High-resolution volumetric imaging constrains compartmental models to explore synaptic integration and temporal processing by cochlear nucleus globular bushy cells

Globular bushy cells (GBCs) of the cochlear nucleus play central roles in the temporal processing of sound. Despite investigation over many decades, fundamental questions remain about their dendrite structure, afferent innervation, and integration of synaptic inputs. Here, we use volume electron microscopy (EM) of the mouse cochlear nucleus to construct synaptic maps that precisely specify convergence ratios and synaptic weights for auditory- nerve innervation and accurate surface areas of all postsynaptic compartments. Detailed biophysically-based compartmental models can help develop hypotheses regarding how GBCs integrate inputs to yield their recorded responses to sound. We established a pipeline to export a precise reconstruction of auditory nerve axons and their endbulb terminals together with high-resolution dendrite, soma, and axon reconstructions into biophysically-detailed compartmental models that could be activated by a standard cochlear transduction model. With these constraints, the models predict auditory nerve input profiles whereby all endbulbs onto a GBC are subthreshold (coincidence detection mode), or one or two inputs are suprathreshold (mixed mode). The models also predict the relative importance of dendrite geometry, soma size, and axon initial segment length in setting action potential threshold and generating heterogeneity in sound-evoked responses, and thereby propose mechanisms by which GBCs may homeostatically adjust their excitability. Volume EM also reveals new dendritic structures and dendrites that lack innervation. This framework defines a pathway from subcellular morphology to synaptic connectivity, and facilitates investigation into the roles of specific cellular features in sound encoding. We also clarify the need for new experimental measurements to provide missing cellular parameters, and predict responses to sound for further in vivo studies, thereby serving as a template for investigation of other neuron classes

Sensory and Quasi-Sensory Experiences of the Deceased in Bereavement : An Interdisciplinary and Integrative Review

Bereaved people often report having sensory and quasi-sensory experiences of the deceased (SED), and there is an ongoing debate over whether SED are associated with pathology, such as grief complications. Research into these experiences has been conducted in various disciplines, including psychiatry, psychology, and anthropology, without much crossover. This review brings these areas of research together, drawing on the expertise of an interdisciplinary working group formed as part of the International Consortium for Hallucination Research (ICHR). It examines existing evidence on the phenomenology, associated factors, and impact of SED, including the role of culture, and discusses the main theories on SED and how these phenomena compare with unusual experiences in other contexts. The review concludes that the vast majority of these experiences are benign and that they should be considered in light of their biographical, relational, and sociocultural contexts

Aid on Demand: African Leaders and the Geography of China's Foreign Assistance

This article investigates whether China’s foreign aid is particularly prone to political capture by political leaders of aid-receiving countries. Specifically, we examine whether more Chinese aid is allocated to the political leaders’ birth regions and regions populated by the ethnic group to which the leader belongs, controlling for indicators of need and various fixed effects. We have collected data on 117 African leaders’ birthplaces and ethnic groups and geocoded 1,650 Chinese development finance projects across 3,097 physical locations committed to Africa over the 2000-2012 period. Our econometric results show that current political leaders’ birth regions receive substantially larger financial ows from China than other regions. On the contrary, when we replicate the analysis for the World Bank, our regressions with region-fixed effects show no evidence of such favoritism. For Chinese and World Bank aid alike, we also find no evidence that African leaders direct more aid to areas populated by groups who share their ethnicity, when controlling for region-fixed effects

Convergence of Auditory Nerve Fibers onto Globular Bushy Cells

Globular bushy cells (GBCs) of the cochlear nucleus are specialized neurons that encode the temporal features of sound. Multiple auditory nerve inputs are known to synapse onto a single GBC, but the exact number and sizes of these inputs have not been systematically investigated in adult mice. To gain a high-resolution and unbiased look at the auditory inputs contacting GBCs, our lab utilized Serial Block-Face Scanning Electron Microscopy. Specifically, 21 GBCs and all their large inputs were reconstructed at nanometer resolution. To produce the most precise results, we applied careful attention to the reconstruction and implemented cutting-edge meshing algorithms. We found that a range of 5 – 12 large auditory nerve terminals converge onto each GBC, which is higher than previously reported electrophysiological estimates. Interestingly, some GBCs were found to have a single large, dominant input, whereas others did not. Thus, we conclude that there are two models of GBC innervation, i.e., a mixed model (1 or 2 suprathreshold inputs and multiple subthreshold) and a coincidence detection model (all subthreshold inputs). The detailed reconstructions were then combined with a GBC computational model which confirmed the presence of two innervation models. We also present novel discoveries about the structure of GBCs that could only be seen in volume electron microscopy

