Biology subjects

Katz, B.

Publications and source records attributed to Katz, B..

11 recordsLinked to original sources

bioRxiv2025

Automated Locus Coeruleus segmentation and age-related signal changes across Neuromelanin-sensitive MRI and T1/T2-weighted images

The locus coeruleus (LC) plays a key role in stress response, attention, and cognitive function, with its integrity closely linked to neuromelanin accumulation. Neuromelanin-sensitive MRI (NM-MRI) has enabled in vivo imaging of the LC, but automated segmentation remains challenging due to its small size, low contrast, and anatomical variability. This study aimed to evaluate the accuracy of automatic LC segmentation using multi-atlas nonlinear warping applied to high-resolution T1/T2-weighted images and to compare LC intensity characteristics across NM-MRI, T1w, and T2w images. Additionally, we examined developmental changes in LC signal from childhood through adulthood. We analyzed MRI data from 134 participants (ages 8[~]64) with NM-MRI, T1w, and T2w scans, alongside 652 participants (ages 6[~]22) from the Human Connectome Project in Development (HCP-D). LC intensity measures were compared across imaging modalities and analyzed for age-related trends. Automatic LC segmentation achieved high spatial overlap with manual tracings (up to 95% after one voxel 2D-dilation). Statistically estimated high (or low)-intensity values (mean {+/-} 2{sigma}) from automated LC masks provided a more stable and noise-resilient alternative to local peak intensity measures. Age-related LC signal changes are most clearly observed in NM-MRI and T2w imaging, with significant developmental shifts emerging during adolescence. These findings support the conventional T2w imaging as an indirect marker of neuromelanin accumulation and highlight the possibility of age-specific analyses in LC imaging studies.

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bioRxiv2025

Efferent signaling along nociceptive peripheral terminals in vivo is enhanced during inflammation

Primary nociceptors are essentially characterized as afferent neurons carrying noxious sensory information from the periphery to the CNS. However, the information flow on primary nociceptors is bidirectional. Nociceptor peripheral terminals release a variety of mediators to the target organ in the vicinity of the injured area. These mediators promote sensitization of adjacent sensory neurons, vasodilation, and edema and affect innate and adaptive immunity, leading to hyperalgesia and inflammation that often expands beyond the injured areas. Many theories associate these phenomena with the antidromic action potential propagation along nociceptor terminals; however, the antidromic efferent signaling at the single nociceptor terminals has never been demonstrated. Here, using in vivo calcium imaging from the individual nociceptive terminals innervating the mouse cornea together with a computational approach, we demonstrated that short-lasting activation of a single terminal in vivo was sufficient to activate the remote, non-activated terminal, which branches from the same nociceptor fiber. This increase was dependent on the activation of voltage-gated sodium and calcium channels. Moreover, we showed that the efferent signaling along nociceptive terminals increases under inflammatory conditions, culminating in enhanced calcium signaling in the remote non-activated terminals. This inflammation-induced increase in intra-terminal calcium could trigger the enhanced release of inflammatory mediators, spilling over wider areas and affecting terminals from adjacent unstimulated receptive fields, leading to the expansion of hyperalgesia and inflammation.

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bioRxiv2024

Inversed association of locus coeruleus MRI integrity with structural volume and its impact on individual's inattentiveness

The locus coeruleus (LC) is a nucleus within the brainstem associated with physiological arousal and altered structure and function in the context of neurodegenerative disorders. Pathologies related to difficulties with attention have previously been associated with abnormalities in neurotransmitter production and sensitivity, suggesting the possibility of abnormality in neurotransmitter producing neural regions. One such region is the LC, associated with norepinephrine production. To examine the possibility that LC alteration is associated with inattentive symptom reporting, a set of analyses have been performed with 141 individuals age-ranged from 8 to 54. We found that the structural integrity value of the LC, especially on the right hemisphere, showed a significant negative association with the level of individuals inattentiveness score. Furthermore, LC volume size was significantly positively associated with inattention, and this finding was also lateralized to the right LC. Interestingly, an inverse association was found between structural integrity and volume size. These findings support the relationship between LC and attention-related behavior through both neuromelanin-sensitive and structural imaging, with important implications for the association between regional structure and function.

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bioRxiv2024

Adaptation of pain-related projection neurons in acute but not chronic pain

Pain hypersensitivity is associated with increased activity of peripheral and central neurons along the pain neuroaxis1. On the other hand, in other neuronal systems, increased activity leads to adaptive reduction of neuronal excitability to maintain homeostasis2-4. Projection neurons (PNs) of spinal and medullary dorsal horns summate the activity of primary nociceptive and local central interneurons and convey it to higher centers5. We show that at the peak of acute inflammatory pain, PNs reduce their intrinsic excitability and, consequently, action potential firing. When pain resolves, the excitability of PNs returns to baseline. Using electrophysiological and computational approaches, we found that an increase in potassium A-current (IA) underlies the decrease in the excitability of PNs in acute pain conditions. We hypothesized that an IA-induced decrease in PNs firing may restrain the output from the dorsal horn to prevent sensitization and pain chronification. Indeed, no changes of IA in PNs were observed in chronic pain conditions, and PNs exhibit increased intrinsic excitability and firing. Our results reveal an adaptive mechanism in acute pain conditions for regulating the output from the dorsal horn network, which, if interrupted, could trigger pain chronification.

