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Biology subjects

Griffin, F.

Publications and source records attributed to Griffin, F..

9 recordsLinked to original sources
bioRxiv2021

A whole-brain monosynaptic input connectome to neuron classes in mouse visual cortex

Identification of the structural connections between neurons is a prerequisite to understanding brain function. We developed a pipeline to systematically map brain-wide monosynaptic inputs to specific neuronal populations using Cre-driver mouse lines and the recombinant rabies tracing system. We first improved the rabies virus tracing strategy to accurately identify starter cells and to efficiently quantify presynaptic inputs. We then mapped brain-wide presynaptic inputs to different excitatory and inhibitory neuron subclasses in the primary visual cortex and seven higher visual areas. Our results reveal quantitative target-, layer- and cell-class-specific differences in the retrograde connectomes, despite similar global input patterns to different neuronal populations in the same anatomical area. The retrograde connectivity we define is consistent with the presence of the ventral and dorsal visual information processing streams and reveals further subnetworks within the dorsal stream. The hierarchical organization of the entire visual cortex can be derived from intracortical feedforward and feedback pathways mediated by upper- and lower-layer input neurons, respectively. This study expands our knowledge of the brain-wide inputs regulating visual areas and demonstrates that our improved rabies virus tracing strategy can be used to scale up the effort in dissecting connectivity of genetically defined cell populations in the whole mouse brain.

neuroscience↗
bioRxiv2021

cellxgene: a performant, scalable exploration platform for high dimensional sparse matrices

Quickly and flexibly exploring high-dimensional datasets, such as scRNAseq data, is underserved but critical for hypothesis generation, dataset annotation, publication, sharing, and community reuse. cellxgene is a highly generalizable, web-based interface for exploring high dimensional datasets along categorical, continuous and spatial dimensions, as well as feature annotation. cellxgene is differentiated by its ability to performantly handle millions of observations, and bridges a critical gap by enabling computational and experimental biologists to iteratively ask questions of private and public datasets. In doing so, cellxgene increases the utility and reusability of datasets across the single-cell ecosystem. The codebase can be accessed at https://github.com/chanzuckerberg/cellxgene. For questions and inquiries, please contact cellxgene@chanzuckerberg.com.

systems biology↗
bioRxiv2020

A standardized behavioral event equally impacts the activity of cortical visual areas and layers

Multiple recent studies have shown that motor activity greatly impacts the activity of primary sensory areas like V1. Yet, the role of this motor related activity in sensory processing is still unclear. Here we dissect how these behavior signals are broadcast to different layers and areas of the visual cortex. To do so, we leveraged a standardized and spontaneous behavioral fidget event in passively viewing mice. Importantly, this behavior event had no relevance to any ongoing task allowing us to compare its neuronal correlate with visually relevant behavior like running. A large two-photon Ca2+ imaging database of neuronal responses uncovered four neural response types during fidgets that were surprisingly consistent in their proportion and response patterns across all visual areas and layers of the visual cortex. Indeed, the layer and area identity could not be decoded above chance level based only on neuronal recordings. In contrast to running behavior, fidget evoked neural responses were independent to visual processing. The broad availability of visually orthogonal standardized behavior signals could be a key component in how the cortex selects, learns and binds local sensory information with motor outputs. Contrary to relevant motor outputs, irrelevant motor signals would use a separate neural subspaces. Significance StatementRecent studies have shown contextual and behavioral variables to dominate brain-wide activity, but yet it is unknown how this information is broadcast across cortical layers and areas. Using a large two-photon dataset collected in mice passively viewing a battery of visual stimuli, we characterized the neuronal response of neurons of the visual cortex to a standardized fidget behavior. We found that as much as 47% of excitatory neurons show significant co-activity with fidgets. Throughout all areas and layers we recorded from, those responses were distributed across surprisingly consistent three neural response types. Further analysis showed no interaction between fidget neural events and cells visual stimulus responses, contrasting with feedback neural signals induced by running. These contrasting response distribution patterns suggest that behavioral neuronal correlates are broadly available but will modulate sensory responses depending on their relevance to local sensory inputs.

neuroscience↗
bioRxiv2020

Measuring stimulus-evoked neurophysiological differentiation in distinct populations of neurons in mouse visual cortex

