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BioRxiv : the Preprint Server For... Jun 2024Recording and modulation of neuronal activity enables the study of brain function in health and disease. While translational neuroscience relies on electrical recording...
Recording and modulation of neuronal activity enables the study of brain function in health and disease. While translational neuroscience relies on electrical recording and modulation techniques, mechanistic studies in rodent models leverage genetic precision of optical methods, such as optogenetics and imaging of fluorescent indicators. In addition to electrical signal transduction, neurons produce and receive diverse chemical signals which motivate tools to probe and modulate neurochemistry. Although the past decade has delivered a wealth of technologies for electrophysiology, optogenetics, chemical sensing, and optical recording, combining these modalities within a single platform remains challenging. This work leverages materials selection and convergence fiber drawing to permit neural recording, electrical stimulation, optogenetics, fiber photometry, drug and gene delivery, and voltammetric recording of neurotransmitters within individual fibers. Composed of polymers and non-magnetic carbon-based conductors, these fibers are compatible with magnetic resonance imaging, enabling concurrent stimulation and whole-brain monitoring. Their utility is demonstrated in studies of the mesolimbic reward pathway by simultaneously interfacing with the ventral tegmental area and nucleus accumbens in mice and characterizing the neurophysiological effects of a stimulant drug. This study highlights the potential of these fibers to probe electrical, optical, and chemical signaling across multiple brain regions in both mechanistic and translational studies.
PubMed: 38895451
DOI: 10.1101/2024.06.07.598004 -
BioRxiv : the Preprint Server For... Jun 2024Several studies have revealed that midbrain dopamine (DA) neurons, even within a single neuroanatomical area, display heterogeneous properties. In parallel, studies...
Several studies have revealed that midbrain dopamine (DA) neurons, even within a single neuroanatomical area, display heterogeneous properties. In parallel, studies using single cell profiling techniques have begun to cluster DA neurons into subtypes based on their molecular signatures. Recent work has shown that molecularly defined DA subtypes within the substantia nigra (SNc) display distinctive anatomic and functional properties, and differential vulnerability in Parkinson's disease (PD). Based on these provocative results, a granular understanding of these putative subtypes and their alterations in PD models, is imperative. We developed an optimized pipeline for single-nuclear RNA sequencing (snRNA-seq) and generated a high-resolution hierarchically organized map revealing 20 molecularly distinct DA neuron subtypes belonging to three main families. We integrated this data with spatial MERFISH technology to map, with high definition, the location of these subtypes in the mouse midbrain, revealing heterogeneity even within neuroanatomical sub-structures. Finally, we demonstrate that in the preclinical LRRK2 knock-in mouse model of PD, subtype organization and proportions are preserved. Transcriptional alterations occur in many subtypes including those localized to the ventral tier SNc, where differential expression is observed in synaptic pathways, which might account for previously described DA release deficits in this model. Our work provides an advancement of current taxonomic schemes of the mouse midbrain DA neuron subtypes, a high-resolution view of their spatial locations, and their alterations in a prodromal mouse model of PD.
PubMed: 38895448
DOI: 10.1101/2024.06.06.597807 -
BioRxiv : the Preprint Server For... Jun 2024Sequenced reactivations of hippocampal neurons called replays, concomitant with sharp-wave ripples in the local field potential, are critical for the consolidation of...
Sequenced reactivations of hippocampal neurons called replays, concomitant with sharp-wave ripples in the local field potential, are critical for the consolidation of episodic memory, but whether replays depend on the brain's reward or novelty signals is unknown. Here we combined chemogenetic silencing of dopamine neurons in ventral tegmental area (VTA) and simultaneous electrophysiological recordings in dorsal hippocampal CA1, in freely behaving rats experiencing changes to reward magnitude and environmental novelty. Surprisingly, VTA silencing did not prevent ripple increases where reward was increased, but caused dramatic, aberrant ripple increases where reward was unchanged. These increases were associated with increased reverse-ordered replays. On familiar tracks this effect disappeared, and ripples tracked reward prediction error, indicating that non-VTA reward signals were sufficient to direct replay. Our results reveal a novel dependence of hippocampal replay on dopamine, and a role for a VTA-independent reward prediction error signal that is reliable only in familiar environments.
