The quality of the signal a retinal ganglion cell transmits to the brain is important for preception because it sets the minimum detectable stimulus. The ganglion cell converts graded potentials into a spike train with a selective filter but in the process adds noise. To explore how efficiently information is transferred to spikes, we measured contrast detection threshold and increment threshold from graded potential and spike responses of brisk-transient ganglion cells. Intracellular responses to a spot flashed over the receptive field center of the cell were recorded in an intact mammalian retina maintained in vitro at 37°C. Thresholds were measured in a single-interval forced-choice procedure with an ideal observer. The graded potential gave a detection threshold of 1.5% contrast, whereas spikes gave 3.8%. The graded potential also gave increment thresholds approximately twofold lower and carried ϳ60% more gray levels. Increment threshold "dipped" below the detection threshold at a low contrast (Ͻ5%) but increased rapidly at higher contrasts. The magnitude of the "dipper" for both graded potential and spikes could be predicted from a threshold nonlinearity in the responses. Depolarization of the cell by current injection reduced the detection threshold for spikes but also reduced the range of contrasts they can transmit. This suggests that contrast sensitivity and dynamic range are related in an essential trade-off.

Several subtypes of melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs) have been reported. The M1 type of ipRGCs exhibit distinct properties compared with the remaining (non-M1) cells. They differ not only in their soma size and dendritic arbor, but also in their physiological properties, projection patterns, and functions. However, it is not known how these differences arise. We tested the hypothesis that M1 and non-M1 cells express Brn3 transcription factors differentially. The Brn3 family of class IV POU-domain transcription factors (Brn3a, Brn3b, and Brn3c) is involved in the regulation of differentiation, dendritic stratification, and axonal projection of retinal ganglion cells during development. By using double immunofluorescence for Brn3 transcription factors and melanopsin, and with elaborate morphometric analyses, we show in mouse retina that neither Brn3a nor Brn3c are expressed in ipRGCs. However, Brn3b is expressed in a subset of ipRGCs, particularly those with larger somas and lower melanopsin levels, suggesting that Brn3b is expressed preferentially in the non-M1 cells. By using dendritic stratification to distinguish M1 from non-M1 cells, we found that whereas nearly all non-M1 cells expressed Brn3b, a vast majority of the M1 cells were negative for Brn3b. Interestingly, in the small proportion of the M1 cells that did express Brn3b, the expression level of Brn3b was significantly lower than in the non-M1 cells. These results provide insights about how expression of specific molecules in a ganglion cell could be linked to its role in visual function.

. We measured the contrast threshold for mammalian brisk-transient ganglion cells in vitro. Spikes were recorded extracellularly in the intact retina (guinea pig) in response to a spot with sharp onset, flashed for 100 ms over the receptive field center. Probability density functions were constructed from spike responses to stimulus contrasts that bracketed threshold. Then an "ideal observer" (IO) compared additional trials to these probability distributions and decided, using a single-interval, two-alternative forced-choice procedure, which contrasts had most likely been presented. From these decisions we constructed neurometric functions that yielded the threshold contrast by linear interpolation. Based on the number of spikes in a response, the IO detected contrasts as low as 1% [4.2 Ϯ 0.4% (SE); n ϭ 35]; based on the temporal pattern of spikes, the IO detected contrasts as low as 0.8% (2.8 Ϯ 0.2%). Contrast increments above a very low "basal contrast" were discriminated with greater sensitivity than they were detected against the background. Performance was optimal near 37°C and declined with a Q 10 of about 2, similar to that of retinal metabolism. By the method used by previous in vivo studies of brisk-transient cells, our most sensitive cells had similar thresholds. The in vitro measurements thus provide an important benchmark for comparing sensitivity of neurons upstream (cone and bipolar cell) and downstream to assess efficiency of retinal and central circuits.

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The molecular mechanisms underlying the involvement of oligodendrocytes in formation of the nodes of Ranvier (NORs) remain poorly understood. Here we show that oligodendrocyte-myelin glycoprotein (OMgp) aggregates specifically at NORs. Nodal location of OMgp does not occur along demyelinated axons of either Shiverer or proteolipid protein (PLP) transgenic mice. Over-expression of OMgp in OLN-93 cells facilitates process outgrowth. In transgenic mice in which expression of OMgp is down-regulated, myelin thickness declines, and lateral oligodendrocyte loops at the node-paranode junction are less compacted and even join together with the opposite loops, which leads to shortened nodal gaps. Notably, each of these structural abnormalities plus modest down-regulation of expression of Na(+) channel alpha subunit result in reduced conduction velocity in the spinal cords of the mutant mice. Thus, OMgp that is derived from glia has distinct roles in regulating nodal formation and function during CNS myelination.