title: The AII amacrine cell connectome: a dense network hub.
abstract: The mammalian AII retinal amacrine cell is a narrow-field, multistratified glycinergic neuron best known for its role in collecting scotopic signals from rod bipolar cells and distributing them to ON and OFF cone pathways in a crossover network via a combination of inhibitory synapses and heterocellular AII::ON cone bipolar cell gap junctions. Long considered a simple cell, a full connectomics analysis shows that AII cells possess the most complex interaction repertoire of any known vertebrate neuron, contacting at least 28 different cell classes, including every class of retinal bipolar cell. Beyond its basic role in distributing rod signals to cone pathways, the AII cell may also mediate narrow-field feedback and feedforward inhibition for the photopic OFF channel, photopic ON-OFF inhibitory crossover signaling, and serves as a nexus for a collection of inhibitory networks arising from cone pathways that likely negotiate fast switching between cone and rod vision. Further analysis of the complete synaptic counts for five AII cells shows that (1) synaptic sampling is normalized for anatomic target encounter rates; (2) qualitative targeting is specific and apparently errorless; and (3) that AII cells strongly differentiate partner cohorts by synaptic and/or coupling weights. The AII network is a dense hub connecting all primary retinal excitatory channels via precisely weighted drive and specific polarities. Homologs of AII amacrine cells have yet to be identified in non-mammalians, but we propose that such homologs should be narrow-field glycinergic amacrine cells driving photopic ON-OFF crossover via heterocellular coupling with ON cone bipolar cells and glycinergic synapses on OFF cone bipolar cells. The specific evolutionary event creating the mammalian AII scotopic-photopic hub would then simply be the emergence of large numbers of pure rod bipolar cells.
authors.affiliation: Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah School of Medicine Salt Lake City, UT, USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Marc
authors.affiliation: Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah School of Medicine Salt Lake City, UT, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Anderson
authors.affiliation: Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah School of Medicine Salt Lake City, UT, USA.
authors.forename: Bryan W
authors.initials: BW
authors.lastname: Jones
authors.affiliation: Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah School of Medicine Salt Lake City, UT, USA.
authors.forename: Crystal L
authors.initials: CL
authors.lastname: Sigulinsky
authors.affiliation: Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah School of Medicine Salt Lake City, UT, USA.
authors.forename: James S
authors.initials: JS
authors.lastname: Lauritzen
mesh_terms: D025042:Amacrine Cells / Q000145:classification / Q000502:physiology* / Q000648:ultrastructure; D000818:Animals; D063132:Connectome; D066264:Datasets as Topic; D025461:Feedback, Physiological / Q000502:physiology; D005260:Female; D017629:Gap Junctions / Q000378:metabolism / Q000648:ultrastructure; D005998:Glycine / Q000378:metabolism; D066298:In Vitro Techniques; D046529:Microscopy, Electron, Transmission; D009415:Nerve Net / Q000502:physiology* / Q000648:ultrastructure; D009433:Neural Inhibition / Q000502:physiology; D011817:Rabbits; D012160:Retina / Q000166:cytology*; D013569:Synapses / Q000378:metabolism / Q000648:ultrastructure; D014795:Visual Pathways / Q000502:physiology / Q000648:ultrastructure; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D005680:gamma-Aminobutyric Acid; D005998:Glycine
keywords: amacrine cells; bipolar cells; connectomics; gap junctions; hub; networks; retina; synapses