendritic tree of a pyramidal cell. Synaptically evoked voltage waves propagating through the cortical neuropil (dendrites and axons) were not static but rather they changed on a millisecond scale. Voltage imaging can identify areas of brain slices in which the neuropil was in a sustained depolarization (plateau), long after the stimulus onset. Upon a barrage of synaptic inputs, a cortical pyramidal neuron experiences: (a) weak temporal summation of evoked voltage transients (EPSPs); and (b) afterhyperpolarization (intracellular recording), which are not represented in the GEVI population imaging signal (optical signal). To explain these findings [(a) and (b)], we used four voltage indicators (ArcLightD, chi-VSFP, Archon1, and di-4-ANEPPS) with different optical sensitivity, optical response speed, labeling strategy, and a target neuron type. All four imaging methods were used in an identical experimental paradigm: layer 1 (L1) synaptic stimulation, to allow direct comparisons. The population voltage signal showed paired-pulse facilitation, caused in part by additional recruitment of new neurons and dendrites. “Synaptic stimulation” delivered in L1 depolarizes almost an entire cortical column to some degree.

scholarly journals Sag currents are a major contributor to human pyramidal cell intrinsic differences across cortical layers

2019 ◽  
Author(s):  
Homeira Moradi Chameh ◽  
Scott Rich ◽  
Lihua Wang ◽  
Fu-Der Chen ◽  
Liang Zhang ◽  
...  
Keyword(s):  
Deep Layer ◽  
Pyramidal Cells ◽  
Theta Oscillations ◽  
Cortical Layers ◽  
Electrophysiological Properties ◽  
Human Neocortex ◽  
Cation Current ◽  
Subthreshold Resonance ◽  
Whole Cell Recordings

AbstractIn the human neocortex, coherent theta (∼8Hz) oscillations between superficial and deep cortical layers are driven by deep layer neurons, suggesting distinct intrinsic electrophysiological properties of L5 neurons. We used in vitro whole-cell recordings to characterize pyramidal cells in layer 2/3 (L2/3), layer 3c (L3c) and layer 5 (L5) of the human neocortex. L5 pyramidal cells were more excitable and had a more prominent sag relative to L2/3 and L3c neurons that was abolished by blockade of the hyperpolarization activated cation current (Ih). We found a greater proportion of L5 and L3c neurons displaying subthreshold resonance relative to L2/3. Although no theta subthreshold resonance was observed in either L5 and L2/3 neurons, L5 neurons were more adept at tracking both delta (4Hz) and theta oscillations, the former being dependent on Ih. The unique features of human L5 neurons likely contribute to the emergence of theta oscillations in human cortical microcircuits.

Distinct neuron phenotypes may serve object feature sensing in the electrosensory lobe of Gymnotus omarorum

2021 ◽  
Author(s):  
Javier Nogueira ◽  
María E. Castelló ◽  
Carolina Lescano ◽  
Ángel A. Caputi
Keyword(s):  
Stimulus Intensity ◽  
Pyramidal Neurons ◽  
Receptive Fields ◽  
Weakly Electric Fish ◽  
High Threshold ◽  
Electrophysiological Properties ◽  
Clear Cut ◽  
Low Pass ◽  
Object Feature

Early sensory relays circuits in the vertebrate medulla often adopt a cerebellum-like organization specialized for comparing primary afferent inputs with central expectations. These circuits usually have a dual output, carried by center ON and center OFF neurons responding in opposite ways to the same stimulus at the center of their receptive fields. Here we show in the electrosensory lateral line lobe of Gymnotiform weakly electric fish that basilar pyramidal neurons, representing ‘ON’ cells, and non-basilar pyramidal neurons, representing ‘OFF’ cells, have different intrinsic electrophysiological properties. We used classical anatomical techniques and electrophysiological in vitro recordings to compare these neurons. Basilar neurons are silent at rest, have a high threshold to intracellular stimulation, delayed responses to steady state depolarization and low pass responsiveness to membrane voltage variations. They respond to low intensity depolarizing stimuli with large, isolated spikes. As stimulus intensity increases the spikes are followed by a depolarizing after-potential from which phase-locked spikes often arise. Non-basilar neurons show a pacemaker-like spiking activity, smoothly modulated in frequency by slow variations of stimulus intensity. Spike frequency adaptation provides a memory of their recent firing, facilitating non-basilar response to stimulus transients. Considering anatomical and functional dimensions we conclude that basilar and non-basilar pyramidal neurons are clear-cut, different anatomo-functional phenotypes. We propose that, in addition to their role in contrast processing, basilar pyramidal neurons encode sustained global stimuli as those elicited by large or distant objects while non-basilar pyramidal neurons respond to transient stimuli due to movement textured nearby objects.

scholarly journals Analyzing Branch‐specific Dendritic Spikes Using an Ultrafast Laser Scalpel

2020 ◽  
Vol 8 ◽  
Author(s):  
Michael L. Castañares ◽  
Hans-A. Bachor ◽  
Vincent R. Daria
Keyword(s):  
Cortical Neurons ◽  
Pyramidal Neurons ◽  
Dendritic Tree ◽  
Cortical Layer ◽  
Ultrafast Laser ◽  
Laser Scalpel ◽  
Dendritic Spikes ◽  
Dendritic Spike ◽  
Neuronal Computation

