Biology subjects

Berson, D.

Publications and source records attributed to Berson, D..

5 recordsLinked to original sources

bioRxiv2026

Eyewire II - A connectomic resource for resolving cell types and circuits of the mouse retina

Comprehensive wiring diagrams from electron microscopy (EM) are a powerful tool to understand the inner workings of the brain. The retina is an easily accessible part of the brain that performs complex visual computations. Its thin, layered structure offers a unique opportunity to decipher neural cell types and map their connectivity. A major obstacle has been the limited size of existing retinal EM datasets, which could not resolve rare cell types and neurons with large dendritic arbors. Here, we describe Eyewire II, a large-scale EM dataset covering nearly 1 mm2 of the adult mouse retina - roughly 10-100 times larger than previous retinal EM volumes. Human proofreading of an automated reconstruction has so far yielded more than 8, 000 bipolar cells, 13, 000 amacrine cells, and 4, 000 retinal ganglion cells. Automated detection is complete for synaptic ribbons and in progress for conventional synapses. Prior to EM imaging, visual responses to diverse stimuli - including natural movies - were recorded in a subset of neurons using two-photon Ca2+ imaging, enabling direct alignment of morphological and functional cell type identity. To enable high-throughput, automatic cell typing, we devised a human-in-the-loop approach that combines deep learning with human expert annotations. As a proof-of-principle, we show that morphological features of reconstructed bipolar cells are sufficient to recover all 15 known bipolar cell types with regular, non-overlapping mosaics. Together, these data and tools establish Eyewire II as a shared resource for the field of retina research. Already now, more than 30 laboratories worldwide are contributing proofreading, expert annotations, and software tools, advancing Eyewire II towards a complete cell type catalog and synaptic wiring diagram of a mammalian retina.

neuroscience↗

bioRxiv2021

Gain control by sparse, ultra-slow glycinergic synapses

SO_SCPLOWUMMARYC_SCPLOWRetinal ON starburst amacrine cells (SACs) play a critical role in computing stimulus direction, partly in service of image stabilization by optokinetic nystagmus. ON SAC responses are sculpted by rich GABAergic innervation, mostly from neighbouring SACs. Surprisingly, however, we find that glycinergic narrow field amacrine cells (NACs) serve as their dominant source of inhibition during sustained activity. Although NAC inputs constitute only [~]5% of inhibitory synapses to ON SACs, their distinct input patterns enable them to drive glycine inhibition during the both light increments and decrements. NAC-to-ON-SAC inhibition appears to be mediated by ultra-slow non-canonical glycine receptors containing the 4 subunit, which effectively summate during repetitive stimulation. Glycinergic inhibition strongly decreases the output gain of the SACs, ensuring that their direction-selective output is maintained over their operating range. These results reveal an unexpected role for glycinergic pathways and receptor kinetics in modulating direction selectivity in the retina.

neuroscience↗

bioRxiv2020

Spatially displaced excitation contributes to the encoding of interrupted motion by the retinal direction-selective circuit

Spatially distributed excitation and inhibition collectively shape a visual neurons receptive field (RF) properties. In the direction-selective circuit of the mammalian retina, the role of strong null-direction inhibition of On-Off direction-selective ganglion cells (ON-OFF DSGCs) on their direction selectivity is well-studied. However, how excitatory inputs influence the On-Off DSGCs visual response is underexplored. Here, we report that On-Off DSGCs have a spatially displaced glutamatergic receptive field along their preferred-null motion axis. This displaced receptive field contributes to DSGC null-direction spiking during interrupted motion trajectories. Theoretical analyses indicate that population responses during interrupted motion may help populations of On-Off DSGCs signal the spatial location of moving objects in complex, naturalistic visual environments. Our study highlights that the direction-selective circuit exploits separate sets of mechanisms under different stimulus conditions, and these mechanisms may help encode multiple visual features.

neuroscience↗

bioRxiv2020

Rapid 'multi-directed' cholinergic transmission at central synapses

Acetylcholine (ACh) is a key neurotransmitter that plays diverse roles in many parts of the central nervous system, including the retina. However, assessing the precise spatiotemporal dynamics of ACh is technically challenging and whether ACh transmits signals via rapid, point-to-point synaptic mechanisms, or broader-scale non-synaptic mechanisms has been difficult to ascertain. Here, we examined the properties of cholinergic transmission at individual contacts made between direction-selective starburst amacrine cells and downstream ganglion cells in the retina. Using a combination of electrophysiology, serial block-face electron microscopy, and two-photon ACh imaging, we demonstrate that ACh signaling bears the hallmarks of both non-synaptic and synaptic forms of transmission. ACh co-activates nicotinic ACh receptors located on the intersecting dendrites of pairs of ganglion cells, with equal efficiency (non-synaptic)-- and yet retains the ability to generate rapid miniature currents ([~]1 ms rise times: synaptic). Fast cholinergic signals do not appear to depend on anatomically well-defined synaptic structures. We estimate that ACh spread is limited to [~]1-2 {micro}m from its sites of release, which may help starbursts drive local direction-selective cholinergic responses in ganglion cell dendrites. Together, our results establish the functional architecture for cholinergic signaling at a central synapse and propose a novel motif whereby single presynaptic sites can co-transmit information to multiple neurons on a millisecond timescale.

neuroscience↗

bioRxiv2018

Molecular Diversity of Intrinsically Photosensitive Ganglion Cells

Intrinsically photosensitive retinal ganglion cells (ipRGCs) are rare mammalian photoreceptors essential for non-image-forming vision functions, such as circadian photoentrainment and the pupillary light reflex. They comprise multiple subtypes distinguishable by morphology, physiology, projections, and levels of expression of melanopsin (Opn4), their photopigment. The molecular programs that differentiate ipRGCs from other ganglion cells and ipRGC subtypes from one another remain elusive. Here, we present comprehensive gene expression profiles of early postnatal and adult mouse ipRGCs purified from two lines of reporter mice marking different sets of ipRGC subtypes. We find dozens of novel genes highly enriched in ipRGCs. We reveal that Rasgrp1 and Tbx20 are selectively expressed in subsets of ipRGCs, though these molecularly defined groups imperfectly match established ipRGC subtypes. We demonstrate that the ipRGCs regulating circadian photoentrainment are unexpectedly diverse at the molecular level. Our findings reveal unexpected complexity in gene expression patterns across mammalian ipRGC subtypes.

neuroscience↗