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bioRxiv2023

Distinct neurochemical influences on fMRI response polarity in the striatum

The striatum is the primary input nucleus of the basal ganglia, widely studied for its complex roles in health and disease. Functional magnetic resonance imaging (fMRI) studies are essential for discerning striatal function, however the relationship between neuronal and hemodynamic activity, critical for interpreting fMRI signals, has not been rigorously examined in striatum. We find that optogenetic stimulation of striatal neurons or afferents evokes negative striatal fMRI responses in rats that can occur despite broad increases in local neuronal activity. Intra-striatal pharmacological manipulations suggest that opioidergic, but not dopaminergic transmission contributes to negative striatal fMRI signals (the latter instead associated with positive signals). Striatal neuronal activity peaks are also associated with negative hemodynamic signals in behaving rats. Negative fMRI responses are observed in human striatum under conditions of anticipated neuronal activity increases. Our results prompt consideration of local cellular and neurochemical environments along with neuronal activity in fMRI signal interpretation.

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bioRxiv2022

Association of intrinsic functional connectivity between the locus coeruleus and salience network with attentional ability

The LC is a brainstem region associated with broad physiological and neural arousal as part of the release of norepinephrine, but it has increasingly been associated with multiple specific cognitive processes. These include sustained attention, deficits in which are associated with a variety of neuropsychological disorders. Neural models of attention deficits to date have focused on interrupted dynamics between the salience network (SAL) with the fronto-parietal network (FPN), which has been associated with task-switching and processing of external stimuli, respectively. Conflicting findings based on these regions suggest the possibility of upstream signaling leading to attention dysfunction, and recent research suggest the LC may play this role. In this study, resting-state functional connectivity (FC) and behavioral performance on an attention task was examined within 584 individuals. Analysis revealed significant clusters connected to the LC activity in the bilateral insula, anterior cingulate cortex (ACC), and bilateral ventral striatum, all regions associated with the SAL. Given previous findings that attention deficits may be caused by dysfunctions in network switching by the SAL, our findings here further suggest that dysfunction in LC signaling to the SAL may interfere with attention.

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bioRxiv2022

Structural plasticity of axon initial segment in spinal cord neurons underlies inflammatory pain

Activity-dependent structural plasticity of axon initial segment (AIS) regulates neuronal excitability, thus fine-tuning neuronal and overall network output. Here using behavioral, immunohistochemical, electrophysiological and computational approaches, we describe the structural plasticity of AIS in rats superficial spinal cord dorsal horn (SDH) neurons, which underlies inflammatory pain. We show an inflammation-mediated distal shift of the AIS away from the soma in inhibitory but not excitatory SDH neurons, concomitant with the peak of inflammatory pain. This AIS translocation was accompanied by a decrease in excitability of the inhibitory neurons. Following recovery from inflammatory hyperalgesia, the AIS location and neuronal excitability reversed to baseline levels. The computational model of SDH inhibitory neurons predicts that the distal shift of AIS is sufficient to decrease the intrinsic excitability of these neurons. Our results provide evidence of differential inflammation-mediated AIS plasticity, reducing the excitability of inhibitory but not excitatory SDH neurons and contributing to inflammatory hyperalgesia.

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bioRxiv2021

Neural Regression, Representational Similarity, Model Zoology & Neural Taskonomy at Scale in Rodent Visual Cortex

How well do deep neural networks fare as models of mouse visual cortex? A majority of research to date suggests results far more mixed than those produced in the modeling of primate visual cortex. Here, we perform a large-scale benchmarking of dozens of deep neural network models in mouse visual cortex with both representational similarity analysis and neural regression. Using the Allen Brain Observatorys 2-photon calcium-imaging dataset of activity in over 6,000 reliable rodent visual cortical neurons recorded in response to natural scenes, we replicate previous findings and resolve previous discrepancies, ultimately demonstrating that modern neural networks can in fact be used to explain activity in the mouse visual cortex to a more reasonable degree than previously suggested. Using our benchmark as an atlas, we offer preliminary answers to overarching questions about levels of analysis (e.g. do models that better predict the representations of individual neurons also predict representational similarity across neural populations?); questions about the properties of models that best predict the visual system overall (e.g. is convolution or category-supervision necessary to better predict neural activity?); and questions about the mapping between biological and artificial representations (e.g. does the information processing hierarchy in deep nets match the anatomical hierarchy of mouse visual cortex?). Along the way, we catalogue a number of models (including vision transformers, MLP-Mixers, normalization free networks, Taskonomy encoders and self-supervised models) outside the traditional circuit of convolutional object recognition. Taken together, our results provide a reference point for future ventures in the deep neural network modeling of mouse visual cortex, hinting at novel combinations of mapping method, architecture, and task to more fully characterize the computational motifs of visual representation in a species so central to neuroscience, but with a perceptual physiology and ecology markedly different from the ones we study in primates.

