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BioRxiv : the Preprint Server For... Jun 2024The striatum is required for normal action selection, movement, and sensorimotor learning. Although action-specific striatal ensembles have been well documented, it is...
The striatum is required for normal action selection, movement, and sensorimotor learning. Although action-specific striatal ensembles have been well documented, it is not well understood how these ensembles are formed and how their dynamics may evolve throughout motor learning. Here we used longitudinal 2-photon Ca imaging of dorsal striatal neurons in head-fixed mice as they learned to self-generate locomotion. We observed a significant activation of both direct- and indirect-pathway spiny projection neurons (dSPNs and iSPNs, respectively) during early locomotion bouts and sessions that gradually decreased over time. For dSPNs, onset- and offset-ensembles were gradually refined from active motion-nonspecific cells. iSPN ensembles emerged from neurons initially active during opponent actions before becoming onset- or offset-specific. Our results show that as striatal ensembles are progressively refined, the number of active nonspecific striatal neurons decrease and the overall efficiency of the striatum information encoding for learned actions increases.
PubMed: 38895486
DOI: 10.1101/2024.06.06.596654 -
BioRxiv : the Preprint Server For... Jun 2024Chimpanzees () are humans' closest living relatives, making them the most directly relevant comparison point for understanding human brain evolution. Zeroing in on the...
Chimpanzees () are humans' closest living relatives, making them the most directly relevant comparison point for understanding human brain evolution. Zeroing in on the differences in brain connectivity between humans and chimpanzees can provide key insights into the specific evolutionary changes that might have occured along the human lineage. However, conducting comparisons of brain connectivity between humans and chimpanzees remains challenging, as cross-species brain atlases established within the same framework are currently lacking. Without the availability of cross-species brain atlases, the region-wise connectivity patterns between humans and chimpanzees cannot be directly compared. To address this gap, we built the first Chimpanzee Brainnetome Atlas (ChimpBNA) by following a well-established connectivity-based parcellation framework. Leveraging this new resource, we found substantial divergence in connectivity patterns across most association cortices, notably in the lateral temporal and dorsolateral prefrontal cortex between the two species. Intriguingly, these patterns significantly deviate from the patterns of cortical expansion observed in humans compared to chimpanzees. Additionally, we identified regions displaying connectional asymmetries that differed between species, likely resulting from evolutionary divergence. Genes associated with these divergent connectivities were found to be enriched in cell types crucial for cortical projection circuits and synapse formation. These genes exhibited more pronounced differences in expression patterns in regions with higher connectivity divergence, suggesting a potential foundation for brain connectivity evolution. Therefore, our study not only provides a fine-scale brain atlas of chimpanzees but also highlights the connectivity divergence between humans and chimpanzees in a more rigorous and comparative manner and suggests potential genetic correlates for the observed divergence in brain connectivity patterns between the two species. This can help us better understand the origins and development of uniquely human cognitive capabilities.
PubMed: 38895242
DOI: 10.1101/2024.06.03.597252 -
Animals : An Open Access Journal From... May 2024Although the presence of female contact sex pheromones in . has been hypothesized, to date its existence has not been proven. To gather more evidence of their...
Although the presence of female contact sex pheromones in . has been hypothesized, to date its existence has not been proven. To gather more evidence of their existence, cuticular liposoluble extracts were obtained from the following samples of adult females to be used as the experimental treatments: (1) ventral exoskeleton of immature female (VI), (2) dorsolateral exoskeleton of immature female (DI), (3) ventral exoskeleton of mature female (VM), and (4) dorsolateral exoskeleton of mature female (DM). Polyvinyl chloride tubes (artificial females; AF) were coated with each extract and the behavior displayed by sexually mature males in contact with the AF was recorded and classified as follows: 0 = no response; 1 = contact; 2 = pushing; and 3 = prolonged contact (≥10 s). To test the hypothesis that the extracts collected from the ventral portion of the abdomen exoskeleton have a higher effect on the behavior of males than the extracts collected from the dorsolateral portion of the abdomen exoskeleton, the experiment was divided into two bioassays: Bioassay I (VI vs. DI) and Bioassay II (VM vs. DM). In each bioassay, all experimental treatments were significantly different ( > 0.05) from the CTL group (AF coated with hexane). Notably, the pushing behavior was significantly higher ( < 0.05) in the VI treatment compared to the CTL and DI treatment. These results provide evidence of the existence of contact female sex pheromones with sexual recognition function located primarily in the ventral portion of the abdomen exoskeleton of . .
