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Frontiers In Neuroanatomy[JOURNAL]

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Transcription factor 4 expression in the developing non-human primate brain: a comparative analysis with the mouse brain.

Burette AC, Vihma H, Smith AL … +4 more , Ozarkar SS, Bennett J, Amaral DG, Philpot BD

Front Neuroanat · 2024 · PMID 39502395 · Full text

Transcription factor 4 (TCF4) has been implicated in a range of neuropsychiatric disorders, including major depressive disorder, bipolar disorder, and schizophrenia. Mutations or deletions in TCF4 cause Pitt-Hopkins synd... Transcription factor 4 (TCF4) has been implicated in a range of neuropsychiatric disorders, including major depressive disorder, bipolar disorder, and schizophrenia. Mutations or deletions in TCF4 cause Pitt-Hopkins syndrome (PTHS), a rare neurodevelopmental disorder. A detailed understanding of its spatial expression across the developing brain is necessary for comprehending TCF4 biology and, by extension, to develop effective treatments for TCF4-associated disorders. However, most current knowledge is derived from mouse models, which are invaluable for preclinical studies but may not fully capture the complexities of human neuropsychiatric phenotypes. This study compared TCF4 expression in the developing mouse brain to its regional and cellular expression patterns in normal prenatal, neonatal, and young adult rhesus macaque brains, a species more relevant to human neurodevelopment. While the general developmental expression of TCF4 is largely conserved between macaques and mice, we saw several interspecies differences. Most notably, a distinct layered pattern of TCF4 expression was clear in the developing macaque neocortex but largely absent in the mouse brain. High TCF4 expression was seen in the inner dentate gyrus of adult mice but not in macaques. Conversely, TCF4 expression was higher in the adult macaque striatum compared to the mouse striatum. Further research is needed to show the significance of these interspecies differences. Still, they underscore the importance of integrating rodent and primate studies to comprehensively understand TCF4 function and its implications for human disorders. Moreover, the primate-specific expression patterns of TCF4 will inform genetic and other therapeutic strategies to treat TCF4-associated disorders.

Editorial: The four streams of the prefrontal cortex.

Ben Shalom D

Front Neuroanat · 2024 · PMID 39479367 · Full text

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Algal polysaccharides: new perspectives for the treatment of basal ganglia neurodegenerative diseases.

Lucena AMM, de Souza Lucena EE, Neto SPD … +3 more , Nobre LTDB, Rocha HAO, Câmara RBG

Front Neuroanat · 2024 · PMID 39479366 · Full text

The objective of this review was to verify the therapeutic effect of polysaccharides derived from algae in neurodegenerative disease models involving the basal ganglia. To achieve this goal, a literature search was condu... The objective of this review was to verify the therapeutic effect of polysaccharides derived from algae in neurodegenerative disease models involving the basal ganglia. To achieve this goal, a literature search was conducted in PubMed, Science Direct, Scopus, Web of Science, Embase, and Google Scholar databases. The descriptors "neuroprotective or neural regenerative or immunomodulatory activity or neuroprotection," "polysaccharide or carbohydrate or carbohydrate polymers," "marine algae or seaweed," and "basal ganglia" according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) methodology were used. This methodology involved the steps of searching, pre-selection, and inclusion of articles. A total of 737 records were identified. Following the data analysis, 698 studies were excluded, resulting in a final sample of 8 studies. Species such as , , , , , and have demonstrated significant neuroprotective effects. This review suggests that polysaccharides derived from marine algae possess therapeutic potential for neuroprotection, modulation of inflammation, and amelioration of functional deficits. Their use in neurodegenerative disease models warrants further consideration.

Deep peroneal neuropathy induced by prolonged squatting: a case report.

Jo HS, Kim KH, Song MK … +3 more , Park HK, Choi IS, Han JY

Front Neuroanat · 2024 · PMID 39445169 · Full text

Prolonged squatting is a well-documented cause of common peroneal neuropathy, wherein the common peroneal nerve is thought to be compressed between the biceps femoris tendon and the lateral head of the gastrocnemius musc... Prolonged squatting is a well-documented cause of common peroneal neuropathy, wherein the common peroneal nerve is thought to be compressed between the biceps femoris tendon and the lateral head of the gastrocnemius muscle or the fibular head. However, deep peroneal neuropathy resulting from prolonged squatting has not been previously reported. We present the case of a tile installer who developed unilateral deep peroneal neuropathy following extended squatting, diagnosed through ultrasonography, which identified the bilateral division of the common peroneal nerves between the knee joint and the fibular head. This case underscores the value of ultrasonography, particularly when electrodiagnostic results are inconsistent with clinical expectations.

