Neural Circuit Revision in Retinal Remodeling, A Pathoconnectomics Approach DOI Creative Commons
Rebecca L. Pfeiffer,

Jeebika Dahal,

Crystal Sigulinsky

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 15, 2024

Abstract The Aii glycinergic amacrine cell (Aii) plays a central role in bridging rod pathways with cone pathways, enabling an increased dynamic range of vision from scotopic to photopic ranges. integrates signals via chemical synapses bipolar cells (RodBCs) onto the arboreal processes ACs, injecting into ON-cone (CBbs) gap junctions Aiis on and waist ACs. CBbs then carry this information ON OFF ganglion classes. In addition, is involved surround inhibition (CBas) through ACs CBas. We have previously shown changes RodBC connectivity as consequence photoreceptor degeneration pathoconnectome early retinal degeneration: RPC1. Here, we evaluated impact determine impacts downstream network neural retina its suitability for integrating therapeutic interventions photoreceptors are lost. Previously, reported that degeneration, prior loss, Rod BCs make pathological Aiis. further characterize altered additional shifts both excitatory drive junctional coupling along discussion broader networks. New findings here demonstrate CBas increasing number BC classes degenerating retina. study, also report Aii, tertiary neuron alters their synaptic contacts indicating rewiring occurs more distant members earlier than was predicted. This processing, presumably acuity, ultimately ability support therapeutics designed restore image-forming vision. Finally, these alterations may be cellular level finding explains one first clinical complaints human patients degenerative disease, inability adapt back forth conditions.

Language: Английский

Review of the Brain’s Behaviour after Injury and Disease for Its Application in an Agent-Based Model (ABM) DOI Creative Commons
Luis Irastorza-Valera, Edgar Soria‐Gómez, José María Benítez

et al.

Biomimetics, Journal Year: 2024, Volume and Issue: 9(6), P. 362 - 362

Published: June 14, 2024

The brain is the most complex organ in human body and, as such, its study entails great challenges (methodological, theoretical, etc.). Nonetheless, there a remarkable amount of studies about consequences pathological conditions on development and functioning. This bibliographic review aims to cover mostly findings related changes physical distribution neurons their connections—the connectome—both structural functional, well modelling approaches. It does not intend offer an extensive description all affecting brain; rather, it presents common ones. Thus, here, we highlight need for accurate that can subsequently be used understand function applied diagnose, track, simulate treatments prevalent pathologies brain.

Language: Английский

Citations

1

High-throughput ultrastructural analysis of macular telangiectasia type 2 DOI Creative Commons
Charles L. Zucker, Paul S. Bernstein, Richard Schalek

et al.

Frontiers in Ophthalmology, Journal Year: 2024, Volume and Issue: 4

Published: July 30, 2024

Introduction Macular Telangiectasia type 2 (MacTel), is an uncommon form of late-onset, slowly-progressive macular degeneration. Associated with regional Müller glial cell loss in the retina and amino acid serine synthesized by cells, disease functionally confined to a central retinal region – MacTel zone. Methods We have used high-throughput multi-resolution electron microscopy techniques, optimized for analysis, study retinas from two women, mother daughter, aged 79 48 years respectively, suffering MacTel. Results In both eyes, principal observations made were changes specific mitochondrial structure outside within zone all types, exception those pigment epithelium (RPE). The lesion areas, which are hallmark MacTel, extend Bruch’s membrane choriocapillaris, through depths retina, include cells RPE, vascular elements, extensive hypertrophic basement material. Where lost, we identified significant population microglial exclusively Henle fiber layer, appear ensheathe fibers, similar that seen normally cells. Discussion Since synthesize serine, whereas neurons do not, propose deficiency, required normal function, may relate underlie development With occurring retina-wide, question remains as why uniquely susceptible

Language: Английский

Citations

1

Mechanisms underlying activation of retinal bipolar cells through targeted electrical stimulation: a computational study DOI
Javad Paknahad, Pragya Kosta, Jean‐Marie C. Bouteiller

et al.

