Frontiers in Neuroanatomy最新文献

{"title":"Comparison of histological procedures and antigenicity of human post-mortem brains fixed with solutions used in gross anatomy laboratories","authors":"Eve-Marie Frigon, Amy Gérin-Lajoie, Mahsa Dadar, Denis Boire, Josefina Maranzano","doi":"10.3389/fnana.2024.1372953","DOIUrl":"https://doi.org/10.3389/fnana.2024.1372953","url":null,"abstract":"BackgroundBrain banks provide small tissue samples to researchers, while gross anatomy laboratories could provide larger samples, including complete brains to neuroscientists. However, they are preserved with solutions appropriate for gross-dissection, different from the classic neutral-buffered formalin (NBF) used in brain banks. Our previous work in mice showed that two gross-anatomy laboratory solutions, a saturated-salt-solution (SSS) and an alcohol-formaldehyde-solution (AFS), preserve antigenicity of the main cellular markers (neurons, astrocytes, microglia, and myelin). Our goal is now to compare the quality of histology and antigenicity preservation of human brains fixed with NBF by immersion (practice of brain banks) vs. those fixed with a SSS and an AFS by whole body perfusion, practice of gross-anatomy laboratories.MethodsWe used a convenience sample of 42 brains (31 males, 11 females; 25–90 years old) fixed with NBF (N = 12), SSS (N = 13), and AFS (N = 17). One cm<jats:sup>3</jats:sup> tissue blocks were cut, cryoprotected, frozen and sliced into 40 μm sections. The four cell populations were labeled using immunohistochemistry (Neurons = neuronal-nuclei = NeuN, astrocytes = glial-fibrillary-acidic-protein = GFAP, microglia = ionized-calcium-binding-adaptor-molecule1 = Iba1 and oligodendrocytes = myelin-proteolipid-protein = PLP). We qualitatively assessed antigenicity and cell distribution, and compared the ease of manipulation of the sections, the microscopic tissue quality, and the quality of common histochemical stains (e.g., Cresyl violet, Luxol fast blue, etc.) across solutions.ResultsSections of SSS-fixed brains were more difficult to manipulate and showed poorer tissue quality than those from brains fixed with the other solutions. The four antigens were preserved, and cell labeling was more often homogeneous in AFS-fixed specimens. NeuN and GFAP were not always present in NBF and SSS samples. Some antigens were heterogeneously distributed in some specimens, independently of the fixative, but an antigen retrieval protocol successfully recovered them. Finally, the histochemical stains were of sufficient quality regardless of the fixative, although neurons were more often paler in SSS-fixed specimens.ConclusionAntigenicity was preserved in human brains fixed with solutions used in human gross-anatomy (albeit the poorer quality of SSS-fixed specimens). For some specific variables, histology quality was superior in AFS-fixed brains. Furthermore, we show the feasibility of frequently used histochemical stains. These results are promising for neuroscientists interested in using brain specimens from anatomy laboratories.","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"243 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140598148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Topographic organization across foveal visual areas in macaques","authors":"Hangqi Li, Danling Hu, Hisashi Tanigawa, Toru Takahata","doi":"10.3389/fnana.2024.1389067","DOIUrl":"https://doi.org/10.3389/fnana.2024.1389067","url":null,"abstract":"IntroductionWhile the fovea on the retina covers only a small region of the visual field, a significant portion of the visual cortex is dedicated to processing information from the fovea being a critical center for object recognition, motion control, and visually guided attention. Despite its importance, prior functional imaging studies in awake monkeys often focused on the parafoveal visual field, potentially leading to inaccuracies in understanding the brain structure underlying function.MethodsIn this study, our aim is to unveil the neuronal connectivity and topography in the foveal visual cortex in comparison to the parafoveal visual cortex. Using four different types of retrograde tracers, we selectively injected them into the striate cortex (V1) or V4, encompassing the regions between the fovea and parafovea.ResultsV1 and V4 exhibited intense mutual connectivity in the foveal visual field, in contrast to the parafoveal visual field, possibly due to the absence of V3 in the foveal visual field. While previous live brain imaging studies failed to reveal retinotopy in the foveal visual fields, our results indicate that the foveal visual fields have continuous topographic connectivity across V1 through V4, as well as the parafoveal visual fields. Although a simple extension of the retinotopic isoeccentricity maps from V1 to V4 has been suggested from previous fMRI studies, our study demonstrated that V3 and V4 possess gradually smaller topographic maps compared to V1 and V2. Feedback projections to