Biology subjects

Churchland, A. K.

Publications and source records attributed to Churchland, A. K..

5 recordsLinked to original sources

bioRxiv2018

High-throughput mapping of mesoscale connectomes in individual mice

Comprehensive analysis of neuronal networks requires brain-wide measurement of connectivity, activity, and gene expression. Although high-throughput methods are available for mapping brain-wide activity and transcriptomes, comparable methods for mapping region-to-region connectivity remain slow and expensive because they require averaging across hundreds of brains. Here we describe BRICseq, which leverages DNA barcoding and sequencing to map connectivity from single individuals in a few weeks and at low cost. Applying BRICseq to the mouse neocortex, we find that region-to-region connectivity provides a simple bridge relating transcriptome to activity: The spatial expression patterns of a few genes predict region-to-region connectivity, and connectivity predicts activity correlations. We also exploited BRICseq to map the mutant BTBR mouse brain, which lacks a corpus callosum, and recapitulated its known connectopathies. BRICseq allows individual laboratories to compare how age, sex, environment, genetics and species affect neuronal wiring, and to integrate these with functional activity and gene expression.

neuroscience↗

bioRxiv2018

Chronically-implanted Neuropixels probes enable high yield recordings in freely moving mice

The advent of high-yield electrophysiology using Neuropixels probes is now enabling researchers to simultaneously record hundreds of neurons with remarkably high signal to noise. However, these probes have not been comprehensively tested in freely moving mice. It is critical to study neural activity in unrestricted animals, and the field would benefit from the inclusion of ethological approaches to studying the neural circuitry of behavior. We therefore adapted Neuropixels probes for chronically-implanted experiments in freely moving mice. We demonstrate the ease and utility of this approach in recording hundreds of neurons across weeks, and provide the methodological details for other researchers to do the same. Importantly, our approach enables researchers to explant and reuse these valuable probes.

neuroscience↗

bioRxiv2018

Inhibitory and excitatory populations in parietal cortex are equally selective for decision outcome in both novices and experts

Inhibitory neurons, which play a critical role in decision-making models, are often simplified as a single pool of non-selective neurons lacking connection specificity. This assumption is supported by observations in primary visual cortex: inhibitory neurons are broadly tuned in vivo, and show non-specific connectivity in slice. Selectivity of excitatory and inhibitory neurons within decision circuits, and hence the validity of decision-making models, is unknown. We simultaneously measured excitatory and inhibitory neurons in posterior parietal cortex of mice judging multisensory stimuli. Surprisingly, excitatory and inhibitory neurons were equally selective for the animals choice, both at the single cell and population level. Further, both cell types exhibited similar changes in selectivity and temporal dynamics during learning, paralleling behavioral improvements. These observations, combined with modeling, argue against circuit architectures assuming non-selective inhibitory neurons. Instead, they argue for selective subnetworks of inhibitory and excitatory neurons that are shaped by experience to support expert decision-making.

neuroscience↗

bioRxiv2017

OnACID: Online Analysis of Calcium Imaging Data in Real Time

Optical imaging methods using calcium indicators are critical for monitoring the activity of large neuronal populations in vivo. Imaging experiments typically generate a large amount of data that needs to be processed to extract the activity of the imaged neuronal sources. While deriving such processing algorithms is an active area of research, most existing methods require the processing of large amounts of data at a time, rendering them vulnerable to the volume of the recorded data, and preventing realtime experimental interrogation. Here we introduce OnACID, an Online framework for the Analysis of streaming Calcium Imaging Data, including i) motion artifact correction, ii) neuronal source extraction, and iii) activity denoising and deconvolution. Our approach combines and extends previous work on online dictionary learning and calcium imaging data analysis, to deliver an automated pipeline that can discover and track the activity of hundreds of cells in real time, thereby enabling new types of closed-loop experiments. We apply our algorithm on two large scale experimental datasets, benchmark its performance on manually annotated data, and show that it outperforms a popular offline approach.

neuroscience↗

bioRxiv2017

Visual evidence accumulation behavior in unrestrained mice

A major challenge to studying the neural circuits underlying perceptual decision making has been the limited availability of tools for manipulation of neural activity. In recent years, rodents have emerged as a desirable model for overcoming the technical hurdle. However, mice, which offer abundant genetic tools for circuit manipulation, are underrepresented in perceptual evidence accumulation studies. Here we describe the behavior of mice performing a visual evidence accumulation task similar to one previously used in rats and humans. We found that although mice were capable of achieving similar accuracy levels as rats, differences in accumulation strategy were apparent. To test the engagement of cortex in the visual evidence accumulation task, we optogenetically inhibited activity in the anteromedial (AM) visual area using JAWS. Importantly, light activation biased choices in both injected and uninjected animals. Fortunately, by varying the stimulus-response contingency while holding constant the stimulated hemisphere, we surmounted this obstacle and demonstrated a role for AM in contralateral choices. Taken together, our results argue that mice accumulate visual evidence to guide decisions, an ability that is supported in part by area AM.

neuroscience↗