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Domingo Sánchez y Sánchez (1860-1947): Cajal's man on the nervous system of invertebrates.

Serrano-Herrera A, Espinosa-Sanchez JM

Front Neuroanat · 2023 · PMID 38264082 · Full text

UNLABELLED: Domingo Sánchez y Sánchez (1860-1947), a distinguished disciple of Santiago Ramón y Cajal, played a fundamental role in the Spanish School of Neurohistology through the meticulous use of diverse staining and... UNLABELLED: Domingo Sánchez y Sánchez (1860-1947), a distinguished disciple of Santiago Ramón y Cajal, played a fundamental role in the Spanish School of Neurohistology through the meticulous use of diverse staining and microscopic techniques in the study of the histology and physiology of the invertebrate nervous system, generating valuable contributions that were recognized and cited by the scientific community. His research covered a wide range of areas: he was initially an anthropologist and zoologist, later earning a doctorate in Medicine and specializing in the neurohistology of invertebrates, including the detailed study of the retina and nerve centers of insects, and the discovery of histolysis in nerve centers of insect larvae during metamorphosis, challenging scientific paradigms of the time. Furthermore, Sánchez's work on the neurofibrils of insects was crucial in supporting Cajal's neuronal theory and refuting Bethe and Apathy's reticularist hypothesis. Additionally, he also made preliminary observations of the Golgi apparatus, the lysosomal system, the endoplasmic reticulum, and the sarcoplasmic reticulum of skeletal muscles (Cajal-Fusari network). Domingo Sánchez y Sánchez's exceptional scientific research and contributions to neurohistology in 20th century Spain continue to serve as a significant legacy. LIFE SCIENCE IDENTIFIERS: : urn:lsid:zoobank.org:act:9082C709-6347-4768-A0DC-27DC44400CB2: urn:lsid:zoobank.org:act:9099927E-24DF-4F89-B352-6B7902CD4A38.

Micropopulation mapping of the mouse parafascicular nucleus connections reveals diverse input-output motifs.

Gonzalo-Martín E, Alonso-Martínez C, Sepúlveda LP … +1 more , Clasca F

Front Neuroanat · 2023 · PMID 38260117 · Full text

INTRODUCTION: In primates, including humans, the centromedian/parafascicular (CM-Pf) complex is a key thalamic node of the basal ganglia system. Deep brain stimulation in CM-Pf has been applied for the treatment of motor... INTRODUCTION: In primates, including humans, the centromedian/parafascicular (CM-Pf) complex is a key thalamic node of the basal ganglia system. Deep brain stimulation in CM-Pf has been applied for the treatment of motor disorders such as Parkinson's disease or Tourette syndrome. Rodents have become widely used models for the study of the cellular and genetic mechanisms of these and other motor disorders. However, the equivalence between the primate CM-Pf and the nucleus regarded as analogous in rodents (Parafascicular, Pf) remains unclear. METHODS: Here, we analyzed the neurochemical architecture and carried out a brain-wide mapping of the input-output motifs in the mouse Pf at micropopulation level using anterograde and retrograde labeling methods. Specifically, we mapped and quantified the sources of cortical and subcortical input to different Pf subregions, and mapped and compared the distribution and terminal structure of their axons. RESULTS: We found that projections to Pf arise predominantly (>75%) from the cerebral cortex, with an unusually strong (>45%) Layer 5b component, which is, in part, contralateral. The intermediate layers of the superior colliculus are the main subcortical input source to Pf. On its output side, Pf neuron axons predominantly innervate the striatum. In a sparser fashion, they innervate other basal ganglia nuclei, including the subthalamic nucleus (STN), and the cerebral cortex. Differences are evident between the lateral and medial portions of Pf, both in chemoarchitecture and in connectivity. Lateral Pf axons innervate territories of the striatum, STN and cortex involved in the sensorimotor control of different parts of the contralateral hemibody. In contrast, the mediodorsal portion of Pf innervates oculomotor-limbic territories in the above three structures. DISCUSSION: Our data thus indicate that the mouse Pf consists of several neurochemically and connectively distinct domains whose global organization bears a marked similarity to that described in the primate CM-Pf complex.