PubMed: 38895442
DOI: 10.1101/2024.06.04.597435 -
BioRxiv : the Preprint Server For... Jun 2024In most complex nervous systems there is a clear anatomical separation between the nerve cord, which contains most of the final motor outputs necessary for behaviour,...
In most complex nervous systems there is a clear anatomical separation between the nerve cord, which contains most of the final motor outputs necessary for behaviour, and the brain. In insects, the neck connective is both a physical and information bottleneck connecting the brain and the ventral nerve cord (VNC, spinal cord analogue) and comprises diverse populations of descending (DN), ascending (AN) and sensory ascending neurons, which are crucial for sensorimotor signalling and control. Integrating three separate EM datasets, we now provide a complete connectomic description of the ascending and descending neurons of the female nervous system of and compare them with neurons of the male nerve cord. Proofread neuronal reconstructions have been matched across hemispheres, datasets and sexes. Crucially, we have also matched 51% of DN cell types to light level data defining specific driver lines as well as classifying all ascending populations. We use these results to reveal the general architecture, tracts, neuropil innervation and connectivity of neck connective neurons. We observe connected chains of descending and ascending neurons spanning the neck, which may subserve motor sequences. We provide a complete description of sexually dimorphic DN and AN populations, with detailed analysis of circuits implicated in sex-related behaviours, including female ovipositor extrusion (DNp13), male courtship (DNa12/aSP22) and song production (AN hemilineage 08B). Our work represents the first EM-level circuit analyses spanning the entire central nervous system of an adult animal.
PubMed: 38895426
DOI: 10.1101/2024.06.04.596633 -
Sensors (Basel, Switzerland) Jun 2024This study aimed to investigate near-infrared spectroscopy (NIRS) in combination with classification methods for the discrimination of fresh and once- or...
This study aimed to investigate near-infrared spectroscopy (NIRS) in combination with classification methods for the discrimination of fresh and once- or twice-freeze-thawed fish. An experiment was carried out with common carp (). From each fish, test pieces were cut from the dorsal and ventral regions and measured from the skin side as fresh, after single freezing at minus 18 °C for 15 ÷ 28 days and 15 ÷ 21 days for the second freezing after the freeze-thawing cycle. NIRS measurements were performed via a NIRQuest 512 spectrometer at the region of 900-1700 nm in Reflection mode. The Pirouette 4.5 software was used for data processing. SIMCA and PLS-DA models were developed for classification, and their performance was estimated using the F1 score and total accuracy. The predictive power of each model was evaluated for fish samples in the fresh, single-freezing, and second-freezing classes. Additionally, aquagrams were calculated. Differences in the spectra between fresh and frozen samples were observed. They might be assigned mainly to the O-H and N-H bands. The aquagrams confirmed changes in water organization in the fish samples due to freezing-thawing. The total accuracy of the SIMCA models for the dorsal samples was 98.23% for the calibration set and 90.55% for the validation set. For the ventral samples, respective values were 99.28 and 79.70%. Similar accuracy was found for the PLS-PA models. The NIR spectroscopy and tested classification methods have a potential for nondestructively discriminating fresh from frozen-thawed fish in as methods to protect against fish meat food fraud.
Topics: Carps; Animals; Spectroscopy, Near-Infrared; Freezing
PubMed: 38894411
DOI: 10.3390/s24113620 -
Sensors (Basel, Switzerland) May 2024The paranasal sinuses, a bilaterally symmetrical system of eight air-filled cavities, represent one of the most complex parts of the equine body. This study aimed to...
Three-Dimensional Segmentation of Equine Paranasal Sinuses in Multidetector Computed Tomography Datasets: Preliminary Morphometric Assessment Assisted with Clustering Analysis.