Therapeutic ultrasound: an innovative approach for targeting neurological disorders affecting the basal ganglia.

Singh A, Reynolds JNJ

Front Neuroanat · 2024 · PMID 39417047 · Full text

The basal ganglia are involved in motor control and action selection, and their impairment manifests in movement disorders such as Parkinson's disease (PD) and dystonia, among others. The complex neuronal circuitry of th... The basal ganglia are involved in motor control and action selection, and their impairment manifests in movement disorders such as Parkinson's disease (PD) and dystonia, among others. The complex neuronal circuitry of the basal ganglia is located deep inside the brain and presents significant treatment challenges. Conventional treatment strategies, such as invasive surgeries and medications, may have limited effectiveness and may result in considerable side effects. Non-invasive ultrasound (US) treatment approaches are becoming increasingly recognized for their therapeutic potential for reversibly permeabilizing the blood-brain barrier (BBB), targeting therapeutic delivery deep into the brain, and neuromodulation. Studies conducted on animals and early clinical trials using ultrasound as a therapeutic modality have demonstrated promising outcomes for controlling symptom severity while preserving neural tissue. These results could improve the quality of life for patients living with basal ganglia impairments. This review article explores the therapeutic frontiers of ultrasound technology, describing the brain mechanisms that are triggered and engaged by ultrasound. We demonstrate that this cutting-edge method could transform the way neurological disorders associated with the basal ganglia are managed, opening the door to less invasive and more effective treatments.

Topographic anatomy of the lateral surface of the parietal lobe and its relationship with white matter tracts.

Oğlin V, Orhun Ö, Quiñones-Hinojosa A … +7 more , Middlebrooks EH, Çevik OM, Usseli Mİ, Güdük M, Aksoy ME, Pamir MN, Bozkurt B

Front Neuroanat · 2024 · PMID 39417046 · Full text

Aim of this study was to define sulcal and gyral variations of the lateral parietal cortex and underlying white matter tracts and emphasize the importance of relationship between topographic anatomy of parietal lobe and... Aim of this study was to define sulcal and gyral variations of the lateral parietal cortex and underlying white matter tracts and emphasize the importance of relationship between topographic anatomy of parietal lobe and white matter tracts underlying it in approaches to deep parietal and atrial lesions. Twenty-eight formalin-fixed cerebral hemispheres of 14 adult cadavers were used. Ten hemispheres were dissected from lateral to medial by fiber dissection and all stages were photographed. Our anatomic findings were supported by MRI tractography. Postcentral sulcus and intraparietal sulcus were continuous in most of the cadavers (71% in right, 64% in left side). Intermediate sulcus of Jensen was in bayonet shape in 86 and 50 percent of cadavers at right and left side, respectively. The range of perpendicular distance between the meeting point and interhemispheric fissure was 2.5-4.9 cm in right and 2.8-4.2 cm in left hemisphere whereas the range of distance between meeting point and the sylvian fissure was 3-6 cm and 2.5-5.6 in left and right hemispheres, respectively. When the meeting point was located more laterally, the probability of damaging the arcuate fasciculus and superior longitudinal fasciculus II during dissection was increased. We also found that the intraparietal sulcus and intermediate sulcus of Jensen were associated with the superior longitudinal fasciculus II, middle longitudinal fasciculus, inferior frontooccipital fasciculus, tapetum, and optic radiation. These variations and their relation to subcortical tracts should be considered in atrium and deep parietal lobe surgeries.

Cajal's contributions to vestibular research.

Espinosa-Sanchez JM, Perez-Fernandez N, de Castro F … +1 more , Batuecas-Caletrio A

Front Neuroanat · 2024 · PMID 39355319 · Full text

The Spanish neurohistologist Santiago Ramón y Cajal (1852-1934) is widely regarded as the father of modern Neuroscience. In addition to identifying the individuality of cells in the nervous system (the neuron theory) or... The Spanish neurohistologist Santiago Ramón y Cajal (1852-1934) is widely regarded as the father of modern Neuroscience. In addition to identifying the individuality of cells in the nervous system (the neuron theory) or the direction followed by nerve impulses (the principle of dynamic polarization), he described numerous details regarding the organization of the different structures of the nervous system. This task was compiled in his magnum opus, "Textura del Sistema Nervioso del Hombre y los Vertebrados," first published in Spanish between 1899 and 1904, and later revised and updated in French as "Histologie du système nerveux de l'homme et des vertébrés" between 1909 and 1911 for wider distribution among the international scientific community. Some of Cajal's findings are fundamental to our understanding of the anatomy and histology of the vestibular system. He depicted the nerve endings in the sensory epithelia, the structure of the vestibular nerve and Scarpa ganglion, afferent vestibular fibers, vestibular nuclei, lateral vestibulospinal tract, vestibulocerebellar connections, and the fine structure of the cerebellum. However, most of these pioneering descriptions were published years earlier in Spanish journals with limited circulation. Our study aimed to gather Cajal's findings on the vestibular system and identify his original publications. After this endeavor, we claim a place for Cajal among the founders of anatomy and histology of the vestibular system.