Dendritic spikes facilitate neuronal computation and they have been reported to occur in various regions of the dendritic tree of cortical neurons. Spikes that occur only on a select few branches are particularly difficult to analyze especially in complex and intertwined dendritic arborizations where highly localized application of pharmacological blocking agents is not feasible. Here, we present a technique based on highly targeted dendrotomy to tease out and study dendritic spikes that occur in oblique branches of cortical layer five pyramidal neurons. We first analyze the effect of cutting dendrites in silico and then confirmed in vitro using an ultrafast laser scalpel. A dendritic spike evoked in an oblique branch manifests at the soma as an increase in the afterdepolarization (ADP). The spikes are branch-specific since not all but only a few oblique dendrites are observed to evoke spikes. Both our model and experiments show that cutting certain oblique branches, where dendritic spikes are evoked, curtailed the increase in the ADP. On the other hand, cutting neighboring oblique branches that do not evoke spikes maintained the ADP. Our results show that highly targeted dendrotomy can facilitate causal analysis of how branch-specific dendritic spikes influence neuronal output.

scholarly journals Ipsi- and contralateral corticocortical projection-dependent subcircuits in layer 2 of the rat frontal cortex

2019 ◽  
Vol 122 (4) ◽  
pp. 1461-1472 ◽  
Author(s):  
Yoshifumi Ueta ◽  
Jaerin Sohn ◽  
Fransiscus Adrian Agahari ◽  
Sanghun Im ◽  
Yasuharu Hirai ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Frontal Cortex ◽  
Pyramidal Cell ◽  
Pyramidal Tract ◽  
Pyramidal Cells ◽  
Cortical Layer ◽  
Electrophysiological Properties ◽  
Monosynaptic Connection ◽  
Layer 2 ◽  
Rat Frontal Cortex

In the neocortex, both layer 2/3 and layer 5 contain corticocortical pyramidal cells projecting to other cortices. We previously found that among L5 pyramidal cells of the secondary motor cortex (M2), not only intratelencephalic projection cells but also pyramidal tract cells innervate ipsilateral cortices and that the two subtypes are different in corticocortical projection diversity and axonal laminar distributions. Layer 2/3 houses intratelencephalically projecting pyramidal cells that also innervate multiple ipsilateral and contralateral cortices. However, it remained unclear whether layer 2/3 pyramidal cells can be divided into projection subtypes each with distinct innervation to specific targets. In the present study we show that layer 2 pyramidal cells are organized into subcircuits on the basis of corticocortical projection targets. Layer 2 corticocortical cells of the same projection subtype were monosynaptically connected. Between the contralaterally and ipsilaterally projecting corticocortical cells, the monosynaptic connection was more common from the former to the latter. We also found that ipsilaterally and contralaterally projecting corticocortical cell subtypes differed in their morphological and physiological characteristics. Our results suggest that layer 2 transfers separate outputs from M2 to individual cortices and that its subcircuits are hierarchically organized to form the discrete corticocortical outputs. NEW & NOTEWORTHY Pyramidal cell subtypes and their dependent subcircuits are well characterized in cortical layer 5, but much less is understood for layer 2/3. We demonstrate that in layer 2 of the rat secondary motor cortex, ipsilaterally and contralaterally projecting corticocortical cells are largely segregated. These layer 2 cell subtypes differ in dendrite morphological and intrinsic electrophysiological properties, and form subtype-dependent connections. Our results suggest that layer 2 pyramidal cells form distinct subcircuits to provide discrete corticocortical outputs.

scholarly journals Spike Firing and IPSPs in Layer V Pyramidal Neurons during Beta Oscillations in Rat Primary Motor Cortex (M1) In Vitro

PLoS ONE ◽  
2014 ◽  
Vol 9 (1) ◽  
pp. e85109 ◽  
Author(s):  
Michael G. Lacey ◽  
Gerard Gooding-Williams ◽  
Emma J. Prokic ◽  
Naoki Yamawaki ◽  
Stephen D. Hall ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Primary Motor Cortex ◽  
Pyramidal Neurons ◽  
Beta Oscillations ◽  
Layer V ◽  
Spike Firing

scholarly journals A multi-scale computational model of the effects of TMS on motor cortex

F1000Research ◽  
2017 ◽  
Vol 5 ◽  
pp. 1945 ◽  
Author(s):  
Hyeon Seo ◽  
Natalie Schaworonkow ◽  
Sung Chan Jun ◽  
Jochen Triesch
Keyword(s):  
Motor Cortex ◽  
Computational Model ◽  
Electric Fields ◽  
Pyramidal Cell ◽  
Action Potentials ◽  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Cell Types ◽  
Cortical Layer ◽  
Multi Scale

The detailed biophysical mechanisms through which transcranial magnetic stimulation (TMS) activates cortical circuits are still not fully understood. Here we present a multi-scale computational model to describe and explain the activation of different pyramidal cell types in motor cortex due to TMS. Our model determines precise electric fields based on an individual head model derived from magnetic resonance imaging and calculates how these electric fields activate morphologically detailed models of different neuron types. We predict neural activation patterns for different coil orientations consistent with experimental findings. Beyond this, our model allows us to calculate activation thresholds for individual neurons and precise initiation sites of individual action potentials on the neurons’ complex morphologies. Specifically, our model predicts that cortical layer 3 pyramidal neurons are generally easier to stimulate than layer 5 pyramidal neurons, thereby explaining the lower stimulation thresholds observed for I-waves compared to D-waves. It also shows differences in the regions of activated cortical layer 5 and layer 3 pyramidal cells depending on coil orientation. Finally, it predicts that under standard stimulation conditions, action potentials are mostly generated at the axon initial segment of cortical pyramidal cells, with a much less important activation site being the part of a layer 5 pyramidal cell axon where it crosses the boundary between grey matter and white matter. In conclusion, our computational model offers a detailed account of the mechanisms through which TMS activates different cortical pyramidal cell types, paving the way for more targeted application of TMS based on individual brain morphology in clinical and basic research settings.

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