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Bohlen, M. O.

Publications and source records attributed to Bohlen, M. O..

3 recordsLinked to original sources

Decomposition of retinal ganglion cell electrical images for cell type and functional inference

ObjectiveIdentifying neuronal cell types and their biophysical properties based on their extracellular electrical features is a major challenge for experimental neuroscience and for the development of high-resolution brain-machine interfaces. One example is identification of retinal ganglion cell (RGC) types and their visual response properties, which is fundamental for developing future electronic implants that can restore vision. ApproachThe electrical image (EI) of a RGC, or the mean spatio-temporal voltage footprint of its recorded spikes on a high-density electrode array, contains substantial information about its anatomical, morphological, and functional properties. However, the analysis of these properties is complex because of the high-dimensional nature of the EI. We present a novel optimization-based algorithm to decompose electrical image into a low-dimensional, biophysically-based representation: the temporally-shifted superposition of three learned basis waveforms corresponding to spike waveforms produced in the somatic, dendritic and axonal cellular compartments. ResultsThe decomposition was evaluated using large-scale multi-electrode recordings from the macaque retina. The decomposition accurately localized the somatic and dendritic compartments of the cell. The imputed dendritic fields of RGCs correctly predicted the location and shape of their visual receptive fields. The inferred waveform amplitudes and shapes accurately identified the four major primate RGC types (ON and OFF midget and parasol cells) substantially more accurately than previous approaches. SignificanceThese findings contribute to more accurate inference of RGC types and their original light responses based purely on their electrical features, with potential implications for vision restoration technology.

neuroscience↗

Direct comparison of epifluorescence and immunostaining for assessing viral mediated gene expression in the primate brain

Viral vector technologies are commonly used in neuroscience research to understand and manipulate neural circuits, but successful applications of these technologies in non-human primate models have been inconsistent. An essential component to improve these technologies is an impartial and accurate assessment of the effectiveness of different viral constructs in the primate brain. We tested a diverse array of viral vectors delivered to the brain and extraocular muscles of macaques and compared three methods for histological assessment of viral-mediated fluorescent transgene expression: epifluorescence (Epi), immunofluorescence (IF), and immunohistochemistry (IHC). Importantly, IF and IHC identified a greater number of transduced neurons compared to Epi. Furthermore, IF and IHC reliably provided enhanced visualization of transgene in most cellular compartments (i.e., dendritic, axonal, and terminal fields), whereas the degree of labeling provided by Epi was inconsistent and predominantly restricted to somas and apical dendrites. Because Epi signals are unamplified (in contrast to IF and IHC), Epi likely provides a more veridical assessment for the amount of accumulated transgene and, thus, the potential to chemo- or optogenetically manipulate neuronal activity. The comparatively weak Epi signals suggest that the current generations of viral constructs, regardless of delivered transgene, are not optimized for primates. This reinforces an emerging viewpoint that viral vectors tailored for the primate brain are necessary for basic research and human gene therapy.

neuroscience↗

A single-cell multi-omic atlas spanning the adult rhesus macaque brain

Cataloging the diverse cellular architecture of the primate brain is crucial for understanding cognition, behavior and disease in humans. Here, we generated a brain-wide single-cell multimodal molecular atlas of the rhesus macaque brain. Altogether, we profiled 2.58M transcriptomes and 1.59M epigenomes from single nuclei sampled from 30 regions across the adult brain. Cell composition differed extensively across the brain, revealing cellular signatures of region-specific functions. We also identified 1.19M candidate regulatory elements, many novel, allowing us to explore the landscape of cis-regulatory grammar and neurological disease risk in a cell-type-specific manner. Together, this multi-omic atlas provides an open resource for investigating the evolution of the human brain and identifying novel targets for disease interventions.

neuroscience↗