scholarly journals New Molecular Players in the Development of Callosal Projections

Cells ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 29
Author(s):  
Ray Ku ◽  
Masaaki Torii
Keyword(s):  
Corpus Callosum ◽  
Recent Progress ◽  
Neural Circuitry ◽  
Projection Neurons ◽  
The Novel ◽  
Cellular Processes ◽  
Axonal Projections ◽  
Main Component ◽  
Callosal Projection ◽  
The Brain

Cortical development in humans is a long and ongoing process that continuously modifies the neural circuitry into adolescence. This is well represented by the dynamic maturation of the corpus callosum, the largest white matter tract in the brain. Callosal projection neurons whose long-range axons form the main component of the corpus callosum are evolved relatively recently with a substantial, disproportionate increase in numbers in humans. Though the anatomy of the corpus callosum and cellular processes in its development have been intensively studied by experts in a variety of fields over several decades, the whole picture of its development, in particular, the molecular controls over the development of callosal projections, still has many missing pieces. This review highlights the most recent progress on the understanding of corpus callosum formation with a special emphasis on the novel molecular players in the development of axonal projections in the corpus callosum.

scholarly journals Increased Callosal Connectivity in Reeler Mice Revealed by Brain-Wide Input Mapping of VIP Neurons in Barrel Cortex

2020 ◽  
Author(s):  
Georg Hafner ◽  
Julien Guy ◽  
Mirko Witte ◽  
Pavel Truschow ◽  
Alina Rüppel ◽  
...  
Keyword(s):  
Long Range ◽  
Cortical Neurons ◽  
Barrel Cortex ◽  
Projection Neurons ◽  
Subcortical Structures ◽  
Virus Tracing ◽  
Cortical Inputs ◽  
Callosal Projection ◽  
To Receive ◽  
The Brain

Abstract The neocortex is composed of layers. Whether layers constitute an essential framework for the formation of functional circuits is not well understood. We investigated the brain-wide input connectivity of vasoactive intestinal polypeptide (VIP) expressing neurons in the reeler mouse. This mutant is characterized by a migration deficit of cortical neurons so that no layers are formed. Still, neurons retain their properties and reeler mice show little cognitive impairment. We focused on VIP neurons because they are known to receive strong long-range inputs and have a typical laminar bias toward upper layers. In reeler, these neurons are more dispersed across the cortex. We mapped the brain-wide inputs of VIP neurons in barrel cortex of wild-type and reeler mice with rabies virus tracing. Innervation by subcortical inputs was not altered in reeler, in contrast to the cortical circuitry. Numbers of long-range ipsilateral cortical inputs were reduced in reeler, while contralateral inputs were strongly increased. Reeler mice had more callosal projection neurons. Hence, the corpus callosum was larger in reeler as shown by structural imaging. We argue that, in the absence of cortical layers, circuits with subcortical structures are maintained but cortical neurons establish a different network that largely preserves cognitive functions.

scholarly journals An evolutionarily acquired microRNA shapes development of mammalian cortical projections

2020 ◽  
Author(s):  
Jessica L Diaz ◽  
Verl B Siththanandan ◽  
Victoria Lu ◽  
Nicole Gonzalez-Nava ◽  
Lincoln Pasquina ◽  
...  
Keyword(s):  
Corpus Callosum ◽  
Cognitive Skills ◽  
Corticospinal Tract ◽  
Projection Neuron ◽  
Projection Neurons ◽  
Cortical Projection ◽  
Complex Motor ◽  
Callosal Projection ◽  
Cortical Projection Neuron

AbstractThe corticospinal tract is unique to mammals and the corpus callosum is unique to placental mammals (eutherians). The emergence of these structures is thought to underpin the evolutionary acquisition of complex motor and cognitive skills. Corticospinal motor neurons (CSMN) and callosal projection neurons (CPN) are the archetypal projection neurons of the corticospinal tract and corpus callosum, respectively. Although a number of conserved transcriptional regulators of CSMN and CPN development have been identified in vertebrates, none are unique to mammals and most are co-expressed across multiple projection neuron subtypes. Here, we discover seventeen CSMN-enriched microRNAs (miRNAs), fifteen of which map to a single genomic cluster that is exclusive to eutherians. One of these, miR-409-3p, promotes CSMN subtype identity in part via repression of LMO4, a key transcriptional regulator of CPN development. In vivo, miR-409-3p is sufficient to convert deep-layer CPN into CSMN. This is the first demonstration of an evolutionarily acquired miRNA in eutherians that refines cortical projection neuron subtype development. Our findings implicate miRNAs in the eutherians’ increase in neuronal subtype and projection diversity, the anatomic underpinnings of their complex behavior.Significance StatementThe mammalian central nervous system contains unique projections from the cerebral cortex thought to underpin complex motor and cognitive skills, including the corticospinal tract and corpus callosum. The neurons giving rise to these projections - corticospinal and callosal projection neurons - develop from the same progenitors, but acquire strikingly different fates. The broad evolutionary conservation of known genes controlling cortical projection neuron fates raises the question of how the more narrowly conserved corticospinal and callosal projections evolved. We identify a microRNA cluster selectively expressed by corticospinal projection neurons and exclusive to placental mammals. One of these microRNAs promotes corticospinal fate via regulation of the callosal gene LMO4, suggesting a mechanism whereby microRNA regulation during development promotes evolution of neuronal diversity.