NECAB1-3, parvalbumin, calbindin, and calretinin in the hippocampus of the European mole.

Maliković J, Amrein I, Vinciguerra L … +2 more , Wolfer DP, Slomianka L

Front Neuroanat · 2024 · PMID 39296922 · Full text

Many calcium-binding proteins are expressed in a region-and cell-type specific manner in the mammalian hippocampus. Neuronal calcium-binding proteins (NECABs) are also expressed in hippocampal neurons, but few species ha... Many calcium-binding proteins are expressed in a region-and cell-type specific manner in the mammalian hippocampus. Neuronal calcium-binding proteins (NECABs) are also expressed in hippocampal neurons, but few species have been investigated, with partly controversial findings. We here describe NECAB1, NECAB2 and NECAB3 as well as parvalbumin, calbindin, and calretinin in the European mole, and compare staining patterns of these proteins with those in mouse and other species. While subtle differences are present, NECAB staining in the European mole was generally similar to those in mouse. Common to European moles, mice, and other species we investigated, large hilar polymorphic cells, likely to represent mossy cells, were positive for all three NECABs. NECAB1 and 2 are suitable as markers for these cells along the entire septotemporal axis of the hippocampus. In the European mole, parvalbumin, calbindin and calretinin showed traits that have been described in other species before, albeit in a unique combination. In summary, we provide the first description of distribution of these proteins in the hippocampus of the European mole. This subterranean, insectivorous, and solitary living species belongs to the Order of Eulipotyphla. Despite many similarities with other subterranean species from the rodent order in terms of lifestyle, its hippocampus is cytoarchitecturally much more elaborated than in, e.g., mole-rats. It remains an open question if the hippocampal structure of the European mole reflects evolutionary constraints or ecology. Our descriptive study highlights the diversity in hippocampal cytoarchitecture even in small mammalian species.

Mapping brain morphology to cognitive deficits: a study on PD-CRS scores in Parkinson's disease with mild cognitive impairment.

Brandão PR, Pereira DA, Grippe TC … +7 more , Bispo DDC, Maluf FB, Titze-de-Almeida R, de Almeida E Castro BM, Munhoz RP, Tavares MCH, Cardoso F

Front Neuroanat · 2024 · PMID 39206076 · Full text

BACKGROUND: The Parkinson's Disease-Cognitive Rating Scale (PD-CRS) is a widely used tool for detecting mild cognitive impairment (MCI) in Parkinson's Disease (PD) patients, however, the neuroanatomical underpinnings of... BACKGROUND: The Parkinson's Disease-Cognitive Rating Scale (PD-CRS) is a widely used tool for detecting mild cognitive impairment (MCI) in Parkinson's Disease (PD) patients, however, the neuroanatomical underpinnings of this test's outcomes require clarification. This study aims to: (a) investigate cortical volume (CVol) and cortical thickness (CTh) disparities between PD patients exhibiting mild cognitive impairment (PD-MCI) and those with preserved cognitive abilities (PD-IC); and (b) identify the structural correlates in magnetic resonance imaging (MRI) of overall PD-CRS performance, including its subtest scores, within a non-demented PD cohort. MATERIALS AND METHODS: This study involved 51 PD patients with Hoehn & Yahr stages I-II, categorized into two groups: PD-IC ( = 36) and PD-MCI ( = 15). Cognitive screening evaluations utilized the PD-CRS and the Montreal Cognitive Assessment (MoCA). PD-MCI classification adhered to the Movement Disorder Society Task Force criteria, incorporating extensive neuropsychological assessments. The interrelation between brain morphology and cognitive performance was determined using FreeSurfer. RESULTS: Vertex-wise analysis of the entire brain demonstrated a notable reduction in CVol within a 2,934 mm cluster, encompassing parietal and temporal regions, in the PD-MCI group relative to the PD-IC group. Lower PD-CRS total scores correlated with decreased CVol in the middle frontal, superior temporal, inferior parietal, and cingulate cortices. The PD-CRS subtests for Sustained Attention and Clock Drawing were associated with cortical thinning in distinct regions: the Clock Drawing subtest correlated with changes in the parietal lobe, insula, and superior temporal cortex morphology; while the PD-CRS frontal-subcortical scores presented positive correlations with CTh in the transverse temporal, medial orbitofrontal, superior temporal, precuneus, fusiform, and supramarginal regions. Additionally, PD-CRS subtests for Semantic and Alternating verbal fluency were linked to CTh changes in orbitofrontal, temporal, fusiform, insula, and precentral regions. CONCLUSION: PD-CRS performance mirrors neuroanatomical changes across extensive fronto-temporo-parietal areas, covering both lateral and medial cortical surfaces, in PD patients without dementia. The observed changes in CVol and CTh associated with this cognitive screening tool suggest their potential as surrogate markers for cognitive decline in PD. These findings warrant further exploration and validation in multicenter studies involving independent patient cohorts.

