Biology subjects

Steinmetz, N. A.

Publications and source records attributed to Steinmetz, N. A..

30 records · Page 2Linked to original sources

bioRxiv2020

Neuropixels 2.0: A miniaturized high-density probe for stable, long-term brain recordings

To study the dynamics of neural processing across timescales, we require the ability to follow the spiking of thousands of individually separable neurons over weeks and months, during unrestrained behavior. To address this need, we introduce the Neuropixels 2.0 probe together with novel analysis algorithms. The new probe has over 5,000 sites and is miniaturized such that two probes plus a headstage, recording 768 sites at once, weigh just over 1 g, suitable for implanting chronically in small mammals. Recordings with high quality signals persisting for at least two months were reliably obtained in two species and six different labs. Improved site density and arrangement combined with new data processing methods enable automatic post-hoc stabilization of data despite brain movements during behavior and across days, allowing recording from the same neurons in the mouse visual cortex for over 2 months. Additionally, an optional configuration allows for recording from multiple sites per available channel, with a penalty to signal-to-noise ratio. These probes and algorithms enable stable recordings from >10,000 sites during free behavior in small animals such as mice.

neuroscience↗

bioRxiv2020

Influence of On-Off dynamics and selective attention on the spatial pattern of correlated variability in neocortex

Correlated activity fluctuations in neocortex influence sensory responses and behavior. Neural correlations reflect anatomical connectivity and change dynamically with cognitive states, such as attention. Yet, how anatomical connectivity and cognitive states define the population structure of correlations is not known. We measured correlations in single cortical columns and found that the magnitude of correlations, their attentional modulation and dependence on lateral distance are predicted by On-Off dynamics, synchronous fluctuations in population activity across cortical layers. We developed a network model, in which spatial connectivity correlates the On-Off dynamics across nearby columns. We show that attentional inputs modulate the spatial extent of On-Off dynamics, resulting in spatially non-uniform changes in correlations. We confirm this prediction in our columnar recordings by showing that attentional modulation of correlations depends on lateral distance. Our results reveal how heterogeneous spatial patterns of correlations arise from the connectivity and network dynamics during attention.

neuroscience↗

bioRxiv2020

Top-down coordination of local cortical state during selective attention

Spontaneous fluctuations in cortical excitability influence sensory processing and behavior. These fluctuations, long known to reflect global changes in cortical state, were recently found to be modulated locally within a retinotopic map during spatially selective attention. We found that periods of vigorous (On) and faint (Off) spiking activity, the signature of cortical state fluctuations, were coordinated across brain areas along the visual hierarchy and tightly coupled to their retinotopic alignment. During top-down attention, this interareal coordination was enhanced and progressed along the reverse cortical hierarchy. The extent of local state coordination between areas was predictive of behavioral performance. Our results show that cortical state dynamics are shared across brain regions, modulated by cognitive demands and relevant for behavior. One Sentence SummaryInterareal coordination of local cortical state is retinotopically precise and progresses in a reverse hierarchical manner during selective attention.

neuroscience↗

bioRxiv2019

Data architecture and visualization for a large-scale neuroscience collaboration

Effective data management is a major challenge for neuroscience labs, and even greater for collaborative projects. In the International Brain laboratory (IBL), ten experimental labs spanning 7 geographically distributed sites measure neural activity across the brains of mice making perceptual decisions. Here, we report a novel, modular architecture that allows users to contribute, access, and analyze data across this collaboration. Users contribute data using a web-based electronic lab notebook (Alyx), which automatically registers recorded data files and uploads them to a central server. Users access data with a lightweight interface, the Open Neurophysiology Environment (ONE), which searches data from all labs and loads it into MATLAB or Python. To analyze data, we have developed pipelines based on DataJoint, which automatically populate a website displaying a graphical summary of results to date. This architecture provides a new framework to contribute, access and analyze data, surmounting many challenges currently faced by neuroscientists.

neuroscience↗

bioRxiv2019

Striatal activity reflects cortical activity patterns

The dorsal striatum is organized into domains that drive characteristic behaviors1-7, and receive inputs from different parts of the cortex8,9 which modulate similar behaviors10-12. Striatal responses to cortical inputs, however, can be affected by changes in connection strength13-15, local striatal circuitry16,17, and thalamic inputs18,19. Therefore, it is unclear whether the pattern of activity across striatal domains mirrors that across the cortex20-23 or differs from it24-28. Here we use simultaneous large-scale recordings in the cortex and the striatum to show that striatal activity can be accurately predicted by spatiotemporal activity patterns in the cortex. The relationship between activity in the cortex and the striatum was spatially consistent with corticostriatal anatomy, and temporally consistent with a feedforward drive. Each striatal domain exhibited specific sensorimotor responses that predictably followed activity in the associated cortical regions, and the corticostriatal relationship remained unvaried during passive states or performance of a task probing visually guided behavior. However, the tasks visual stimuli and corresponding behavioral responses evoked relatively more activity in the striatum than in associated cortical regions. This increased striatal activity involved an additive offset in firing rate, which was independent of task engagement but only present in animals that had learned the task. Thus, striatal activity largely reflects patterns of cortical activity, deviating from them in a simple additive fashion for learned stimuli or actions.

