Frontiers in Neuroanatomy

A novel approach to cytoarchitectonics: developing an objective framework for the morphological analysis of the cerebral cortex
Prkačin MV, Petanjek Z and Banovac I
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.
Understanding subcortical projections to the lateral posterior thalamic nucleus and its subregions using retrograde neural tracing
Nakamura H and Ohta K
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.
NECAB1-3, parvalbumin, calbindin, and calretinin in the hippocampus of the European mole
Maliković J, Amrein I, Vinciguerra L, Wolfer DP and Slomianka L
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, Bispo DDC, Maluf FB, Titze-de-Almeida R, de Almeida E Castro BM, Munhoz RP, Tavares MCH and Cardoso F
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.
Cajal and his love for Nature: a sentimental essence in the legacy of neurosciences
Garrido E
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.
Parkinson's disease models and death signaling: what do we know until now?
Pedrão LFAT, Medeiros POS, Leandro EC and Falquetto B
Parkinson's disease (PD) is the second neurodegenerative disorder most prevalent in the world, characterized by the loss of dopaminergic neurons in the Substantia Nigra (SN). It is well known for its motor and non-motor symptoms including bradykinesia, resting tremor, psychiatric, cardiorespiratory, and other dysfunctions. Pathological apoptosis contributes to a wide variety of diseases including PD. Various insults and/or cellular phenotypes have been shown to trigger distinct signaling events leading to cell death in neurons affected by PD. The intrinsic or mitochondrial pathway, inflammatory or oxidative stress-induced extrinsic pathways are the main events associated with apoptosis in PD-related neuronal loss. Although SN is the main brain area studied so far, other brain nuclei are also affected by the disease leading to non-classical motor symptoms as well as non-motor symptoms. Among these, the respiratory symptoms are often overlooked, yet they can cause discomfort and may contribute to patients shortened lifespan after disease diagnosis. While animal and models are frequently used to investigate the mechanisms involved in the pathogenesis of PD in both the SN and other brain regions, these models provide only a limited understanding of the disease's actual progression. This review offers a comprehensive overview of some of the most studied forms of cell death, including recent research on potential treatment targets for these pathways. It highlights key findings and milestones in the field, shedding light on the potential role of understanding cell death in the prevention and treatment of the PD. Therefore, unraveling the connection between these pathways and the notable pathological mechanisms observed during PD progression could enhance our comprehension of the disease's origin and provide valuable insights into potential molecular targets for the developing therapeutic interventions.
Deep peroneal neuropathy induced by prolonged squatting: a case report
Jo HS, Kim KH, Song MK, Park HK, Choi IS and Han JY
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.
Triangular fossa of the third cerebral ventricle - an original 3D model and morphometric study
Nedelcu AH, Lupu VV, Lupu A, Tepordei RT, Ioniuc I, Stan CI, Vicoleanu SAP, Haliciu AM, Statescu G, Ursaru M, Danielescu C and Tarniceriu CC
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.
Editorial: The four streams of the prefrontal cortex
Ben Shalom D
Algal polysaccharides: new perspectives for the treatment of basal ganglia neurodegenerative diseases
Lucena AMM, de Souza Lucena EE, Neto SPD, Nobre LTDB, Rocha HAO and Câmara RBG
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.
Transcription factor 4 expression in the developing non-human primate brain: a comparative analysis with the mouse brain
Burette AC, Vihma H, Smith AL, Ozarkar SS, Bennett J, Amaral DG and Philpot BD
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: 15 years of frontiers in neuroanatomy: the circuits behind the visual cortex
Takahata T and Ding SL
From Sudoscan to bedside: theory, modalities, and application of electrochemical skin conductance in medical diagnostics
Vittrant B, Ayoub H and Brunswick P
The human body has two main types of sweat glands: apocrine and eccrine. Eccrine glands are widely distributed across the skin, including areas with hair. While the eccrine glands on palms and soles help improve grip, those on the rest of the body primarily aid in thermoregulation. Sudomotor function, which controls sweating, is regulated by the sympathetic division of the autonomic nervous system through cholinergic and adrenergic pathways. The activation of eccrine glands involves intricate processes, including neurotransmitter binding, ion channel modulation, and voltage generation. Sudoscan technology utilizes electrochemical skin conductance (ESC) to non-invasively measure sudomotor function. This method, which has been standardized for accuracy, has established normative benchmarks and has proven reliable across diverse populations. Sudoscan's diagnostic performance is comparable to invasive methods such as intraepidermal nerve fiber density testing, making it a valuable tool for diagnosing small fiber neuropathy. Moreover, it has been shown to correlate with corneal nerve fiber length, providing insights into various neuropathic conditions. Compared to traditional sudomotor function tests, Sudoscan proves superior in terms of its accessibility, simplicity, and reliability, with the potential to replace or complement existing diagnostic methods. It is important to differentiate ESC, as measured by Sudoscan, from other skin conductance measures, such as galvanic skin response (GSR) or electrodermal activity (EDA). Although these methods share a common physiological principle, ESC is specifically designed for diagnosing sudomotor function, unlike GSR/EDA, which is typically used for continuous monitoring. Sudoscan's success has led to its integration into consumer health devices, such as the BodyScan from Withings, showcasing its versatility beyond clinical settings. Future research may explore ESC applications in diverse medical fields, leveraging real-world data from integrated consumer devices. Collaborative efforts between researchers and engineers promise to offer new insights into sudomotor function and its implications for broader health monitoring. This study provides a comprehensive overview of ESC, including topics such as eccrine gland physiology, sudomotor function, Sudoscan technology, normative benchmarks, diagnostic comparisons, and potential future applications.
Geometric morphometric analysis of the brainstem and cerebellum in Chiari I malformation
Perera IR, Zahed M, Moriarty S, Simmons Z, Rodriguez M, Botkin C, Dickson T, Kasper B, Fahmy K and Millard JA
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.
Therapeutic ultrasound: an innovative approach for targeting neurological disorders affecting the basal ganglia
Singh A and Reynolds JNJ
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.
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 and Sato K
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.
Topographic anatomy of the lateral surface of the parietal lobe and its relationship with white matter tracts
Oğlin V, Orhun Ö, Quiñones-Hinojosa A, Middlebrooks EH, Çevik OM, Usseli Mİ, Güdük M, Aksoy ME, Pamir MN and Bozkurt B
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.
Anatomical topology of extrahippocampal projections from dorsoventral CA pyramidal neurons in mice
Lee J, Park J, Jeong M, Oh SJ, Yoon JH and Oh YS
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's contributions to vestibular research
Espinosa-Sanchez JM, Perez-Fernandez N, de Castro F and Batuecas-Caletrio A
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.
Differently increased volumes of multiple brain areas in mutant mice following various drug treatments
Antipova V, Heimes D, Seidel K, 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 and Wree A
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.
Anatomical study of single incision contralateral C7 nerve transfer through subdural pathway
Yao L, Yan Z, Wang X, Gu J, Liu H and Zhang H
To explore the feasibility of single incision C7 nerve transfer surgery through the subarachnoid pathway on the healthy side through anatomical research.