Biology subjects

Lee, A. K.

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

At least 19 recordsLinked to original sources

bioRxiv2026

Multi-scale place fields provide a predictive basis for hierarchical control

Hippocampal place cells typically exhibit unimodal spatial selectivity in small enclosures, but express multiple, irregularly spaced fields in environments of naturalistic scale. However, existing predictive-map theories of the hippocampus do not scale well to large environments and do not account for these heterogeneous place field characteristics. Here, we introduce the factorised hierarchical successor representation (fHSR), a predictive map that supports hierarchical control using subgoal-directed subroutines. We show that the fHSR allows efficient generalisation across tasks, scaling favourably with environmental size, and it reproduces key statistical and topological characteristics of multi-scale CA1 place cell activity in rats and bats. Analyses of experimental data further confirmed a novel prediction of the fHSR: population firing rates exhibit spatial periodicity with a characteristic wavelength independent of environmental size. These results identify the integration of hierarchical control and predictive representations as a normative principle that unifies efficient navigation with the spatial organisation of hippocampal activity.

neuroscience↗

bioRxiv2026

SorCS1 promotes synaptic and cognitive resilience despite amyloid pathology in Alzheimer's disease model mice

Alzheimer's disease (AD) lacks effective therapies despite extensive efforts targeting amyloid {beta} (A{beta}) and its precursor processing. Synapse loss is the strongest correlate of cognitive decline, driven partly by A{beta} oligomers (A{beta}Os), which bind multiple synaptic membrane proteins including the synaptic organizer neurexin and disrupt synaptic integrity and function. The protein sorting receptor SorCS1 blocks interactions between A{beta}Os and {beta}-isoforms of neurexins ({beta}-Nrxns), but its therapeutic relevance in vivo remains unclear. Using 5xFAD mice, which overproduce A{beta}Os, combined with forebrain specific neuronal SorCS1 overexpression, we show that SorCS1 preserves working memory, synaptic integrity, and basal excitatory transmission without altering amyloid deposition, in part by restoring synaptic {beta}-Nrxn expression. SorCS1 also reduces tau hyperphosphorylation in 5xFAD synaptosomes and binds the tau kinase GSK3{beta}. These results identify SorCS1 as an AD resilience promoting factor that maintains synaptic connectivity and attenuates tau pathology, revealing a therapeutic strategy that operates independently of amyloid reduction.

neuroscience↗

bioRxiv2026

A lipid compendium of a metabolically compromised bacterium provides insights into lipid acquisition, biosynthesis, and metabolism

The Lyme disease agent Borrelia burgdorferi belongs to a class of metabolically compromised bacteria that cannot survive without host-derived lipids. Survival of the agent in tick and vertebrate hosts requires substantial nutrient acquisition and potential cell envelope remodeling. While prior studies identified cholesterol, cholesterol glycolipids, and phosphatidylcholines as membrane lipids in B. burgdorferi, the identity of many other membrane lipids, their origin, and their physiological relevance remain unknown. Here, we used a suite of untargeted and targeted high-resolution mass spectrometry methods to reveal a complex lipid profile of the pathogen and to identify the origin of its lipids. The analysis detected more than 500 lipids in B. burgdorferi, the majority of which are sourced from the environment. However, the bacterium selectively accumulates certain lipids while excluding others, suggesting discriminatory uptake. These include cholesteryl esters and triglycerides that are organized in foci within the pathogen. Intriguingly, the pathogen also synthesizes predominantly eukaryotic lipids such as the lysosomal bis(monoacylglycerol)phosphate and the plant glycolipid sulfoquinovosyl diacylglycerol (SQDG). The biosynthesis of the latter is carried out by enzymes that exhibit structural homology to plant oxidoreductases and galactosyltransferases, yet their closest orthologs are found in bacteria. This hints that the capability of SQDG synthesis is more widespread in spirochaetes and other bacteria. Together, the comprehensive lipid profiling we report here uncovers novel aspects of the physiology of the metabolically challenged B. burgdorferi and highlights lipid acquisition and synthesis pathways as potentially critical for pathogen survival.