A novel approach to cytoarchitectonics: developing an objective framework for the morphological analysis of the cerebral cortex.

Prkačin MV, Petanjek Z, Banovac I

Front Neuroanat · 2024 · PMID 39188851 · Full text

INTRODUCTION: The cytoarchitectonic boundaries between cortical regions and layers are usually defined by the presence or absence of certain cell types. However, these cell types are often not clearly defined and determi... INTRODUCTION: The cytoarchitectonic boundaries between cortical regions and layers are usually defined by the presence or absence of certain cell types. However, these cell types are often not clearly defined and determining the exact boundaries of regions and layers can be challenging. Therefore, in our research, we attempted to define cortical regions and layers based on clear quantitative criteria. METHODS: We performed immunofluorescent anti-NeuN labelling on five adult human brains in three cortical regions-Brodmann areas (BA) 9, 14r, and 24. We reconstructed the cell bodies of 90,723 NeuN-positive cells and analyzed their morphometric characteristics by cortical region and layer. We used a supervised neural network prediction algorithm to classify the reconstructions into morphological cell types. We used the results of the prediction algorithm to determine the proportions of different cell types in BA9, BA14r and BA24. RESULTS: Our analysis revealed that the cytoarchitectonic descriptions of BA9, BA14r and BA24 were reflected in the morphometric measures and cell classifications obtained by the prediction algorithm. BA9 was characterized by the abundance of large pyramidal cells in layer III, BA14r was characterized by relatively smaller and more elongated cells compared to BA9, and BA24 was characterized by the presence of extremely elongated cells in layer V as well as relatively higher proportions of irregularly shaped cells. DISCUSSION: The results of the prediction model agreed well with the qualitative expected cytoarchitectonic descriptions. This suggests that supervised machine learning could aid in defining the morphological characteristics of the cerebral cortex.

Understanding subcortical projections to the lateral posterior thalamic nucleus and its subregions using retrograde neural tracing.

Nakamura H, Ohta K

Front Neuroanat · 2024 · PMID 39170852 · Full text

The rat lateral posterior thalamic nucleus (LP) is composed of the rostromedial (LPrm), lateral (LPl), and caudomedial parts, with LPrm and LPl being areas involved in information processing within the visual cortex. Nev... The rat lateral posterior thalamic nucleus (LP) is composed of the rostromedial (LPrm), lateral (LPl), and caudomedial parts, with LPrm and LPl being areas involved in information processing within the visual cortex. Nevertheless, the specific differences in the subcortical projections to the LPrm and LPl remain elusive. In this study, we aimed to reveal the subcortical regions that project axon fibers to the LPl and LPrm using a retrograde neural tracer, Fluorogold (FG). After FG injection into the LPrm or LPl, the area was visualized immunohistochemically. Retrogradely labeled neurons from the LPrm were distributed in the retina and the region from the diencephalon to the medulla oblongata. Diencephalic labeling was found in the reticular thalamic nucleus (Rt), zona incerta (ZI), ventral lateral geniculate nucleus (LGv), intergeniculate leaflet (IGL), and hypothalamus. In the midbrain, prominent labeling was found in the periaqueductal gray (PAG) and deep layers of the superior colliculus. Additionally, retrograde labeling was observed in the cerebellar and trigeminal nuclei. When injected into the LPl, several cell bodies were labeled in the visual-related regions, including the retina, LGv, IGL, and olivary pretectal nucleus (OPT), as well as in the Rt and anterior pretectal nucleus (APT). Less labeling was found in the cerebellum and medulla oblongata. When the number of retrogradely labeled neurons from the LPrm or LPl was compared as a percentage of total subcortical labeling, a larger percentage of subcortical inputs to the LPl included projections from the APT, OPT, and Rt, whereas a large proportion of subcortical inputs to the LPrm originated from the ZI, reticular formation, and PAG. These results suggest that LPrm not only has visual but also multiple sensory-and motor-related functions, whereas the LPl takes part in a more visual-specific role. This study enhances our understanding of subcortical neural circuits in the thalamus and may contribute to our exploration of the mechanisms and disorders related to sensory perception and sensory-motor integration.

