Predictably manipulating photoreceptor light responses to reveal their role in downstream visual responses.

Computation in neural circuits relies on the judicious use of nonlinear circuit components. In many cases, multiple nonlinear components work collectively to control circuit outputs. Separating the contributions of these different components is difficult, and this limits our understanding of the mechanistic basis of many important computations.

Predictably manipulating photoreceptor light responses to reveal their role in downstream visual responses.

Computation in neural circuits relies on the judicious use of nonlinear circuit components. In many cases, multiple nonlinear components work collectively to control circuit outputs. Separating the contributions of these different components is difficult, and this limits our understanding of the mechanistic basis of many important computations.

Adaptation in cone photoreceptors contributes to an unexpected insensitivity of primate On parasol retinal ganglion cells to spatial structure in natural images.

Neural circuits are constructed from nonlinear building blocks, and not surprisingly overall circuit behavior is often strongly nonlinear. But neural circuits can also behave near linearly, and some circuits shift from linear to nonlinear behavior depending on stimulus conditions. Such control of nonlinear circuit behavior is fundamental to neural computation.

Predicting and Manipulating Cone Responses to Naturalistic Inputs.

Primates explore their visual environment by making frequent saccades, discrete and ballistic eye movements that direct the fovea to specific regions of interest. Saccades produce large and rapid changes in input. The magnitude of these changes and the limited signaling range of visual neurons mean that effective encoding requires rapid adaptation.

S-cone photoreceptors in the primate retina are functionally distinct from L and M cones.

Daylight vision starts with signals in three classes of cone photoreceptors sensitive to short (S), middle (M), and long (L) wavelengths. Psychophysical studies show that perceptual sensitivity to rapidly varying inputs differs for signals originating in S cones versus L and M cones; notably, S-cone signals appear perceptually delayed relative to L- and M-cone signals. These differences could originate in the cones themselves or in the post-cone circuitry.

Range, routing and kinetics of rod signaling in primate retina.

Stimulus- or context-dependent routing of neural signals through parallel pathways can permit flexible processing of diverse inputs. For example, work in mouse shows that rod photoreceptor signals are routed through several retinal pathways, each specialized for different light levels. This light-level-dependent routing of rod signals has been invoked to explain several human perceptual results, but it has not been tested in primate retina.

Cellular and Circuit Mechanisms Shaping the Perceptual Properties of the Primate Fovea.

The fovea is a specialized region of the retina that dominates the visual perception of primates by providing high chromatic and spatial acuity. While the foveal and peripheral retina share a similar core circuit architecture, they exhibit profound functional differences whose mechanisms are unknown. Using intracellular recordings and structure-function analyses, we examined the cellular and synaptic underpinnings of the primate fovea.

Genome sequencing of idiopathic pulmonary fibrosis in conjunction with a medical school human anatomy course.

Even in cases where there is no obvious family history of disease, genome sequencing may contribute to clinical diagnosis and management. Clinical application of the genome has not yet become routine, however, in part because physicians are still learning how best to utilize such information. As an educational research exercise performed in conjunction with our medical school human anatomy course, we explored the potential utility of determining the whole genome sequence of a patient who had died following a clinical diagnosis of idiopathic pulmonary fibrosis (IPF).