Revisiting the two rhythm generators for respiration in lampreys.

Missaghi K, Le Gal JP, Mercier J … +6 more , Grover M, Beauséjour PA, Chartré S, Messihad O, Auclair F, Dubuc R

Front Neuroanat · 2023 · PMID 38250023 · Full text

In lampreys, respiration consists of a fast and a slow rhythm. This study was aimed at characterizing both anatomically and physiologically the brainstem regions involved in generating the two rhythms. The fast rhythm ge... In lampreys, respiration consists of a fast and a slow rhythm. This study was aimed at characterizing both anatomically and physiologically the brainstem regions involved in generating the two rhythms. The fast rhythm generator has been located by us and others in the rostral hindbrain, rostro-lateral to the trigeminal motor nucleus. More recently, this was challenged by researchers reporting that the fast rhythm generator was located more rostrally and dorsomedially, in a region corresponding to the mesencephalic locomotor region. These contradictory observations made us re-examine the location of the fast rhythm generator using anatomical lesions and physiological recordings. We now confirm that the fast respiratory rhythm generator is in the rostro-lateral hindbrain as originally described. The slow rhythm generator has received less attention. Previous studies suggested that it was composed of bilateral, interconnected rhythm generating regions located in the caudal hindbrain, with ascending projections to the fast rhythm generator. We used anatomical and physiological approaches to locate neurons that could be part of this slow rhythm generator. Combinations of unilateral injections of anatomical tracers, one in the fast rhythm generator area and another in the lateral tegmentum of the caudal hindbrain, were performed to label candidate neurons on the non-injected side of the lateral tegmentum. We found a population of neurons extending from the facial to the caudal vagal motor nuclei, with no clear clustering in the cell distribution. We examined the effects of stimulating different portions of the labeled population on the respiratory activity. The rostro-caudal extent of the population was arbitrarily divided in three portions that were each stimulated electrically or chemically. Stimulation of either of the three sites triggered bursts of discharge characteristic of the slow rhythm, whereas inactivating any of them stopped the slow rhythm. Substance P injected locally in the lateral tegmentum accelerated the slow respiratory rhythm in a caudal hindbrain preparation. Our results show that the fast respiratory rhythm generator consists mostly of a population of neurons rostro-lateral to the trigeminal motor nucleus, whereas the slow rhythm generator is distributed in the lateral tegmentum of the caudal hindbrain.

Age-related changes in the primary auditory cortex of newborn, adults and aging bottlenose dolphins () are located in the upper cortical layers.

Graïc JM, Corain L, Finos L … +7 more , Vadori V, Grisan E, Gerussi T, Orekhova K, Centelleghe C, Cozzi B, Peruffo A

Front Neuroanat · 2023 · PMID 38250022 · Full text

INTRODUCTION: The auditory system of dolphins and whales allows them to dive in dark waters, hunt for prey well below the limit of solar light absorption, and to communicate with their conspecific. These complex behavior... INTRODUCTION: The auditory system of dolphins and whales allows them to dive in dark waters, hunt for prey well below the limit of solar light absorption, and to communicate with their conspecific. These complex behaviors require specific and sufficient functional circuitry in the neocortex, and vicarious learning capacities. Dolphins are also precocious animals that can hold their breath and swim within minutes after birth. However, diving and hunting behaviors are likely not innate and need to be learned. Our hypothesis is that the organization of the auditory cortex of dolphins grows and mature not only in the early phases of life, but also in adults and aging individuals. These changes may be subtle and involve sub-populations of cells specificall linked to some circuits. METHODS: In the primary auditory cortex of 11 bottlenose dolphins belonging to three age groups (calves, adults, and old animals), neuronal cell shapes were analyzed separately and by cortical layer using custom computer vision and multivariate statistical analysis, to determine potential minute morphological differences across these age groups. RESULTS: The results show definite changes in interneurons, characterized by round and ellipsoid shapes predominantly located in upper cortical layers. Notably, neonates interneurons exhibited a pattern of being closer together and smaller, developing into a more dispersed and diverse set of shapes in adulthood. DISCUSSION: This trend persisted in older animals, suggesting a continuous development of connections throughout the life of these marine animals. Our findings further support the proposition that thalamic input reach upper layers in cetaceans, at least within a cortical area critical for their survival. Moreover, our results indicate the likelihood of changes in cell populations occurring in adult animals, prompting the need for characterization.