PubMed: 38891570
DOI: 10.3390/ani14111523 -
IScience Jun 2024The dorsolateral striatum (DLS) is important for performing actions persistently, even when it becomes suboptimal, reflecting a function that is reflexive and habitual....
The dorsolateral striatum (DLS) is important for performing actions persistently, even when it becomes suboptimal, reflecting a function that is reflexive and habitual. However, there are also ways in which persistent behaviors can result from a more prospective, planning mode of behavior. To help tease apart these possibilities for DLS function, we trained animals to perform a lever press for reward and then inhibited the DLS in key test phases: as the task shifted from a 1-press to a 3-press rule (upshift), as the task was maintained, as the task shifted back to the one-press rule (downshift), and when rewards came independent of pressing. During DLS inhibition, animals always favored their initially learned strategy to press just once, particularly so during the free-reward period. DLS inhibition surprisingly changed performance speed bidirectionally depending on the task shifts. DLS inhibition thus encouraged habitual behavior, suggesting it could normally help adapt to changing conditions.
PubMed: 38883824
DOI: 10.1016/j.isci.2024.110044 -
Scientific Reports Jun 2024Children with attention deficit/hyperactivity disorder (ADHD) typically exhibit difficulties in emotion regulation. It has been shown that the dorsolateral prefrontal...
Children with attention deficit/hyperactivity disorder (ADHD) typically exhibit difficulties in emotion regulation. It has been shown that the dorsolateral prefrontal cortex (dlPFC) and ventromedial prefrontal cortex (vmPFC) are crucially involved in these deficient processes. In this study, we aimed to explore the impact of electrical stimulation over the left dlPFC and right vmPFC on emotion regulation in children with ADHD. Twenty-four children with ADHD completed the Emotional Go/No-Go and Emotional 1-Back tasks while undergoing transcranial direct current stimulation (tDCS) in three separate sessions, each with a different electrode placement: anodal dlPFC (F3)/cathodal vmPFC (Fp2), anodal vmPFC (Fp2)/cathodal dlPFC (F3), and sham stimulation. During both real tDCS conditions, the accuracy of pre-potent inhibitory control and working memory performance improved, but not speed. This study provides evidence that the left dlPFC and the right vmPFC are involved in emotion regulation in ADHD.
Topics: Humans; Attention Deficit Disorder with Hyperactivity; Transcranial Direct Current Stimulation; Child; Male; Female; Emotional Regulation; Prefrontal Cortex; Memory, Short-Term; Emotions; Dorsolateral Prefrontal Cortex; Adolescent
PubMed: 38880826
DOI: 10.1038/s41598-024-64886-9 -
ELife Jun 2024Epithelial to mesenchymal transition (EMT) is a cellular process that converts epithelial cells to mesenchymal cells with migratory potential in developmental and...
