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ELife Jun 2024Adaptive motor behavior depends on the coordinated activity of multiple neural systems distributed across the brain. While the role of sensorimotor cortex in motor...
Adaptive motor behavior depends on the coordinated activity of multiple neural systems distributed across the brain. While the role of sensorimotor cortex in motor learning has been well established, how higher-order brain systems interact with sensorimotor cortex to guide learning is less well understood. Using functional MRI, we examined human brain activity during a reward-based motor task where subjects learned to shape their hand trajectories through reinforcement feedback. We projected patterns of cortical and striatal functional connectivity onto a low-dimensional manifold space and examined how regions expanded and contracted along the manifold during learning. During early learning, we found that several sensorimotor areas in the dorsal attention network exhibited increased covariance with areas of the salience/ventral attention network and reduced covariance with areas of the default mode network (DMN). During late learning, these effects reversed, with sensorimotor areas now exhibiting increased covariance with DMN areas. However, areas in posteromedial cortex showed the opposite pattern across learning phases, with its connectivity suggesting a role in coordinating activity across different networks over time. Our results establish the neural changes that support reward-based motor learning and identify distinct transitions in the functional coupling of sensorimotor to transmodal cortex when adapting behavior.
Topics: Humans; Magnetic Resonance Imaging; Reward; Male; Learning; Female; Adult; Young Adult; Sensorimotor Cortex; Brain Mapping; Motor Activity; Cerebral Cortex
PubMed: 38916598
DOI: 10.7554/eLife.91928 -
Cureus May 2024Background Spinal dysraphism, characterized by incomplete closure of neural and bone spinal structures, manifests as congenital fusion abnormalities along the dorsal...
Background Spinal dysraphism, characterized by incomplete closure of neural and bone spinal structures, manifests as congenital fusion abnormalities along the dorsal midline, involving the skin, subcutaneous tissue, meninges, vertebrae, and neural tissue. Magnetic resonance imaging (MRI), the preferred imaging modality for assessing spinal dysraphism across all age groups, provides direct visualization of the spinal cord without the need for contrast or ionizing radiation while also eliminating bone artifacts and allowing multiplanar imaging. The objective of this study was to evaluate the range of spinal dysraphism lesions and assess the significance of MRI in their evaluation. Methodology Thirty patients with suspected spinal dysraphism underwent evaluation at the Medical College Hospital and Study Centre in Vijayapur, India. This cross-sectional observational study included patients diagnosed or provisionally diagnosed with spinal dysraphism based on clinical and imaging profiles. Cases were identified through preliminary findings on radiographs. Results The study encompassed individuals aged one month to 20 years, with the largest proportion of patients (36.67%) falling within the 1-5-year age group. Spina bifida was the most prevalent spinal abnormality, accounting for 70% of cases. In 12 patients (40%), the most prevalent location of involvement was the lumbosacral spine. Conclusion MRI provides excellent tissue differentiation, particularly of lipomatous tissue, with reproducible and comprehensive section planes and relative operator independence. Moreover, MRI is beneficial for children with suspected spinal dysraphism as it can be performed without ionizing radiation, biological risks, or the need for intrathecal contrast media.
PubMed: 38916024
DOI: 10.7759/cureus.60972 -
Clinical Case Reports Jul 2024Botulinum toxin (BTX) injection can be an effective treatment for persistent pain and functional impairment associated with hypertrophy of the first dorsal interosseous...
Botulinum toxin (BTX) injection can be an effective treatment for persistent pain and functional impairment associated with hypertrophy of the first dorsal interosseous muscle. It offers a non-surgical and minimally invasive alternative for those who have failed conservative treatment, showcasing the therapeutic promise of BTX for addressing similar musculoskeletal conditions.
PubMed: 38915929
DOI: 10.1002/ccr3.9094 -
BioRxiv : the Preprint Server For... Jun 2024Striatonigral neurons, known to promote locomotion, reside in both the patch and matrix compartments of the dorsal striatum. However, their compartment-specific...
Striatonigral neurons, known to promote locomotion, reside in both the patch and matrix compartments of the dorsal striatum. However, their compartment-specific contributions to locomotion remain largely unexplored. Using molecular identifier and , we showed in mouse models that patch and matrix striatonigral neurons exert opposite influences on locomotion. Matrix striatonigral neurons reduced their activity before the cessation of self-paced locomotion, while patch striatonigral neuronal activity increased, suggesting an inhibitory function. Indeed, optogenetic activation of patch striatonigral neurons suppressed ongoing locomotion with reduced striatal dopamine release, contrasting with the locomotion-promoting effect of matrix striatonigral neurons, which showed an initial increase in dopamine release. Furthermore, genetic deletion of the GABA-B receptor in Aldehyde dehydrogenase 1A1-positive (ALDH1A1 ) nigrostriatal dopaminergic neurons completely abolished the locomotion-suppressing effect of patch striatonigral neurons. Our findings unravel a compartment-specific mechanism governing locomotion in the dorsal striatum, where patch striatonigral neurons suppress locomotion by inhibiting ALDH1A1 nigrostriatal dopaminergic neurons.