Ontogenetic changes in the tyrosine hydroxylase immunoreactive preoptic area in the small-spotted catshark (L., 1758) females: catecholaminergic involvement in sexual maturation.

Porceddu R, Porcu C, Mulas G … +2 more , Spiga S, Follesa MC

Front Neuroanat · 2023 · PMID 38239387 · Full text

INTRODUCTION: The catecholaminergic component of the brain-pituitary-gonadal axis, which mediates the influence of external and internal stimuli on the central nervous system and gonad development in vertebrates, is larg... INTRODUCTION: The catecholaminergic component of the brain-pituitary-gonadal axis, which mediates the influence of external and internal stimuli on the central nervous system and gonad development in vertebrates, is largely unexplored in Chondrichthyes. We considered (L., 1758) females as a model for this vertebrate's class, to assess the involvement of the catecholaminergic system of the brain in its reproduction. Along the reproductive cycle, we characterized and evaluated differences in somata morphometry and the number of putative catecholaminergic neurons in two brain nuclei: the periventricular preoptic nucleus, hypothesized to be a positive control for ovarian development, and the suprachiasmatic nucleus, examined as a negative control. MATERIALS AND METHODS: 16 wild females were sampled and grouped in maturity stages (immature, maturing, mature, and mature egg-laying). The ovary was histologically processed for the qualitative description of maturity stages. Anti-tyrosine hydroxylase immunofluorescence was performed on the diencephalic brain sections. The immunoreactive somata were investigated for morphometry and counted using the optical fractionator method, throughout the confocal microscopy. RESULTS AND DISCUSSIONS: Qualitative and quantitative research confirmed two separate populations of immunoreactive neurons. The modifications detected in the preoptic nucleus revealed that somata were more numerous, significantly smaller in size, and more excitable during the maturing phase but decreased, becoming slightly bigger and less excitable in the egg-laying stage. This may indicate that the catecholaminergic preoptic nucleus is involved in the control of reproduction, regulating both the onset of puberty and the imminent spawning. In contrast, somata in the suprachiasmatic nucleus grew in size and underwent turnover in morphometry, increasing the total number from the immature-virgin to maturing stage, with similar values in the more advanced maturity stages. These changes were not linked to a reproductive role. These findings provide new valuable information on Chondrichthyes, suggesting the existence of an additional brain system implicated in the integration of internal and environmental cues for reproduction.

Editorial: Interactions between the mammalian main and accessory olfactory systems, volume II.

Larriva-Sahd J, Sanchez-Quinteiro P

Front Neuroanat · 2023 · PMID 38169707 · Full text

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Increase of glutamate in satellite glial cells of the trigeminal ganglion in a rat model of craniofacial neuropathic pain.