Epithelial to mesenchymal transition (EMT) is a cellular process that converts epithelial cells to mesenchymal cells with migratory potential in developmental and pathological processes. Although originally considered a binary event, EMT in cancer progression involves intermediate states between a fully epithelial and a fully mesenchymal phenotype, which are characterized by distinct combinations of epithelial and mesenchymal markers. This phenomenon has been termed epithelial to mesenchymal plasticity (EMP), however, the intermediate states remain poorly described and it's unclear whether they exist during developmental EMT. Neural crest cells (NCC) are an embryonic progenitor cell population that gives rise to numerous cell types and tissues in vertebrates, and their formation and delamination is a classic example of developmental EMT. However, whether intermediate states also exist during NCC EMT and delamination remains unknown. Through single-cell RNA sequencing of mouse embryos, we identified intermediate NCC states based on their transcriptional signature and then spatially defined their locations in situ in the dorsolateral neuroepithelium. Our results illustrate the importance of cell cycle regulation and functional role for the intermediate stage marker in facilitating mammalian cranial NCC delamination and may provide new insights into mechanisms regulating pathological EMP.
Topics: Neural Crest; Animals; Epithelial-Mesenchymal Transition; Mice; Single-Cell Analysis
PubMed: 38873887
DOI: 10.7554/eLife.92844 -
Nature Communications Jun 2024Single administration of low-dose ketamine has both acute and sustained anti-depressant effects. Sustained effect is associated with restoration of glutamatergic...
Single administration of low-dose ketamine has both acute and sustained anti-depressant effects. Sustained effect is associated with restoration of glutamatergic synapses in medial prefrontal cortic (mFPC) neurons. Ketamine induced profound changes in a number of molecular pathways in a mouse model for chronic stress. Cell-cell communication analyses predicted that planar-cell-polarity (PCP) signaling was decreased after chronic administration of corticosterone but increased following ketamine administration in most of the excitatory neurons. Similar decrease of PCP signaling in excitatory neurons was predicted in dorsolateral prefrontal cortical (dl-PFC) neurons of patients with major depressive disorder (MDD). We showed that the basolateral amygdala (BLA)-projecting infralimbic prefrontal cortex (IL PFC) neurons regulate immobility time in the tail suspension test and food consumption. Conditionally knocking out Celsr2 and Celsr3 or Prickle2 in the BLA-projecting IL PFC neurons abolished ketamine-induced synapse restoration and behavioral remission. Therefore, PCP proteins in IL PFC-BLA neurons mediate synapse restoration induced by of low-dose ketamine.
Topics: Animals; Ketamine; Prefrontal Cortex; Synapses; Neurons; Mice; Disease Models, Animal; Male; Humans; Cell Polarity; Depressive Disorder, Major; Mice, Knockout; Stress, Psychological; Corticosterone; Basolateral Nuclear Complex; Mice, Inbred C57BL; LIM Domain Proteins; Glutamic Acid; Antidepressive Agents
PubMed: 38858386
DOI: 10.1038/s41467-024-48257-6 -
World Journal of Otorhinolaryngology -... Jun 20242019 novel coronavirus disease (COVID-19) infection is commonly associated with olfactory dysfunctions, but the basic pathogenesis of these complications remains...
OBJECTIVES
2019 novel coronavirus disease (COVID-19) infection is commonly associated with olfactory dysfunctions, but the basic pathogenesis of these complications remains controversial. This study seeks to evaluate the value of magnetic resonance spectroscopy (MRS) in determining the molecular neurometabolite alterations within the main brain olfactory areas in patients with COVID-19-related anosmia.
METHODS
In a cross-sectional study, seven patients with persistent COVID-19-related anosmia (mean age: 29.57 years) and seven healthy volunteers (mean age: 27.28 years) underwent MRS in which N-acetyl-aspartate (NAA), choline (Cho), creatine (Cr), and their ratios were measured in the anterior cingulate cortex, dorsolateral prefrontal cortex, orbitofrontal cortex (OFC), insular cortex, and ventromedial prefrontal cortex. Data were analyzed using TARQUIN software (version 4.3.10), and the results were compared with an independent sample -test and nonparametric Mann-Whitney test based on the normality of the MRS data distribution.