foveal V1 primarily originate from the infragranular layers of foveal V2 and V4, while feedforward projections to foveal V4 arise from both supragranular and infragranular layers of foveal V1 and V2, consistent with previous findings in the parafoveal visual fields.DiscussionThis study provides valuable insights into the connectivity of the foveal visual cortex, which was ambiguous in previous imaging studies.","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"16 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140810841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modular horizontal network within mouse primary visual cortex","authors":"Andreas Burkhalter, Weiqing Ji, Andrew M. Meier, Rinaldo D. D’Souza","doi":"10.3389/fnana.2024.1364675","DOIUrl":"https://doi.org/10.3389/fnana.2024.1364675","url":null,"abstract":"Interactions between feedback connections from higher cortical areas and local horizontal connections within primary visual cortex (V1) were shown to play a role in contextual processing in different behavioral states. Layer 1 (L1) is an important part of the underlying network. This cell-sparse layer is a target of feedback and local inputs, and nexus for contacts onto apical dendrites of projection neurons in the layers below. Importantly, L1 is a site for coupling inputs from the outside world with internal information. To determine whether all of these circuit elements overlap in L1, we labeled the horizontal network within mouse V1 with anterograde and retrograde viral tracers. We found two types of local horizontal connections: short ones that were tangentially limited to the representation of the point image, and long ones which reached beyond the receptive field center, deep into its surround. The long connections were patchy and terminated preferentially in M2 muscarinic acetylcholine receptor-negative (M2-) interpatches. Anterogradely labeled inputs overlapped in M2-interpatches with apical dendrites of retrogradely labeled L2/3 and L5 cells, forming module-selective loops between topographically distant locations. Previous work showed that L1 of M2-interpatches receive inputs from the lateral posterior thalamic nucleus (LP) and from a feedback network from areas of the medial dorsal stream, including the secondary motor cortex. Together, these findings suggest that interactions in M2-interpatches play a role in processing visual inputs produced by object-and self-motion.","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"56 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140598385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unambiguous identification of asymmetric and symmetric synapses using volume electron microscopy","authors":"Nicolás Cano-Astorga, Sergio Plaza-Alonso, Marta Turegano-Lopez, José Rodrigo-Rodríguez, Angel Merchan-Perez, Javier DeFelipe","doi":"10.3389/fnana.2024.1348032","DOIUrl":"https://doi.org/10.3389/fnana.2024.1348032","url":null,"abstract":"The brain contains thousands of millions of synapses, exhibiting diverse structural, molecular, and functional characteristics. However, synapses can be classified into two primary morphological types: Gray’s type I and type II, corresponding to Colonnier’s asymmetric (AS) and symmetric (SS) synapses, respectively. AS and SS have a thick and thin postsynaptic density, respectively. In the cerebral cortex, since most AS are excitatory (glutamatergic), and SS are inhibitory (GABAergic), determining the distribution, size, density, and proportion of the two major cortical types of synapses is critical, not only to better understand synaptic organization in terms of connectivity, but also from a functional perspective. However, several technical challenges complicate the study of synapses. Potassium ferrocyanide has been utilized in recent volume electron microscope studies to enhance electron density in cellular membranes. However, identifying synaptic junctions, especially SS, becomes more challenging as the postsynaptic densities become thinner with increasing concentrations of potassium ferrocyanide. Here we describe a protocol employing Focused Ion Beam Milling and Scanning Electron Microscopy for studying brain tissue. The focus is on the unequivocal identification of AS and SS types. To validate SS observed using this protocol as GABAergic, experiments with immunocytochemistry for the vesicular GABA transporter were conducted on fixed mouse brain tissue sections. This material was processed with different concentrations of potassium ferrocyanide, aiming to determine its optimal concentration. We demonstrate that using a low concentration of potassium ferrocyanide (0.1%) improves membrane visualization while allowing unequivocal identification of synapses as AS or SS.","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"54 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140598246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences in vocal brain areas and astrocytes between the house wren