scholarly journals Vocal learning as a preadaptation for the evolution of human beat perception and synchronization

2021 ◽  
Vol 376 (1835) ◽  
pp. 20200326 ◽  
Author(s):  
Aniruddh D. Patel
Keyword(s):  
Recent Progress ◽  
Temporal Structure ◽  
Vocal Learning ◽  
Neural Circuitry ◽  
Behavioural Ecology ◽  
Theme Issue ◽  
Significant Challenge ◽  
Brain Circuits ◽  
Learning Hypothesis ◽  
The Brain

The human capacity to synchronize movements to an auditory beat is central to musical behaviour and to debates over the evolution of human musicality. Have humans evolved any neural specializations for music processing, or does music rely entirely on brain circuits that evolved for other reasons? The vocal learning and rhythmic synchronization hypothesis proposes that our ability to move in time with an auditory beat in a precise, predictive and tempo-flexible manner originated in the neural circuitry for complex vocal learning. In the 15 years since the hypothesis was proposed a variety of studies have supported it. However, one study has provided a significant challenge to the hypothesis. Furthermore, it is increasingly clear that vocal learning is not a binary trait animals have or lack, but varies more continuously across species. In the light of these developments and of recent progress in the neurobiology of beat processing and of vocal learning, the current paper revises the vocal learning hypothesis. It argues that an advanced form of vocal learning acts as a preadaptation for sporadic beat perception and synchronization (BPS), providing intrinsic rewards for predicting the temporal structure of complex acoustic sequences. It further proposes that in humans, mechanisms of gene-culture coevolution transformed this preadaptation into a genuine neural adaptation for sustained BPS. The larger significance of this proposal is that it outlines a hypothesis of cognitive gene-culture coevolution which makes testable predictions for neuroscience, cross-species studies and genetics. This article is part of the theme issue ‘Synchrony and rhythm interaction: from the brain to behavioural ecology’.

scholarly journals Novelty detection in early olfactory processing of the honey bee, Apis mellifera

2021 ◽  
Author(s):  
Hong Lei ◽  
Seth Haney ◽  
Christopher Michael Jernigan ◽  
Chelsea Cook ◽  
Xiaojiao Guo ◽  
...  
Keyword(s):  
Sensory Processing ◽  
Fundamental Problem ◽  
Novelty Detection ◽  
Odor Stimulus ◽  
Projection Neurons ◽  
The Novel ◽  
Neuronal Responses ◽  
Air Stream ◽  
The Brain ◽  
Meaningful Stimuli

Animals are constantly bombarded with stimuli, which presents a fundamental problem of sorting among pervasive uninformative stimuli and novel, possibly meaningful stimuli. We evaluated novelty detection behaviorally in honey bees as they position their antennae differentially in an air stream carrying familiar or novel odors. We then characterized neuronal responses to familiar and novel odors in the first synaptic integration center in the brain, the antennal lobes. We found that the neurons that exhibited stronger initial responses to the odor that was to be familiarized are the same units that later distinguish familiar and novel odors, independently of chemical identities. These units, including both projection neurons and local neurons, showed a decreased response to the familiar odor but an increased response to the novel odor. Our results suggest that the antennal lobe may assign a category of familiarity or novelty to an odor stimulus in addition to its chemical identity code. Therefore, the mechanisms for novelty detection may be present in early sensory processing, either as a result of local synaptic interaction or via feedback from higher brain centers.

scholarly journals miR-409-3p represses Cited2 at the evolutionary emergence of the callosal and corticospinal projections

2021 ◽  
Author(s):  
Nikolaus R Wagner ◽  
Ashis Sinha ◽  
Verl B Siththanandan ◽  
Angelica N Kowalchuk ◽  
Jessica MacDonald ◽  
...  
Keyword(s):  
Corpus Callosum ◽  
Cognitive Abilities ◽  
Molecular Mechanisms ◽  
Deep Layer ◽  
Projection Neuron ◽  
Superficial Layer ◽  
Projection Neurons ◽  
Loss Of Function ◽  
Full Extension ◽  
Callosal Projection