The paranasal sinuses, a bilaterally symmetrical system of eight air-filled cavities, represent one of the most complex parts of the equine body. This study aimed to extract morphometric measures from computed tomography (CT) images of the equine head and to implement a clustering analysis for the computer-aided identification of age-related variations. Heads of 18 cadaver horses, aged 2-25 years, were CT-imaged and segmented to extract their volume, surface area, and relative density from the frontal sinus (FS), dorsal conchal sinus (DCS), ventral conchal sinus (VCS), rostral maxillary sinus (RMS), caudal maxillary sinus (CMS), sphenoid sinus (SS), palatine sinus (PS), and middle conchal sinus (MCS). Data were grouped into young, middle-aged, and old horse groups and clustered using the K-means clustering algorithm. Morphometric measurements varied according to the sinus position and age of the horses but not the body side. The volume and surface area of the VCS, RMS, and CMS increased with the age of the horses. With accuracy values of 0.72 for RMS, 0.67 for CMS, and 0.31 for VCS, the possibility of the age-related clustering of CT-based 3D images of equine paranasal sinuses was confirmed for RMS and CMS but disproved for VCS.
Topics: Horses; Animals; Cluster Analysis; Paranasal Sinuses; Imaging, Three-Dimensional; Multidetector Computed Tomography; Algorithms
PubMed: 38894336
DOI: 10.3390/s24113538 -
Diagnostics (Basel, Switzerland) May 2024Peyronie's disease (PD) affects the penile albuginea, resulting in penile deformity, pain, erectile dysfunction (ED), and an anxious-depressive state. PD diagnosis...
Peyronie's disease (PD) affects the penile albuginea, resulting in penile deformity, pain, erectile dysfunction (ED), and an anxious-depressive state. PD diagnosis involves a thorough medical history, penile palpation, documentation of the penile deformation, a dynamic penile echo color Doppler ultrasound (PCDU), and the completion of questionnaires for the evaluation of pain, ED, and psychometric tests. The aim of this study was to evaluate the symptoms of PD and their prevalence in PD patients in the active phase who had access to our andrology clinic. Inclusion criteria: availability of data on patients diagnosed with PD, including detailed medical history, blood tests, penile palpation, photographic documentation of penile deformity, and penile PCDU. Exclusion criteria: PD patients in the stable phase or those without the specified tests and data mentioned above. Our study found a higher prevalence of PD in younger patients (24.2%), a higher coexistence of PD with chronic prostatitis (35.6%), a higher percentage of cases of association between penile deformity and penile curvature (84.4%), a higher prevalence of "significant anxiety" (88.4%), a higher presence of plaque calcification (35.6%), and the detection of a longer duration of the first phase of PD (>18 months). The most frequently observed type of penile curvature was dorsal, followed by left lateral, right lateral, and, less commonly, ventral. We observed a significant statistical correlation between patient age and IIEF score, indicating that patients over the age of 40 years are at a higher risk of experiencing ED. We found a strong statistical relationship between VAS score and age. As age increases, the VAS score decreases, suggesting that younger patients reported more penile pain compared to those who were older than 40 years. Furthermore, we found that penile pain has a significant impact on the psychological state of PD patients. We also found that 38.8% of PD patients suffered from severe anxiety. In relation to this, psychotherapy should be integrated into PD treatment to improve the quality of life and treatment adherence.
PubMed: 38893650
DOI: 10.3390/diagnostics14111125 -
Cancers May 2024Resection margins are an important prognostic factor for patients with head and neck cancer. In general, for head and neck surgery, a margin >5 mm is advised by the...
BACKGROUND
Resection margins are an important prognostic factor for patients with head and neck cancer. In general, for head and neck surgery, a margin >5 mm is advised by the Royal College of Pathologists. However, this cannot always be achieved during laryngeal and hypopharyngeal surgery. The aim of this study is to identify the resection surfaces and measure the maximum feasible margins per subsite. The clinical relevance of these maximum feasible resection margins were analyzed in this descriptive anatomical study.
METHODS
head and neck surgeons and a pathologist from the Erasmus MC performed a total laryngectomy and laryngopharyngectomy on a head and neck specimen specifically available for research.
