Biology subjects

Cafaro, J.

Publications and source records attributed to Cafaro, J..

4 recordsLinked to original sources

bioRxiv2021

Generative adversarial neural networks maintain decoder accuracy during signal disruption in simulated long-term recordings from brain computer interfaces

Chronically implanted brain-computer interfaces (BCIs) provide amazing opportunities to those living with disability and for the treatment of chronic disorders of the nervous system. However, this potential has yet to be fully realized in part due to the lack of stability in measured signals over time. Signal disruption stems from multiple sources including mechanical failure of the interface, changes in neuron health, and glial encapsulation of the electrodes that alter the impedance. In this study we present an algorithmic solution to the problem of long-term signal disruption in chronically implanted neural interfaces. Our approach utilizes a generative adversarial network (GAN), based on the original Unsupervised Image to Image Translation (UNIT) algorithm, which learns how to recover degraded signals back to their analogous non-disrupted ("clean") exemplars measured at the time of implant. We demonstrate that this approach can reliably recover simulated signals in two types of commonly used neural interfaces: multi-electrode arrays (MEA), and electrocorticography (ECoG). To test the accuracy of signal recovery we employ a common BCI paradigm wherein a classification algorithm (neural decoder) is trained on the starting (non-disrupted) set of signals. Performance of the decoder demonstrates expected failure over time as the signal disruption accumulates. In simulated MEA experiments, our approach recovers decoder accuracy to >90% when as many as 13/ 32 channels are lost, or as many as 28/32 channels have their neural responses altered. In simulated ECoG experiments, our approach shows stabilization of the neural decoder indefinitely with decoder accuracies >95% over simulated lifetimes of over 1 year. Our results suggest that these types of neural networks can provide a useful tool to improve the long-term utility of chronically implanted neural interfaces.

neuroscience↗

bioRxiv2019

Natural global motion processing by populations of direction-selective retinal ganglion cells

Simple stimuli have been critical to understanding neural population codes in sensory systems. Yet it remains necessary to determine the extent to which this understanding generalizes to more complex conditions. To explore this problem, we measured how populations of direction-selective ganglion cells (DSGCs) from mouse retina respond to a global motion stimulus with its direction and speed changing dynamically. We then examined the encoding and decoding of motion direction in both individual and populations of DSGCs. Individual cells integrated global motion over ~200 ms, and responses were tuned to direction. However, responses were sparse and broadly tuned, which severely limited decoding performance from small DSGC populations. In contrast, larger populations compensated for response sparsity, enabling decoding with high temporal precision (<100 ms). At these timescales, correlated spiking was minimal and had little impact on decoding performance, unlike results obtained using simpler local motion stimuli decoded over longer timescales. We use these data to define different DSGC population decoding regimes that utilize or mitigate correlated spiking to achieve high spatial versus high temporal resolution.

neuroscience↗

bioRxiv2018

Activation of rod input in a in a model of retinal degeneration reverses retinal remodeling and induces formation of normal synapses, circuitry and visual signaling in the adult retina

A major cause of human blindness is the death of rod photoreceptors. As rods degenerate, synaptic structures between rod and rod bipolar cells dissolve and the rod bipolar cells extend their dendrites and occasionally make aberrant contacts. Such changes are broadly observed in blinding disorders caused by photoreceptor cell death and is thought to occur in response to deafferentation. How the remodeled retinal circuit affect visual processing following rod rescue is not known. To address this question, we generated transgenic mice wherein a disrupted cGMP-gated channel (CNG) gene can be repaired at the endogenous locus and at different stages of degeneration by tamoxifen-inducible cre-mediated recombination. In normal rods, light-induced closure of CNG channels leads to hyperpolarization of the cell, reducing neurotransmitter release at the synapse. Similarly, rods lacking CNG channel exhibit a resting membrane potential that was ~10mV hyperpolarized compared to WT rods, indicating diminished glutamate release. Retinas from these mice undergo stereotypic retinal remodeling as a consequence of rod malfunction and degeneration. Upon tamoxifen-induced expression of CNG channels, rods recovered their structure and exhibited normal light responses. Moreover, we show that the adult mouse retina displays a surprising degree of plasticity upon activation of rod input. Wayward bipolar cell dendrites establish contact with rods to support normal synaptic transmission, which is propagated to the retinal ganglion cells. These findings demonstrate remarkable plasticity extending beyond the developmental period and support efforts to repair or replace defective rods in patients blinded by rod degeneration.\n\nSignificance StatementCurrent strategies for treatment of neurodegenerative disorders are focused on the repair of the primary affected cell type. However, the defective neuron functions within a complex neural circuitry, which also becomes degraded during disease. It is not known whether a rescued neuron and the remodeled circuit will establish communication to regain normal function. We show that the adult mammalian neural retina exhibits a surprising degree of plasticity following rescue of rod photoreceptors. The wayward rod bipolar cell dendrites re-establish contact with rods to support normal synaptic transmission, which is propagated to the retinal ganglion cells. These findings support efforts to repair or replace defective rods in patients blinded by rod cell loss.

neuroscience↗

bioRxiv2017

Formation of retinal direction-selective circuitry initiated by starburst amacrine cell homotypic contact

Impact statementSelective synapse formation in a retinal motion-sensitive circuit is orchestrated by starburst amacrine cells, which use homotypic interactions to initiate formation of a dendritic scaffold that recruits projections from circuit partners.\n\nSUMMARYA common strategy by which developing neurons locate their synaptic partners is through projections to circuit-specific neuropil sublayers. Once established, sublayers serve as a substrate for selective synapse formation, but how sublayers arise during neurodevelopment remains unknown. Here we identify the earliest events that initiate formation of the direction-selective circuit in the inner plexiform layer of mouse retina. We demonstrate that radially-migrating newborn starburst amacrine cells establish homotypic contacts on arrival at the inner retina. These contacts, mediated by the cell-surface protein MEGF10, trigger neuropil innervation resulting in generation of two sublayers comprising starburst-cell dendrites. This dendritic scaffold then recruits projections from circuit partners. Abolishing MEGF10-mediated contacts profoundly delays and ultimately disrupts sublayer formation, leading to broader direction tuning and weaker direction-selectivity in retinal ganglion cells. Our findings reveal a mechanism by which differentiating neurons transition from migratory to mature morphology, and highlight this mechanisms importance in forming circuit-specific sublayers.

neuroscience↗