Geometric morphometric analysis of the brainstem and cerebellum in Chiari I malformation.

Perera IR, Zahed M, Moriarty S … +7 more , Simmons Z, Rodriguez M, Botkin C, Dickson T, Kasper B, Fahmy K, Millard JA

Front Neuroanat · 2024 · PMID 39170851 · Full text

BACKGROUND: Chiari I malformation (CMI) is characterized by inferior descent of the cerebellar tonsils through the foramen magnum and is associated with headache and neck pain. Many morphometric research efforts have aim... BACKGROUND: Chiari I malformation (CMI) is characterized by inferior descent of the cerebellar tonsils through the foramen magnum and is associated with headache and neck pain. Many morphometric research efforts have aimed to describe CMI anatomy in the midsagittal plane using classical measurement techniques such as linear dimensions and angles. These methods are less frequently applied to parasagittal features and may fall short in quantifying more intricate anatomy with fewer distinct homologous landmarks. METHODS: Landmark-based geometric morphometric techniques were used to asses CMI morphology in five anatomical planes of interest. RESULTS: Significant shape differences between CMI and age/sex-matched controls were found in the midsagittal (Pseudo- = 5.4841,  = 0.001) and axial planes through the rostral medulla (Pseudo- = 7.6319,  = 0.001). In addition to tonsillar descent, CMI principal component 1 (PC1) scores in the midsagittal protocol were associated with marked anterior concavity of the brainstem and generalized verticality of the cerebellum with anterior rotation of its anterior lobe. In the axial medulla/cerebellum protocol, CMI PC1 scores were associated with greater anterior-posterior (A-P) dimension with loss of medial-lateral (M-L) dimension. DISCUSSION: These results suggest that CMI is associated with greater curvature of the brainstem and spinal cord, which may perturb normal neural activities and disrupt cerebrospinal fluid movements. Previous reports on the A-P diameter of the posterior fossa in CMI have conflicted; our findings of greater A-P cerebellar dimensionality with concomitant loss of width alludes to the possibility that more caudal aspects of the posterior cranial fossa are more bowl-like (homogenous in axial dimensions) and less trough-like or elongated in the M-L direction.

The arrangements of the microvasculature and surrounding glial cells are linked to blood-brain barrier formation in the cerebral cortex.

Shigemoto-Mogami Y, Nakayama-Kitamura K, Sato K

Front Neuroanat · 2024 · PMID 39170850 · Full text

The blood-brain barrier (BBB) blocks harmful substances from entering the brain and dictates the central nervous system (CNS)-specific pharmacokinetics. Recent studies have shown that perivascular astrocytes and microgli... The blood-brain barrier (BBB) blocks harmful substances from entering the brain and dictates the central nervous system (CNS)-specific pharmacokinetics. Recent studies have shown that perivascular astrocytes and microglia also control BBB functions, however, information about the formation of BBB glial architecture remains scarce. We investigated the time course of the formation of BBB glial architecture in the rat brain cerebral cortex using Evans blue (EB) and tissue fixable biotin (Sulfo-NHS Biotin). The extent of the leakage into the brain parenchyma showed that the BBB was not formed at postnatal Day 4 (P4). The BBB gradually strengthened and reached a plateau at P15. We then investigated the changes in the configurations of blood vessels, astrocytes, and microglia with age by 3D image reconstruction of the immunohistochemical data. The endfeet of astrocytes covered the blood vessels, and the coverage rate rapidly increased after birth and reached a plateau at P15. Interestingly, microglia were also in contact with the capillaries, and the coverage rate was highest at P15 and stabilized at P30. It was also clarified that the microglial morphology changed from the amoeboid type to the ramified type, while the areas of the respective contact sites became smaller during P4 and P15. These results suggest that the perivascular glial architecture formation of the rat BBB occurs from P4 to P15 because the paracellular transport and the arrangements of perivascular glial cells at P15 are totally the same as those of P30. In addition, the contact style of perivascular microglia dramatically changed during P4-P15.

Triangular fossa of the third cerebral ventricle - an original 3D model and morphometric study.

