Materials and neuroscience: validating tools for large-scale, high-density neural recording

Extracellular recording remains the only technique capable of measuring the activity of many neurons simultaneously with a sub-millisecond precision, in multiple brain areas, including deep structures. Nevertheless, many questions about the nature of the detected signal and the limitations/capabilities of this technique remain unanswered. The general goal of this work is to apply the methodology and concepts of materials science to answer some of the major questions surrounding extracellular recording, and thus take full advantage of this seminal technique. We start out by quantifying the effect of electrode impedance on the amplitude of measured extracellular spikes and background noise. Can we improve data quality by lowering electrode impedance? We demonstrate that if the proper recording system is used, then the impedance of a microelectrode, within the range typical of standard polytrodes (~ 0.1 to 2 MΩ), does not significantly affect a neural spike amplitude or the background noise, and therefore spike sorting. In addition to improving the performance of each electrode, increasing the number of electrodes in a single neural probe has also proven advantageous for simultaneously monitoring the activity of more neurons with better spatiotemporal resolution. How can we achieve large-scale, highdensity extracellular recordings without compromising brain tissue? Here we report the design and in vivo validation of a complementary metal–oxide–semiconductor (CMOS)-based scanning probe with 1356 electrodes arranged along approximately 8 mm of a thin shaft (50 μm thick and 100 μm wide). Additionally, given the ever-shrinking dimensions of CMOS technology, there is a drive to fabricate sub-cellular electrodes (< 10 μm). Therefore, to evaluate electrode configurations for future probe designs, several recordings from many different brain regions were performed with an ultra-dense probe containing 255 electrodes, each with a geometric area of 5 x 5 μm and a pitch of 6 μm. How can we validate neural probes with different electrode materials/configurations and different sorting algorithms? We describe a new procedure for precisely aligning two probes for in vivo “paired-recordings” such that the spiking activity of a single neuron is monitored with both a dense extracellular silicon polytrode and a juxtacellular micro-pipette. We gathered a dataset of paired-recordings, which is available online. The “ground truth” data, for which one knows exactly when a neuron in the vicinity of an extracellular probe generates an action potential, has been used for several groups to validate and quantify the performance of new algorithms to automatically detect/sort single-units

Reconstruction of recurrent synaptic connectivity of thousands of neurons from simulated spiking activity

Dynamics and function of neuronal networks are determined by their synaptic connectivity. Current experimental methods to analyze synaptic network structure on the cellular level, however, cover only small fractions of functional neuronal circuits, typically without a simultaneous record of neuronal spiking activity. Here we present a method for the reconstruction of large recurrent neuronal networks from thousands of parallel spike train recordings. We employ maximum likelihood estimation of a generalized linear model of the spiking activity in continuous time. For this model the point process likelihood is concave, such that a global optimum of the parameters can be obtained by gradient ascent. Previous methods, including those of the same class, did not allow recurrent networks of that order of magnitude to be reconstructed due to prohibitive computational cost and numerical instabilities. We describe a minimal model that is optimized for large networks and an efficient scheme for its parallelized numerical optimization on generic computing clusters. For a simulated balanced random network of 1000 neurons, synaptic connectivity is recovered with a misclassification error rate of less than 1% under ideal conditions. We show that the error rate remains low in a series of example cases under progressively less ideal conditions. Finally, we successfully reconstruct the connectivity of a hidden synfire chain that is embedded in a random network, which requires clustering of the network connectivity to reveal the synfire groups. Our results demonstrate how synaptic connectivity could potentially be inferred from large-scale parallel spike train recordings.Comment: This is the final version of the manuscript from the publisher which supersedes our original pre-print version. The spike data used in this paper and the code that implements our connectivity reconstruction method are publicly available for download at http://dx.doi.org/10.5281/zenodo.17662 and http://dx.doi.org/10.5281/zenodo.17663 respectivel

Computational Neuroscience

In Fall 2019, the Computational Neuroscience class at Bates College collaborated to begin an open textbook. Eight students across three majors collaborated to present the content they were learning to students who were similar to themselves. This project serves both pedagogical and social goals. By writing for fellow students, we leveraged the power of teaching for learning. By bringing together students of diverse academic backgrounds, we leveraged the power of peer instruction. Finally, by writing in the open, students not only brought their best work forward, but are working to contribute to an open knowledge environment that democratizes information. This is version 1.0 of a living document that will be extended and revised over the course of several generations of students.https://scarab.bates.edu/oer/1000/thumbnail.jp

Allocation of Computational Resources in the Nervous System.

The nervous system integrates past information together with predictions about the future in order to produce rewarding actions for the organism. This dissertation focuses on the resources underlying these computations, and the task-dependent allocation of these resources. We present evidence that principles from optimal coding and optimal estimation account for overt and covert orienting phenomena, as observed from both behavioral experiments and neuronal recordings. First, we review behavioral measurements related to selective attention and discuss models that account for these data. We show that reallocation of resources emerges as a natural property of systems that encode their inputs efficiently under non-uniform constraints. We continue by discussing the attentional modulation of neuronal activity, and showthat: (1) Modulation of coding strategies does not require special mechanisms: it is possible to obtain dramatic modulation even when signals informing the system about fidelity requirements enter the system in a fashion indistinguishable from sensory signals. (2) Optimal coding under non-uniform fidelity requirements is sufficient to account for the firing rate modulation observed during selective attention experiments. (3) The response of a single neuron cannot bewell characterized by measurements of attentional modulation of only a single sensory stimulus. (4) The magnitude of the activity modulation depends on the capacity of the neural circuit. A later chapter discusses the neural mechanisms for resource allocation, and the relation between attentional mechanisms and receptive field formation. The remainder of the dissertation focuses on overt orienting phenomena and active perception. We present a theoretical analysis of the allocation of resources during state estimation of multiple targets with different uncertainties, together with eye-tracking experiments that confirm our predictions. We finish by discussing the implications of these results to our current understanding of orienting phenomena and the neural code

Transsacadic Information and Corollary Discharge in Local Field Potentials of Macaque V1

Approximately three times per second, human visual perception is interrupted by a saccadic eye movement. In addition to taking the eyes to a new location, several lines of evidence suggest that the saccades play multiple roles in visual perception. Indeed, it may be crucial that visual processing is informed about movements of the eyes in order to analyze visual input distinctly and efficiently on each fixation and preserve stable visual perception of the world across saccades. A variety of studies has demonstrated that activity in multiple brain areas is modulated by saccades. The hypothesis tested here is that these signals carry significant information that could be used in visual processing. To test this hypothesis, local field potentials (LFPs) were simultaneously recorded from multiple electrodes in macaque primary visual cortex (V1); support vector machines (SVMs) were used to classify the peri-saccadic LFPs. We find that LFPs in area V1 carry information that can be used to distinguish neural activity associated with fixations from saccades, precisely estimate the onset time of fixations, and reliably infer the directions of saccades. This information may be used by the brain in processes including visual stability, saccadic suppression, receptive field (RF) remapping, fixation amplification, and trans-saccadic visual perception