biochemistry↗

bioRxiv2026

Visual Cortical Response Variability in Infants at High Familial Likelihood for Autism

Visual processing undergoes rapid development in the first year of life, supporting the emergence of higher-order cognitive, language, and motor functions. Visual evoked potentials (VEPs) provide a non-invasive measure of visual system maturation that may shed light on heterogeneous developmental trajectories among infants at high familial likelihood for autism. Infants with an older sibling with autism spectrum disorder (N = 177 at 6 months; N = 132 at 12 months) participated in the Infant Brain Imaging Study-Early Prediction (IBIS-EP) study. Pattern-reversal VEPs were recorded at 6 and 12 months, and developmental skills were assessed at 24 months using the Bayley Scales of Infant and Toddler Development (Bayley-4). VEP components (P1 and N1) were characterized by their amplitude and latency, as well as trial-to-trial variability in these measures. Associations with 24-month cognitive, language, and motor scores were examined using general linear models controlling for age, site, sex, and trial count. Robust VEPs were observed at both time points, with age-appropriate morphology and expected developmental changes, including decreases in P1 latency and amplitude from 6 to 12 months. Greater trial-to-trial variability in P1 latency at both time points was associated with higher cognitive and language scores at 24 months. In contrast, conventional measures of mean P1 latency and amplitude were not associated with developmental outcomes. These findings suggest that temporal variability in early visual responses may index adaptive sensory-circuit flexibility during a period of rapid experience-dependent development. VEP response-timing variability may therefore provide an early mechanistic marker of sensory-circuit organization relevant to later developmental trajectories. Research HighlightsO_LIGreater trial-to-trial variability in visual cortical response timing was associated with higher cognitive and language scores in infants at high familial likelihood for autism. C_LIO_LIConventional average VEP measures were unrelated to outcomes, suggesting temporal variability may more sensitively capture relevant neural-circuit differences in this population. C_LIO_LIGreater variability in early visual responses may reflect adaptive sensory-circuit flexibility during a critical period of neurodevelopment. C_LIO_LIVEP response-timing measures provide an early mechanistic window into sensory-circuit organization and its relation to later developmental trajectories. C_LI

neuroscience↗

bioRxiv2026

A sterol reductase responsible for the unusual 8(14)-unsaturation in bacterial sterol production and degradation

Sterols are a class of lipids that play a crucial role in human health through their essential physiological roles and as a point of interaction between commensal and pathogenic bacteria. The biosynthesis and modification of these lipids is a well-characterized process in many eukaryotes and increasingly in bacteria. However, the proteins responsible for formation of the unusual 8(14)-unsaturation found in the sterols produced by aerobic methanotrophs, dinoflagellates, nematodes, and marine sponges, remains unknown. Here, we utilize a heterologous expression system to identify a bacterial 8,14-sterol reductase (8,14-Bsr) responsible for generating the 8(14)-unsaturation in the aerobic methanotroph Methylococcus capsulatus. This enzyme modifies the direct product of C-14 demethylation, reducing one double bond in the nuclear core structure and isomerizing the other to produce an 8(14)-sterol. We subsequently tested the requirement of putative active site residues for catalysis through site directed mutagenesis, identifying residues likely involved in interacting with the sterol substrate and directly catalyzing this reaction. Bioinformatic analysis of the distribution of 8,14-Bsr reveals it is unique to the bacterial domain, found primarily in the Methylococcaceae family, the Mycobacteriales order, and yet uncultured members of the Myxococcota phylum. Further phylogenetic analysis of 8,14-Bsr suggests it shares an evolutionary history with the C-14 demethylase in these organisms and that these two enzymes were likely inherited together. These results provide insight into novel sterol biochemistry, further delimiting sterol biosynthesis in the bacterial domain from eukaryotes and illustrating the importance of molecular characterization to identify bacterial proteins that interact with sterols. ImportanceMany of the eukaryotic proteins required for the biosynthesis of sterols, such as cholesterol, have been characterized. However, the pathways governing analogous processes in the bacterial domain are less characterized. Here, we identify an 8,14-sterol reductase in aerobic methanotrophs. This enzyme carries out a unique biochemical reaction, saturating and isomerizing double bonds in the nuclear core structure to produce an 8(14)-sterol. This reductase is restricted to the bacterial domain, further separating the evolution of bacterial sterol production from eukaryotes. Additionally, we find this reductase is prevalent in members of the sterol degrading order Mycobacteriales, highlighting a potential role for this protein in the remodeling of host sterol production by these pathogens.