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bioRxiv2021

Encoding of inflammatory hyperalgesia in mice spinal cord

Inflammation modifies the input-output properties of peripheral nociceptive neurons, thus leading to hyperalgesia, a condition in which the perception of noxious heat stimuli is altered such that the same stimulus produces enhanced pain. The increased nociceptive output enters the superficial dorsal spinal cord (SDH), which comprises the first CNS network integrating the noxious information. Here we used in vivo calcium imaging and a computational approach to investigate how the SDH network in mice encodes the injury-mediated abnormal input from peripheral nociceptive neurons. We show that the application of noxious heat stimuli to the hind paw in naive mice before induction of injury affects the activity of 70% of recorded neurons by either increasing or suppressing it. Application of the same noxious heat stimuli to hyperalgesic skin following injury leads to activation of previously non-responded cells and de-suppression of the "suppressed" neurons. We further demonstrate that reduction in synaptic inhibition mimics the response to the noxious stimuli in hyperalgesic conditions. Using a computational model of the SDH network, we predict that the "disinhibitory" effect of hyperalgesic stimuli results from the inflammation-mediated increased afferent input to the SDH network and a decrease in SDH inhibition. Both of these processes synergistically contribute to the injury-mediated increase in SDH output towards higher brain centers.

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bioRxiv2020

The input-output relation of primary nociceptive neurons is determined by the morphology of the peripheral nociceptive terminals

The output from the peripheral terminals of primary nociceptive neurons, which detect and encode the information regarding noxious stimuli, is crucial in determining pain sensation. The nociceptive terminal endings are morphologically complex structures assembled from multiple branches of different geometry, which converge in a variety of forms to create the terminal tree. The output of a single terminal is defined by the properties of the transducer channels producing the generation potentials and voltage-gated channels, translating the generation potentials into action potential firing. However, in the majority of cases, noxious stimuli activate multiple terminals; thus, the output of the nociceptive neuron is defined by the integration and computation of the inputs of the individual terminals. Here we used a computational model of nociceptive terminal tree to study how the architecture of the terminal tree affects input-output relation of the primary nociceptive neurons. We show that the input-output properties of the nociceptive neurons depend on the length, the axial resistance, and location of individual terminals. Moreover, we show that activation of multiple terminals by capsaicin-like current allows summation of the responses from individual terminals, thus leading to increased nociceptive output. Stimulation of terminals in simulated models of inflammatory or nociceptive hyperexcitability led to a change in the temporal pattern of action potential firing, emphasizing the role of temporal code in conveying key information about changes in nociceptive output in pathological conditions, leading to pain hypersensitivity. Significance statementNoxious stimuli are detected by terminal endings of the primary nociceptive neurons, which are organized into morphologically complex terminal trees. The information from multiple terminals is integrated along the terminal tree, computing the neuronal output, which propagates towards the CNS, thus shaping the pain sensation. Here we revealed that the structure of the nociceptive terminal tree determines the output of the nociceptive neurons. We show that the integration of noxious information depends on the morphology of the terminal trees and how this integration and, consequently, the neuronal output change under pathological conditions. Our findings help to predict how nociceptive neurons encode noxious stimuli and how this encoding changes in pathological conditions, leading to pain.

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bioRxiv2019

Neural Correlates of Working Memory Training: Evidence for Plasticity in Older Adults

Brain activity typically increases with increasing working memory (WM) load, regardless of age, before reaching an apparent ceiling. However, older adults exhibit greater brain activity and reach ceiling at lower loads than younger adults, possibly reflecting compensation at lower loads and dysfunction at higher loads. We hypothesized that WM training would bolster neural efficiency, such that the activation peak would shift towards higher memory loads after training. Pre-training, older adults showed greater recruitment of the WM network than younger adults across all loads, with decline at the highest load. Ten days of adaptive training on a verbal WM task improved performance and led to greater brain responsiveness at higher loads for both groups. For older adults the activation peak shifted rightward towards higher loads. Finally, training increased task-related functional connectivity in older adults, both within the WM network and between this task-positive network and the task-negative/default-mode network. These results provide new evidence for functional plasticity with training in older adults and identify a potential signature of improvement at the neural level.

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