High synaptic threshold for dendritic NMDA spike generation in human layer 2/3 pyramidal neurons

Testa-Silva, Guilherme; Rosier, Marius; Honnuraiah, Suraj; Guzulaitis, Robertas; Megias, Ana Morello; French, Chris; King, James G.; Drummond, Katharine J.; Palmer, Lucy M.; Stuart, G. W.

doi:10.1016/j.celrep.2022.111787

Cited by 23 publications

(34 citation statements)

References 45 publications

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“…For example, human pyramidal neurons appear to exhibit enhanced dendritic compartmentalisation 262 and distinct h-channel kinetics and expression 263 – 265 . In addition, dendrites of human pyramidal cells show complex calcium-mediated action potentials 266 , a high threshold for NMDA spikes 267 and faster backpropagation of action potentials as well as forward propagation of excitatory postsynaptic potentials 268 . The uniqueness or generality of these recently characterized properties of human neurons with respect to their animal counterparts needs to be investigated in more detail 269 , 270 .…”

Section: Towards Population Models Of Human Neurons and Circuits In E...mentioning

confidence: 99%

Degeneracy in epilepsy: multiple routes to hyperexcitable brain circuits and their repair

et al. 2023

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Due to its complex and multifaceted nature, developing effective treatments for epilepsy is still a major challenge. To deal with this complexity we introduce the concept of degeneracy to the field of epilepsy research: the ability of disparate elements to cause an analogous function or malfunction. Here, we review examples of epilepsy-related degeneracy at multiple levels of brain organisation, ranging from the cellular to the network and systems level. Based on these insights, we outline new multiscale and population modelling approaches to disentangle the complex web of interactions underlying epilepsy and to design personalised multitarget therapies.

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Section: Towards Population Models Of Human Neurons and Circuits In E...mentioning

confidence: 99%

Degeneracy in epilepsy: multiple routes to hyperexcitable brain circuits and their repair

et al. 2023

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“…It has recently been reported that mouse dendrites in cortical pyramidal neurons have lower synaptic thresholds for NMDA spike generation than human dendrites [ 14 ]. To further demonstrate the restorative effects of our repair algorithm on the electrophysiological behaviour of rodent and human dendrites, we performed a computational analysis of their dendritic NMDA spiking.…”

Section: Resultsmentioning

confidence: 99%

A biologically inspired repair mechanism for neuronal reconstructions with a focus on human dendrites

Groden,

Moessinger,

Schaffran

et al. 2024

PLoS Comput Biol

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Investigating and modelling the functionality of human neurons remains challenging due to the technical limitations, resulting in scarce and incomplete 3D anatomical reconstructions. Here we used a morphological modelling approach based on optimal wiring to repair the parts of a dendritic morphology that were lost due to incomplete tissue samples. In Drosophila, where dendritic regrowth has been studied experimentally using laser ablation, we found that modelling the regrowth reproduced a bimodal distribution between regeneration of cut branches and invasion by neighbouring branches. Interestingly, our repair model followed growth rules similar to those for the generation of a new dendritic tree. To generalise the repair algorithm from Drosophila to mammalian neurons, we artificially sectioned reconstructed dendrites from mouse and human hippocampal pyramidal cell morphologies, and showed that the regrown dendrites were morphologically similar to the original ones. Furthermore, we were able to restore their electrophysiological functionality, as evidenced by the recovery of their firing behaviour. Importantly, we show that such repairs also apply to other neuron types including hippocampal granule cells and cerebellar Purkinje cells. We then extrapolated the repair to incomplete human CA1 pyramidal neurons, where the anatomical boundaries of the particular brain areas innervated by the neurons in question were known. Interestingly, the repair of incomplete human dendrites helped to simulate the recently observed increased synaptic thresholds for dendritic NMDA spikes in human versus mouse dendrites. To make the repair tool available to the neuroscience community, we have developed an intuitive and simple graphical user interface (GUI), which is available in the TREES toolbox (www.treestoolbox.org).

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“…Human neocortical pyramidal neurons can generate NMDA spikes 56 . To simulate excitability under biologically realistic conditions, we generated local NMDA spikes in different dendritic compartments and tested how they induced calcium-based plateau potentials and sodium-based action potentials (calcium transients and sodium spikes, Fig.6E, 6F, Suppl.Fig.5).…”

Section: Resultsmentioning

confidence: 99%

Morpho-electric and computational properties of three types of human hippocampal CA1 pyramidal neurons

Mertens,

Leibner,

Pie

et al. 2023

Preprint

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Hippocampal pyramidal neuron activity underlies episodic memory and spatial navigation. Although extensively studied in rodents, extremely little is known about human hippocampal pyramidal neurons, even though human hippocampus underwent strong evolutionary reorganization and shows lower theta rhythm frequencies. To test whether biophysical and computational properties of humanCA1pyramidal neurons can explain observed rhythms, we map the morpho-electric and computational properties of individualCA1pyramidal neurons in human, non-pathological hippocampal slices from neurosurgery. HumanCA1pyramidal neurons have extensive dendrites and resonate at 2.9 Hz, optimally tuned to human theta frequencies. Morphological and biophysical properties reveal three cell types with distinct dendrite bifurcations and physiology. Data-driven biophysical models show that humanCA1pyramidal neurons use i) computationally independent dendritic compartments, ii) preferential routing of electrical activity towards soma or dendritic tree and iii) non-linear input-output transformations. Across cell types, morpho-electric properties consistently increase computational richness in humanCA1pyramidal neurons.TeaserHumanCA1pyramidal neurons have large and intricate morphologies, which translates to complex computational properties.

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High synaptic threshold for dendritic NMDA spike generation in human layer 2/3 pyramidal neurons

Cited by 23 publications

References 45 publications

Degeneracy in epilepsy: multiple routes to hyperexcitable brain circuits and their repair

Degeneracy in epilepsy: multiple routes to hyperexcitable brain circuits and their repair

A biologically inspired repair mechanism for neuronal reconstructions with a focus on human dendrites

Morpho-electric and computational properties of three types of human hippocampal CA1 pyramidal neurons

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