microbiology↗

bioRxiv2025

Signatures of remote planning in hippocampal replay

During brief, intermittent "replay" events, hippocampal activity can express navigational trajectories disconnected from both when and where they originally occurred. While replay biased toward immediate future goals has been observed, there is no evidence yet linking replay to planning beyond the next action. Here, we designed a sequential spatial working memory task which required rats to utilize information across multiple temporally separated actions. Remote replay events matched the animals future navigational choices made after completing an intervening subtask. Critically, this occurred only when the replayed information was useful for reducing memory load, consistent with it being an active process. Our findings suggest these remote replay events are a neural correlate of episodic forethought, allowing animals to use memories to plan beyond their immediate surroundings.

neuroscience↗

bioRxiv2024

A geranylgeranyl reductase homolog required for cholesterol production in Myxococcota

Myxococcota is a phylum of sterol producing bacteria. They exhibit a clade depth for sterol biosynthesis unparalleled in the bacterial domain and produce sterols of a biosynthetic complexity that rivals eukaryotes. Additionally, the sterol biosynthesis pathways found in this phylum have been proposed as a potential source for sterol biosynthesis in the last eukaryotic common ancestor, lending an evolutionary importance to our understanding of this pathway in Myxococcota. However, sterol production has only been characterized in a few species and outstanding questions about the evolutionary history of this pathway remain. Here, we identify two myxobacteria, Minicystis rosea and Sandaracinus amylolyticus, capable of cholesterol biosynthesis. These two myxobacteria possess a cholesterol biosynthesis pathway that differs in both the ordering and enzymes involved in biosynthesis compared to Enhygromyxa salina, a myxobacterium previously demonstrated to produce cholesterol, as well as the canonical pathways found in eukaryotes. We characterize an alternative bacterial reductase responsible for performing C-24 reduction, further delineating bacterial cholesterol production from eukaryotes. Finally, we examine the distribution and phylogenetic relationships of sterol biosynthesis proteins across both cultured and uncultured Myxococcota species, providing evidence for multiple acquisition events and instances of both horizontal and vertical transfer at the family level. Altogether, this work further demonstrates the capacity of myxobacteria to synthesize eukaryotic sterols but with an underlying diversity in the biochemical reactions which govern sterol synthesis, suggesting a complex evolutionary history and refining our understanding of how myxobacterial cholesterol production relates to their eukaryotic counterparts. Significance StatementSterols are essential and ubiquitous lipids in eukaryotes, but their significance in bacteria is less understood. Sterol production in Myxococcota, a phylum of developmentally complex predatory bacteria, has provided insight into novel sterol biochemistry and prompted discussion regarding the evolution of this pathway within both the eukaryotic and bacterial domains. Here, we characterize cholesterol biosynthesis in two myxobacteria, providing evidence for distinct pathway organization and identifying a unique protein responsible for C-24 reduction. We couple these results to phylogenomic analysis of sterol biosynthesis within Myxococcota revealing a complicated evolutionary history marked by vertical and horizontal transfer, suggesting a mosaic acquisition of this pathway in Myxococcota and highlighting the complex role myxobacteria may have had in sterol transfer to eukaryotes.

microbiology↗

bioRxiv2024

Melanoma antigens in pediatric medulloblastoma contribute to tumor heterogeneity and species-specificity of group 3 tumors

