Biology subjects

Benson, J.

Publications and source records attributed to Benson, J..

7 recordsLinked to original sources

bioRxiv2026

Reduced MOV10 reveals novel functional cortical connections in an increased fear response

The RNA helicase MOV10 is highly expressed in developing brain, is present in synapses and is required for embryonic viability. A murine brain-specific knockout of MOV10 (Mov10 Deletion) has a thickened cortex, abnormal dendritic arborization and enhanced fear memory. In human studies, MOV10 is among the loci that is correlated with enhanced cortical brain volumes and is also significantly associated with substance dependence by epigenetic profiling. Here we demonstrate that Mov10 Deletion mice show enhanced fear learning that is aligned with impaired structural connectivity of canonical fear circuits revealed by Diffusion Tensor Imaging. We propose a model where MOV10 loss leads to increased GABRA2 expression in the hippocampus and reduced anatomical connectivity that drives augmented fear learning. Memory reactivation is observable during fear memory retrieval as an overall increase in fMRI functional activity in cortical regions. Taken together, this framework identifies that enhanced fear in the MOV10 model is driven via a "corticalized" fear response during re-exposure to the training context that is not driven by the canonical fear circuit. These findings support a molecular basis for non-traditional enhanced learning mechanisms activated by fearful events that shed light on the intractability of fear memories with the potential to inform PTSD and substance dependence disorders.

neuroscience↗

bioRxiv2025

Multi-modal choroid plexus pathology in aging and Alzheimer's disease

Brain barriers, cerebrospinal fluid (CSF) dynamics, and peripheral factors are implicated as significant contributors to Alzheimers disease (AD). The choroid plexus (ChP) is a blood-brain interface that produces CSF and forms the blood-CSF barrier. However, how ChP pathology develops across the lifespan and contributes to AD has not been systematically characterized. Here, we report a multi-modal ChP atlas integrating single-nucleus transcriptomics from 49 individuals, AI-assisted quantitative histopathology across >500 postmortem samples age 16 to 105, spatial transcriptomics, and functional studies in 5xFAD mice. We identify fibrosis, calcification, and macrophage abnormalities as hallmarks of ChP aging, with AD pathology conferring additional effects, including expansion of a pro-inflammatory fibroblast-macrophage signaling niche. In 5xFAD mice, macrophage dysfunction is associated with impaired epithelial barrier maintenance and repair. Together, these data provide a foundational resource for understanding ChP dysfunction in aging and AD and propose the macrophage-fibroblast-epithelial barrier axis as a driver of ChP pathology.

neuroscience↗

bioRxiv2024

Interactive data exploration websites for large-scale electrophysiology

Methodological advances in neuroscience have enabled the collection of massive datasets which demand innovative approaches for scientific communication. Existing platforms for data storage lack intuitive tools for data exploration, limiting our ability to interact effectively with these brain-wide datasets. We introduce two public websites: (Data and Atlas) developed for the International Brain Laboratory which provide access to millions of behavioral trials and hundreds of thousands of individual neurons. These interfaces allow users to discover both the raw and processed brain-wide data released by the IBL at the scale of the whole brain, individual sessions, trials, and neurons. By hosting these data interfaces as websites they are available cross-platform with no installation. By releasing each sites code as a modular open-source framework, other researchers can easily develop their own web interfaces and explore their own data. As neuroscience datasets continue to expand, customizable web interfaces offer a glimpse into a future of streamlined data exploration and act as blueprints for future tools.