Despite significant progress in understanding neural coding, it remains unclear how the coordinated activity of large populations of neurons relates to what an observer actually perceives. Since neurophysiological differences must underlie differences among percepts, differentiation analysis--quantifying distinct patterns of neurophysiological activity--is an "inside out" approach that addresses this question. We used two-photon calcium imaging in mice to systematically survey stimulus-evoked neurophysiological differentiation in excitatory populations across 3 cortical layers (L2/3, L4, and L5) in each of 5 visual cortical areas (primary, lateral, anterolateral, posteromedial, and anteromedial) in response to naturalistic and phase-scrambled movie stimuli. We find that unscrambled stimuli evoke greater neurophysiological differentiation than scrambled stimuli specifically in L2/3 of the anterolateral and anteromedial areas, and that this effect is modulated by arousal state and locomotion. Contrariwise, decoding performance was far above chance and did not vary substantially across areas and layers. Differentiation also differed within the unscrambled stimulus set, suggesting that differentiation analysis may be used to probe the ethological relevance of individual stimuli.

neuroscience↗
bioRxiv2018

Remote focusing system for simultaneous dual-plane mesoscopic multiphoton imaging

We present a dual-plane mesoscopic imaging system capable of simultaneous image acquisition from two independent focal planes. The system was designed as an add-on to a recently introduced large field-of-view two-photon microscopy system, developed by Sofroniew, et al., eLife, 5, e14472, 2016. In this work, we merge two advanced multiphoton imaging technologies, i.e., temporal-division multiplexing and remote focusing, to maintain diffraction-limited resolution at both imaging planes, and achieve a more than 2-fold increase in the systems overall imaging throughput. We introduce a novel solution to decode temporally interleaved analog signals at nanosecond timescales to achieve high-speed time-multiplexed imaging. Detailed characterization and comparison of the modified and the original two-photon microscopy system was performed.\n\nOCIS Codes(190.4180) Multiphoton processes; (180.5810) Scanning microscopy; (170.2520) Fluorescence microscopy.

neuroscience↗
bioRxiv2018

Biological variation in the sizes, shapes and locations of visual cortical areas in the mouse

Visual cortex is organized into discrete sub-regions or areas that are arranged into a hierarchy and serve different functions in the processing of visual information. In our previous work, we noted that retinotopic maps of cortical visual areas differed between mice, but did not quantify these differences or determine the relative contributions of biological variation and measurement noise. Here we quantify the biological variation in the size, shape and locations of 11 visual areas in the mouse. We find that there is substantial biological variation in the sizes of visual areas, with some visual areas varying in size by two-fold across the population of mice.

neuroscience↗
bioRxiv2018

A large-scale, standardized physiological survey reveals higher order coding throughout the mouse visual cortex

To understand how the brain processes sensory information to guide behavior, we must know how stimulus representations are transformed throughout the visual cortex. Here we report an open, large-scale physiological survey of neural activity in the awake mouse visual cortex: the Allen Brain Observatory Visual Coding dataset. This publicly available dataset includes cortical activity from nearly 60,000 neurons collected from 6 visual areas, 4 layers, and 12 transgenic mouse lines from 221 adult mice, in response to a systematic set of visual stimuli. Using this dataset, we reveal functional differences across these dimensions and show that visual cortical responses are sparse but correlated. Surprisingly, responses to different stimuli are largely independent, e.g. whether a neuron responds to natural scenes provides no information about whether it responds to natural movies or to gratings. We show that these phenomena cannot be explained by standard local filter-based models, but are consistent with multi-layer hierarchical computation, as found in deeper layers of standard convolutional neural networks.

neuroscience↗
bioRxiv2017

Aberrant Cortical Activity In Multiple GCaMP6-Expressing Transgenic Mouse Lines

Transgenic mouse lines are invaluable tools for neuroscience but as with any technique, care must be taken to ensure that the tool itself does not unduly affect the system under study. Here we report aberrant electrical activity, similar to interictal spikes, and accompanying fluorescence events in some genotypes of transgenic mice expressing GCaMP6 genetically-encoded calcium sensors. These epileptiform events have been observed particularly, but not exclusively, in mice with Emx1-Cre and Ai93 transgenes, across multiple laboratories. The events occur at >0.1 Hz, are very large in amplitude (>1.0 mV local field potentials, >10% df/f widefield imaging signals), and typically cover large regions of cortex. Many properties of neuronal responses and behavior seem normal despite these events, though rare subjects exhibit overt generalized seizures. The underlying mechanisms of this phenomenon remain unclear, but we speculate about possible causes on the basis of diverse observations. We encourage researchers to be aware of these activity patterns while interpreting neuronal recordings from affected mouse lines and when considering which lines to study.

neuroscience↗