BackgroundMedulloblastoma (MB) is the most malignant childhood brain cancer. Group 3 MB subtype accounts for about 25% of MB diagnoses and is associated with the most unfavorable outcomes. Herein, we report that more than half of group 3 MB tumors express melanoma antigens (MAGEs), which are potential prognostic and therapeutic markers. MAGEs are tumor antigens, expressed in several types of adult cancers and associated with poorer prognosis and therapy resistance; however, their expression in pediatric cancers is mostly unknown. The aim of this study was to determine whether MAGEs are activated in pediatric MB. MethodsTo determine MAGE frequency in pediatric MB, we obtained formalin-fixed paraffin-embedded tissue (FFPE) samples of 34 patients, collected between 2008 - 2015, from the Childrens Medical Center Dallas pathology archives and applied our validated reverse transcription quantitative PCR (RT-qPCR) assay to measure the relative expression of 23 MAGE cancer-testis antigen genes. To validate our data, we analyzed several published datasets from pediatric MB patients and patient-derived orthotopic xenografts, totaling 860 patients. We then examined how MAGE expression affects the growth and oncogenic potential of medulloblastoma cells by CRISPR-Cas9- and siRNA-mediated gene depletion. ResultsOur RT-qPCR analysis suggested that MAGEs were expressed in group 3/4 medulloblastoma. Further mining of bulk and single-cell RNA-sequencing datasets confirmed that 50-75% of group 3 tumors activate a subset of MAGE genes. Depletion of MAGEAs, B2, and Cs alter MB cell survival, viability, and clonogenic growth due to decreased proliferation and increased apoptosis. ConclusionsThese results indicate that targeting MAGEs in medulloblastoma may be a potential therapeutic option for group 3 medulloblastomas. Key PointsO_LISeveral Type I MAGE CTAs are expressed in >60% of group 3 MBs. C_LIO_LIType I MAGEs affect MB cell proliferation and apoptosis. C_LIO_LIMAGEs are potential biomarkers and therapeutic targets for group 3 MBs. C_LI Importance of the StudyThis study is the first comprehensive analysis of all Type I MAGE CTAs (MAGEA, -B, and -C subfamily members) in pediatric MBs. Our results show that more than 60% of group 3 MBs express MAGE genes, which are required for the viability and growth of cells in which they are expressed. Collectively, these data provide novel insights into the antigen landscape of pediatric MBs. The activation of MAGE genes in group 3 MBs presents potential stratifying and therapeutic options. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=175 SRC="FIGDIR/small/594201v1_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@1ac274aorg.highwire.dtl.DTLVardef@1479944org.highwire.dtl.DTLVardef@19f5aaforg.highwire.dtl.DTLVardef@fad069_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2023

News without the buzz: reading out weak theta rhythms in the hippocampus

Local field potentials (LFPs) reflect the collective dynamics of neural populations, yet their exact relationship to neural codes remains unknown1. One notable exception is the theta rhythm of the rodent hippocampus, which seems to provide a reference clock to decode the animals position from spatiotemporal patterns of neuronal spiking2 or LFPs3. But when the animal stops, theta becomes irregular4, potentially indicating the breakdown of temporal coding by neural populations. Here we show that no such breakdown occurs, introducing an artificial neural network that can recover position-tuned rhythmic patterns (pThetas) without relying on the more prominent theta rhythm as a reference clock. pTheta and theta preferentially correlate with place cell and interneuron spiking, respectively. When rats forage in an open field, pTheta is jointly tuned to position and head orientation, a property not seen in individual place cells but expected to emerge from place cell sequences5. Our work demonstrates that weak and intermittent oscillations, as seen in many brain regions and species, can carry behavioral information commensurate with population spike codes.

neuroscience↗

bioRxiv2023

Low-latency extracellular spike assignment for high-density electrodes at single-neuron resolution

Real-time neural signal processing is essential for brain-machine interfaces and closed-loop neuronal perturbations. However, most existing applications sacrifice cell-specific identity and temporal spiking information for speed. We developed a hybrid hardware-software system that utilizes a Field Programmable Gate Array (FPGA) chip to acquire and process data in parallel, enabling individual spikes from many simultaneously recorded neurons to be assigned single-neuron identities with 1-millisecond latency. The FPGA assigns labels, validated with ground-truth data, by comparing multichannel spike waveforms from tetrode or silicon probe recordings to a spike-sorted model generated offline in software. This platform allowed us to rapidly inactivate a region in vivo based on spikes from an upstream neuron before these spikes could excite the downstream region. Furthermore, we could decode animal location within 3 ms using data from a population of individual hippocampal neurons. These results demonstrate our systems suitability for a broad spectrum of research and clinical applications.