Callosal projection neurons are a broad population of interhemispheric projection neurons that extend an axon across the corpus callosum to connect the two cerebral hemispheres. The corticospinal tract, comprised of the axons of corticospinal projection neurons, is unique to mammals, and its full extension to the lumbar segments that control walking is, like the corpus callosum, unique to placental mammals. The emergence of these two distinct axonal tracts is thought to underpin the evolutionary expansion of complex motor and cognitive abilities. The molecular mechanisms regulating the divergence of corticospinal and callosal projection neurons are incompletely understood. Our recent work identifies a genomic cluster of microRNAs (12qF1/Mirg) unique to placental mammals. These clustered miRNAs are specifically expressed by corticospinal vs. callosal projection neurons during the molecular refinement of corticospinal vs. callosal projection neuron fate (1). One of these, miR-409-3p, can convert layer V callosal into corticospinal projection neurons, acting in part through repression of the callosal-expressed transcriptional regulator Lmo4. This conversion is partial, however, suggesting that miR-409-3p represses multiple callosal projection neuron control genes in order to specify corticospinal projection neurons. One potential additional target of miR-409-3p repression is the callosal-expressed transcriptional co-activator Cited2. Cited2 interacts genetically with Lmo4, and Lmo4 can partially functionally compensate for Cited2 in thymus development(2). Further, Cited2 and Lmo4 function as opposing molecular controls over specific areal identity within superficial layer callosal projection neurons of the somatosensory and motor cortices, respectively (3). Cited2 is highly expressed by callosal, relative to corticospinal, projection neurons from the earliest stages of neurogenesis. Cited2 is necessary for the expansion of intermediate progenitor cells (IPCs) in the subventricular zone (SVZ), and the resulting generation of superficial layer callosal projection neurons. Here we show that miR-409-3p and Cited2 interact in IPCs and in corticospinal vs. deep layer callosal projection neuron development. miR-409-3p represses the Cited2 3UTR in luciferase assays. Mirg, which encodes miR-409-3p, and Cited2, are reciprocally expressed in IPCs at e15.5 by qPCR. Furthermore, miR-409-3p gain-of-function results in a phenocopy of established Cited2 loss-of-function in IPCs. Later on, miR-409-3p and Cited2 exert opposing effects on the adoption of corticospinal vs. callosal projection neuron subtype identity. Taken together, our work suggests that miR-409-3p, and possibly other 12qF1 miRNAs, represses Cited2 in IPCs to limit their proliferation, and in developing corticospinal and deep layer callosal projection neurons to favor corticospinal fate.

scholarly journals Deep-MEG: spatiotemporal CNN features and multiband ensemble classification for predicting the early signs of Alzheimer’s disease with magnetoencephalography

2021 ◽  
Author(s):  
Antonio Giovannetti ◽  
Gianluca Susi ◽  
Paola Casti ◽  
Arianna Mencattini ◽  
Sandra Pusil ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Regions ◽  
Ensemble Classification ◽  
The Novel ◽  
Ensemble Classifiers ◽  
Deep Convolutional Neural Networks ◽  
Early Signs ◽  
Data Representations ◽  
The Brain

AbstractIn this paper, we present the novel Deep-MEG approach in which image-based representations of magnetoencephalography (MEG) data are combined with ensemble classifiers based on deep convolutional neural networks. For the scope of predicting the early signs of Alzheimer’s disease (AD), functional connectivity (FC) measures between the brain bio-magnetic signals originated from spatially separated brain regions are used as MEG data representations for the analysis. After stacking the FC indicators relative to different frequency bands into multiple images, a deep transfer learning model is used to extract different sets of deep features and to derive improved classification ensembles. The proposed Deep-MEG architectures were tested on a set of resting-state MEG recordings and their corresponding magnetic resonance imaging scans, from a longitudinal study involving 87 subjects. Accuracy values of 89% and 87% were obtained, respectively, for the early prediction of AD conversion in a sample of 54 mild cognitive impairment subjects and in a sample of 87 subjects, including 33 healthy controls. These results indicate that the proposed Deep-MEG approach is a powerful tool for detecting early alterations in the spectral–temporal connectivity profiles and in their spatial relationships.