Cho YS, Mah W, Youn DH … +5 more , Kim YS, Ko HG, Bae JY, Kim YS, Bae YC

Front Neuroanat · 2023 · PMID 38164516 · Full text

INTRODUCTION: Satellite glial cells (SGCs) that envelop the cell bodies of neurons in sensory ganglia have been shown to both release glutamate, and be activated by glutamate in the context of nociceptive signaling. Howe... INTRODUCTION: Satellite glial cells (SGCs) that envelop the cell bodies of neurons in sensory ganglia have been shown to both release glutamate, and be activated by glutamate in the context of nociceptive signaling. However, little is known about the subpopulations of SGCs that are activated following nerve injury and whether glutamate mechanisms in the SGCs are involved in the pathologic pain. METHODS: To address this issue, we used light and electron microscopic immunohistochemistry to examine the change in the glutamate levels in the SGCs and the structural relationship between neighboring neurons in the trigeminal ganglion (TG) in a rat model of craniofacial neuropathic pain, CCI-ION. RESULTS: Administration of ionomycin, ATP and Bz-ATP induced an increase of extracellular glutamate concentration in cultured trigeminal SGCs, indicating a release of glutamate from SGCs. The level of glutamate immunostaining in the SGCs that envelop neurons of all sizes in the TG was significantly higher in rats with CCI-ION than in control rats, suggesting that SGCs enveloping nociceptive as well as non-nociceptive mechanosensitive neurons are activated following nerve injury, and that the glutamate release from SGCs increases in pathologic pain state. Close appositions between substance-P (SP)-immunopositive (+) or calcitonin gene-related peptide (CGRP)+, likely nociceptive neurons, between Piezo1+, likely non-nociceptive, mechanosensitive neurons and SP+ or CGRP+ neurons, and between SGCs of neighboring neurons were frequently observed. DISCUSSION: These findings suggest that glutamate in the trigeminal SGCs that envelop all types of neurons may play a role in the mechanisms of neuropathic pain, possibly via paracrine signaling.

Editorial: Women in Neuroanatomy.

Alonso-Nanclares L

Front Neuroanat · 2023 · PMID 38162284 · Full text

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Erratum: Characterization of primary visual cortex input to specific cell types in the superior colliculus.

Frontiers Production Office

Front Neuroanat · 2023 · PMID 38152457 · Full text

[This corrects the article DOI: 10.3389/fnana.2023.1282941.]. [This corrects the article DOI: 10.3389/fnana.2023.1282941.].

Unveiling the mechanisms of neuropathic pain suppression: perineural resiniferatoxin targets Trpv1 and beyond.

Shehab S, Javed H, Johnson AM … +3 more , Tariq S, Kumar CA, Emerald BS

Front Neuroanat · 2023 · PMID 38099210 · Full text

Neuropathic pain arises from damage or disorders affecting the somatosensory system. In rats, L5 nerve injury induces thermal and mechanical hypersensitivity/hyperalgesia. Recently, we demonstrated that applying resinife... Neuropathic pain arises from damage or disorders affecting the somatosensory system. In rats, L5 nerve injury induces thermal and mechanical hypersensitivity/hyperalgesia. Recently, we demonstrated that applying resiniferatoxin (RTX) directly on uninjured L3 and L4 nerves alleviated thermal and mechanical hypersensitivity resulting from L5 nerve injury. Herein, using immunohistochemistry, Western blot, and qRT-PCR techniques, we reveal that perineural application of RTX (0.002%) on the L4 nerve substantially downregulated the expression of its receptor (Trpv1) and three different voltage-gated ion channels (Nav1.9, Kv4.3, and Cav2.2). These channels are found primarily in small-sized neurons and show significant colocalization with Trpv1 in the dorsal root ganglion (DRG). However, RTX treatment did not affect the expression of Kv1.1, Piezo2 (found in large-sized neurons without colocalization with Trpv1), and Kir4.1 (localized in satellite cells) in the ipsilateral DRGs. Furthermore, RTX application on L3 and L4 nerves reduced the activation of c-fos in the spinal neurons induced by heat stimulation. Subsequently, we investigated whether applying RTX to the L3 and L4 nerves 3 weeks before the L5 nerve injury could prevent the onset of neuropathic pain. Both 0.002 and 0.004% concentrations of RTX produced significant analgesic effects, while complete prevention of thermal and mechanical hypersensitivity required a concentration of 0.008%. Importantly, this preventive effect on neuropathic manifestations was not associated with nerve degeneration, as microscopic examination revealed no morphological changes. Overall, this study underscores the mechanisms and the significance of perineural RTX treatment applied to adjacent uninjured nerves in entirely preventing nerve injury-induced neuropathic pain in humans and animals.

Structural networking of the developing brain: from maturation to neurosurgical implications.