neuroscience↗

bioRxiv2023

Mental navigation and telekinesis with a hippocampal map-based brain-machine interface

The hippocampus is critical for recollecting and imagining experiences. This is believed to involve voluntarily drawing from hippocampal memory representations of people, events, and places, including the hippocampus map-like representations of familiar environments. However, whether the representations in such "cognitive maps" can be volitionally and selectively accessed is unknown. We developed a brain-machine interface to test if rats could control their hippocampal activity in a flexible, goal-directed, model-based manner. We show that rats can efficiently navigate or direct objects to arbitrary goal locations within a virtual reality arena solely by activating and sustaining appropriate hippocampal representations of remote places. This should provide insight into the mechanisms underlying episodic memory recall, mental simulation/planning, and imagination, and open up possibilities for high-level neural prosthetics utilizing hippocampal representations.

neuroscience↗

bioRxiv2023

α-synuclein preformed fibrils bind to β-neurexins and impair β-neurexin-mediated presynaptic organization

Synucleinopathies form a group of neurodegenerative diseases defined by misfolding and aggregation of alpha-synuclein (-syn). Abnormal accumulation and spreading of -syn aggregates lead to synapse dysfunction and neuronal cell death. Yet, little is known about synaptic mechanisms underlying -syn pathology. Here we identified {beta}-isoforms of neurexins ({beta}-NRXs) as presynaptic organizing proteins that interact with -syn preformed fibrils (-syn PFFs), toxic -syn aggregates, but not -syn monomers. Our cell surface protein binding assays and surface plasmon resonance assays reveal that -syn PFFs bind directly to {beta}-NRX through their N-terminal histidine-rich domain (HRD) at nanomolar range (Kd: ~500 nM monomer equivalent). Furthermore, our artificial synapse formation assays show that -syn PFFs diminish excitatory and inhibitory presynaptic organization induced by a specific isoform of neuroligin 1 that binds only {beta}-NRXs, but not -isoforms of neurexins. Thus, our data suggest that -syn PFFs interact with {beta}-NRXs to inhibit {beta}-NRX-mediated presynaptic organization, providing novel molecular insight into how -syn PFFs induce synaptic pathology in synucleinopathies such as Parkinsons disease and dementia with Lewy bodies.

neuroscience↗

bioRxiv2023

Functional specialization and structured representations for space and time in prefrontal cortex

Neurons in prefrontal cortex exhibit selectivity for a range of behaviorally relevant variables, such as sensory stimuli, place, time, choice, context, and category. At the population level, representations of these variables can be organized in various ways--for instance, geometrically or hierarchically. However, how selectivity for each feature is distributed across cells and how this gives rise to such population-level representational structure is unclear. To address these questions, we analyzed coding for space, time, and category in rats performing a navigational task featuring two behavioral categories, starts and goals, each consisting of multiple locations. Population activity was organized hierarchically, with neural distances between elements of a category being smaller than the distances between categories. At the single cell level, individual medial prefrontal cortex (mPFC) neurons were tuned to category and space independently, consistent with hierarchical population geometry emerging from random mixed selectivity, while neurons exhibited preferences for representing space or time across categories, consistent with functional specialization. These distinct selectivity rules across different levels of abstraction suggest that different aspects of prefrontal representations have disparate origins and may enable modularized computations across multiple behaviors and contexts.