PubMed: 38915717
DOI: 10.1101/2024.06.12.598675 -
BioRxiv : the Preprint Server For... Jun 2024How does evolution act on neuronal populations to match computational characteristics to functional demands? We address this problem by comparing visual code and retinal...
How does evolution act on neuronal populations to match computational characteristics to functional demands? We address this problem by comparing visual code and retinal cell composition in closely related murid species with different behaviours. are diurnal and have substantially thicker inner retina and larger visual thalamus than nocturnal . High-density electrophysiological recordings of visual response features in the dorsal lateral geniculate nucleus (dLGN) reveals that attains higher spatiotemporal acuity both by denser coverage of the visual scene and a selective expansion of elements of the code characterised by non-linear spatiotemporal summation. Comparative analysis of single cell transcriptomic cell atlases reveals that realignment of the visual code is associated with increased relative abundance of bipolar and ganglion cell types supporting OFF and ON-OFF responses. These findings demonstrate how changes in retinal cell complement can reconfigure the coding of visual information to match changes in visual needs.
PubMed: 38915685
DOI: 10.1101/2024.06.14.598659 -
BioRxiv : the Preprint Server For... Jun 2024Mice are able to navigate an odor plume with a complex spatiotemporal structure in the dark to find the source of odorants. We developed a protocol to monitor behavior...
UNLABELLED
Mice are able to navigate an odor plume with a complex spatiotemporal structure in the dark to find the source of odorants. We developed a protocol to monitor behavior and record Ca transients in dorsal CA1 stratum pyramidale neurons at the hippocampus (dCA1) in mice navigating an odor plume in a 50 cm x 50 cm x 25 cm odor arena. Ca transients were imaged by an epifluorescence miniscope focused through a GRIN lens on dCA1 neurons expressing the calcium sensor GCaMP6f in Thy1-GCaMP6f mice. We describe the behavioral protocol to train the mice to perform this odor plume navigation task in an automated odor arena. We provide the step-by-step procedure for the surgery for GRIN lens implantation and baseplate placement for imaging GCaMP6f in CA1. We provide information on real time tracking of the mouse position to automate the start of the trials and delivery of a sugar water reward. In addition, we provide information on the use of an Intan board to synchronize metadata describing the automation of the odor navigation task and frame times for the miniscope and a FLIR camera tracking mouse position. Moreover, we delineate the pipeline used to process GCaMP6f fluorescence movies by motion correction using NorMCorre followed by identification of regions of interest (ROIs) with EXTRACT. Finally, we describe use of artificial neural network (ANN) machine learning to decode spatial paths from CA1 neural ensemble activity to predict mouse navigation of the odor plume.
SUMMARY
This protocol describes how to investigate the brain-behavior relationship in hippocampal CA1 in mice navigating an odor plume. We provide a step-by-step protocol including the surgery to access imaging of the hippocampus, behavioral training, miniscope GCaMP6f recording and processing of the brain and behavioral data to decode the mouse position from ROI neural activity.
PubMed: 38915584
DOI: 10.1101/2024.06.12.598681 -
BioRxiv : the Preprint Server For... Jun 2024Prosapip1 is a brain-specific protein localized to the postsynaptic density, where it promotes dendritic spine maturation in primary hippocampal neurons. However,...
Prosapip1 is a brain-specific protein localized to the postsynaptic density, where it promotes dendritic spine maturation in primary hippocampal neurons. However, nothing is known about the role of Prosapip1 . To examine this, we utilized the Cre-loxP system to develop a Prosapip1 neuronal knockout mouse. We found that Prosapip1 controls the synaptic localization of its binding partner SPAR, along with PSD-95 and the GluN2B subunit of the NMDA receptor (NMDAR) in the dorsal hippocampus (dHP). We next sought to identify the potential contribution of Prosapip1 to the activity and function of the NMDAR and found that Prosapip1 plays an important role in NMDAR-mediated transmission and long-term potentiation (LTP) in the CA1 region of the dHP. As LTP is the cellular hallmark of learning and memory, we examined the consequences of neuronal knockout of Prosapip1 on dHP-dependent memory. We found that global or dHP-specific neuronal knockout of Prosapip1 caused a deficit in learning and memory whereas developmental, locomotor, and anxiety phenotypes were normal. Taken together, Prosapip1 in the dHP promotes the proper localization of synaptic proteins which, in turn, facilitates LTP driving recognition, social, and spatial learning and memory.
PubMed: 38915579
DOI: 10.1101/2024.06.13.597459 -
BioRxiv : the Preprint Server For... Jun 2024Vascular stabilization is a mechanosensitive process, in part driven by blood flow. Here, we demonstrate the involvement of the mechanosensitive ion channel, Piezo1, in...
