Biology subjects

Lebedeva, A.

Publications and source records attributed to Lebedeva, A..

9 recordsLinked to original sources

bioRxiv2025

Different representations in layer 2/3 and layer 5 excitatory neurons of the primary visual cortex

The cortex contains multiple types of excitatory neuron, differentiated primarily by their layer of residence. We recorded from neuronal populations in the mouse visual cortex using 2-photon calcium imaging or Neuropixels probes, and found that excitatory neurons in layer 2/3 (L2/3) and layer 5 (L5) differed in their encoding of visual vs. nonvisual signals, with L2/3 more strongly modulated by visual stimuli and L5 more strongly modulated by movement. Movement had opposite effects on population synchrony in the two layers: it desynchronizes L2/3, by abolishing spontaneous synchronous fluctuations that entrain that population, and synchronizes L5, where excitatory cells are less entrained by spontaneous synchronous fluctuations and more strongly correlated with movement itself. Spontaneous activity was lower-dimensional in L2/3 than L5, with L2/3 population activity dominated by a single dimension of overlap between spontaneous and stimulus-evoked subspaces. We conclude that excitatory neurons in different layers of the visual cortex carry different representations of visual and non-visual signals.

neuroscience↗

bioRxiv2025

GABAergic signaling by VIP interneurons gates running-dependent visual recovery in the adult brain

Experience-dependent plasticity in the adult visual cortex is enhanced by locomotion, a process mediated by vasoactive intestinal peptide (VIP)-expressing interneurons. While VIP interneurons are known to signal through both Gamma-aminobutyric acid (GABA) and VIP peptide, the specific contributions of these pathways during different forms of plasticity remain unclear. Monocular deprivation (MD) in adult mice alters cortical responses, though more slowly and differently than during a critical period in early life. Here, we used two-photon calcium imaging in awake adult mice to dissect the roles of VIP and GABA release from VIP interneurons during adult MD and subsequent binocular recovery. We found comparable level of ocular dominance shifts after MD in mice deficient in either peptidergic or GABA signaling, but disrupting GABA signaling impaired recovery of binocular responses. We also showed that running preferentially enhances contralateral eye responses in binocular primary visual cortex. However, this eye-specific modulation of visual responses by running was altered during recovery from MD and was dependent on VIP signaling pathways. These findings highlight the GABA-mediated inhibition by VIP interneurons as a critical pathway for promoting visual restoration in the adult brain. Significance StatementUsing longitudinal two-photon imaging in awake adult mice with genetically altered signaling path-ways in VIP interneurons, we demonstrate that GABAergic, but not peptidergic, signaling from VIP interneurons is essential for the recovery of binocular vision following monocular deprivation. We further reveal that locomotion modulates cortical responses in an eye-specific manner, a property dynamically reshaped by plasticity and dependent on VIP interneuron function. These findings identify a discrete inhibitory circuit element that links behavioral state to sensory recovery and highlight GABA release from VIP cells as a potential therapeutic target for restoring visual function in adulthood.

neuroscience↗

bioRxiv2024

Dorsal prefrontal cortex drives perseverative behavior in mice

Perseveration - repeating one choice when others would generate larger rewards - is a common behavior, but neither its purpose nor neuronal mechanisms are understood. Here we demonstrate a neural correlate and causal role of dorsal prefrontal cortex, specifically anterior supplementary motor cortex (MOs) in perseveration in mice performing a dynamic reward learning task. An auditory go cue signaled mice to turn a wheel either left or right, with the reward probability of each action switching in blocks. Mice perseverated, gaining suboptimal reward, but were faster when making repeated choices. Neuropixels recordings found neurons whose activity correlated with perseveration and predicted rapid reaction times, almost exclusively in anterior MOs. Optogenetically inhibiting this region at choice time reduced perseveration and slowed reactions. In contrast, inactivating medial prefrontal cortex at choice time had no effect, but inactivating it after reward delivery impaired learning. In this task, therefore, anterior MOs reflects a perseverative decision variable, and is necessary for mediating the effect of this decision variable on choice and reaction time.

neuroscience↗

bioRxiv2024

Repix: reliable, reusable, versatile chronic Neuropixels implants using minimal components

