Differences in spike generation instead of synaptic inputs determine the feature selectivity of two retinal cell types.

Retinal ganglion cells (RGCs) are the spiking projection neurons of the eye that encode different features of the visual environment. The circuits providing synaptic input to different RGC types to drive feature selectivity have been studied extensively, but there has been less research aimed at understanding the intrinsic properties and how they impact feature selectivity. We introduce an RGC type in the mouse, the Bursty Suppressed-by-Contrast (bSbC) RGC, and compared it to the OFF sustained alpha (OFFsA). Differences in their contrast response functions arose from differences not in synaptic inputs but in their intrinsic properties. Spike generation was the key intrinsic property behind this functional difference; the bSbC RGC undergoes depolarization block while the OFFsA RGC maintains a high spike rate. Our results demonstrate that differences in intrinsic properties allow these two RGC types to detect and relay distinct features of an identical visual stimulus to the brain.

Identification of retinal ganglion cell types and brain nuclei expressing the transcription factor Brn3c/Pou4f3 using a Cre recombinase knock-in allele.

Members of the POU4F/Brn3 transcription factor family have an established role in the development of retinal ganglion cell (RGCs) types, the main transducers of visual information from the mammalian eye to the brain. Our previous work using sparse random recombination of a conditional knock-in reporter allele expressing alkaline phosphatase (AP) and intersectional genetics had identified three types of Brn3c positive (Brn3c+ ) RGCs. Here, we describe a novel Brn3cCre mouse allele generated by serial Dre to Cre recombination and use it to explore the expression overlap of Brn3c with Brn3a and Brn3b and the dendritic arbor morphologies and visual stimulus response properties of Brn3c+ RGC types. Furthermore, we explore brain nuclei that express Brn3c or receive input from Brn3c+ neurons. Our analysis reveals a much larger number of Brn3c+ RGCs and more diverse set of RGC types than previously reported. Most RGCs expressing Brn3c during development are still Brn3c positive in the adult, and all express Brn3a while only about half express Brn3b. Genetic Brn3c-Brn3b intersection reveals an area of increased RGC density, extending from dorsotemporal to ventrolateral across the retina and overlapping with the mouse binocular field of view. In addition, we report a Brn3c+ RGC projection to the thalamic reticular nucleus, a visual nucleus that was not previously shown to receive retinal input. Furthermore, Brn3c+ neurons highlight a previously unknown subdivision of the deep mesencephalic nucleus. Thus, our newly generated allele provides novel biological insights into RGC type classification, brain connectivity, and cytoarchitectonic.

Typology and Circuitry of Suppressed-by-Contrast Retinal Ganglion Cells.

Retinal ganglion cells (RGCs) relay ~40 parallel and independent streams of visual information, each encoding a specific feature of a visual scene, to the brain for further processing. The polarity of a visual neuron's response to a change in contrast is generally the first characteristic used for functional classification: ON cells increase their spike rate to positive contrast; OFF cells increase their spike rate for negative contrast; ON-OFF cells increase their spike rate for both contrast polarities. Suppressed-by-Contrast (SbC) neurons represent a less well-known fourth category; they decrease firing below a baseline rate for both positive and negative contrasts. SbC RGCs were discovered over 50 years ago, and SbC visual neurons have now been found in the thalamus and primary visual cortex of several mammalian species, including primates. Recent discoveries of SbC RGCs in mice have provided new opportunities for tracing upstream circuits in the retina responsible for the SbC computation and downstream targets in the brain where this information is used. We review and clarify recent work on the circuit mechanism of the SbC computation in these RGCs. Studies of mechanism rely on precisely defined cell types, and we argue that, like ON, OFF, and ON-OFF RGCs, SbC RGCs consist of more than one type. A new appreciation of the diversity of SbC RGCs will help guide future work on their targets in the brain and their roles in visual perception and behavior.