Age-dependent increased sag amplitude in human pyramidal neurons dampens baseline cortical activity

Guet-McCreight, Alexandre; Chameh, Homeira Moradi; Mahallati, Sara; Wishart, Margaret; Tripathy, Shreejoy J.; Valiante, Taufik A.; Hay, Etay

doi:10.1101/2021.11.03.467014

Cited by 4 publications

(2 citation statements)

References 85 publications

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“…These limitations warrant the development of biophysically detailed, human-inspired neuron (Rich et al, 2021) and network models (Guet-McCreight et al, 2022;Yao et al, 2022), allowing for the study of additional types of heterogeneity. In this vein, while we do not model seizures per se in this work, the two most common types of seizure onsets observed in intracranial recordings are the low-voltage fast (Lee et al, 2000) and hyper-synchronous onsets (Velascol et al, 1999).…”

Section: Limitations Of the Studymentioning

confidence: 99%

Loss of neuronal heterogeneity in epileptogenic human tissue impairs network resilience to sudden changes in synchrony

et al. 2022

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Section: Limitations Of the Studymentioning

confidence: 99%

Loss of neuronal heterogeneity in epileptogenic human tissue impairs network resilience to sudden changes in synchrony

et al. 2022

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“…In human studies it is especially challenging to derive general principles considering the differences in genetic and environmental backgrounds and their influence on functional properties of the neurons [18][19][20] . Previous studies on human neuronal and synaptic function relied on electrophysiological approaches with a limited number of samples from each individual 4,5,9,10,12,14,18,20-, requiring pooling across many different individuals.…”

Section: Introductionmentioning

confidence: 99%

Cellular and Synaptic Diversity of Layer 2-3 Pyramidal Neurons in Human Individuals

Planert

Mittermaier

Grosser

et al. 2021

Preprint

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Computation within cortical microcircuits is determined by functional properties of the neurons and their synaptic interactions. While heterogeneity of inhibitory interneurons is well established, the anatomical, physiological, and molecular differentiation of excitatory pyramidal neurons is not fully resolved. To identify functional subtypes within the pyramidal neuron population, we focused on human layer 2-3 cortex which greatly expanded during evolution. We performed multi-neuron patch-clamp recordings in brain slices from the temporal cortex of 22 epilepsy patients. We characterized the electrophysiological properties of up to 80 pyramidal neurons per patient, enabling us to assess inter- and intra-individual functional variability. Hierarchical clustering of the high-dimensional parameter space yielded functionally distinct clusters of pyramidal neurons which were present across individuals. This may represent a generic organizational principle converging with previously described transcriptomic heterogeneity. We further observed substantial heterogeneity in physiological parameters with intra-individual variability being severalfold larger than inter-individual variability. The phenotypic variability within and across pyramidal neuron subtypes has important implications for the computational capacity of the cortical microcircuit.

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Hyperpolarization-activated cation channels shape the spiking frequency preference of human cortical layer 5 pyramidal neurons

Inibhunu

Chameh

Skinner

et al. 2023

Preprint

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Discerning the contribution of specific ionic currents to complex neuronal dynamics is a difficult, but important, task. This challenge is exacerbated in the human setting, although the widely-characterized uniqueness of the human brain as compared to preclinical models necessitates the direct study of human neurons. Neuronal spiking frequency preference is of particular interest given its role in rhythm generation and signal transmission in cortical circuits. Here, we combine the frequency-dependent gain (FDG), a measure of spiking frequency preference, and novelin silicoanalyses to dissect the contributions of individual ionic currents to key FDG features of human L5 neurons. We confirm that a contemporary model of such a neuron, primarily constrained to capture subthreshold activity driven by the hyperpolarization-activated cyclic nucleotide gated (h-) current, replicates key features of thein vitroFDG both with and without h-current activity. With the model confirmed as a viable approximation of the biophysical features of interest, we applied new analysis techniques to quantify the activity of each modeled ionic current in the moments prior to spiking, revealing unique dynamics of the h-current. These findings motivated patch-clamp recordings in analogous rodent neurons to characterize their FDG, which confirmed that a biophysically-detailed model of these neurons captures key inter-species differences in the FDG. These differences are correlated with distinct contributions of the h-current to neuronal activity. Together, this interdisciplinary and multi-species study provides new insights directly relating the dynamics of the h-current to neuronal spiking frequency preference in human L5 neurons.

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Age-dependent increased sag amplitude in human pyramidal neurons dampens baseline cortical activity

Cited by 4 publications

References 85 publications

Loss of neuronal heterogeneity in epileptogenic human tissue impairs network resilience to sudden changes in synchrony

Loss of neuronal heterogeneity in epileptogenic human tissue impairs network resilience to sudden changes in synchrony

Cellular and Synaptic Diversity of Layer 2-3 Pyramidal Neurons in Human Individuals

Hyperpolarization-activated cation channels shape the spiking frequency preference of human cortical layer 5 pyramidal neurons

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