De Benedictis A, Rossi-Espagnet MC, de Palma L … +2 more , Sarubbo S, Marras CE

Front Neuroanat · 2023 · PMID 38099209 · Full text

Modern neuroscience agrees that neurological processing emerges from the multimodal interaction among multiple cortical and subcortical neuronal hubs, connected at short and long distance by white matter, to form a large... Modern neuroscience agrees that neurological processing emerges from the multimodal interaction among multiple cortical and subcortical neuronal hubs, connected at short and long distance by white matter, to form a largely integrated and dynamic network, called the brain "connectome." The final architecture of these circuits results from a complex, continuous, and highly protracted development process of several axonal pathways that constitute the anatomical substrate of neuronal interactions. Awareness of the network organization of the central nervous system is crucial not only to understand the basis of children's neurological development, but also it may be of special interest to improve the quality of neurosurgical treatments of many pediatric diseases. Although there are a flourishing number of neuroimaging studies of the connectome, a comprehensive vision linking this research to neurosurgical practice is still lacking in the current pediatric literature. The goal of this review is to contribute to bridging this gap. In the first part, we summarize the main current knowledge concerning brain network maturation and its involvement in different aspects of normal neurocognitive development as well as in the pathophysiology of specific diseases. The final section is devoted to identifying possible implications of this knowledge in the neurosurgical field, especially in epilepsy and tumor surgery, and to discuss promising perspectives for future investigations.

Structural connectivity of cytoarchitectonically distinct human left temporal pole subregions: a diffusion MRI tractography study.

Sasaki T, Makris N, Shenton ME … +7 more , Savadjiev P, Rathi Y, Eckbo R, Bouix S, Yeterian E, Dickerson BC, Kubicki M

Front Neuroanat · 2023 · PMID 38090110 · Full text

The temporal pole (TP) is considered one of the major paralimbic cortical regions, and is involved in a variety of functions such as sensory perception, emotion, semantic processing, and social cognition. Based on differ... The temporal pole (TP) is considered one of the major paralimbic cortical regions, and is involved in a variety of functions such as sensory perception, emotion, semantic processing, and social cognition. Based on differences in cytoarchitecture, the TP can be further subdivided into smaller regions (dorsal, ventrolateral and ventromedial), each forming key nodes of distinct functional networks. However, the brain structural connectivity profile of TP subregions is not fully clarified. Using diffusion MRI data in a set of 31 healthy subjects, we aimed to elucidate the comprehensive structural connectivity of three cytoarchitectonically distinct TP subregions. Diffusion tensor imaging (DTI) analysis suggested that major association fiber pathways such as the inferior longitudinal, middle longitudinal, arcuate, and uncinate fasciculi provide structural connectivity to the TP. Further analysis suggested partially overlapping yet still distinct structural connectivity patterns across the TP subregions. Specifically, the dorsal subregion is strongly connected with wide areas in the parietal lobe, the ventrolateral subregion with areas including constituents of the default-semantic network, and the ventromedial subregion with limbic and paralimbic areas. Our results suggest the involvement of the TP in a set of extensive but distinct networks of cortical regions, consistent with its functional roles.

Automated pipeline for nerve fiber selection and g-ratio calculation in optical microscopy: exploring staining protocol variations.

Thomson BR, Martin LF, Schmidle PL … +3 more , Schlierbach H, Schänzer A, Richter H