neuroscience↗

bioRxiv2019

Retinal outputs depend on behavioural state

The operating mode of the visual system depends on behavioural states such as arousal1,2. This dependence is seen both in primary visual cortex3-7 (V1) and in subcortical brain structures receiving direct retinal input4,8. Here we show that this effect arises as early as in the output of the retina. We first measured activity in a region that receives retinal projections9, the superficial superior colliculus (sSC), and found that this activity strongly depended on behavioural state. This modulation was not mediated by feedback inputs from V1 as it was immune to V1 inactivation. We then used Neuropixels probes10 to record activity in the optic tract, and we found some retinal axons whose activity significantly varied with arousal, even in darkness. To characterize these effects on a larger sample of retinal outputs, we imaged the activity of retinal boutons11,12 in sSC during behaviour using a calcium indicator. The activity of these boutons correlated with arousal as strongly as that of sSC neurons, and this correlation persisted also during darkness. These results reveal a novel property of retinal function in mice, which could be observed only during behaviour: retinal outputs are modulated by behavioural state before they reach the rest of the brain.

neuroscience↗

bioRxiv2018

Distinct contributions of mouse cortical areas to visual discrimination

Correlates of sensory stimuli and motor actions are found in multiple cortical areas, but such correlates do not indicate whether these areas are causally relevant to task performance. We trained mice to discriminate visual contrast and report their decision by turning a wheel. Widefield calcium imaging and Neuropixels recordings in cortex revealed stimulus-related activity in visual (VIS) and frontal (MOs) areas, and widespread movement-related activity across the whole dorsal cortex. Optogenetic inactivation biased choices only when targeted at VIS and MOs, at times corresponding to peak stimulus decoding. A neurometric model based on summing and subtracting activity in VIS and MOs successfully described behavioral performance and predicted the effect of optogenetic inactivation. Thus, local sensory signals in visual and frontal cortex play a causal role in task performance, while widespread dorsal cortical signals correlating with movement reflect processes that do not play a causal role.

neuroscience↗

bioRxiv2018

A tool for analyzing electrode tracks from slice histology

It is now possible to record from hundreds of neurons across multiple brain regions in a single electrophysiology experiment. An essential step in the ensuing data analysis is to assign recorded neurons to the correct brain regions. Brain regions are typically identified after the recordings by comparing images of brain slices to a reference atlas by eye. This introduces error, in particular when slices are not cut at a perfectly coronal angle or when electrode tracks span multiple slices. Here we introduce SHARP-Track, a tool to localize regions of interest and plot the brain regions they pass through. SHARP-Track offers a MATLAB user interface to explore the Allen Mouse Brain Atlas, register asymmetric slice images to the atlas using manual input, and interactively analyze electrode tracks. We find that it reduces error compared to localizing electrodes in a reference atlas by eye. See github.com/cortex-lab/allenCCF for the software and wiki.

neuroscience↗

bioRxiv2018

Laminar Segregation of Sensory Coding and Behavioral Readout in Macaque V4

Neurons in sensory areas of the neocortex are known to represent information both about sensory stimuli and behavioral state, but how these two disparate signals are integrated across cortical layers is poorly understood. To study this issue, we measured the coding of visual stimulus orientation and of behavioral state by neurons within superficial and deep layers of area V4 in monkeys while they covertly attended or prepared eye movements to visual stimuli. We show that single neurons and neuronal populations in superficial layers convey more information about the orientation of visual stimuli, whereas single neurons and neuronal populations in deep layers convey greater information about the behavioral relevance of those stimuli. In particular, deep layer neurons encode greater information about the direction of prepared eye movements. These results reveal a division of labor between laminae in the coding of visual input and visually guided behavior.

neuroscience↗

bioRxiv2018

Distinct structure of cortical population activity on fast and infraslow timescales

Cortical activity is organised across multiple spatial and temporal scales. Most research on the dynamics of neuronal spiking is concerned with timescales of 1 ms - 1 s, and little is known about spiking dynamics on timescales of tens of seconds and minutes. Here, we used frequency domain analyses to study the structure of individual neurons spiking activity and its coupling to local population rate and to arousal level across frequencies ranging from 0.01 to 100 Hz. In mouse medial prefrontal cortex (mPFC), the spiking dynamics of individual neurons could be quantitatively captured by a combination of interspike interval and firing rate power spectrum distributions. The relative strength of coherence with local population often differed across timescales: a neuron strongly coupled to population rate on fast timescales could be weakly coupled on slow timescales, and vice versa. On slow but not fast timescales, a substantial proportion of neurons showed firing anti-correlated with the population. Infraslow firing rate changes were largely determined by arousal rather than by local factors, which could explain the timescale dependence of population coupling strength of individual neurons. These observations demonstrate how individual neurons simultaneously partake in fast local dynamics, and slow brain-wide dynamics, extending our understanding of infraslow cortical activity beyond the mesoscale resolution of fMRI studies.

neuroscience↗

bioRxiv2018

Cortical state fluctuations during sensory decision making

Neocortical activity varies between states of \"synchronization\" and \"desynchronization\", with desynchronized states believed to occur specifically in regions engaged by the task. To disambiguate whether desynchronization is linked to task performance or engagement, we trained mice on tasks in which incorrect responses due to disengagement (neglect) differed from inaccurate task performance (incorrect choices). Using widefield calcium imaging to measure cortical state across many areas simultaneously, we found that desynchronization was correlated with engagement rather than accuracy. Consistent with this link between desynchronization and engagement, we found that rewards had a long-lasting desynchronizing effect. To determine whether engagement-related changes in cortical state depended on the sensory modality, we trained mice on visual and auditory task versions and found that desynchronization was similar in both and more pronounced in somatomotor than either sensory cortex. We conclude that variations in cortical state are predominately global and closely relate to variations in task engagement.

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↗