scholarly journals The Role of Vitamin D as a Biomarker in Alzheimer’s Disease

2021 ◽  
Vol 11 (3) ◽  
pp. 334
Author(s):  
Giulia Bivona ◽  
Bruna Lo Sasso ◽  
Caterina Maria Gambino ◽  
Rosaria Vincenza Giglio ◽  
Concetta Scazzone ◽  
...  
Keyword(s):  
Vitamin D ◽  
Risk Factor ◽  
Cognitive Decline ◽  
Immune Cell ◽  
Response To Treatment ◽  
Cellular Processes ◽  
Vitamin D Levels ◽  
The Brain ◽  
Key Questions

Vitamin D and cognition is a popular association, which led to a remarkable body of literature data in the past 50 years. The brain can synthesize, catabolize, and receive Vitamin D, which has been proved to regulate many cellular processes in neurons and microglia. Vitamin D helps synaptic plasticity and neurotransmission in dopaminergic neural circuits and exerts anti-inflammatory and neuroprotective activities within the brain by reducing the synthesis of pro-inflammatory cytokines and the oxidative stress load. Further, Vitamin D action in the brain has been related to the clearance of amyloid plaques, which represent a feature of Alzheimer Disease (AD), by the immune cell. Based on these considerations, many studies have investigated the role of circulating Vitamin D levels in patients affected by a cognitive decline to assess Vitamin D’s eventual role as a biomarker or a risk factor in AD. An association between low Vitamin D levels and the onset and progression of AD has been reported, and some interventional studies to evaluate the role of Vitamin D in preventing AD onset have been performed. However, many pitfalls affected the studies available, including substantial discrepancies in the methods used and the lack of standardized data. Despite many studies, it remains unclear whether Vitamin D can have a role in cognitive decline and AD. This narrative review aims to answer two key questions: whether Vitamin D can be used as a reliable tool for diagnosing, predicting prognosis and response to treatment in AD patients, and whether it is a modifiable risk factor for preventing AD onset.

scholarly journals Robust information routing by dorsal subiculum neurons

2021 ◽  
Vol 7 (11) ◽  
pp. eabf1913
Author(s):  
Takuma Kitanishi ◽  
Ryoko Umaba ◽  
Kenji Mizuseki
Keyword(s):  
Nucleus Accumbens ◽  
Large Scale ◽  
Dorsal Hippocampus ◽  
Retrosplenial Cortex ◽  
Projection Neurons ◽  
Target Region ◽  
Ca1 Neurons ◽  
Axonal Projections ◽  
Output Structure ◽  
Hippocampal Ca1

The dorsal hippocampus conveys various information associated with spatial navigation; however, how the information is distributed to multiple downstream areas remains unknown. We investigated this by identifying axonal projections using optogenetics during large-scale recordings from the rat subiculum, the major hippocampal output structure. Subicular neurons demonstrated a noise-resistant representation of place, speed, and trajectory, which was as accurate as or even more accurate than that of hippocampal CA1 neurons. Speed- and trajectory-dependent firings were most prominent in neurons projecting to the retrosplenial cortex and nucleus accumbens, respectively. Place-related firing was uniformly observed in neurons targeting the retrosplenial cortex, nucleus accumbens, anteroventral thalamus, and medial mammillary body. Theta oscillations and sharp-wave/ripples tightly controlled the firing of projection neurons in a target region–specific manner. In conclusion, the dorsal subiculum robustly routes diverse navigation-associated information to downstream areas.

scholarly journals Cinematic rendering of a burst sagittal suture caused by an occipito-frontal gunshot wound

2021 ◽  
Author(s):  
Dominic Gascho ◽  
Michael J. Thali ◽  
Rosa M. Martinez ◽  
Stephan A. Bolliger
Keyword(s):  
Gunshot Wound ◽  
Three Dimensional ◽  
The Novel ◽  
Sagittal Suture ◽  
Resonance Imaging ◽  
Cinematic Rendering ◽  
Reconstruction Methods ◽  
Dimensional Reconstruction ◽  
Magnetic Resonance Imaging Mri ◽  
The Brain

AbstractThe computed tomography (CT) scan of a 19-year-old man who died from an occipito-frontal gunshot wound presented an impressive radiating fracture line where the entire sagittal suture burst due to the high intracranial pressure that arose from a near-contact shot from a 9 mm bullet fired from a Glock 17 pistol. Photorealistic depictions of the radiating fracture lines along the cranial bones were created using three-dimensional reconstruction methods, such as the novel cinematic rendering technique that simulates the propagation and interaction of light when it passes through volumetric data. Since the brain had collapsed, depiction of soft tissue was insufficient on CT images. An additional magnetic resonance imaging (MRI) examination was performed, which enabled the diagnostic assessment of cerebral injuries.

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