Front Neuroanat · 2023 · PMID 38074449 · Full text

G-ratio is crucial for understanding the nervous system's health and function as it measures the relative myelin thickness around an axon. However, manual measurement is biased and variable, emphasizing the need for an a... G-ratio is crucial for understanding the nervous system's health and function as it measures the relative myelin thickness around an axon. However, manual measurement is biased and variable, emphasizing the need for an automated and standardized technique. Although deep learning holds promise, current implementations lack clinical relevance and generalizability. This study aimed to develop an automated pipeline for selecting nerve fibers and calculating relevant g-ratio using quality parameters in optical microscopy. Histological sections from the sciatic nerves of 16 female mice were prepared and stained with either p-phenylenediamine (PPD) or toluidine blue (TB). A custom UNet model was trained on a mix of both types of staining to segment the sections based on 7,694 manually delineated nerve fibers. Post-processing excluded non-relevant nerves. Axon diameter, myelin thickness, and g-ratio were computed from the segmentation results and its reliability was assessed using the intraclass correlation coefficient (ICC). Validation was performed on adjacent cuts of the same nerve. Then, morphometrical analyses of both staining techniques were performed. High agreement with the ground truth was shown by the model, with dice scores of 0.86 (axon) and 0.80 (myelin) and pixel-wise accuracy of 0.98 (axon) and 0.94 (myelin). Good inter-device reliability was observed with ICC at 0.87 (g-ratio) and 0.83 (myelin thickness), and an excellent ICC of 0.99 for axon diameter. Although axon diameter significantly differed from the ground truth ( = 0.006), g-ratio ( = 0.098) and myelin thickness ( = 0.877) showed no significant differences. No statistical differences in morphological parameters (g-ratio, myelin thickness, and axon diameter) were found in adjacent cuts of the same nerve (ANOVA -values: 0.34, 0.34, and 0.39, respectively). Comparing all animals, staining techniques yielded significant differences in mean g-ratio (PPD: 0.48 ± 0.04, TB: 0.50 ± 0.04), myelin thickness (PPD: 0.83 ± 0.28 μm, TB: 0.60 ± 0.20 μm), and axon diameter (PPD: 1.80 ± 0.63 μm, TB: 1.78 ± 0.63 μm). The proposed pipeline automatically selects relevant nerve fibers for g-ratio calculation in optical microscopy. This provides a reliable measurement method and serves as a potential pre-selection approach for large datasets in the context of healthy tissue. It remains to be demonstrated whether this method is applicable to measure g-ratio related with neurological disorders by comparing healthy and pathological tissue. Additionally, our findings emphasize the need for careful interpretation of inter-staining morphological parameters.

Corrigendum: Cerebellar and basal ganglia inputs define three main nuclei in the mouse ventral motor thalamus.

Alonso-Martínez C, Rubio-Teves M, Casas-Torremocha D … +2 more , Porrero C, Clascá F

Front Neuroanat · 2023 · PMID 38074448 · Full text

[This corrects the article DOI: 10.3389/fnana.2023.1242839.]. [This corrects the article DOI: 10.3389/fnana.2023.1242839.].

Secretagogin as a marker to distinguish between different neuron types in human frontal and temporal cortex.

Tapia-González S, DeFelipe J

Front Neuroanat · 2023 · PMID 38020216 · Full text

The principal aim of the present work was to chemically characterize the population of neurons labeled for the calcium binding protein secretagogin (SCGN) in the human frontal and temporal cortices (Brodmann's area 10 an... The principal aim of the present work was to chemically characterize the population of neurons labeled for the calcium binding protein secretagogin (SCGN) in the human frontal and temporal cortices (Brodmann's area 10 and 21, respectively). Both cortical regions are involved in many high cognitive functions that are especially well developed (or unique) in humans, but with different functional roles. The pattern of SCGN immunostaining was rather similar in BA10 and BA21, with all the labeled neurons displaying a non-pyramidal morphology (interneurons). Although SCGN cells were present throughout all layers, they were more frequently observed in layers II, III and IV, whereas in layer I they were found only occasionally. We examined the degree of colocalization of SCGN with parvalbumin (PV) and calretinin (CR), as well as with nitric oxide synthase (nNOS; the enzyme responsible for the synthesis of nitric oxide by neurons) by triple immunostaining. We looked for possible similarities or differences in the coexpression patterns of SCGN with PV, CR and nNOS between BA10 and BA21 throughout the different cortical layers (I-VI). The percentage of colocalization was estimated by counting the number of all labeled cells through columns (1,100-1,400 μm wide) across the entire thickness of the cortex (from the pial surface to the white matter) in 50 μm-thick sections. Several hundred neurons were examined in both cortical regions. We found that SCGN cells include multiple neurochemical subtypes, whose abundance varies according to the cortical area and layer. The present results further highlight the regional specialization of cortical neurons and underline the importance of performing additional experiments to characterize the subpopulation of SCGN cells in the human cerebral cortex in greater detail.

Proportions of four distinct classes of sensory neurons are retained even when axon regeneration is enhanced following peripheral nerve injury.

