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de Vries, S. E. J.

Publications and source records attributed to de Vries, S. E. J..

9 recordsLinked to original sources

Saccade-responsive visual cortical neurons do not exhibit distinct visual response properties

Rapid saccadic eye movements are used by animals to sample different parts of the visual scene. Previous work has investigated neural correlates of these saccades in visual cortical areas such as V1, however how saccade-responsive neurons are distributed across visual areas, cell types, and cortical layers has remained unknown. Through analyzing 818 one-hour experimental sessions from the Allen Brain Observatory, we present a large-scale analysis of saccadic behaviors in head-fixed mice and their neural correlates. We find that saccade-responsive neurons are present across visual cortex, but their distribution varies considerably by transgenically-defined cell type, cortical area, and cortical layer. We also find that saccade-responsive neurons do not exhibit distinct visual response properties from the broader neural population, suggesting the saccadic responses of these neurons are likely not predominantly visually-driven. These results provide insight into the roles played by different cell types within a broader, distributed network of sensory and motor interactions. HighlightsO_LISaccadic eye movement behaviors in head-fixed mice tend to occur in bursts, preferentially along the horizontal axis, and do not strongly depend on visual stimulus. C_LIO_LIDistributions of saccade-responsive neurons vary considerably by transgenically-defined cell type, visual area, and cortical layer. They are most prevalent in dorsal visual areas AL/PM/AM, inhibitory neurons, and deeper cortical layers. C_LIO_LIThe majority of saccade-responsive neurons are selective for saccades in a particular direction, with an overwhelming preference for temporal over nasal saccades. C_LIO_LISaccade-responsive neurons do not exhibit distinct visual response properties, suggesting saccade neural responses are not likely to be predominantly visually-driven. C_LI

neuroscience↗

Reconciling functional differences in populations of neurons recorded with two-photon imaging and electrophysiology

Extracellular electrophysiology and two-photon calcium imaging are widely used methods for measuring physiological activity with single-cell resolution across large populations of neurons in the brain. While these two modalities have distinct advantages and disadvantages, neither provides complete, unbiased information about the underlying neural population. Here, we compare evoked responses in visual cortex recorded in awake mice under highly standardized conditions using either imaging or electrophysiology. Across all stimulus conditions tested, we observe a larger fraction of responsive neurons in electrophysiology and higher stimulus selectivity in calcium imaging. This work explores which data transformations are most useful for explaining these modality-specific discrepancies. We show that the higher selectivity in imaging can be partially reconciled by applying a spikes-to-calcium forward model to the electrophysiology data. However, the forward model could not reconcile differences in responsiveness without sub-selecting neurons based on event rate or level of signal contamination. This suggests that differences in responsiveness more likely reflect neuronal sampling bias or cluster-merging artifacts during spike sorting of electrophysiological recordings, rather than flaws in event detection from fluorescence time series. This work establishes the dominant impacts of the two modalities respective biases on a set of functional metrics that are fundamental for characterizing sensory-evoked responses.

neuroscience↗

The effect of inclusion criteria on the functional properties reported in mouse visual cortex

Neurophysiology studies require the use of inclusion criteria to identify neurons responsive to the experimental stimuli. Five recent studies used calcium imaging to measure the preferred tuning properties of layer 2/3 pyramidal neurons in mouse visual areas. These five studies employed different inclusion criteria and report different, sometimes conflicting results. Here, we examine how different inclusion criteria can impact reported tuning properties, modifying inclusion criteria to select different sub-populations from the same dataset of almost 10,000 layer 2/3 neurons from the Allen Brain Observatory. The choice of inclusion criteria greatly affected the mean tuning properties of the resulting sub-populations; indeed, the differences in mean tuning due to inclusion criteria were often of comparable magnitude to the differences between studies. In particular, the mean preferred temporal frequencies of visual areas changed markedly with inclusion criteria, such that the rank ordering of visual areas based on their temporal frequency preferences changed with the percentage of neurons included. It has been suggested that differences in temporal frequency tuning support a hierarchy of mouse visual areas. These results demonstrate that our understanding of the functional organization of the mouse visual cortex obtained from previous experiments critically depends on the inclusion criteria used.

neuroscience↗

VIP interneurons selectively enhance weak but behaviorally-relevant stimuli.

Vasoactive intestinal peptide-expressing (VIP) interneurons in cortex regulate feedback inhibition of pyramidal neurons through suppression of somatostatin-expressing (SST) interneurons and, reciprocally, SST neurons inhibit VIP neurons. Here, we show that VIP neurons in mouse primary visual cortex have complementary contrast tuning to SST neurons and respond synergistically to front-to-back visual motion and locomotion. Network modeling indicates that this VIP-SST mutual antagonism regulates the gain of cortex to achieve both sensitivity to behaviorally-relevant stimuli and network stability.

neuroscience↗

Widespread presence of direction-reversing neurons in the mouse visual system

Direction selectivity - the preference of motion in one direction over the opposite - is a fundamental property of visual neurons across species. We find that a substantial proportion of direction selective neurons in the mouse visual system reverse their preferred direction of motion in response to drifting gratings at different spatiotemporal parameters. A spatiotemporally asymmetric filter model recapitulates our experimental observations.

neuroscience↗

A survey of spiking activity reveals a functional hierarchy of mouse corticothalamic visual areas

The mammalian visual system, from retina to neocortex, has been extensively studied at both anatomical and functional levels. Anatomy indicates the cortico-thalamic system is hierarchical, but characterization of cellular-level functional interactions across multiple levels of this hierarchy is lacking, partially due to the challenge of simultaneously recording activity across numerous regions. Here, we describe a large, open dataset (part of the Allen Brain Observatory) that surveys spiking from units in six cortical and two thalamic regions responding to a battery of visual stimuli. Using spike cross-correlation analysis, we find that inter-area functional connectivity mirrors the anatomical hierarchy from the Allen Mouse Brain Connectivity Atlas. Classical functional measures of hierarchy, including visual response latency, receptive field size, phase-locking to a drifting grating stimulus, and autocorrelation timescale are all correlated with the anatomical hierarchy. Moreover, recordings during a visual task support the behavioral relevance of hierarchical processing. Overall, this dataset and the hierarchy we describe provide a foundation for understanding coding and dynamics in the mouse cortico-thalamic visual system.

neuroscience↗

Relationship between spiking activity and simultaneously recorded fluorescence signals in transgenic mice expressing GCaMP6

Two-photon calcium imaging is often used with genetically encoded calcium indicators (GECIs) to investigate neural dynamics, but the relationship between fluorescence and action potentials (spikes) remains unclear. Pioneering work linked electrophysiology and calcium imaging in vivo with viral GECI expression, albeit in a small number of cells. Here we characterized the spikefluorescence transfer function in vivo of 91 layer 2/3 pyramidal neurons in primary visual cortex in four transgenic mouse lines expressing GCaMP6s or GCaMP6f. We found that GCaMP6s cells have spike-triggered fluorescence responses of larger amplitude, lower variability and greater single-spike detectability than GCaMP6f. Mean single-spike detection rates at high spatiotemporal resolution measured in our data was >70% for GCaMP6s and ~40-50% for GCaMP6f (at 5% false positive rate). These rates are estimated to decrease to 25-35% for GCaMP6f under generally used population imaging conditions. Our ground-truth dataset thus supports more refined inference of neuronal activity from calcium imaging.

neuroscience↗

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↗

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↗