Nedelcu AH, Lupu VV, Lupu A … +9 more , Tepordei RT, Ioniuc I, Stan CI, Vicoleanu SAP, Haliciu AM, Statescu G, Ursaru M, Danielescu C, Tarniceriu CC

Front Neuroanat · 2024 · PMID 39135984 · Full text

INTRODUCTION: The triangular recess (TR), also called triangular fossa or represents the anterior extension of the diencephalic ventricle, located between the anterior columns of the fornix and the anterior white commis... INTRODUCTION: The triangular recess (TR), also called triangular fossa or represents the anterior extension of the diencephalic ventricle, located between the anterior columns of the fornix and the anterior white commissure. Over time, this structure of the third cerebral ventricle generated many disputes. While some anatomists support its presence, others have opposite opinions, considering that it only becomes visible under certain conditions. The aim of the study is to demonstrate the tangible structure of the triangular recess. Secondly, the quantitative analysis allowed us to establish an anatomical morphometric standard, as well as the deviations from the standard. MATERIALS AND METHODS: Our study is both a quantitative and a qualitative evaluation of the triangular fossa. We dissected 100 non-neurological adult brains, which were fixed in 10% formaldehyde solution for 10 weeks. The samples are part of the collection of the Institute of Anatomy, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi. We highlighted the triangular fossa by performing dissections in two stages at the level of the roof of the III ventricle. RESULTS: The qualitative analysis is a re-evaluation of the classical data concerning the anatomy of the fossa triangularis. We proposed an original 3D model of the triangular recess in which we described a superficial part called vestibule and a deep part called . We measured the sides of the communication between the two proposed segments, as well as the communication with the III ventricle. By applying the Heron's formula, we calculated the area of the two communications. Statistical evaluations have shown that these communications are higher than they are wide. In addition, there is a statistical difference between the surfaces of the two communications: 34.07 mm ± 7.01 vs. 271.43 mm ± 46.36 ( = 0.001). CONCLUSION: The outcome of our study is both qualitative and quantitative. Firstly, we demonstrated the existence of the triangular fossa and we conceived a spatial division of this structure. Secondly, the measurements carried out establish an anatomo-morphometric norm of the triangular recess, which is useful in assessing the degree of hydrocephalus during the third endoscopic ventriculoscopy.

Anatomical topology of extrahippocampal projections from dorsoventral CA pyramidal neurons in mice.

Lee J, Park J, Jeong M … +3 more , Oh SJ, Yoon JH, Oh YS

Front Neuroanat · 2024 · PMID 39108929 · Full text

The hippocampus primarily functions through a canonical trisynaptic circuit, comprised of dentate granule cells and CA1-CA3 pyramidal neurons (PNs), which exhibit significant heterogeneity along the dorsoventral axis. Am... The hippocampus primarily functions through a canonical trisynaptic circuit, comprised of dentate granule cells and CA1-CA3 pyramidal neurons (PNs), which exhibit significant heterogeneity along the dorsoventral axis. Among these, CA PNs are known to project beyond the hippocampus into various limbic areas, critically influencing cognitive and affective behaviors. Despite accumulating evidence of these extrahippocampal projections, the specific topological patterns-particularly variations among CA PN types and between their dorsal and ventral subpopulations within each type-remain to be fully elucidated. In this study, we utilized cell type-specific Cre mice injected with fluorescent protein-expressing AAVs to label each CA PN type distinctly. This method further enabled the dual-fluorescence labeling of dorsal and ventral subpopulations using EGFP and tdTomato, respectively, allowing a comprehensive comparison of their axonal projections in an animal. Our findings demonstrate that CA1 PNs predominantly form unilateral projections to the frontal cortex (PFC), amygdala (Amy), nucleus accumbens (NAc), and lateral septum (LS), unlike CA2 and CA3 PNs making bilateral innervation to the LS only. Moreover, the innervation patterns especially within LS subfields differ according to the CA PN type and their location along the dorsoventral axis of the hippocampus. This detailed topographical mapping provides the neuroanatomical basis of the underlying functional distinctions among CA PN types.

Cajal and his love for Nature: a sentimental essence in the legacy of neurosciences.