Khan S, Carrasco DI, Isaacson R … +1 more , English AW

Front Neuroanat · 2023 · PMID 38020215 · Full text

INTRODUCTION: Recovery from peripheral nerve injuries is poor because axon regeneration is slow and inefficient. Experimental therapies that increase signaling of neuronal brain-derived neurotrophic factor (BDNF) through... INTRODUCTION: Recovery from peripheral nerve injuries is poor because axon regeneration is slow and inefficient. Experimental therapies that increase signaling of neuronal brain-derived neurotrophic factor (BDNF) through its TrkB receptor or through its downstream effectors enhance axon regeneration, increasing the number of motor and sensory neurons whose axons successfully regenerate and reinnervate muscle targets. The goal of this study was to compare the proportions of four different classes of sensory (dorsal root ganglion, DRG) neurons that successfully reinnervate two different muscle targets in control mice and mice treated pharmacologically to enhance axon regeneration. METHODS: Following sciatic nerve transection and repair, C57BL/6 J mice were treated for 2 weeks, either with R13, a prodrug that releases the small molecule TrkB ligand, 7,8-dihydroxyflavone, with compound 11 (CP11), an inhibitor of asparaginyl endopeptidase (δ-secretase), or with a control vehicle. Four weeks after injury, different fluorescent retrograde tracers were injected into the gastrocnemius and tibialis anterior muscles to mark DRG neurons that had successfully reinnervated these muscles. Using immunofluorescence, retrogradely labeled DRG neurons also expressing markers of four different sensory neuronal classes were counted. RESULTS AND DISCUSSION: Treatments with R13 or CP11 resulted in muscle reinnervation by many more DRG neurons than vehicletreated controls, but neurons expressing proteins associated with the different classes of DRG neurons studied were largely in the same proportions found in intact mice.

Characterization of primary visual cortex input to specific cell types in the superior colliculus.

Jiang S, Honnuraiah S, Stuart GJ

Front Neuroanat · 2023 · PMID 38020214 · Full text

The superior colliculus is a critical brain region involved in processing visual information. It receives visual input directly from the retina, as well as via a projection from primary visual cortex. Here we determine w... The superior colliculus is a critical brain region involved in processing visual information. It receives visual input directly from the retina, as well as via a projection from primary visual cortex. Here we determine which cell types in the superficial superior colliculus receive visual input from primary visual cortex in mice. Neurons in the superficial layers of the superior colliculus were classified into four groups - Wide-field, narrow-field, horizontal and stellate - based on their morphological and electrophysiological properties. To determine functional connections between V1 and these four different cell types we expressed Channelrhodopsin2 in primary visual cortex and then optically stimulated these axons while recording from different neurons in the superficial superior colliculus using whole-cell patch-clamp recording . We found that all four cell types in the superficial layers of the superior colliculus received monosynaptic (direct) input from V1. Wide-field neurons were more likely than other cell types to receive primary visual cortex input. Our results provide information on the cell specificity of the primary visual cortex to superior colliculus projection, increasing our understanding of how visual information is processed in the superior colliculus at the single cell level.

Brain plasticity following corpus callosum agenesis or loss: a review of the Probst bundles.