neuroscience↗

bioRxiv2024

A common computational and neural anomaly across mouse models of autism

Computational psychiatry has suggested that humans within the autism spectrum disorder (ASD) inflexibly update their expectations (i.e., Bayesian priors). Here, we leveraged high-yield rodent psychophysics (n = 75 mice), extensive behavioral modeling (including principled and heuristics), and (near) brain-wide single cell extracellular recordings (over 53k units in 150 brain areas) to ask (1) whether mice with different genetic perturbations associated with ASD show this same computational anomaly, and if so, (2) what neurophysiological features are shared across genotypes in subserving this deficit. We demonstrate that mice harboring mutations in Fmr1, Cntnap2, and Shank3B show a blunted update of priors during decision-making. Neurally, the differentiating factor between animals flexibly and inflexibly updating their priors was a shift in the weighting of prior encoding from sensory to frontal cortices. Further, in mouse models of ASD frontal areas showed a preponderance of units coding for deviations from the animals long-run prior, and sensory responses did not differentiate between expected and unexpected observations. These findings demonstrate that distinct genetic instantiations of ASD may yield common neurophysiological and behavioral phenotypes.

neuroscience↗

bioRxiv2023

A Brain-Wide Map of Neural Activity during Complex Behaviour

A key challenge in neuroscience is understanding how neurons in hundreds of interconnected brain regions integrate sensory inputs with prior expectations to initiate movements and thereby make decisions. It is difficult to meet this challenge if different laboratories apply different analyses to different recordings in different regions during different behaviours. Here, we report a comprehensive set of recordings from 621733 neurons across 139 mice in 12 labs performing a decision-making task with sensory, motor, and cognitive components, obtained with 699 Neuropixels probe insertions covering 279 brain areas in the left forebrain and midbrain and the right hindbrain and cerebellum. We provide an initial appraisal of this brain-wide map, assessing how neural activity encoded key task variables. Representations of visual stimuli appeared transiently in classical visual areas after stimulus onset and then spread to ramp-like activity in a collection of mid- and hindbrain regions that also encoded choices. Neural responses correlated with motor action almost everywhere in the brain. Responses to reward delivery and consumption versus negative feedback were also widespread. This publicly available dataset represents an unprecedented resource for understanding how computations distributed across and within brain areas drive behaviour.

neuroscience↗

bioRxiv2023

Brain-wide representations of prior information in mouse decision-making

The neural representations of prior information about the state of the world are poorly understood. To investigate them, we examined brain-wide Neuropixels recordings and widefield calcium imaging collected by the International Brain Laboratory. Mice were trained to indicate the location of a visual grating stimulus, which appeared on the left or right with prior probability alternating between 0.2 and 0.8 in blocks of variable length. We found that mice estimate this prior probability and thereby improve their decision accuracy. Furthermore, we report that this subjective prior is encoded in at least 20% to 30% of brain regions which, remarkably, span all levels of processing, from early sensory areas (LGd, VISp) to motor regions (MOs, MOp, GRN) and high level cortical regions (ACAd, ORBvl). This widespread representation of the prior is consistent with a neural model of Bayesian inference involving loops between areas, as opposed to a model in which the prior is incorporated only in decision-making areas. This study offers the first brain-wide perspective on prior encoding at cellular resolution, underscoring the importance of using large scale recordings on a single standardized task.

neuroscience↗

bioRxiv2022

Reproducibility of in-vivo electrophysiological measurements in mice

Understanding brain function relies on the collective work of many labs generating reproducible results. However, reproducibility has not been systematically assessed within the context of electrophysiological recordings during cognitive behaviors. To address this, we formed a multi-lab collaboration using a shared, open-source behavioral task and experimental apparatus. Experimenters in ten laboratories repeatedly targeted Neuropixels probes to the same location (spanning secondary visual areas, hippocampus, and thalamus) in mice making decisions; this generated a total of 121 experimental replicates, a unique dataset for evaluating reproducibility of electrophysiology experiments. Despite standardizing both behavioral and electrophysiological procedures, some experimental outcomes were highly variable. A closer analysis uncovered that variability in electrode targeting hindered reproducibility, as did the limited statistical power of some routinely used electrophysiological analyses, such as single-neuron tests of modulation by individual task parameters. Reproducibility was enhanced by histological and electrophysiological quality-control criteria. Our observations suggest that data from systems neuroscience is vulnerable to a lack of reproducibility, but that across-lab standardization, including metrics we propose, can serve to mitigate this.

neuroscience↗