and the rufous-tailed hummingbird","authors":"Carolina López-Murillo, Santiago Hinestroza-Morales, Pablo Henny, Jorge Toledo, Gloria Patricia Cardona-Gómez, Héctor Rivera-Gutiérrez, Rafael Posada-Duque","doi":"10.3389/fnana.2024.1339308","DOIUrl":"https://doi.org/10.3389/fnana.2024.1339308","url":null,"abstract":"The house wren shows complex song, and the rufous-tailed hummingbird has a simple song. The location of vocal brain areas supports the song’s complexity; however, these still need to be studied. The astrocytic population in songbirds appears to be associated with change in vocal control nuclei; however, astrocytic distribution and morphology have not been described in these species. Consequently, we compared the distribution and volume of the vocal brain areas: HVC, RA, Area X, and LMAN, cell density, and the morphology of astrocytes in the house wren and the rufous-tailed hummingbird. Individuals of the two species were collected, and their brains were analyzed using serial Nissl- NeuN- and MAP2-stained tissue scanner imaging, followed by 3D reconstructions of the vocal areas; and GFAP and S100β astrocytes were analyzed in both species. We found that vocal areas were located close to the cerebral midline in the house wren and a more lateralized position in the rufous-tailed hummingbird. The LMAN occupied a larger volume in the rufous-tailed hummingbird, while the RA and HVC were larger in the house wren. While Area X showed higher cell density in the house wren than the rufous-tailed hummingbird, the LMAN showed a higher density in the rufous-tailed hummingbird. In the house wren, GFAP astrocytes in the same bregma where the vocal areas were located were observed at the laminar edge of the pallium (LEP) and in the vascular region, as well as in vocal motor relay regions in the pallidum and mesencephalon. In contrast, GFAP astrocytes were found in LEP, but not in the pallidum and mesencephalon in hummingbirds. Finally, when comparing GFAP astrocytes in the LEP region of both species, house wren astrocytes exhibited significantly more complex morphology than those of the rufous-tailed hummingbird. These findings suggest a difference in the location and cellular density of vocal circuits, as well as morphology of GFAP astrocytes between the house wren and the rufous-tailed hummingbird.","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"34 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140311288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and characterization of a non-human primate model of disseminated synucleinopathy","authors":"Alberto J. Rico, Almudena Corcho, Julia Chocarro, Goiaz Ariznabarreta, Elvira Roda, Adriana Honrubia, Patricia Arnaiz, José L. Lanciego","doi":"10.3389/fnana.2024.1355940","DOIUrl":"https://doi.org/10.3389/fnana.2024.1355940","url":null,"abstract":"IntroductionThe presence of a widespread cortical synucleinopathy is the main neuropathological hallmark underlying clinical entities such as Parkinson’s disease with dementia (PDD) and dementia with Lewy bodies (DLB). There currently is a pressing need for the development of non-human primate (NHPs) models of PDD and DLB to further overcome existing limitations in drug discovery.MethodsHere we took advantage of a retrogradely-spreading adeno-associated viral vector serotype 9 coding for the alpha-synuclein A53T mutated gene (AAV9-SynA53T) to induce a widespread synucleinopathy of cortical and subcortical territories innervating the putamen. Four weeks post-AAV deliveries animals were sacrificed and a comprehensive biodistribution study was conducted, comprising the quantification of neurons expressing alpha-synuclein, rostrocaudal distribution and their specific location.ResultsIntraputaminal deliveries of AAV9-SynA53T lead to a disseminated synucleinopathy throughout ipsi- and contralateral cerebral cortices, together with transduced neurons located in the ipsilateral caudal intralaminar nuclei and in the substantia nigra pars compacta (leading to thalamostriatal and nigrostriatal projections, respectively). Cortical afferent systems were found to be the main contributors to putaminal afferents (superior frontal and precentral gyri in particular).DiscussionObtained data extends current models of synucleinopathies in NHPs, providing a reproducible platform enabling the adequate implementation of end-stage preclinical screening of new drugs targeting alpha-synuclein.","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"2 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140316978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring an innovative decellularization protocol for porcine nerve grafts: a translational approach to peripheral nerve repair","authors":"Luisa Muratori, Alessandro Crosio, Giulia Ronchi, Debora Molinaro, Pierluigi Tos, Arianna B. Lovati, Stefania Raimondo","doi":"10.3389/fnana.2024.1380520","DOIUrl":"https://doi.org/10.3389/fnana.2024.1380520","url":null,"abstract":"IntroductionPeripheral nerves