Biology subjects

Packer, O.

Publications and source records attributed to Packer, O..

2 recordsLinked to original sources

bioRxiv2025

Visual pathway origins: an electron microscopic volume for connectomic analysis of the human foveal retina

The fovea is a unique specialization of the primate retina and is a promising site for obtaining the first complete connectome of a human central nervous system (CNS) structure. Within the fovea, neural cells and circuits have been miniaturized and compressed during evolution to sample the visual image at highest spatial resolution and begin the neural processing that serves human form, color, and motion perception. Here we present a comprehensive analysis of a sample of human foveal retina using deep learning-based segmentation to reconstruct all cells and synaptic connections at nanoscale resolution. We classified [~]3,000 cells into 51 distinct morphological types based on their structural features and connectivity patterns. Our observations reveal novel synaptic pathways absent in non-human primates, suggesting specialized circuits contribute uniquely to human trichromatic color vision. A biophysical model of the distinct connectomes made by gap junctions (electrical synapses) between short- (S) and medium-long- (ML) wavelength-sensitive cone photoreceptors, suggests chromatic interactions between S and ML cones prior to the first chemical synapse. Segmentation of retinal ganglion cells (RGCs) suggests the presence of only 11 visual pathways, with 5 high-density RGC pathways accounting for over 95% of foveal output to the brain: a dramatic contrast to the 40+ ganglion cell types recognized in mouse retina. Our connectomic analysis reveals distinctive features of human neural circuitry and demonstrates how AI-based computational approaches can advance understanding of human brain structure and function. Significant statementVision begins in the retina, an accessible outpost of the brain located at the back of the eye. When we directly view an object, we use the fovea--a tiny region containing over 50 distinct, densely packed neuron types. How these diverse cells interconnect through synapses to transmit visual information has been difficult to determine. Here, we used artificial intelligence-based computational methods to create a complete wiring diagram--a connectome--mapping every neuron and synapse in a sample of human fovea. This connectomic resource will be freely available to researchers worldwide. Discoveries so far include synaptic circuits linked to human color vision, demonstrating how connectomics can reveal what makes the human nervous system unique.

neuroscience↗

bioRxiv2018

Short-wavelength cone signals contribute to sparse, high-dimensional color tuning in primate OFF midget ganglion cells

In the trichromatic primate retina, the midget retinal ganglion cell is the classical substrate for red-green color signaling, with a circuitry that enables antagonistic responses between long (L)- and medium (M)-wavelength sensitive cone inputs. Previous physiological studies show that some OFF midget ganglion cells may receive sparse input from short (S)-wavelength sensitive cones, but the effect of S-cone inputs on the chromatic tuning properties of such cells has been unexplored. Moreover, anatomical evidence for a synaptic pathway from S cones to OFF midget ganglion cells through OFF-midget bipolar cells remains ambiguous. In this study we address both questions for the macaque monkey retina. First, we used serial block-face electron microscopy (SBEM) to show that every S-cone in the parafoveal retina synapses principally with a single OFF-midget bipolar cell which in turn forms a private-line connection with an OFF midget ganglion cell. Second, we used patch electrophysiology to characterize the chromatic tuning of OFF midget ganglion cells in the near peripheral retina that receive combined input from L, M and S cones. These S-OFF midget cells have a characteristic S-cone spatial signature, but demonstrate heterogeneous color properties due to variable strength of L, M, and S cone input across the receptive field. Together these findings strongly support the hypothesis that the OFF midget pathway is the major conduit for S-OFF signals in primate retina, and redefines the pathway as a chromatically complex substrate that encodes color signals beyond the classically recognized L vs. M and S vs. L+M cardinal mechanisms.\n\nSignificance statementThe first step of color processing in the visual pathway of primates occurs when signals from short- (S), middle- (M) and long- (L) wavelength sensitive cone types interact antagonistically within the retinal circuitry to create color-opponent pathways. The midget (L vs. M or red-green) and small bistratified (S vs. L+M, or blue-yellow) appear to provide the physiological origin of the cardinal axes of human color vision. Here we confirm the presence of an additional S-OFF midget circuit in the macaque monkey fovea with scanning block-face electron microscopy (SBEM) and show physiologically that a subpopulation of S-OFF midget cells combine S, L and M cone inputs along non-cardinal directions of color space, expanding the retinal role in color coding.

neuroscience↗