RESULTS
For a total laryngectomy, resection margins >5 mm were not feasible for the ventral and dorsal resection surface. For a total laryngopharyngectomy, resection margins >5 mm were not feasible for the ventral, dorsal and lateral resection surface.
CONCLUSION
Clear resection margins, defined as a margin >5 mm, are not always feasible in laryngeal and hypopharyngeal surgery, due to the anatomy of the larynx and tumor location. However, striving for a maximum feasible margin is still the main goal. We propose a new guideline for maximum feasible but adequate resection margins in larynx and hypopharynx tumor surgery.
PubMed: 38893176
DOI: 10.3390/cancers16112058 -
Journal of Clinical Medicine May 2024Cervical spine fractures in ankylosing spondylitis (AS) are characterized as highly unstable fractures posing an elevated risk of neurological deficit and a...
Cervical spine fractures in ankylosing spondylitis (AS) are characterized as highly unstable fractures posing an elevated risk of neurological deficit and a significantly elevated mortality rate. This study assesses the efficacy and safety of single-stage plate stabilization with ventral cement augmentation in treating subaxial cervical spine fractures in patients with AS. Over 86 months, 38 patients diagnosed with AS received ventral plate stabilization with cement augmentation after suffering unstable subaxial cervical fractures. No additional dorsal stabilization was used in any of these surgeries. There were no complications as a result of cement leakage. During the follow-up period, screw loosening and implant displacement were documented in two out of 38 cases. At the time of data analysis, 17 patients who had undergone treatment had died, representing 44.7% of the total cases. Seven patients died within 1 month, two patients died within 6 months, four patients died within 1 year, and four patients died after 1 year. Our study shows that a single-stage anterior screw and plate fixation of the cervical spine with cement augmentation could be a feasible and effective method to treat cervical spine fractures in patients with AS.
PubMed: 38892842
DOI: 10.3390/jcm13113131 -
International Journal of Molecular... May 2024A total of 3102 neurons were recorded before and following acute and chronic methylphenidate (MPD) administration. Acute MPD exposure elicits mainly increases in...
Differential Roles of Key Brain Regions: Ventral Tegmental Area, Locus Coeruleus, Dorsal Raphe, Nucleus Accumbens, Caudate Nucleus, and Prefrontal Cortex in Regulating Response to Methylphenidate: Insights from Neuronal and Behavioral Studies in Freely Behaving Rats.
A total of 3102 neurons were recorded before and following acute and chronic methylphenidate (MPD) administration. Acute MPD exposure elicits mainly increases in neuronal and behavioral activity in dose-response characteristics. The response to chronic MPD exposure, as compared to acute 0.6, 2.5, or 10.0 mg/kg MPD administration, elicits electrophysiological and behavioral sensitization in some animals and electrophysiological and behavioral tolerance in others when the neuronal recording evaluations were performed based on the animals' behavioral responses, or amount of locomotor activity, to chronic MPD exposure. The majority of neurons recorded from those expressing behavioral sensitization responded to chronic MPD with further increases in firing rate as compared to the initial MPD responses. The majority of neurons recorded from animals expressing behavioral tolerance responded to chronic MPD with decreases in their firing rate as compared to the initial MPD exposures. Each of the six brain areas studied-the ventral tegmental area, locus coeruleus, dorsal raphe, nucleus accumbens, prefrontal cortex, and caudate nucleus (VTA, LC, DR, NAc, PFC, and CN)-responds significantly ( < 0.001) differently to MPD, suggesting that each one of the above brain areas exhibits different roles in the response to MPD. Moreover, this study demonstrates that it is essential to evaluate neuronal activity responses to psychostimulants based on the animals' behavioral responses to acute and chronic effects of the drug from several brain areas simultaneously to obtain accurate information on each area's role in response to the drug.
Topics: Animals; Methylphenidate; Prefrontal Cortex; Rats; Neurons; Caudate Nucleus; Male; Ventral Tegmental Area; Nucleus Accumbens; Behavior, Animal; Locus Coeruleus; Rats, Sprague-Dawley; Dorsal Raphe Nucleus; Central Nervous System Stimulants
PubMed: 38892125
DOI: 10.3390/ijms25115938