Vascular stabilization is a mechanosensitive process, in part driven by blood flow. Here, we demonstrate the involvement of the mechanosensitive ion channel, Piezo1, in promoting arterial accumulation of vascular smooth muscle cells (vSMCs) during zebrafish development. Using a series of small molecule antagonists or agonists to temporally regulate Piezo1 activity, we identified a role for the Piezo1 channel in regulating levels and altered targeting of vSMCs between arteries and veins. Increasing Piezo1 activity suppressed and increased vSMC association with the cardinal vein, while inhibition of Piezo1 activity increased levels and decreased vSMC association with arteries. We supported the small molecule data with genetic suppression of and in zebrafish, resulting in loss of vSMCs on the dorsal aorta. Further, endothelial cell (EC)-specific knockout in mice was sufficient to decrease vSMC accumulation along the descending dorsal aorta during development, thus phenocopying our zebrafish data, and supporting functional conservation of Piezo1 in mammals. To determine mechanism, we used modeling assays to demonstrate that differential sensing of pulsatile versus laminar flow forces across endothelial cells changes the expression of mural cell differentiation genes. Together, our findings suggest a crucial role for EC Piezo1 in sensing force within large arteries to mediate mural cell differentiation and stabilization of the arterial vasculature.
PubMed: 38915529
DOI: 10.1101/2024.06.11.598539 -
BioRxiv : the Preprint Server For... Jun 2024Chronic pain is a wide-spread condition that is debilitating and expensive to manage, costing the United States alone around $600 billion in 2010. In a common type of...
Chronic pain is a wide-spread condition that is debilitating and expensive to manage, costing the United States alone around $600 billion in 2010. In a common type of chronic pain called allodynia, non-painful stimuli produce painful responses with highly variable presentations across individuals. While the specific mechanisms remain unclear, allodynia is hypothesized to be caused by the dysregulation of excitatory-inhibitory (E-I) balance in pain-processing neural circuitry in the dorsal horn of the spinal cord. In this work, we analyze biophysically-motivated subcircuit structures that represent common motifs in neural circuits in layers I-II of the dorsal horn. These circuits are hypothesized to be part of the neural pathways that mediate two different types of allodynia: static and dynamic. We use neural firing rate models to describe the activity of populations of excitatory and inhibitory interneurons within each subcircuit. By accounting for experimentally-observed responses under healthy conditions, we specify model parameters defining populations of subcircuits that yield typical behavior under normal conditions. Then, we implement a sensitivity analysis approach to identify the mechanisms most likely to cause allodynia-producing dysregulation of the subcircuit's E-I signaling. We find that disruption of E-I balance generally occurs either due to downregulation of inhibitory signaling so that excitatory neurons are "released" from inhibitory control, or due to upregulation of excitatory neuron responses so that excitatory neurons "escape" their inhibitory control. Which of these mechanisms is most likely to occur, the subcircuit components involved in the mechanism, and the proportion of subcircuits exhibiting the mechanism can vary depending on the subcircuit structure. These results suggest specific hypotheses about diverse mechanisms that may be most likely responsible for allodynia, thus offering predictions for the high interindividual variability observed in allodynia and identifying targets for further experimental studies on the underlying mechanisms of this chronic pain condition.
PubMed: 38915505
DOI: 10.1101/2024.06.10.598179 -
Nature Communications Jun 2024Neuromuscular control of bionic arms has constantly improved over the past years, however, restoration of sensation remains elusive. Previous approaches to reestablish...
Neuromuscular control of bionic arms has constantly improved over the past years, however, restoration of sensation remains elusive. Previous approaches to reestablish sensory feedback include tactile, electrical, and peripheral nerve stimulation, however, they cannot recreate natural, intuitive sensations. Here, we establish an experimental biological sensorimotor interface and demonstrate its potential use in neuroprosthetics. We transfer a mixed nerve to a skeletal muscle combined with glabrous dermal skin transplantation, thus forming a bi-directional communication unit in a rat model. Morphological analyses indicate reinnervation of the skin, mechanoreceptors, NMJs, and muscle spindles. Furthermore, sequential retrograde labeling reveals specific sensory reinnervation at the level of the dorsal root ganglia. Electrophysiological recordings show reproducible afferent signals upon tactile stimulation and tendon manipulation. The results demonstrate the possibility of surgically creating an interface for both decoding efferent motor control, as well as encoding afferent tactile and proprioceptive feedback, and may indicate the way forward regarding clinical translation of biological communication pathways for neuroprosthetic applications.
Topics: Animals; Bionics; Rats; Muscle, Skeletal; Feedback, Sensory; Proprioception; Ganglia, Spinal; Mechanoreceptors; Muscle Spindles; Male; Female; Touch; Skin
PubMed: 38914540
DOI: 10.1038/s41467-024-49580-8