Lynton Z, Suárez R, Fenlon LR

Front Neuroanat · 2023 · PMID 38020213 · Full text

The corpus callosum is the largest axonal tract in the human brain, connecting the left and right cortical hemipheres. This structure is affected in myriad human neurodevelopmental disorders, and can be entirely absent a... The corpus callosum is the largest axonal tract in the human brain, connecting the left and right cortical hemipheres. This structure is affected in myriad human neurodevelopmental disorders, and can be entirely absent as a result of congenital or surgical causes. The age when callosal loss occurs, for example via surgical section in cases of refractory epilepsy, correlates with resulting brain morphology and neuropsychological outcomes, whereby an earlier loss generally produces relatively improved interhemispheric connectivity compared to a loss in adulthood (known as the "Sperry's paradox"). However, the mechanisms behind these age-dependent differences remain unclear. Perhaps the best documented and most striking of the plastic changes that occur due to developmental, but not adult, callosal loss is the formation of large, bilateral, longitudinal ectopic tracts termed Probst bundles. Despite over 100 years of research into these ectopic tracts, which are the largest and best described stereotypical ectopic brain tracts in humans, much remains unclear about them. Here, we review the anatomy of the Probst bundles, along with evidence for their faciliatory or detrimental function, the required conditions for their formation, patterns of etiology, and mechanisms of development. We provide hypotheses for many of the remaining mysteries of the Probst bundles, including their possible relationship to preserved interhemispheric communication following corpus callosum absence. Future research into naturally occurring plastic tracts such as Probst bundles will help to inform the general rules governing axon plasticity and disorders of brain miswiring.

Twelve protections evolved for the brain, and their roles in extending its functional life.

Stone J, Mitrofanis J, Johnstone DM … +1 more , Robinson SR

Front Neuroanat · 2023 · PMID 38020212 · Full text

As human longevity has increased, we have come to understand the ability of the brain to function into advanced age, but also its vulnerability with age, apparent in the age-related dementias. Against that background of... As human longevity has increased, we have come to understand the ability of the brain to function into advanced age, but also its vulnerability with age, apparent in the age-related dementias. Against that background of success and vulnerability, this essay reviews how the brain is protected by (by our count) 12 mechanisms, including: the cranium, a bony helmet; the hydraulic support given by the cerebrospinal fluid; the strategically located carotid body and sinus, which provide input to reflexes that protect the brain from blood-gas imbalance and extremes of blood pressure; the blood brain barrier, an essential sealing of cerebral vessels; the secretion of molecules such as haemopexin and (we argue) the peptide Aβ to detoxify haemoglobin, at sites of a bleed; autoregulation of the capillary bed, which stabilises metabolites in extracellular fluid; fuel storage in the brain, as glycogen; oxygen storage, in the haemoprotein neuroglobin; the generation of new neurones, in the adult, to replace cells lost; acquired resilience, the stress-induced strengthening of cell membranes and energy production found in all body tissues; and cognitive reserve, the ability of the brain to maintain function despite damage. Of these 12 protections, we identify 5 as unique to the brain, 3 as protections shared with all body tissues, and another 4 as protections shared with other tissues but specialised for the brain. These protections are a measure of the brain's vulnerability, of its need for protection. They have evolved, we argue, to maintain cognitive function, the ability of the brain to function despite damage that accumulates during life. Several can be tools in the hands of the individual, and of the medical health professional, for the lifelong care of our brains.

A technology platform for standardized cryoprotection and freezing of large-volume brain tissues for high-resolution histology.

Kumarasami R, Verma R, Pandurangan K … +8 more , Ramesh JJ, Pandidurai S, Savoia S, Jayakumar J, Bota M, Mitra P, Joseph J, Sivaprakasam M

Front Neuroanat · 2023 · PMID 38020211 · Full text

Understanding and mapping the human connectome is a long-standing endeavor of neuroscience, yet the significant challenges associated with the large size of the human brain during cryosectioning remain unsolved. While sm... Understanding and mapping the human connectome is a long-standing endeavor of neuroscience, yet the significant challenges associated with the large size of the human brain during cryosectioning remain unsolved. While smaller brains, such as rodents and marmosets, have been the focus of previous connectomics projects, the processing of the larger human brain requires significant technological advancements. This study addresses the problem of freezing large brains in aligned neuroanatomical coordinates with minimal tissue damage, facilitating large-scale distortion-free cryosectioning. We report the most effective and stable freezing technique utilizing an appropriate choice of cryoprotection and leveraging engineering tools such as brain master patterns, custom-designed molds, and a continuous temperature monitoring system. This standardized approach to freezing enables high-quality, distortion-free histology, allowing researchers worldwide to explore the complexities of the human brain at a cellular level. Our approach combines neuroscience and engineering technologies to address this long-standing challenge with limited resources, enhancing accessibility of large-scale scientific endeavors beyond developed countries, promoting diverse approaches, and fostering collaborations.
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