Neuropixels probes represent the state-of-the-art for high-yield electrophysiology in neuroscience: the simultaneous recording of hundreds of neurons is now routinely carried out in head-restrained animals. In contrast, neural recording in unrestrained animals, as well as recording and tracking neurons over days, remains challenging, though it is possible using chronic implants. A major challenge is the availability of simple methods that can be implemented with limited or no prior experience with Neuropixels probes, while achieving reliable, reusable, versatile high-density electrophysiology. Here we developed, deployed, and evaluated the real-world performance of Repix, a chronic implantation system that permits the repeated re-use of Neuropixels probes. The lightweight system allows implanted animals to express a full range of natural behaviors, including social behaviors. We show that Repix allows the recording of hundreds of neurons across many months, up to a year, with implants across cortical and subcortical brain regions. Probes can be reused repeatedly with stable yield. Repix has been used by 16 researchers in 10 laboratories to date, and we evaluated the real-world performance of Repix in a variety of chronic recording paradigms in both mice and rats with a combined 209 implantations. We found that the key advantage of Repix is robustness and simplicity. Adopters of Repix became proficient at five procedures on average, regardless of prior experience with in vivo electrophysiology. With the companion protocol alongside this article, the performance and user-friendliness of Repix should facilitate a wide uptake of chronic Neuropixels recordings.

neuroscience↗

bioRxiv2023

DREDge: robust motion correction for high-density extracellular recordings across species

High-density microelectrode arrays (MEAs) have opened new possibilities for systems neuroscience in human and non-human animals, but brain tissue motion relative to the array poses a challenge for downstream analyses, particularly in human recordings. We introduce DREDge (Decentralized Registration of Electrophysiology Data), a robust algorithm which is well suited for the registration of noisy, nonstationary extracellular electrophysiology recordings. In addition to estimating motion from spikes in the action potential (AP) frequency band, DREDge enables automated tracking of motion at high temporal resolution in the local field potential (LFP) frequency band. In human intraoperative recordings, which often feature fast (period <1s) motion, DREDge correction in the LFP band enabled reliable recovery of evoked potentials, and significantly reduced single-unit spike shape variability and spike sorting error. Applying DREDge to recordings made during deep probe insertions in nonhuman primates demonstrated the possibility of tracking probe motion of centimeters across several brain regions while simultaneously mapping single unit electrophysiological features. DREDge reliably delivered improved motion correction in acute mouse recordings, especially in those made with an recent ultra-high density probe. We also implemented a procedure for applying DREDge to recordings made across tens of days in chronic implantations in mice, reliably yielding stable motion tracking despite changes in neural activity across experimental sessions. Together, these advances enable automated, scalable registration of electrophysiological data across multiple species, probe types, and drift cases, providing a stable foundation for downstream scientific analyses of these rich datasets.

neuroscience↗

bioRxiv2023

Tracking neurons across days with high-density probes

Neural activity spans multiple scales from milliseconds to months. Its evolution can be recorded with chronic electrodes, and especially with high-density arrays such as Neuropixels probes, which measure each spike at tens of sites and record hundreds of neurons. These arrays often record units with consistent spike waveforms over time, but produce vast amounts of data that require new approaches for tracking neurons across recordings. To meet this need, we developed UnitMatch, an open-access pipeline that operates after spike sorting, based only on each units average spike waveform. We tested UnitMatch in Neuropixels recordings from the mouse brain, where it tracked neurons across weeks. In visual cortex, a neurons selectivity for visual stimuli and correlation with other neurons remained stable over days. In striatum, neuronal responses changed across days during learning of a task. UnitMatch is thus a promising tool to reveal invariance or plasticity in neural activity across days.

neuroscience↗

bioRxiv2023

Multi-day Neuron Tracking in High Density Electrophysiology Recordings using EMD

Accurate tracking of the same neurons across multiple days is crucial for studying changes in neuronal activity during learning and adaptation. Advances in high density extracellular electrophysiology recording probes, such as Neuropixels, provide a promising avenue to accomplish this goal. Identifying the same neurons in multiple recordings is, however, complicated by non-rigid movement of the tissue relative to the recording sites (drift) and loss of signal from some neurons. Here we propose a neuron tracking method that can identify the same cells independent of firing statistics, that are used by most existing methods. Our method is based on between-day non-rigid alignment of spike sorted clusters. We verified the same cell identity in mice using measured visual receptive fields. This method succeeds on datasets separated from one to 47 days, with an 84% average recovery rate.

neuroscience↗

bioRxiv2021

Behavioral origin of sound-evoked activity in visual cortex

Sensory cortices can be affected by stimuli of multiple modalities and are thus increasingly thought to be multisensory. For instance, primary visual cortex (V1) is influenced not only by images but also by sounds. Here we show that the activity evoked by sounds in V1 is highly stereotyped across neurons and even across mice. It resembles activity measured elsewhere in the brain and is independent of projections from auditory cortex. Its low-dimensional nature starkly contrasts the high dimensional code that V1 uses to represent images. Furthermore, this sound-evoked activity can be precisely predicted by small body movements that are elicited by each sound and are highly stereotyped across trials and across mice. Thus, neural activity that is apparently multisensory may simply arise from low-dimensional signals associated with changes in internal state and behavior.

neuroscience↗

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↗