Tag Archives: Bryan William Jones

Ultrastructural Connectomics Reveals The Entire Chemical And Electrical Synaptic Cohort Of An ON Cone Bipolar Cell In The Inner Plexiform Layer Of The Rabbit Retina

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This abstract was presented at the 2014 Society for Neuroscience meeting in Washington D.C. by J. Scott Lauritzen, Crystal L. Sigulinsky, Danny P. Emrich, Joshua M. Dudleston, Noah T. Nelson, Rebecca L. Pfeiffer, Nathan R. Sherbotie, John V. Hoang, Jefferson R. Brown, Carl B. WattJames R. Anderson, Bryan W. Jones and Robert E. Marc.

Purpose: Despite large-scale efforts aimed at mapping the mammalian nervous system, the entire synaptic cohort of a single mammalian neuron of any class has never been mapped. To this end we reconstructed all chemical and electrical synaptic partners of a single ON cone bipolar cell (ON CBC) in the inner plexiform layer (IPL) of the rabbit retina. We then searched all members of the same cell class for repeating network motifs and explored postsynaptic cell sampling topologies from this bipolar cell (BC).

Methods: Cells in retinal connectome 1 (RC1) were annotated with Viking viewer, and explored via graph visualization of connectivity and 3D rendering (Anderson et al., 2011 J Microscopy). Small molecule signals in RC1, e.g. GABA, glycine, and L-glutamate, combined with morphological reconstruction and connectivity analysis allow robust cell classification. The default resolution of RC1 is 2.18nm/pixel, however goniometric recapture at 0.273 nm/pixel was performed as needed for synapse verification.

Results: ON CBC 593 is one of 20 BCs of this class in RC1, the axonal arbors of which tile with gap junctions between nearest neighbors at their distal axonal tips. ON CBC 593 contains 194 ribbons, 274 postsynaptic densities, 20 gap junctions, and 66 conventional synapses, for a total of 554 synaptic connections. Twenty ganglion cells sample the glutamatergic output. ON CBC 593 is presynaptic to 262 amacrine cell (AC) processes, and is postsynaptic to 228 AC processes. Of these, 33% form reciprocal connections. We approximate that ON CBC 593 forms synapses with 50 distinct ACs. ON CBC 593 is routinely pre- and postsynaptic to within-class, cross-class, feedback, and feedforward inhibition motifs, including 1 instance of OFF-ON crossover inhibition. ON CBC 593 forms 12 gap junctions with at least 2 AII ACs, 7 with 5 ON CBCs, and 1 with itself. We searched for repeating network motifs across all ON CBCs of this class in RC1. Thus far, 80% of these form in-class inhibitory motifs, and 75% form cross-class inhibitory motifs. All ACs and GCs discovered to contact multiple branches of ON CBC 593 form synapses on every branch.

Conclusions: An individual bipolar cell is inherently multi-kinetic, receiving inhibition driven by all ON CBC classes, sharing these signals via gap junctions with ON CBCs of the same class, and driving inhibition of all ON CBC classes. This constitutes a substrate for multi-channel coordination throughout the IPL, and predicts multi-kinetic BC responses. The results establish a normative framework against which members of the same and different classes may be compared, and foster interpretation of BC physiological behavior under different stimulus regimes.

A Multi-Scale Computational Model For The Study Of Retinal Prosthetic Stimulation

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We have a new publication in IEEE, A Multi-Scale Computational Model For The Study Of Retinal Prosthetic Stimulation.  Authors are: Kyle LoizosGianluca Lazzi, J. Scott Lauritzen, James R. Anderson, Bryan W. Jones and Robert E. Marc.

Abstract: An implantable retinal prosthesis has been developed to restore vision to patients who have been blinded by degenerative diseases that destroy photoreceptors. By electrically stimulating the surviving retinal cells, the damaged photoreceptors may be bypassed and limited vision can be restored. While this has been shown to restore partial vision, the understanding of how cells react to this systematic electrical stimulation is largely unknown. Better predictive models and a deeper understanding of neural responses to electrical stimulation is necessary for designing a successful prosthesis. In this work, a computational model of an epi-retinal implant was built and simulated, spanning multiple spatial scales, including a large-scale model of the retina and implant electronics, as well as underlying neuronal networks.

