To understand the function of cortical circuits, it is necessary to catalog their cellular diversity. Past attempts to do so using anatomical, physiological or molecular features of cortical cells have not resulted in a unified taxonomy of neuronal or glial cell types, partly due to limited data. Single-cell transcriptomics is enabling, for the first time, systematic high-throughput measurements of cortical cells and generation of datasets that hold the promise of being complete, accurate and permanent. Statistical analyses of these data reveal clusters that often correspond to cell types previously defined by morphological or physiological criteria and that appear conserved across cortical areas and species. To capitalize on these new methods, we propose the adoption of a transcriptome-based taxonomy of cell types for mammalian neocortex. This classification should be hierarchical and use a standardized nomenclature. It should be based on a probabilistic definition of a cell type and incorporate data from different approaches, developmental stages and species. A community-based classification and data aggregation model, such as a knowledge graph, could provide a common foundation for the study of cortical circuits. This community-based classification, nomenclature and data aggregation could serve as an example for cell type atlases in other parts of the body.
Dendritic spines’ electrical function? Dendritic spines are small protrusions that cover the dendrites of most neurons in the brain. Their electrical properties are still controversially discussed. Cornejo et al . used an array of techniques to investigate the degree of voltage attenuation by dendritic spine necks in pyramidal neurons of the mouse neocortex. Spines not only synchronously depolarized in response to backpropagating action potentials, but local and transient depolarization also occurred. Isolated depolarization in individual spines reflected localized synaptic activation. A significant voltage gradient between dendritic spine and dendrite indicated that spines may constitute elementary electric compartments. The spine neck resistance is thus not negligible and may substantially contribute to the regulation of synaptic efficacy in the central nervous system. —PRS
Dendritic spines are membranous protrusions that receive essentially all excitatory inputs in most mammalian neurons. Spines, with a bulbous head connected to the dendrite by a thin neck, have a variety of morphologies that likely impact their functional properties. Nevertheless, the question of whether spines belong to distinct morphological subtypes is still open. Addressing this quantitatively requires clear identification and measurements of spine necks. Recent advances in electron microscopy enable large-scale systematic reconstructions of spines with nanometer precision in 3D. Analyzing ultrastructural reconstructions from mouse neocortical neurons with computer vision algorithms, we demonstrate that the vast majority of spine structures can be rigorously separated into heads and necks, enabling morphological measurements of spine necks. We then used a database of spine morphological parameters to explore the potential existence of different spine classes. Without exception, our analysis revealed unimodal distributions of individual morphological parameters of spine heads and necks, without evidence for subtypes of spines. The postsynaptic density size was strongly correlated with the spine head volume. The spine neck diameter, but not the neck length, was also correlated with the head volume. Spines with larger head volumes often had a spine apparatus and pairs of spines in a post-synaptic cell contacted by the same axon had similar head volumes. Our data reveal a lack of morphological subtypes of spines and indicate that the spine neck length and head volume must be independently regulated. These results have repercussions for our understanding of the function of dendritic spines in neuronal circuits.
Computational modeling of signal propagation in neurons is critical to our understanding of basic principles underlying brain organization and activity. Exploring these models is used to address basic neuroscience questions as well as to gain insights for clinical applications. The seminal Hodgkin Huxley model is a common theoretical framework to study brain activity. It was mainly used to investigate the electrochemical and physical properties of neurons. The influence of neuronal structure on activity patterns was explored, however, the rich dynamics observed in neurons with different morphologies is not yet fully understood. Here, we study signal propagation in fundamental building blocks of neuronal branching trees, unbranched and branched axons. We show how these simple axonal elements can code information on spike trains, and how asymmetric responses can emerge in axonal branching points. This asymmetric phenomenon has been observed experimentally but until now lacked theoretical characterization. Together, our results suggest that axonal morphological parameters are instrumental in activity modulation and information coding. The insights gained from this work lay the ground for better understanding the interplay between function and form in real-world complex systems. It may also supply theoretical basis for the development of novel therapeutic approaches to damaged nervous systems.
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