Garrido E

Front Neuroanat · 2024 · PMID 39091637 · Full text

Santiago Ramón y Cajal (1852-1934) revolutionized the branches of neuroscience in a forceful way, and he did it with extreme delicacy and candor. His scientific writings and drawings are full of allusions to Nature, a fa... Santiago Ramón y Cajal (1852-1934) revolutionized the branches of neuroscience in a forceful way, and he did it with extreme delicacy and candor. His scientific writings and drawings are full of allusions to Nature, a fact that demonstrates how he saw, understood and enjoyed it with exquisite sensitivity and pressing emotion. Neuroscience awakened in him the utmost curiosity to delve into the powerful mysteries of the mind, and neurohistology allowed him to satisfy his deepest concerns for fascinating scenarios, a desire not sufficiently fulfilled throughout the fields, mountains and forests of his childhood and youth. Through that wonderful microscopic world Cajal changed the size of the dreamed landscapes but not the dimension of the longed-for adventures. Exploring and entering unknown paths he unraveled some of the greatest enigmas that the nervous system hid, but he would do so with a deep feeling toward the infinite beauty that Nature itself offered him. In short, Nature was the vital axis of Cajal's overwhelming and complex personality, his most genuine essence and the inexhaustible source of inspiration where he poured his imagination and fantasy. He became a vocational adventurer, an insatiable explorer, a talented artist and an exquisite humanist. An eminently romantic soul who knew how to link Nature and Neuroscience with unconditional and perpetual emotionality.

Differently increased volumes of multiple brain areas in mutant mice following various drug treatments.

Antipova V, Heimes D, Seidel K … +12 more , Schulz J, Schmitt O, Holzmann C, Rolfs A, Bidmon HJ, González de San Román Martín E, Huesgen PF, Amunts K, Keiler J, Hammer N, Witt M, Wree A

Front Neuroanat · 2024 · PMID 39081805 · Full text

BACKGROUND: Niemann-Pick disease type C1 (NPC1, MIM 257220) is a heritable lysosomal storage disease characterized by a progressive neurological degeneration that causes disability and premature death. A murine model of... BACKGROUND: Niemann-Pick disease type C1 (NPC1, MIM 257220) is a heritable lysosomal storage disease characterized by a progressive neurological degeneration that causes disability and premature death. A murine model of displays a rapidly progressing form of Npc1 disease, which is characterized by weight loss, ataxia, and increased cholesterol storage. mice receiving a combined therapy (COMBI) of miglustat (MIGLU), the neurosteroid allopregnanolone (ALLO) and the cyclic oligosaccharide 2-hydroxypropyl-β-cyclodextrin (HPßCD) showed prevention of Purkinje cell loss, improved motor function and reduced intracellular lipid storage. Although therapy of mice with COMBI, MIGLU or HPßCD resulted in the prevention of body weight loss, reduced total brain weight was not positively influenced. METHODS: In order to evaluate alterations of different brain areas caused by pharmacotherapy, fresh volumes (volumes calculated from the volumes determined from paraffin embedded brain slices) of various brain structures in sham- and drug-treated wild type and mutant mice were measured using stereological methods. RESULTS: In the wild type mice, the volumes of investigated brain areas were not significantly altered by either therapy. Compared with the respective wild types, fresh volumes of specific brain areas, which were significantly reduced in sham-treated mice, partly increased after the pharmacotherapies in all treatment strategies; most pronounced differences were found in the CA1 area of the hippocampus and in olfactory structures. DISCUSSION: Volumes of brain areas of mice were not specifically changed in terms of functionality after administering COMBI, MIGLU, or HPßCD. Measurements of fresh volumes of brain areas in mice could monitor region-specific changes and response to drug treatment that correlated, in part, with behavioral improvements in this mouse model.

Intra-articular sprouting of nociceptors accompanies progressive osteoarthritis: comparative evidence in four murine models.

Obeidat AM, Ishihara S, Li J … +7 more , Adamczyk NS, Lammlin L, Junginger L, Maerz T, Miller RJ, Miller RE, Malfait AM