are frequently affected by lesions caused by traumatic or iatrogenic damages, resulting in loss of motor and sensory function, crucial in orthopedic outcomes and with a significant impact on patients’ quality of life. Many strategies have been proposed over years to repair nerve injuries with substance loss, to achieve musculoskeletal reinnervation and functional recovery. Allograft have been tested as an alternative to the gold standard, the autograft technique, but nerves from donors frequently cause immunogenic response. For this reason, several studies are focusing to find the best way to decellularize nerves preserving either the extracellular matrix, either the basal lamina, as the key elements used by Schwann cells and axons during the regenerative process.MethodsThis study focuses on a novel decellularization protocol for porcine nerves, aimed at reducing immunogenicity while preserving essential elements like the extracellular matrix and basal lamina, vital for nerve regeneration. To investigate the efficacy of the decellularization protocol to remove immunogenic cellular components of the nerve tissue and to preserve the basal lamina and extracellular matrix, morphological analysis was performed through Masson’s Trichrome staining, immunofluorescence, high resolution light microscopy and transmission electron microscopy. Decellularized porcine nerve graft were then employed in vivo to repair a rat median nerve lesion. Morphological analysis was also used to study the ability of the porcine decellularized graft to support the nerve regeneration.Results and DiscussionThe decellularization method was effective in preparing porcine superficial peroneal nerves for grafting as evidenced by the removal of immunogenic components and preservation of the ECM. Morphological analysis demonstrated that four weeks after injury, regenerating fibers colonized the graft suggesting a promising use to repair severe nerve lesions. The idea of using a porcine nerve graft arises from a translational perspective. This approach offers a promising direction in the orthopedic field for nerve repair, especially in severe cases where conventional methods are limited.","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"161 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140171091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phylogenetic reduction of the magnocellular red nucleus in primates and inter-subject variability in humans","authors":"Martin Stacho, A. Niklas Häusler, Andrea Brandstetter, Francesca Iannilli, Hartmut Mohlberg, Christian Schiffer, Jeroen B. Smaers, Katrin Amunts","doi":"10.3389/fnana.2024.1331305","DOIUrl":"https://doi.org/10.3389/fnana.2024.1331305","url":null,"abstract":"IntroductionThe red nucleus is part of the motor system controlling limb movements. While this seems to be a function common in many vertebrates, its organization and circuitry have undergone massive changes during evolution. In primates, it is sub-divided into the magnocellular and parvocellular parts that give rise to rubrospinal and rubro-olivary connection, respectively. These two subdivisions are subject to striking variation within the primates and the size of the magnocellular part is markedly reduced in bipedal primates including humans. The parvocellular part is part of the olivo-cerebellar circuitry that is prominent in humans. Despite the well-described differences between species in the literature, systematic comparative studies of the red nucleus remain rare.MethodsWe therefore mapped the red nucleus in cytoarchitectonic sections of 20 primate species belonging to 5 primate groups including prosimians, new world monkeys, old world monkeys, non-human apes and humans. We used Ornstein-Uhlenbeck modelling, ancestral state estimation and phylogenetic analysis of covariance to scrutinize the phylogenetic relations of the red nucleus volume.ResultsWe created openly available high-resolution cytoarchitectonic delineations of the human red nucleus in the microscopic BigBrain model and human probabilistic maps that capture inter-subject variations in quantitative terms. Further, we compared the volume of the nucleus across primates and showed that the parvocellular subdivision scaled proportionally to the brain volume across the groups while the magnocellular part deviated significantly from the scaling in humans and non-human apes. These two groups showed the lowest size of the magnocellular red nucleus relative to the whole brain volume and the largest relative difference between the parvocellular and magnocellular subdivision.DiscussionThat is, the red nucleus has transformed from a magnocellular-dominated to a parvocellular-dominated station. It is reasonable to assume that these changes are intertwined with evolutionary developments in other brain regions, in particular the motor system. We speculate that the interspecies variations might partly reflect the differences in hand dexterity but also the tentative involvement