The Journal of Neuroscience, January 15, 2002, 22(2):413-427
Molecular Phenotyping of Retinal Ganglion Cells
Robert E.
Marc and
Bryan W.
Jones
John Moran Eye Center, University of Utah School of Medicine, Salt
Lake City, Utah 84132
Classifying all of the ganglion cells in the mammalian retina has
long been a goal of anatomists, physiologists, and cell biologists. The
rabbit retinal ganglion cell layer was phenotyped using intrinsic small
molecule signals (aspartate, glutamate, glycine, glutamine, GABA, and
taurine) and glutamate receptor-gated 1-amino-4-guanidobutane
excitation signals as the clustering dimensions for formal
classification. Intrinsic signals alone yielded 7 ganglion cell
superclasses and 1 amacrine cell superclass; the addition of excitation
signals ultimately resolved 14 natural ganglion cell classes and 3 amacrine cell classes. Ganglion cells comprise two-thirds to
three-quarters of the cells in the ganglion cell layer and exhibited
distinct metabolic, coupling, and excitation phenotypes, as well as
characteristic sizes, population fractions, and patterns. Metabolic
signatures (mixtures of glutamate, aspartate, glutamine, and GABA)
chemically discriminated ganglion from amacrine cells. Coupling
signatures reflected heterologous coupling states across ganglion
cells: (1) uncoupled, (2) coupled to GABAergic amacrine cells, and (3)
coupled to glycinergic amacrine cells. Excitation signatures reflected
differential channel permeation rates across classes after AMPA
activation. Extraction of unique size and patterning features from the
data sets further validated the robustness of the classification.
Because the classifications were explicitly blinded to structure, this
is strong evidence that molecular phenotype classes are natural
classes. Correspondences of molecular phenotype classes to functional
classes were inferred from size, coupling, encounter, and physiological
attributes. Ganglion cell classes display markedly different ionotropic
drives, which may partly explain the physiological brisk-sluggish
spectrum of ganglion cell spiking patterns.
Key words:
neuronal classification; molecular phenotyping; 1-amino-4-guanidobutane; AGB; retina; ganglion cells; amacrine cells; patterning
Copyright © 2002 Society for Neuroscience 0270-6474/02/222413-15$05.00/0
Previous Article | Next Article