neuroscience↗

bioRxiv2022

De novo cholesterol biosynthesis in the bacterial domain

Sterols are versatile lipids primarily associated with eukaryotes. While bacteria also produce sterols and studies of bacterial biosynthesis proteins have revealed novel biosynthetic pathways and a potential evolutionary role in the origin of sterol biosynthesis, no bacterium has been shown to synthesize highly modified eukaryotic sterols, such as cholesterol. This has led to the notion that bacteria only produce biosynthetically simple sterols and has lessened the consideration of bacterial production in discussions of sterol biosynthesis. In this study, we demonstrate two phylogenetically distinct bacteria, Enhygromyxa salina and Calothrix sp. NIES-4105, are capable of de novo cholesterol production. We also identified 25-hydroxycholesterol released as a product of acid hydrolysis in extracts from both bacteria, suggesting cholesterol exists as a conjugated molecule in these organisms. We coupled our lipid extractions to bioinformatic analyses and heterologous expression experiments to identify genetic pathways driving cholesterol production in each bacterium. E. salina shares much of its cholesterol biosynthesis pathway with the canonical eukaryotic pathway, except for C-4 demethylation where we identified a unique variation on the bacterial C-4 demethylation pathway. Calothrix lacks homologs for several steps in cholesterol biosynthesis, suggesting this bacterium may harbor a novel mechanism for completing cholesterol biosynthesis. Altogether, these results demonstrate the complexity underpinning bacterial sterol biosynthesis and raise further questions about the functional and regulatory roles of sterols in bacteria.

microbiology↗

bioRxiv2021

A structured scaffold underlies activity in the hippocampus

Place cells are believed to organize memory across space and time, inspiring the idea of the cognitive map. Yet unlike the structured activity in the associated grid and head-direction cells, they remain an enigma: their responses have been difficult to predict and are complex enough to be statistically well-described by a random process. Here we report one step toward the ultimate goal of understanding place cells well enough to predict their fields. Within a theoretical framework in which place fields are derived as a conjunction of external cues with internal grid cell inputs, we predict that even apparently random place cell responses should reflect the structure of their grid inputs and that this structure can be unmasked if probed in sufficiently large neural populations and large environments. To test the theory, we design experiments in long, locally featureless spaces to demonstrate that structured scaffolds undergird place cell responses. Our findings, together with other theoretical and experimental results, suggest that place cells build memories of external inputs by attaching them to a largely prespecified grid scaffold.

neuroscience↗

bioRxiv2021

Oxygenated hemoglobin signal provides greater predictive performance of experimental condition than de-oxygenated

Continuous-wave functional near-infrared spectroscopy (fNIRS) neuroimaging provides an estimate of relative changes in oxygenated and de-oxygenated hemoglobin content, from which regional neural activity is inferred. The relation between both signals is governed by neurovascular coupling mechanisms. However, the magnitude of concentration changes and the contribution of noise sources to each chromophore is unique. Subsequently, it is not apparent if either chromophore signal practically provides greater information about the underlying neural state and relation to an experimental condition. To assess this question objectively, we applied a machine-learning approach to four datasets and evaluated which hemoglobin signal best differentiated between experimental conditions. To further ensure the objective nature of the analysis, the algorithm utilized all samples from the epoched data rather than pre-selected features. Regardless of experimental task, brain region, or stimulus, the oxygenated hemoglobin signal was better able to differentiate between conditions than the de-oxygenated signal. Incorporating both signals into the analysis provided no additional improvement over oxygenated hemoglobin alone. These results indicate that oxyhemoglobin is the most informative fNIRS signal in relation to experimental condition.

neuroscience↗

bioRxiv2020

Analysis methods for measuring fNIRS responses generated by a block-design paradigm

OverviewO_ST_ABSSignificanceC_ST_ABSfNIRS is an increasingly popular tool in auditory research, but the range of analysis procedures employed across studies complicates interpretation of data. AimTo assess the impact of different analysis procedures on the morphology, detection, and lateralization of auditory responses in fNIRS. Specifically, whether averaging or GLM-based analyses generate different experimental conclusions, when applied to a block-protocol design. The impact of parameter selection of GLMs on detecting auditory-evoked responses was also quantified. Approach17 listeners were exposed to three commonly employed auditory stimuli: noise, speech, and silence. A block design was employed, comprising sounds of 5-s duration, and 10-20 s silent intervals. ResultsBoth analysis procedures generated similar response morphologies and amplitude estimates, and both also indicated responses to speech to be significantly greater than to noise and silence. Neither approach indicated a significant effect of brain hemisphere on responses to speech. Methods to correct for systemic hemodynamic responses using short channels improved detection at the individual level. ConclusionsConsistent with theoretical considerations, simulations, and other experimental domains, GLM and averaging analyses generate the same group-level experimental conclusions. We release this dataset publicly for use in future development and optimization of algorithms.

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↗