RESULTS
The mean duration of anosmia before imaging was 8.5 months in COVID-19-related anosmia group. MRS analysis elucidated a significant association between MRS findings within OFC and COVID-19-related anosmia ( < 0.01), and NAA was among the most important neurometabolites ( = 0.006). Reduced levels of NAA ( < 0.001), Cr ( < 0.001) and / ratio ( = 0.007) within OFC characterize COVID-19-related anosmia.
CONCLUSIONS
This study emphasizes that MRS can be illuminating in COVID-19-related anosmia and indicates a possible association between central nervous system impairment and persistent COVID-19-related anosmia.
PubMed: 38855283
DOI: 10.1002/wjo2.132 -
BioRxiv : the Preprint Server For... May 2024The cardinal symptoms of Parkinson's disease (PD) such as bradykinesia and akinesia are debilitating, and treatment options remain inadequate. The loss of nigrostriatal...
The cardinal symptoms of Parkinson's disease (PD) such as bradykinesia and akinesia are debilitating, and treatment options remain inadequate. The loss of nigrostriatal dopamine neurons in PD produces motor symptoms by shifting the balance of striatal output from the direct (go) to indirect (no-go) pathway in large part through changes in the excitatory connections and intrinsic excitabilities of the striatal projection neurons (SPNs). Here, we report using two different experimental models that a transient increase in striatal dopamine and enhanced D1 receptor activation, during 6-OHDA dopamine depletion, prevent the loss of mature spines and dendritic arbors on direct pathway projection neurons (dSPNs) and normal motor behavior for up to 5 months. The primary motor cortex and midline thalamic nuclei provide the major excitatory connections to SPNs. Using ChR2-assisted circuit mapping to measure inputs from motor cortex M1 to dorsolateral dSPNs, we observed a dramatic reduction in both experimental model mice and controls following dopamine depletion. Changes in the intrinsic excitabilities of SPNs were also similar to controls following dopamine depletion. Future work will examine thalamic connections to dSPNs. The findings reported here reveal previously unappreciated plasticity mechanisms within the basal ganglia that can be leveraged to treat the motor symptoms of PD.
PubMed: 38854096
DOI: 10.1101/2024.05.28.596192 -
BioRxiv : the Preprint Server For... May 2024Astrocytes use Ca signals to regulate multiple aspects of normal and pathological brain function. Astrocytes display context-specific diversity in their functions, and...
Astrocytes use Ca signals to regulate multiple aspects of normal and pathological brain function. Astrocytes display context-specific diversity in their functions, and in their response to noxious stimuli between brain regions. Indeed, astrocytic mitochondria have emerged as key players in governing astrocytic functional heterogeneity, given their ability to dynamically adapt their morphology to regional demands on their ATP generation and Ca buffering functions. Although there is reciprocal regulation between mitochondrial dynamics and mitochondrial Ca signaling in astrocytes, the extent of this regulation into the rich diversity of astrocytes in different brain regions remains largely unexplored. Brain-wide, experimentally induced mitochondrial DNA (mtDNA) loss in astrocytes showed that mtDNA integrity is critical for proper astrocyte function, however, few insights into possible diverse responses to this noxious stimulus from astrocytes in different brain areas were reported in these experiments. To selectively damage mtDNA in astrocytes in a brain-region-specific manner, we developed a novel adeno-associated virus (AAV)-based tool, Mito-PstI, which expresses the restriction enzyme PstI, specifically in astrocytic mitochondria. Here, we applied Mito-PstI to two distinct brain regions, the dorsolateral striatum, and the hippocampal dentate gyrus, and we show that Mito-PstI can induce astrocytic mtDNA loss , but with remarkable brain-region-dependent differences on mitochondrial dynamics, spontaneous Ca fluxes and astrocytic as well as microglial reactivity. Thus, AAV-Mito-PstI is a novel tool to explore the relationship between astrocytic mitochondrial network dynamics and astrocytic mitochondrial Ca signaling in a brain-region-selective manner.
PubMed: 38853966
DOI: 10.1101/2024.05.29.596517