 

Retinal Prosthetics, Optogenetics and Photoswitches

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We have a new publication, Retinal Prosthetics, Optogenetics and Photoswitches in ACS Chemical Neuroscience.  Authors are:  Robert E. MarcRebecca L. Pfeiffer, and Bryan W. Jones.

Abstract:

Three technologies have emerged as therapies to restore light sensing to profoundly blind patients suffering from late-stage retinal degenerations: (1) retinal prosthetics, (2) optogenetics, and (3) chemical photoswitches. Prosthetics are the most mature and the only approach in clinical practice. Prosthetic implants require complex surgical intervention and provide only limited visual resolution but can potentially restore navigational ability to many blind patients. Optogenetics uses viral delivery of type 1 opsin genes from prokaryotes or eukaryote algae to restore light responses in survivor neurons. Targeting and expression remain major problems, but are potentially soluble. Importantly, optogenetics could provide the ultimate in high-resolution vision due to the long persistence of gene expression achieved in animal models. Nevertheless, optogenetics remains challenging to implement in human eyes with large volumes, complex disease progression, and physical barriers to viral penetration. Now, a new generation of photochromic ligands or chemical photoswitches (azobenzene-quaternary ammonium derivatives) can be injected into a degenerated mouse eye and, in minutes to hours, activate light responses in neurons. These photoswitches offer the potential for rapidly and reversibly screening the vision restoration expected in an individual patient. Chemical photoswitch variants that persist in the cell membrane could make them a simple therapy of choice, with resolution and sensitivity equivalent to optogenetics approaches. A major complexity in treating retinal degenerations is retinal remodeling: pathologic network rewiring, molecular reprogramming, and cell death that compromise signaling in the surviving retina. Remodeling forces a choice between upstream and downstream targeting, each engaging different benefits and defects. Prosthetics and optogenetics can be implemented in either mode, but the use of chemical photoswitches is currently limited to downstream implementations. Even so, given the high density of human foveal ganglion cells, the ultimate chemical photoswitch treatment could deliver cost-effective, high-resolution vision for the blind.

Synapse Classification And Localization In Electron Micrographs

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We have a new publication, Synapse Classification And Localization In Electron Micrographs in Pattern Recognition Letters.  Authors are: Vignesh JagadeeshJames Anderson, Bryan W. JonesRobert MarcSteven Fisher and B.S. Manjunath.

Abstract:  Classification and detection of biological structures in Electron Micrographs (EM) is a relatively new large scale image analysis problem. The primary challenges are in modeling diverse visual characteristics and development of scalable techniques. In this paper we propose novel methods for synapse detection and localization, an important problem in connectomics. We first propose an attribute based descriptor for characterizing synaptic junctions. These descriptors are task specific, low dimensional and can be scaled across large image sizes. Subsequently, techniques for fast localization of these junctions are proposed. Experimental results on images acquired from a mammalian retinal tissue compare favorably with state of the art descriptors used for object detection.

Robust Segmentation based Tracking using an Adaptive Wrapper for Inducing Priors

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We have published another manuscript, Robust Segmentation based Tracking using an Adaptive Wrapper for Inducing Priors.  This manuscript describes the work on adaptive tracing and proposes an algorithm that adapts a generic tracing algorithm to an application of interest.  In our specific case, it is boundaries of cells in high frequency space in transmission electron microscopy images.  But the approach in this paper is applicable to biological, medical, remote sensing and surveillance data as well utilizing priors specific to the application.  The co-authors on the paper are: Vignesh JagadeeshJames Anderson, Bryan W. JonesRobert E. MarcSteven K Fisher and B.S Manjunath.

FASEB Bio-Art Competition Winner 2013

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Bryan W. Jones and Robert E. Marc and were selected as 2013 FASEB BioArt Winners (Press release here).  This image shows a region of an amazingly complex retina from a goldfish (Carassius auratus auratus) analyzed using tools called Computational Molecular Phenotyping (CMP) that reveal the metabolic state of the all cell types in tissues.  These cells were labeled with antibodies for the presence of two fundamental amino acid metabolites (anti-glycine in red, anti-GABA in blue) and an amino acid tracer of physiologic activity (anti-AGB in green).   These labels allow us to visualize the metabolic state and therefore, classes of bipolaramacrine and horizontal cells.  More details on the image here.