Convergence of Auditory Nerve Fibers onto Globular Bushy Cells

Globular bushy cells (GBCs) of the cochlear nucleus are specialized neurons that encode the temporal features of sound. Multiple auditory nerve inputs are known to synapse onto a single GBC, but the exact number and sizes of these inputs have not been systematically investigated in adult mice. To gain a high-resolution and unbiased look at the auditory inputs contacting GBCs, our lab utilized Serial Block-Face Scanning Electron Microscopy. Specifically, 21 GBCs and all their large inputs were reconstructed at nanometer resolution. To produce the most precise results, we applied careful attention to the reconstruction and implemented cutting-edge meshing algorithms. We found that a range of 5 – 12 large auditory nerve terminals converge onto each GBC, which is higher than previously reported electrophysiological estimates. Interestingly, some GBCs were found to have a single large, dominant input, whereas others did not. Thus, we conclude that there are two models of GBC innervation, i.e., a mixed model (1 or 2 suprathreshold inputs and multiple subthreshold) and a coincidence detection model (all subthreshold inputs). The detailed reconstructions were then combined with a GBC computational model which confirmed the presence of two innervation models. We also present novel discoveries about the structure of GBCs that could only be seen in volume electron microscopy

Matthew Shane Kersting's Quick Files

The Quick Files feature was discontinued and it’s files were migrated into this Project on March 11, 2022. The file URL’s will still resolve properly, and the Quick Files logs are available in the Project’s Recent Activity

Movement-related cortical potentials in paraplegic patients : abnormal patterns and considerations for BCI-rehabilitation

Non-invasive EEG-based Brain-Computer Interfaces (BCI) can be promising for the motor neuro-rehabilitation of paraplegic patients. However, this shall require detailed knowledge of the abnormalities in the EEG signatures of paraplegic patients. The association of abnormalities in different subgroups of patients and their relation to the sensorimotor integration are relevant for the design, implementation and use of BCI systems in patient populations. This study explores the patterns of abnormalities of movement related cortical potentials (MRCP) during motor imagery tasks of feet and right hand in patients with paraplegia (including the subgroups with/without central neuropathic pain (CNP) and complete/incomplete injury patients) and the level of distinctiveness of abnormalities in these groups using pattern classification. The most notable observed abnormalities were the amplified execution negativity and its slower rebound in the patient group. The potential underlying mechanisms behind these changes and other minor dissimilarities in patients' subgroups, as well as the relevance to BCI applications, are discussed. The findings are of interest from a neurological perspective as well as for BCI-assisted neuro-rehabilitation and therapy

A Multi-Memristive Unit-Cell Array With Diagonal Interconnects for In-Memory Computing

Memristive crossbar arrays can be used to realize matrix-vector multiplication (MVM) operations in constant time complexity by exploiting the Kirchhoff's circuit laws. This is enabled by the parallel read of the entire array in a single time step. However, parallel writing is prohibitive in such arrays due to limitations on the current that could be accumulated along the wires. Hence, loading the matrix elements into such an array still incurs significant time penalty. Another key challenge is the achievable computational precision. To overcome these challenges, we propose a unit-cell array design where each unit-cell comprises four memristive devices each attached to a selection transistor. Moreover, the array is organized in such a way that the selection transistors can be turned on in a diagonal fashion. We experimentally demonstrated this concept by fabricating a 2 x 2 unit-cell array based on projected phase-change memory (PCM) devices in 90 nm CMOS technology. It is shown that using the diagonal connections, the write operations can be parallelized while maintaining the current limit of the back-end-of-the-line metallization. Moreover, the increase in write time due to having more devices per unit-cell is minimized through a combination of single-shot and iterative programming schemes. Finally, we present experimental results on MVM operations that demonstrate improved computational precision exceeding that of a 4-bit fixed-point implementation.ISSN:1549-7747ISSN:1057-7130ISSN:1558-3791ISSN:1558-125

High-resolution volumetric imaging constrains compartmental models to explore synaptic integration and temporal processing by cochlear nucleus globular bushy cells

Globular bushy cells (GBCs) of the cochlear nucleus play central roles in the temporal processing of sound. Despite investigation over many decades, fundamental questions remain about their dendrite structure, afferent innervation, and integration of synaptic inputs. Here, we use volume electron microscopy (EM) of the mouse cochlear nucleus to construct synaptic maps that precisely specify convergence ratios and synaptic weights for auditory nerve innervation and accurate surface areas of all postsynaptic compartments. Detailed biophysically based compartmental models can help develop hypotheses regarding how GBCs integrate inputs to yield their recorded responses to sound. We established a pipeline to export a precise reconstruction of auditory nerve axons and their endbulb terminals together with high-resolution dendrite, soma, and axon reconstructions into biophysically detailed compartmental models that could be activated by a standard cochlear transduction model. With these constraints, the models predict auditory nerve input profiles whereby all endbulbs onto a GBC are subthreshold (coincidence detection mode), or one or two inputs are suprathreshold (mixed mode). The models also predict the relative importance of dendrite geometry, soma size, and axon initial segment length in setting action potential threshold and generating heterogeneity in sound-evoked responses, and thereby propose mechanisms by which GBCs may homeostatically adjust their excitability. Volume EM also reveals new dendritic structures and dendrites that lack innervation. This framework defines a pathway from subcellular morphology to synaptic connectivity, and facilitates investigation into the roles of specific cellular features in sound encoding. We also clarify the need for new experimental measurements to provide missing cellular parameters, and predict responses to sound for further in vivo studies, thereby serving as a template for investigation of other neuron classes