Front Neuroanat · 2024 · PMID 39076825 · Full text

OBJECTIVE: Knee joints are densely innervated by nociceptors. In human knees and rodent models, sprouting of nociceptors has been reported in late-stage osteoarthritis (OA). Here, we sought to describe progressive nocice... OBJECTIVE: Knee joints are densely innervated by nociceptors. In human knees and rodent models, sprouting of nociceptors has been reported in late-stage osteoarthritis (OA). Here, we sought to describe progressive nociceptor remodeling in early and late-stage OA, using four distinct experimental mouse models. METHODS: Sham surgery, destabilization of the medial meniscus (DMM), partial meniscectomy (PMX), or non-invasive anterior cruciate ligament rupture (ACLR) was performed in the right knee of 10-12-week old male C57BL/6 Na1.8-tdTomato mice. Mice were euthanized (1) 4, 8 or 16 weeks after DMM or sham surgery; (2) 4 or 12 weeks after PMX or sham; (3) 1 or 4 weeks after ACLR injury or sham. Additionally, a cohort of naïve male wildtype mice was evaluated at age 6 and 24 months. Mid-joint cryosections were assessed qualitatively and quantitatively for Na1.8+ or PGP9.5+ innervation. Cartilage damage, synovitis, and osteophytes were assessed. RESULTS: Progressive OA developed in the medial compartment after DMM, PMX, and ACLR. Synovitis and associated neo-innervation of the synovium by nociceptors peaked in early-stage OA. In the subchondral bone, channels containing sprouting nociceptors appeared early, and progressed with worsening joint damage. Two-year old mice developed primary OA in the medial and the lateral compartment, accompanied by nociceptor sprouting in the synovium and the subchondral bone. All four models showed increased nerve signal in osteophytes. CONCLUSION: These findings suggest that anatomical neuroplasticity of nociceptors is intrinsic to OA pathology. The detailed description of innervation of the OA joint and its relationship to joint damage might help in understanding OA pain.

The parasympathetic and sensory innervation of the proximal and distal colon in male mice.

Wang L, Taché Y

Front Neuroanat · 2024 · PMID 39045348 · Full text

INTRODUCTION: The distributions of extrinsic neurons innervating the colon show differences in experimental animals from humans, including the vagal and spinal parasympathetic innervation to the distal colon. The neuroan... INTRODUCTION: The distributions of extrinsic neurons innervating the colon show differences in experimental animals from humans, including the vagal and spinal parasympathetic innervation to the distal colon. The neuroanatomical tracing to the mouse proximal colon has not been studied in details. This study aimed to trace the locations of extrinsic neurons projecting to the mouse proximal colon compared to the distal colon using dual retrograde tracing. METHODS: The parasympathetic and sensory neurons projecting to colon were assessed using Cholera Toxin subunit B conjugated to Alexa-Fluor 488 or 555 injected in the proximal and distal colon of the same mice. RESULTS: Retrograde tracing from the proximal and distal colon labeled neurons in the dorsal motor nucleus of the vagus (DMV) and the nodose ganglia, while the tracing from the distal colon did not label the parasympathetic neurons in the lumbosacral spinal cord at L6-S1. Neurons in the pelvic ganglia which were cholinergic projected to the distal colon. There were more neurons in the DMV and nodose ganglia projecting to the proximal than distal colon. The right nodose ganglion had a higher number of neurons than the left ganglion innervating the proximal colon. In the dorsal root ganglia (DRG), the highest number of neurons traced from the distal colon were at L6, and those from the proximal colon at T12. DRG neurons projected closely to the cholinergic neurons in the intermediolateral column of L6 spinal cord. Small percentages of neurons with dual projections to both the proximal and distal colon existed in the DMV, nodose ganglia and DRG. We also observed long projecting neurons traced from the caudal distal colon to the transverse and proximal colon, some of which were calbindin immunoreactive, while there were no retrogradely labeled neurons traced from the proximal to distal colon. DISCUSSION: These data demonstrated that the vagal motor and motor and sensory neurons innervate both the proximal and distal colon in mice, and the autonomic neurons in the intermediate zone of the lumbosacral spinal cord do not project directly to the mouse colon, which differs from that in humans.

Communicating pain: emerging axonal signaling in peripheral neuropathic pain.

Testa L, Dotta S, Vercelli A … +1 more , Marvaldi L

Front Neuroanat · 2024 · PMID 39045347 · Full text

Peripheral nerve damage often leads to the onset of neuropathic pain (NeuP). This condition afflicts millions of people, significantly burdening healthcare systems and putting strain on families' financial well-being. He... Peripheral nerve damage often leads to the onset of neuropathic pain (NeuP). This condition afflicts millions of people, significantly burdening healthcare systems and putting strain on families' financial well-being. Here, we will focus on the role of peripheral sensory neurons, specifically the Dorsal Root Ganglia neurons (DRG neurons) in the development of NeuP. After axotomy, DRG neurons activate regenerative signals of axons-soma communication to promote a gene program that activates an axonal branching and elongation processes. The results of a neuronal morphological cytoskeleton change are not always associated with functional recovery. Moreover, any axonal miss-targeting may contribute to NeuP development. In this review, we will explore the epidemiology of NeuP and its molecular causes at the level of the peripheral nervous system and the target organs, with major focus on the neuronal cross-talk between intrinsic and extrinsic factors. Specifically, we will describe how failures in the neuronal regenerative program can exacerbate NeuP.
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