Abstract
The complete understanding of the mammalian brain requires exact knowledge of the function of each neuron subpopulation composing its parts. To achieve this goal, an exhaustive, precise, reproducible, and robust neuronal taxonomy should be defined. In this paper, a new circular taxonomy based on transcriptomic features and novel electrophysiological features is proposed. The approach is validated by analysing more than 1850 electrophysiological signals of different mouse visual cortex neurons proceeding from the Allen Cell Types database. The study is conducted on two different levels: neurons and their cell-type aggregation into Cre lines. At the neuronal level, electrophysiological features have been extracted with a promising model that has already proved its worth in neuronal dynamics. At the Cre line level, electrophysiological and transcriptomic features are joined on cell types with available genetic information. A taxonomy with a circular order is revealed by a simple transformation of the first two principal components that allow the characterization of the different Cre lines. Moreover, the proposed methodology locates other Cre lines in the taxonomy that do not have transcriptomic features available. Finally, the taxonomy is validated by Machine Learning methods which are able to discriminate the different neuron types with the proposed electrophysiological features.
Highlights
Understanding the nervous system’s mechanisms and capabilities, such as the conscience and cognition, remain one of the most challenging and interesting unresolved problems in biology
Glutamatergic neurons can be grouped based on gene markers, such as cut like homeobox 2 (Cux2) (Cut like homeobox 2), Rorb (RAR related orphan receptor B), or connective tissue growth factor (Ctgf) (Connective tissue growth factor), or alternatively based on their laminar locations and the locations to which they project their axons
A Shiny app has been developed to illustrate the differences in the typical action potential curve (AP) of the various GABAergic and glutamatergic Cre lines
Summary
Understanding the nervous system’s mechanisms and capabilities, such as the conscience and cognition, remain one of the most challenging and interesting unresolved problems in biology. Many authors consider GABAergic neurons to belong to four classes based on the expression of certain principal markers: Pvalb (parvalbumin) positive, Vip (vasoactive intestinal peptide) positive, Sst (somatostatin) positive, and cells that express Htr3a (5-hydroxytryptamine receptor 3A) but are Vip negative These groups are suitable for classification because they account for nearly the totality of neurons in certain brain regions as well as being largely expressed in a non-overlapping manner revealing neuron types with different properties (Tremblay et al, 2016). Glutamatergic neurons can be grouped based on gene markers, such as Cux (Cut like homeobox 2), Rorb (RAR related orphan receptor B), or Ctgf (Connective tissue growth factor), or alternatively based on their laminar locations and the locations to which they project their axons Aside from these previous statements, the different studies unearth discrepancies in terms of number of neuronal types, their characteristics, and the existing order between them as is reviewed in the paragraph
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