of the red nucleus in sensory and cognitive functions.","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"112 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140129875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Localization of hyperpolarization-activated cyclic nucleotide-gated channels in the vertebrate retinas across species and their physiological roles","authors":"Daniel Kim, Hyeonhee Roh, Hyung-Min Lee, Sang Jeong Kim, Maesoon Im","doi":"10.3389/fnana.2024.1385932","DOIUrl":"https://doi.org/10.3389/fnana.2024.1385932","url":null,"abstract":"<p>Transmembrane proteins known as hyperpolarization-activated cyclic nucleotide-gated (HCN) channels control the movement of Na⁺ and K⁺ ions across cellular membranes. HCN channels are known to be involved in crucial physiological functions in regulating neuronal excitability and rhythmicity, and pacemaker activity in the heart. Although HCN channels have been relatively well investigated in the brain, their distribution and function in the retina have received less attention, remaining their physiological roles to be comprehensively understood. Also, because recent studies reported HCN channels have been somewhat linked with the dysfunction of photoreceptors which are affected by retinal diseases, investigating HCN channels in the retina may offer valuable insights into disease mechanisms and potentially contribute to identifying novel therapeutic targets for retinal degenerative disorders. This paper endeavors to summarize the existing literature on the distribution and function of HCN channels reported in the vertebrate retinas of various species and discuss the potential implications for the treatment of retinal diseases. Then, we recapitulate current knowledge regarding the function and regulation of HCN channels, as well as their relevance to various neurological disorders.</p>","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"21 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140150222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anterograde trans-neuronal labeling of striatal interneurons in relation to dopamine neurons in the substantia nigra pars compacta","authors":"Fuyuki Karube, Yang Yang, Kenta Kobayashi, Fumino Fujiyama","doi":"10.3389/fnana.2024.1325368","DOIUrl":"https://doi.org/10.3389/fnana.2024.1325368","url":null,"abstract":"Recent advances in neural tracing have unveiled numerous neural circuits characterized by brain region and cell type specificity, illuminating the underpinnings of specific functions and behaviors. Dopaminergic (DA) neurons in the midbrain are highly heterogeneous in terms of gene and protein expression and axonal projections. Different cell types within the substantia nigra pars compacta (SNc) tend to project to the striatum in a cell-type-dependent manner characterized by specific topography. Given the wide and dense distribution of DA axons, coupled with a combination of synaptic and volume transmission, it remains unclear how DA release is spatially and temporally regulated, to appropriately achieve specific behaviors and functions. Our hypothesis posits that hidden rules governing synapse formation between pre-synaptic DA neuron types and striatal neuron types may modulate the effect of DA at a single-cell level. To address this conjecture, we employed adeno-associated virus serotype 1 (AAV1) to visualize the neural circuitry of DA neurons. AAV1 has emerged as a potent anatomical instrument capable of labeling and visualizing pre- and post-synaptic neurons simultaneously through anterograde trans-synaptic labeling. First, AAV1-Cre was injected into the SNc, resulting in Cre expression in both medium spiny neurons and interneurons in the striatum. Due to the potential occurrence of the retrograde transfer of AAV1, only striatal interneurons were considered for trans-synaptic or trans-neuronal labeling. Interneuron types expressing parvalbumin, choline acetyltransferase, somatostatin, or nitrogen oxide synthase exhibited Cre expression. Using a combination of AAV1-Cre and Cre-driven fluorophore expressing AAVs, striatal interneurons and the axons originating from the SNc were visualized in distinct colors. Using immunofluorescence against neurotransmitter transporters, almost all axons in the striatum visualized using this approach were confirmed to be dopaminergic. Moreover, individual DA axons established multiple appositions on the somata and proximal dendrites of interneurons. This finding suggests that irrespective of the extensive and widespread axonal arborization of DA neurons, a particular DA neuron may exert a significant influence on specific interneurons. Thus, AAV1-based labeling of the DA system can be a valuable tool to uncover the concealed rules governing these intricate relationships.","PeriodicalId":12572,"journal":{"name":"Frontiers in Neuroanatomy","volume":"3 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140002898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}