Journal of Neural Engineering, Journal Year: 2021, Volume and Issue: 18(6), P. 066034 - 066034

Published: Nov. 26, 2021

Objective. Retinal implants have been developed to electrically stimulate healthy retinal neurons in the progressively degenerated retina. Several stimulation approaches proposed improve visual percept induced patients with prostheses. We introduce a computational model capable of simulating effects electrical on neurons. Leveraging this platform, we delve into underlying mechanisms influencing sensitivity neurons' response various stimulus waveforms.Approach. implemented spiking bipolar cells (BCs) magnocellular pathway primate retina, diffuse BC subtypes (DB4), and utilized our multiscale admittance method (AM)-NEURON platform characterize BCs epiretinal monophasic, symmetric, asymmetric biphasic pulses.Main results. Our investigations yielded four notable results: (a) latency increases as pulse duration lengthens; conversely, decreases current amplitude increases. (b) Stimulation long anodic-first symmetric (duration > 8 ms) results significant decrease threshold compared similar cathodic-first pulses (from 98.2 57.5µA). (c) The hyperpolarization-activated cyclic nucleotide-gated channel was prominent contributor reduced pulses. (d) Finally, extending study waveforms, predict lower using that short stimulation.Significance. This predicts several parameters stimulation. Of importance, findings shed light experimental observations from literature, thus highlighting capability methodology guide development protocols generate desired biological response, thereby constituting an ideal testbed for electroceutical devices.

Language: Английский

Citations

8

Impact of Retinal Degeneration on Response of ON and OFF Cone Bipolar Cells to Electrical Stimulation DOI Creative Commons
Shayan Farzad, Pragya Kosta, Ege Iseri

et al.

IEEE Transactions on Neural Systems and Rehabilitation Engineering, Journal Year: 2023, Volume and Issue: 31, P. 2424 - 2437

Published: Jan. 1, 2023

In retinal degenerative diseases, such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD), the photoreceptors become stressed start to degenerate in early stages of disease. Retinal prosthetic devices have been developed restore vision patients by applying electrical stimulation surviving cells. However, these provide limited visual perception therapeutic interventions are generally considered later disease when only inner layer cells left. A potential treatment option for diseases can be stimulating bipolar cells, which receive presynaptic signals from photoreceptors. this work, we constructed computational models healthy degenerated (both ON OFF-type) cone (CBCs) with realistic morphologies extracted connectomes early-stage rabbit retina. We examined cells' membrane axon terminal calcium current differences subjected stimulation. addition, investigated how differently behave respect various parameters, including pulse duration distance electrode. The results suggested that regardless position OFF CBCs retina model, there is not a significant difference between electrically stimulated. CBC rising time-constant shorter (0.29 ± 0.03 ms) than (0.8 0.07 ms). Moreover, ionic channels at terminals higher concentration (32.24 6.12 pA) (13.64 2.88 independently cell's position.

Language: Английский

Citations

3

Neural Circuit Revision in Retinal Remodeling, A Pathoconnectomics Approach DOI Creative Commons
Rebecca L. Pfeiffer,

Jeebika Dahal,

Crystal Sigulinsky

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 15, 2024

Abstract The Aii glycinergic amacrine cell (Aii) plays a central role in bridging rod pathways with cone pathways, enabling an increased dynamic range of vision from scotopic to photopic ranges. integrates signals via chemical synapses bipolar cells (RodBCs) onto the arboreal processes ACs, injecting into ON-cone (CBbs) gap junctions Aiis on and waist ACs. CBbs then carry this information ON OFF ganglion classes. In addition, is involved surround inhibition (CBas) through ACs CBas. We have previously shown changes RodBC connectivity as consequence photoreceptor degeneration pathoconnectome early retinal degeneration: RPC1. Here, we evaluated impact determine impacts downstream network neural retina its suitability for integrating therapeutic interventions photoreceptors are lost. Previously, reported that degeneration, prior loss, Rod BCs make pathological Aiis. further characterize altered additional shifts both excitatory drive junctional coupling along discussion broader networks. New findings here demonstrate CBas increasing number BC classes degenerating retina. study, also report Aii, tertiary neuron alters their synaptic contacts indicating rewiring occurs more distant members earlier than was predicted. This processing, presumably acuity, ultimately ability support therapeutics designed restore image-forming vision. Finally, these alterations may be cellular level finding explains one first clinical complaints human patients degenerative disease, inability adapt back forth conditions.

Language: Английский

Citations

0